Clinical trial NCT03172494
Conditions: Diabetes Diabetes Mellitus, Type 2
Sponsor: Novo Nordisk A/S
Start date: 2017-05-26; Completion date: 2019-07-13
Enrollment: 720 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial is conducted in Asia. The aim of this trial is to confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Insulin degludec/liraglutide intervention 2: Insulin degludec intervention 3: Liraglutide
Intervention descriptions: intervention 1: Subcutaneously (s.c., under the skin)administration once daily in combination with metformin.

For 26 weeks. intervention 2: Subcutaneously (s.c., under the skin)administration once daily in combination with metformin.

For 26 weeks. intervention 3: Subcutaneously (s.c., under the skin)administration once daily in combination with metformin.

For 26 weeks.

Protocol documents:
Prot_000.pdf: 
Cover Page for Protocol 
 
Sponsor name: 
Novo Nordisk A/S 
NCT number 
NCT03172494 
Sponsor trial ID: 
NN9068-4148 
Official title of study: 
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral antidiabetic drugs (OADs). 
Document date: 
16 December 2019 
 


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List of contents
Protocol ...............................................................................................................................................
Appendix A .........................................................................................................................................
Appendix B..........................................................................................................................................
Appendix C .........................................................................................................................................
Appendix D .........................................................................................................................................
Attachment I and II............................................................................................................................
Protocol amendment 1 .......................................................................................................................
Protocol amendment 2 .......................................................................................................................
Protocol amendment 3 .......................................................................................................................
Protocol amendment 4 .......................................................................................................................
Protocol amendment 5 .......................................................................................................................
CONFIDENTIAL
Date:
Novo Nordisk
Version:
Status:
IDegLira
Trial ID: NN9068-4148
Clinical Trial Report
Appendix 16.1.1
16 December 2019
1.0
Final
16.1.1 Protocol and protocol amendments
CONFIDENTIAL
 
 
 
 
 
Redacted protocol 
Includes redaction of personal identifiable information only. 
 
 
 
. 
 
 


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
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Protocol
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in Chinese 
subjects with type 2 diabetes inadequately controlled on oral anti-
diabetic drugs (OADs)
Trial phase: 3a
Protocol originator
 
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
2 of 84
Table of Contents   
Page
Table of Contents..............................................................................................................................................2
Table of Tables..................................................................................................................................................5
Table of Figures................................................................................................................................................5
List of abbreviations.........................................................................................................................................6
1
Summary....................................................................................................................................................9
2
Flow chart ................................................................................................................................................12
3
Background information and rationale for the trial............................................................................15
3.1
Background information..............................................................................................................15
3.2
Rationale for the trial...................................................................................................................15
4
Objectives and endpoints........................................................................................................................16
4.1
Objectives ....................................................................................................................................16
4.1.1
Primary objective.......................................................................................................16
4.1.2
Secondary objectives .................................................................................................16
4.2
Endpoints .....................................................................................................................................16
4.2.1
Primary endpoint........................................................................................................16
4.2.2
Secondary endpoints..................................................................................................16
4.2.2.1
Confirmatory secondary endpoints .....................................................16
4.2.2.2
Supportive secondary endpoints..........................................................17
5
Trial design ..............................................................................................................................................19
5.1
Type of trial .................................................................................................................................19
5.2
Rationale for trial design..............................................................................................................20
5.3
Treatment of subjects...................................................................................................................20
5.4
Treatment in the follow-up period...............................................................................................21
5.5
Treatment after end of trial ..........................................................................................................21
5.6
Rationale for treatment ................................................................................................................21
6
Trial population.......................................................................................................................................22
6.1
Number of subjects......................................................................................................................22
6.2
Inclusion criteria ..........................................................................................................................22
6.3
Exclusion criteria.........................................................................................................................23
6.4
Withdrawal criteria ......................................................................................................................24
6.5
Subject replacement.....................................................................................................................24
6.6
Rationale for trial population.......................................................................................................25
7
Milestones.................................................................................................................................................25
8
Methods and assessments .......................................................................................................................26
8.1
Visit procedures...........................................................................................................................26
8.1.1
Fasting requirement for blood sampling and body weight ........................................26
8.1.2
Screening (Visit 1).....................................................................................................26
8.1.3
Screening failures ......................................................................................................27
8.1.4
Randomisation (Visit 2).............................................................................................27
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Protocol
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671 
Status:
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8.1.5
Treatment period (Visits 2 to 28)...............................................................................28
8.1.6
Follow-up (Visit 29) ..................................................................................................28
8.1.7
Unscheduled visits.....................................................................................................28
8.1.8
Subject withdrawal ....................................................................................................29
8.2
Subject related information..........................................................................................................29
8.2.1
Demography...............................................................................................................29
8.2.2
Concomitant illness and medical history...................................................................29
8.2.3
Adverse events...........................................................................................................30
8.2.4
Diabetes complications and treatment history...........................................................30
8.2.5
Smoking habits ..........................................................................................................30
8.2.6
Concomitant medication............................................................................................30
8.2.7
Body measurements...................................................................................................30
8.2.8
Vital signs (blood pressure and pulse).......................................................................31
8.2.9
Physical examination.................................................................................................32
8.2.10
Eye examination ........................................................................................................32
8.2.11
ECG ...........................................................................................................................33
8.2.12
Self-measured plasma glucose...................................................................................33
8.2.13
Self-measured 9-point plasma glucose profile...........................................................33
8.2.14
Hypoglycaemic episodes ...........................................................................................34
8.3
Laboratory assessments ...............................................................................................................35
8.3.1
Blood and urine sampling (central laboratory analysis) ............................................35
8.3.2
Calcitonin sampling (central laboratory analysis) .....................................................36
8.3.3
Antibody sampling (special laboratory analysis).......................................................37
8.3.4
PK blood sampling (special laboratory analysis).......................................................37
8.4
Pancreatitis...................................................................................................................................38
8.5
Thyroid disease............................................................................................................................38
8.6
Subject diaries..............................................................................................................................38
8.7
Subject compliance......................................................................................................................39
9
Trial supplies ...........................................................................................................................................40
9.1
Trial products...............................................................................................................................40
9.2
Labelling......................................................................................................................................40
9.3
Storage .........................................................................................................................................41
9.4
Drug accountability and destruction............................................................................................42
9.5
Auxiliary supplies........................................................................................................................42
10 Interactive voice/web response system ..................................................................................................43
11 Randomisation procedure ......................................................................................................................43
12 Adverse events, MESIs, technical complaints and pregnancies..........................................................44
12.1
Definitions ...................................................................................................................................44
12.2
Reporting of adverse events.........................................................................................................47
12.3
Follow-up of adverse events........................................................................................................49
12.4
Technical complaints and technical complaint samples ..............................................................50
12.4.1
Reporting of technical complaints .............................................................................50
12.4.2
Collection, storage and shipment of technical complaint samples ............................51
12.5
Pregnancies in female subjects ....................................................................................................52
12.6
Precautions and/or overdose ........................................................................................................53
12.7
Committees related to safety........................................................................................................54
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
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12.7.1
Novo Nordisk safety committee ................................................................................54
12.7.2
Calcitonin monitoring committee ..............................................................................54
12.7.3
Event adjudication committee....................................................................................54
13 Case report forms....................................................................................................................................55
13.1
Corrections to case report forms..................................................................................................55
13.2
Case report form flow..................................................................................................................56
14 Monitoring procedures ...........................................................................................................................57
14.1
Source data verification and source data requirements................................................................57
15 Data management....................................................................................................................................58
16 Computerised systems.............................................................................................................................58
17 Statistical considerations ........................................................................................................................59
17.1
Sample size calculation................................................................................................................60
17.2
Definition of analysis sets............................................................................................................61
17.3
Primary endpoint..........................................................................................................................62
17.3.1
Sensitivity analysis ....................................................................................................62
17.4
Secondary endpoints....................................................................................................................63
17.4.1
Confirmatory secondary endpoints............................................................................63
17.4.2
Supportive secondary endpoints ................................................................................64
17.4.2.1
Efficacy endpoints...............................................................................64
17.4.2.2
Safety endpoints..................................................................................66
17.5
Pharmacokinetic modelling .........................................................................................................72
18 Ethics........................................................................................................................................................74
18.1
Informed consent .........................................................................................................................74
18.2
Data handling...............................................................................................................................75
18.3
Information to subject during trial...............................................................................................75
18.4
Premature termination of the trial and/or trial site.......................................................................75
19 Protocol compliance................................................................................................................................76
20 Audits and inspections ............................................................................................................................76
21 Critical documents ..................................................................................................................................77
22 Responsibilities........................................................................................................................................78
22.1
Source data handling....................................................................................................................78
22.2
Delegation of responsibilities ......................................................................................................78
23 Reports and publications........................................................................................................................79
23.1
Communication of results............................................................................................................79
23.1.1
Authorship .................................................................................................................80
23.1.2
Site-specific publication(s) by investigator(s) ...........................................................80
23.2
Investigator access to data and review of results.........................................................................80
24 Retention of clinical trial documentation and human bio specimens.................................................81
24.1
Retention of clinical trial documentation.....................................................................................81
24.2
Retention of human bio specimens..............................................................................................81
25 Institutional Review Boards/Independent Ethics Committees and regulatory authorities..............82
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
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26 Indemnity statement ...............................................................................................................................82
27 References................................................................................................................................................83
Appendices and attachments to the protocol
Appendix A - Titration guideline
Appendix B - Medical events of special interest and events requiring adjudication 
Appendix C - New York Heart Association criteria for functional capacity in heart failure
Appendix D - Monitoring of calcitonin levels
Attachment I – List of key staff and relevant departments and vendors
Attachment II – Country list of key staff and relevant departments   
Table of Tables   
Page
Table 9–1
Trial products..........................................................................................................................40
Table 9–2
Storage conditions for trial products.......................................................................................41
Table of Figures   
Page
Figure 5–1
Trial Design ............................................................................................................................19
Figure 12–1
Initial reporting of AEs...........................................................................................................49
Figure 17–1
Novo Nordisk classification of hypoglycaemia......................................................................68
Figure 17–2
ADA classification of hypoglycaemia....................................................................................69
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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List of abbreviations
ADA
American Diabetes Association
AE
adverse event
AGI
α-glucosidase inhibitors
ALAT
alanine transaminase
ANCOVA
analysis of covariance
ASAT
aspartate aminotransferase 
BG
blood glucose
BMI
body mass index
CAS
completer analysis set
CFDA
China Food and Drug Administration
CRF
case report form
CTR
clinical trial report
DPP-4
dipeptidyl-peptidase-4 inhibitors
DUN
dispensing unit number
EASD
European Association for the Study of Diabetes
ECG
electrocardiogram
eCRF
electronic case report form
EMA
European Medicines Agency
EOT
end of treatment
FAS
full analysis set
FDA
Food and Drug Administration
FPG
fasting plasma glucose
GCP
good clinical practice
GLP-1
glucagon-like peptide-1
HbA1c
glycosylated haemoglobin
hCG
human chorionic gonadotrophin
HDL
high density lipoprotein
HOMA-β
homeostatic model assessment for β-cell function
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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ICH
International Conference on Harmonisation
ICMJE
International Committee of Medical Journal Editors
IDeg
insulin degludec
IDeglira
insulin degludec/liraglutide
IEC
independent ethics committee
IMP
investigational medicinal product
IRB
Institutional Review Board
IV/WRS
interactive voice/web response system
LDL
low density lipoprotein
LOCF
last observation carried forward
MAP
modelling analysis plan
MESI
medical event of special interest
MEN2
multiple endocrine neoplasia type 2
MMRM
mixed model for repeated measurements
NYHA
New York Heart Association
OAD
oral anti-diabetic drug
OD
once daily
PK
pharmacokinetics
PP
per protocol
SAE
serious adverse event
SAS
safety analysis set
SIF
safety information form
SmPC
summary of product characteristics
SMPG
self-measured plasma glucose
SU
sulphonylureas
SUSAR
suspected unexpected serious adverse reaction
T2DM
type 2 diabetes mellitus
TEAE
treatment emergent adverse event
TTT
treat-to-target
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
8 of 84
TZD
thiazolidinedione
UNR
upper normal range
UTN
universal trial number
VLDL
very low density lipoprotein
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Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
9 of 84
1
Summary
Primary objective
To confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects 
with type 2 diabetes mellitus inadequately controlled on oral anti-diabetic agents
Primary endpoint
Change from baseline in HbA1c after 26 weeks of treatment.
Secondary objectives
!
To confirm superiority of insulin degludec/liraglutide vs. insulin degludec on the following:
o
Change from baseline in body weight after 26 weeks of treatment
o
Number of treatment emergent severe or blood glucose confirmed hypoglycaemic 
episodes during 26 weeks of treatment 
!
To compare general efficacy and safety of insulin degludec/liraglutide to insulin degludec and 
liraglutide after 26 weeks of treatment
!
To compare the pharmacokinetics of insulin degludec/liraglutide and its individual components 
at clinically relevant doses during 26 weeks of treatment
Confirmatory secondary endpoints
!
Change from baseline in body weight after 26 weeks of treatment
!
Number of treatment emergent severe or blood glucose confirmed hypoglycaemic episodes 
during 26 weeks of treatment.
Trial design
This is a 26 week, randomised, parallel three-arm, open-label, multi-centre, treat-to-target 
confirmatory trial in Chinese subjects with type 2 diabetes mellitus inadequately controlled with 
metformin ± one other oral anti-diabetic agent: α-glucosidase inhibitors, sulphonylureas, glinides 
and thiazolidinediones. 
Subjects will be randomised in a 2:1:1 manner to receive insulin degludec/liraglutide, insulin 
degludec or liraglutide all once daily in combination with metformin. Other pre-trial oral anti-
diabetic agent treatment will be discontinued at randomisation. 
The randomisation of subjects to treatment groups will be stratified by previous treatment with
metformin ± one other oral anti-diabetic agent. 
The total trial duration for the individual subject will be approximately 29 weeks. 
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
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Trial population
A total of 720 subjects will be randomised. 
Key inclusion criteria
!
Informed consent obtained before any trial-related activities. Trial-related activities are any 
procedures that are carried out as part of the trial, including activities to determine suitability for 
the trial
!
Type 2 diabetes mellitus (clinically diagnosed)
!
Male or female, age ≥ 18 years at the time of signing informed consent
!
HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis, with the aim of a median of 
8.3%. When approximately 50% of the randomised subjects have a HbA1c above 8.3%, the 
remaining subjects randomised must have a HbA1c below or equal to 8.3%; or when 
approximately 50% of the randomised subjects have a HbA1c below or equal to 8.3%, the 
remaining subjects randomised must have a HbA1c above 8.3%
!
Current treatment for at least 90 calendar days prior to screening with metformin ± one other 
OAD: α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. For ≥60 
calendar days prior to screening subjects should be on a stable dose of: 
a.
Metformin (≥1500 mg or max tolerated dose) or
b. Metformin (≥1500 mg or max tolerated dose) and sulphonylureas (≥half of the max 
approved dose according to local label) or
c.
Metformin (≥1500 mg or max tolerated dose) and glinides (≥half of the max 
approved dose according to local label) or 
d. Metformin (≥1500 mg or max tolerated dose) and α-glucosidase inhibitors (≥half of 
the max approved dose according to local label) or
e. Metformin (≥1500 mg or max tolerated dose) and thiazolidinediones (≥half of the 
max approved dose according to local label)
Key exclusion criteria
!
Treatment with insulin (except for short-term treatment at the discretion of the investigator)
!
Treatment with glucagon-like-peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors 
within 90 days prior to screening
!
Impaired liver function, defined as alanine aminotransferase ≥ 2.5 times upper normal range
!
Impaired renal function defined as serum-creatinine ≥ 133 μmol/L for males and ≥ 125 μmol/L
for females, or as defined according to local contraindications for metformin
!
Screening calcitonin ≥ 50 ng/L
!
Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 
2 (MEN2)
!
Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable 
angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months prior to 
screening and/or planned coronary, carotid or peripheral artery revascularisation procedures
CONFIDENTIAL


Protocol
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Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
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!
Severe uncontrolled treated or untreated hypertension (systolic blood pressure ≥ 180 mmHg or 
diastolic blood pressure ≥ 100 mmHg
!
Proliferative retinopathy or maculopathy (macular oedema), requiring acute treatment
!
History of pancreatitis (acute or chronic)
Key efficacy assessments
!
HbA1c
!
Weight
!
Fasting plasma glucose 
!
Insulin dose at end of treatment 
Key safety assessments 
!
Hypoglycaemic episodes
!
Adverse events
Key pharmacokinetic assessments
!
Serum concentrations of insulin degludec and plasma concentrations of liraglutide for 
population pharmacokinetics
Trial products
Trial products for subcutaneous injection in this trial are:
!
Insulin degludec/liraglutide 100 units/mL + 3.6 mg/mL, 3 mL pre-filled pen
!
Insulin degludec 100 Units/mL, 3 mL pre-filled pen
!
Liraglutide 6 mg/mL (Victoza®), 3 mL pre-filled pen
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Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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2
Flow chart
Screening (SC) 
Randomisation (R)
Site visit (V) 
Telephone contact (T) 
Follow-up visit (FU)
SC
R
V
V
T
V
T
V
T
V
T
V
T
V
T
V
FU
Visit number
1
2
3
4
5
6
7
8    
9
10
11 
12
13
14
15
16
17
18
19 
20
21
22
23
24 
25 
26 
27
28
29
Time of visit (week)
-21
0
1
2
3
4
5 
6 
7
8
9 
10 
11
12
13 
14 
15
16
17 
18 
19
20
21 
22 
23 
24 
25
26
27
Visit window (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
+3
Subject related information/assessments
Informed consent
X
In/exclusion criteria
X
X
Randomisation
X
Withdrawal criteria
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant illness/Medical 
history
X
Concomitant medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Smoking habits
X
X
Demography
X
Diagnosis of diabetes
X
Diabetes treatment history
X
Diabetes complications
X
Family history of diabetes
X
Body measurements
Height
X
Body weight
X
X
X
X
X
X
X
X
Waist circumference
X
X
X
BMI
X
X
EFFICACY
Glucose metabolism
HbA1c
X
X
X
X
X
X
X
X
Fasting plasma glucose
X
X
X
X
X
X
X
Fasting insulin
X
X
X
Fasting glucagon
X
X
X
Fasting C-peptide
X
X
X
PK Sampling2
X
X
X
X
X
X
X
X
X
Self-measured plasma glucose
1-point SMPG profile3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
9-point SMPG profile
X
X
X
SAFETY
Adverse events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Technical complaints
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
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Protocol
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
13 of 84
Screening (SC) 
Randomisation (R)
Site visit (V) 
Telephone contact (T) 
Follow-up visit (FU)
SC
R
V
V
T
V
T
V
T
V
T
V
T
V
T
V
FU
Visit number
1
2
3
4
5
6
7
8    
9
10
11 
12
13
14
15
16
17
18
19 
20
21
22
23
24 
25 
26 
27
28
29
Time of visit (week)
-21
0
1
2
3
4
5 
6 
7
8
9 
10 
11
12
13 
14 
15
16
17 
18 
19
20
21 
22 
23 
24 
25
26
27
Visit window (days)
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
+3
Hypoglycaemic episodes
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECG4
X
X
Eye examination5
X
X
Physical examination
X
X
Vital signs
X
X
X
X
Antibodies
X
X
X
X
Biochemistry
X
X
X
X
Haematology
X
X
X
X
Hormones, calcitonin
X
X
X
X
Lipids
X
X
X
Urine dipstick
X
X
X
Pregnancy test (blood sample)6
X
X
REMINDERS
Handout ID card
X
Handout and instruct in BG-meter
use
X
Attend visit fasting 
X
X
X
X
X
X
X
X7
IV/WRS call
X
X
X
X
X
X
X
X
Dispense trial product. Instruct 
and hand out Directions for Use.
X
X
X
X
X
X
Drug accountability
X
X
X
X
X
X
X
Handout and instruct in/collect 
diary
X
X
X
X
X
X
X
X
X
X
X
Collect first date and dose of trial 
product
X
Collect last date and dose of trial 
product
X
Confirmation of unchanged dose 
of metformin 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
For liraglutide arm:
Confirmation of unchanged dose 
of liraglutide8
X
X
X
X
X
X
X
X
X
X
X
End of trial and sign off on case 
book
X
1.
Screening must take place within 14 calendar days prior to randomisation.
2.
For source data to be recorded in subject’s diary prior to every PK sampling visit, please see section 8.3.4.
3.
For IDeglira and IDeg arm: Daily pre-breakfast SMPG, last dose prior to titration and dose to be taken after titration must be recorded.       
For liraglutide arm: Pre-breakfast SMPG on 3 consecutive days prior to each visit/telephone contact must be recorded.
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4.
ECG obtained within 14 calendar days prior to Visit 2 as part of routine practice may replace the screening assessment, if results are available 
for evaluation at Visit 2. See section 8.2.11.
5.
Eye examination obtained within 90 calendar days prior to Visit 2 as part of routine practise may replace the screening assessment if results are 
available for evaluation at Visit 2. See section 8.2.10.
6.
For females of childbearing potential a urine pregnancy test should be performed at site if pregnancy is suspected or a menstrual period is 
missed. If the subject reports missing menstrual period at a telephone contact the subject must attend the site for an unscheduled visit as soon as 
possible for a urine pregnancy test. If positive, a confirmatory serum hCG test should be sent to the central laboratory.
7.
Please see section 8.1.6 for special fasting requirement at Visit 29.
8.
Subjects are to confirm unchanged dose of liraglutide once they have reached a dose of 1.8 mg.
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3
Background information and rationale for the trial
The trial will be conducted in compliance with this protocol, ICH GCP1and applicable regulatory 
requirements and in accordance with the Declaration of Helsinki2. In this document, the term 
investigator refers to the individual responsible for the overall conduct of the clinical trial at a trial 
site.
3.1
Background information
Type 2 diabetes mellitus (T2DM) is a progressive disorder characterised by insulin resistance and 
impaired insulin secretion. A number of landmark studies have demonstrated the importance of 
maintaining good glycaemic control to reduce the risk of long-term complications associated with 
diabetes3,4. Given the progressive nature of T2DM, current anti-diabetic therapies with one or two 
oral anti-diabetic drugs (OADs) often fail to provide sustained glycaemic control. The current 
treatment cascade by the Chinese Diabetes Society, American Diabetes Association (ADA) and 
European Association for the Study of Diabetes (EASD) consensus follows a stepwise approach 
comprising lifestyle changes with pharmacological intervention. Metformin is recommended as 
initial pharmacological therapy, followed by combination therapy with other OADs, glucagon-like 
peptide 1 (GLP-1) receptor agonists or insulin as the disease progresses5,6. The successful outcome 
of recent global trials combining basal insulin and GLP-1 receptor agonist treatment as separate 
injections has led to the inclusion of this treatment combination in the most recent ADA/EASD 
position statement on management of hyperglycaemia in T2DM5.
3.2
Rationale for the trial
Insulin degludec/liraglutide (IDegLira) is a combination drug containing the long acting basal 
insulin analogue, insulin degludec (IDeg) and the GLP-1 analogue, liraglutide intended for once 
daily (OD) use in a single injection in subjects with T2DM. IDegLira was developed to take 
advantage of the combined effects of a basal insulin and GLP-1 analogue on glycaemic control 
through the actions on fasting glucose mediated by IDeg and liraglutide, and on postprandial 
glycaemic control mediated by liraglutide. The global clinical development programme for 
IDegLira has confirmed that the modes of action of IDeg and liraglutide result in clinically 
important improvements in glycaemic control with low risk of hypoglycaemia and weight gain in 
patients with T2DM7. In addition, the convenience of administering both components in a single 
daily injection, using a titration scheme similar to that used for basal insulin products, is expected to 
facilitate treatment compliance for patients.  
This protocol describes a clinical trial with the aim to confirm the safety and efficacy of OD
treatment with IDegLira compared to each of the monocomponents. The trial will be used for 
registration of IDegLira in China. For detailed information on IDeglira, IDeg or liraglutide, please 
see Investigator’s Brochure, any updates hereof, and/or SmPCs/ local labelling, as applicable.
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4
Objectives and endpoints
4.1
Objectives
4.1.1
Primary objective
To confirm the efficacy of IDegLira in controlling glycaemia in Chinese subjects with T2DM
inadequately controlled on oral anti-diabetic agents
This is done by comparing the difference in change from baseline in HbA1c after 26 weeks of 
treatment to a superiority margin of 0.0% for IDegLira vs. liraglutide and to a non-inferiority 
margin of 0.4% for IDegLira vs. IDeg.
4.1.2
Secondary objectives
!
To confirm superiority of IDegLira vs. IDeg on the following:
o
Change from baseline in body weight after 26 weeks of treatment
o
Number of treatment emergent severe or blood glucose confirmed hypoglycaemic 
episodes during 26 weeks of treatment 
!
To compare general efficacy and safety of IDegLira to IDeg and liraglutide after 26 weeks of 
treatment
!
To compare the pharmacokinetics of IDegLira and its individual components at clinically 
relevant doses during 26 weeks of treatment
4.2
Endpoints
4.2.1
Primary endpoint
Change from baseline in HbA1c after 26 weeks of treatment.
4.2.2
Secondary endpoints
4.2.2.1
Confirmatory secondary endpoints
The below endpoints will be tested with the aim to confirm superiority of IDegLira vs. IDeg:
!
Change from baseline in body weight after 26 weeks of treatment
!
Number of treatment emergent severe or blood glucose (BG) confirmed hypoglycaemic 
episodes during 26 weeks of treatment
To protect the type 1 error rate when testing the confirmatory endpoints, a closed test procedure will 
be used. 
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4.2.2.2
Supportive secondary endpoints
Efficacy endpoints
!
Insulin dose after 26 weeks of treatment
!
Responder for HbA1c after 26 weeks of treatment (Yes/No)
-
HbA1c < 7.0% 
-
HbA1c ≤ 6.5%  
-
HbA1c < 7.0% and change from baseline in body weight below or equal to zero
-
HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero
-
HbA1c < 7.0% without severe or BG confirmed hypoglycaemic episodes during the last 
12 weeks of treatment
-
HbA1c ≤ 6.5% without severe or BG confirmed hypoglycaemic episodes during the last 
12 weeks of treatment
-
HbA1c < 7.0% and change from baseline in body weight below or equal to zero and 
without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of 
treatment
-
HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero and 
without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of 
treatment 
!
Change from baseline after 26 weeks of treatment in:
-
Fasting plasma glucose (FPG)
-
Waist circumference 
-
9-point profile
-
Mean of the 9-point profile
-
Mean post prandial increment (from before meal to 90 min after breakfast, lunch and 
dinner). The mean increment over all meals will be derived as the mean of all available 
meal increments
!
Fasting C-peptide, fasting insulin, and fasting glucagon after 26 weeks of treatment
!
Beta-cell function, quantified by homeostatic model assessment (HOMA-β) after 26 weeks of 
treatment
!
Fasting lipid profile after 26 weeks of treatment
Safety endpoints
!
Number of treatment emergent adverse events (TEAEs) during 26 weeks of treatment
!
Number of treatment emergent nocturnal severe or BG confirmed hypoglycaemic episodes 
during 26 weeks of treatment
!
Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes 
during 26 weeks of treatment
!
Number of treatment emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic 
episodes during 26 weeks of treatment
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!
Number of treatment emergent hypoglycaemic episodes according to ADA definition during 26 
weeks of treatment
!
Change from baseline in clinical evaluations after 26 weeks of treatment
-
Physical examination
-
Fundoscopy or fundusphotography
-
Electrocardiogram (ECG)
-
Pulse
-
Blood pressure
!
Change from baseline in laboratory assessments during 26 weeks of treatment 
-
Biochemistry 
-
Haematology 
-
Calcitonin
!
Urinalysis (dipstick for erythrocytes, protein, glucose and ketones)
!
Antibodies towards trial product
Pharmacokinetic (PK) endpoint
!
Serum concentrations of IDeg and plasma concentrations of liraglutide to be evaluated in a 
population PK analysis
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5
Trial design
5.1
Type of trial
This is a 26 week, randomised, parallel three-arm, open-label, multi-centre, treat-to-target (TTT)
confirmatory trial in Chinese subjects with T2DM inadequately controlled with metformin ± one 
other OAD: α-glucosidase inhibitors (AGI), sulphonylureas (SU), glinides and thiazolidinediones 
(TZD). Inadequately controlled diabetes will be defined as a HbA1c level of 7.0-10% (both 
inclusive).
Subjects will be randomised in a 2:1:1 manner to receive IDegLira, IDeg or liraglutide all once 
daily (OD) in combination with metformin. Other pre-trial OAD treatment will be discontinued at 
randomisation. The randomisation of subjects to treatment groups will be stratified by previous 
treatment with metformin ± one other OAD. 
The duration of the trial from screening (Visit 1) to follow-up (Visit 29) will be approximately 29
weeks with treatment duration of 26 weeks. At the screening visit, eligibility of the subjects is
determined followed by randomisation (Visit 2). One week after end of treatment (Visit 28), the 
follow-up (Visit 29) will be conducted. 
The trial design is summarised schematically below.
Figure 5–1
Trial Design
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5.2
Rationale for trial design
Based on prior experience from IDegLira trials, the treatment duration of 26 weeks is sufficient to 
reach a stable HbA1c level, and to obtain sufficient data for efficacy and safety evaluation. The 
parallel design has been chosen instead of a cross-over design to avoid the risk of carry-over effect 
and to keep the treatment period as short as possible. 
An open label design has been chosen due to two different regimens; fixed dose treatment of 
liraglutide with a maximal recommended dose of 1.8 mg/mL per day and treat-to-target for the IDeg 
and IDegLira arms. For the IDegLira treatment arm the maximal dose is 50 dose-steps per day since 
this will contain the liraglutide component maximal recommended dose of 1.8 mg/mL per day.
Blinding of the trial by use of double dummy design would mean an unacceptable number of 
injections, increase the complexity and thereby introduce an increased risk of non-compliance or 
withdrawal. 
To obtain improved HbA1c results the TTT approach has been chosen in order to ensure optimal 
treatment with frequent visits and titration of IDeg and IDegLira based on pre-breakfast self-
measured plasma glucose (SMPG) values. 
5.3
Treatment of subjects
Subjects treated with metformin ± one other OAD (AGI, SU, glinides or TZD) in accordance with 
the inclusion criterion are eligible for the trial. At randomisation subjects will have to discontinue 
all OADs except for metformin, leaving this at pre-trial dose in combination with one of the 
treatments for subcutaneous injection described below:
1. IDegLira added to current metformin therapy. Start dose will be 10 dose steps (10 U of IDeg 
and 0.36 mg of liraglutide) and will be titrated according to the Titration Guideline (appendix 
A) aiming for a FPG target of 4.0-5.0 mmol/L
2. IDeg added to current metformin therapy. Start dose will be 10 U and will be titrated according 
to the Titration Guideline aiming for a FPG target of 4.0-5.0 mmol/L
3. Liraglutide added to current metformin therapy. Start dose will be 0.6 mg and subsequent 0.6 
mg weekly dose escalation to the target dose of 1.8 mg. If subjects are not able to tolerate the 
dose escalation as described above, the visit window may be used to prolong exposure time for 
a given dose. Liraglutide dose of 1.8 mg/day will be continued for the remaining part of the trial 
and at each site visit/telephone contact subjects must be asked to confirm their dose
The Titration Guideline contains more detailed guidance on switching from pre-trial treatment to 
trial products, timing of injection, and titration of these.
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5.4
Treatment in the follow-up period
After 26 weeks of trial product exposure, a 1-week interval between the end of treatment (Visit 28) 
and the follow-up (Visit 29) is necessary to allow for trial product washout. Subjects must at the 
investigator’s discretion be switched to a suitable marketed product excluding insulin detemir
(Levemir®), IDeg, or any GLP-1 receptor agonists as these may interfere with antibody 
measurements performed at Visit 29. 
5.5
Treatment after end of trial
When completing the trial subjects should be switched to a suitable marketed product at the 
discretion of the investigator.
5.6
Rationale for treatment
Enrolment of insulin-naïve subjects with T2DM, inadequately controlled on 1-2 OADs, has been 
chosen to demonstrate the efficacy and safety of IDegLira, when added to metformin. 
The rationale for including subjects with pre-trial treatment metformin ± one other OAD is to 
mimic common practice of diabetes treatment in subjects with T2DM failing on 1-2 OADs and will 
prevent undue heterogeneity of the treatment arms due to diverse treatment. The daily dose of
metformin (∀1500 mg or max tolerated dose) is close to the maximum recommended dose as per 
local labelling for the treatment of type 2 diabetes.
When glycaemic control is not achieved or sustained on this background, the addition of another 
OAD, or initiation of GLP-1 receptor agonists, basal insulin or IDegLira can be considered. 
The expected outcome after 26 weeks of treatment with IDegLira compared to IDeg is similar 
change in HbA1c, less weight gain, lower post-prandial glucose levels, and a lower rate of 
hypoglycaemic events. In comparison with liraglutide a greater decrease in HbA1c, a lower FPG
level and fewer gastro intestinal AEs are anticipated for IDegLira. For more detailed information on 
IDegLira, please see Investigator’s Brochure7 or any updates hereof.
IDeg and liraglutide have been included as comparators in order to comply with regulatory 
requirements to assess the risk benefit profile of the combination product as compared to the 
individual components.
Apart from metformin, other OADs are primarily excluded at randomisation because they are not 
approved for use combined with liraglutide and metformin by the CFDA and are also not supported 
by the China clinical programme for liraglutide in terms of safety (and efficacy).
Metformin treatment will be in accordance with locally approved label. 
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6
Trial population
6.1
Number of subjects 
Countries planned to participate: China
Number of subjects planned to be screened: 1200
Number of subjects planned to be randomised: 720
Number of subjects expected to complete the trial: 612
A screening failure rate of 40% and a withdrawal rate of 15% are anticipated.
6.2
Inclusion criteria
For an eligible subject, all inclusion criteria must be answered "yes".
1. Informed consent obtained before any trial-related activities. Trial-related activities are any 
procedures that are carried out as part of the trial, including activities to determine suitability for 
the trial
2. Male or female, age ≥ 18 years at the time of signing informed consent
3. Type 2 diabetes mellitus (clinically diagnosed)
4. HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis, with the aim of a median of 
8.3%. When approximately 50% of the randomised subjects have a HbA1c above 8.3%, the 
remaining subjects randomised must have a HbA1c below or equal to 8.3%; or when 
approximately 50% of the randomised subjects have a HbA1c below or equal to 8.3%, the 
remaining subjects randomised must have a HbA1c above 8.3%
5. Current treatment for at least 90 calendar days prior to screening with metformin ± one other 
OAD: AGI, SU, glinides or TZD. For ≥60 calendar days prior to screening subjects should be 
on a stable dose of: 
a.
Metformin (≥1500 mg or max tolerated dose) or
b. Metformin (≥1500 mg or max tolerated dose) and SU (≥half of the max approved 
dose according to local label) or
c.
Metformin (≥1500 mg or max tolerated dose) and glinides (≥half of the max 
approved dose according to local label) or 
d. Metformin (≥1500 mg or max tolerated dose) and AGI (≥half of the max approved 
dose according to local label) or
e. Metformin (≥1500 mg or max tolerated dose) and TZD (≥half of the max approved 
dose according to local label)
6. Body mass index (BMI) ≤40 kg/m2
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7. Able and willing to adhere to the protocol including performing self-monitoring of plasma 
glucose profiles, keeping a trial diary and using a pre-filled pen device
6.3
Exclusion criteria
For an eligible subject, all exclusion criteria must be answered "no".
1. Known or suspected hypersensitivity to trial product(s) or related products
2. Previous participation in this trial. Participation is defined as informed consent
3. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing 
potential and not using adequate contraceptive methods (sterilisation, intrauterine device (IUD), 
oral contraceptives or barrier methods)
4. Receipt of any investigational medicinal product within 30 calendar days prior to Visit 1
5. Current use of any antidiabetic drug (except for metformin, AGI, SU, glinides or TZD) or 
anticipated change in concomitant medication, that in the investigator’s opinion could interfere 
with glucose level (e.g. systemic corticosteroids)
6. Use of non-herbal Chinese medicine or other non-herbal local medicine with 
unknown/unspecified content within 90 calendar days prior to screening. Herbal traditional 
Chinese medicine or other local herbal medicines may, at the investigator’s discretion, be 
continued throughout the trial 
7. Treatment with insulin (except for short-term treatment at the discretion of the investigator)
8. Treatment with GLP-1 receptor agonists or DPP-4 inhibitors within 90 calendar days prior to 
screening
9. Impaired liver function, defined as alanine aminotransferase (ALAT) ≥ 2.5 times upper normal 
range (UNR)
10. Impaired renal function defined as serum-creatinine ≥ 133 μmol/L for males and ≥ 125 μmol/L
for females, or as defined according to local contraindications for metformin
11. Screening calcitonin ≥ 50 ng/L
12. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine 
neoplasia type 2 (MEN2)
13. Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable 
angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months prior to 
screening and/or planned coronary, carotid or peripheral artery revascularisation procedures
14. Severe uncontrolled treated or untreated hypertension (systolic blood pressure ≥ 180 mm Hg or 
diastolic blood pressure ≥ 100 mm Hg
15. Proliferative retinopathy or maculopathy (macular oedema), requiring acute treatment
16. Subject with a clinically significant, active (during the past 12 months) disease of the 
gastrointestinal, pulmonary, neurological, genitourinary or haematological system (except for 
conditions associated with T2DM) that in the opinion of the investigator may confound the 
results of the trial or pose additional risk in administering trial drug
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17. Mental incapacity, unwillingness or language barrier precluding adequate understanding of the 
trial procedure or cooperation with the trial site personnel
18. Known or suspected abuse of alcohol or narcotics
19. History of pancreatitis (acute or chronic)
20. Suffer from a life threatening disease including malignant neoplasms and medical malignant 
neoplasms within the last 5 years (except basal and squamous cell skin cancer)
6.4
Withdrawal criteria
The subject may withdraw at will at any time without explanation.
The subject may be withdrawn from the trial at the discretion of the investigator due to a safety 
concern or if judged non-compliant with trial procedures
A subject must be withdrawn if the following applies:
1. Inclusion in the trial in violation of the inclusion and/or exclusion criteria
2. Pregnancy 
3. Intention of becoming pregnant
4. Initiation of any systemic treatment with products which in the investigator’s opinion could 
interfere with glucose metabolism (e.g. systemic corticosteroids)
5. If all pre-breakfast SMPG values taken on three consecutive days or if any FPG samples 
analysed by the central laboratory exceeds the limit of:
-
15.0 mmol/L after baseline to week 6 
-
13.3 mmol/L from week 6 to week 12 
-
11.1 mmol/L from week 12 to last week prior to end of treatment 
-
and given there is no intercurrent cause for the hyperglycaemia, a confirmatory FPG 
must be performed  at the next scheduled visit, or if deemed necessary by the 
investigator at an unscheduled visit. If the confirmatory FPG exceeds the limits stated 
above, the subject must be withdrawn
6. If the investigator suspects acute pancreatitis, all drugs suspected to relate to this condition 
should be discontinued until confirmatory tests have been conducted and appropriate treatment 
should be initiated. Subjects who are diagnosed with acute pancreatitis with minimum 2 of 3 
characteristics: abdominal pain, amylase and/or lipase > 3x UNR or characteristic findings on 
computer axial tomography (CT)/magnetic resonance imaging (MRI) must be withdrawn from 
the trial
6.5
Subject replacement
Subjects who are withdrawn will not be replaced.
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6.6
Rationale for trial population
The rationale for this specific trial population is to ensure inclusion of subjects resembling the target 
population in common practice. The HbA1c range is chosen to include subjects for whom diabetes is 
not optimally controlled on their current treatment and hence would benefit from an intensified 
treatment regimen. 
A BMI limit of ≤40 kg/m2 is chosen to include as broad a population as possible while excluding 
morbidly obese individuals who are extremely insulin resistant. 
Only serious concomitant conditions i.e. NYHA class III-IV (see appendix C), history of recent 
serious cardiac event, neoplastic disease, renal or hepatic impairment, major surgery etc.), which 
could interfere with trial schedule/procedures, preclude subjects from entering into the trial.
7
Milestones
Planned duration of recruitment period (First Subject First Visit - Last Subject First Visit): 54
weeks. End of trial is defined as Last Subject Last Visit.
Recruitment will be performed according to an agreement made up-front with the individual 
investigational site. The screening will be monitored closely during the entire recruitment period. In 
order to secure recruitment timelines, the agreed distribution of subjects between sites may be 
changed. The screening and randomisation rate will be followed closely in order to estimate when 
to stop screening. Please see section 11 for randomisation procedure.
Trial registration:
Information of the trial will be disclosed at clinicaltrials.gov, chinadrugtrials.org.cn and 
novonordisk-trials.com. According to the Novo Nordisk Code of Conduct for Clinical Trial 
Disclosure, it will also be disclosed according to other requirements such as those of the 
International Committee of Medical Journal Editors (ICMJE)8, the Food and Drug Administration 
Amendment Act (FDAAA)9, European Commission Regulation for European Drug Regulatory 
Authorities Clinical Trials (EudraCT)10and other relevant recommendations or regulations. If a 
subject requests to be included in the trial via the Novo Nordisk e-mail contact at these web sites, 
Novo Nordisk may disclose the investigator's contact details to the subject. As a result of increasing 
requirements for transparency, some countries require public disclosure of investigator names and 
their affiliations.
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8
Methods and assessments
8.1
Visit procedures
Timing of site visits, telephone contacts, their windows and assessments to be performed are 
specified in the flow chart in section 2. In the following section instructions on how to perform and 
record results of all assessments are described in more detail.
The investigator must keep a subject screening log, a subject identification code list and a subject 
enrolment log. The screening log and enrolment log may be combined into one list. 
8.1.1
Fasting requirement for blood sampling and body weight
As outlined in the flow chart subjects must attend most of the site visits fasting, i.e. at least eight 
hours without food and drink intake, except for water. Trial products and metformin should be 
withheld on the day of the site visit until blood sampling and body weight assessment (if applicable) 
have been performed. Any other prescribed medication should be taken as usual. If the subjects 
attend the visit in a non-fasting state the blood sampling should be rescheduled as per section 8.1.7.
Please see section 8.1.6  for special requirement in relation to fasting and administration of insulin 
prior to the follow-up Visit 29.
8.1.2
Screening (Visit 1)
Must take place within 14 calendar days prior to randomisation.
Before screening, the trial site staff must provide the subjects with oral and written information 
about the trial. See section 18.1 for instructions on informed consent. Ensure subject has signed the 
informed consent before any trial related procedures can take place.
At screening, subjects will be assigned a unique number. This will remain the same throughout the 
trial. The number will be registered in an interactive voice/web response system (IV/WRS) which 
will be used for screening, randomisation and allocation of trial product to each subject throughout 
the trial (see section 9.4 and 10 for use of the IV/WRS). Subject numbers will automatically be 
transferred into an electronic case report form (eCRF) system used by the investigator or other
relevant trial site staff for transcription of source data throughout the trial. See section 13 for more 
information on the eCRF.
At screening subjects will be provided with a card stating that they are participating in a trial and 
giving contact address(es) and telephone number(s) of relevant trial site staff. Subjects should be 
instructed to return the card to the investigator at the last trial visit or to destroy the card after the 
last visit.
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All inclusion/exclusion criteria must be reviewed and if any of the criteria cannot be assessed e.g. 
criteria related to results from blood sampling performed at screening or if a valid eye examination 
is missing, the investigator must ensure these are obtained for assessment of eligibility prior to 
being able to randomise the subject at Visit 2. If the subject is ineligible, please see section 8.1.3 for
how to screen fail subjects.
Eligible subjects should be instructed to continue on their current OAD treatment until Visit 2.
Subjects will be provided with diaries for completion of source data in between site visits. Please 
see section 8.6 for source data to be recorded in the diaries and how review is to be done by the 
investigator.
Subjects will be provided with a BG-meter for use throughout the trial. Please see section 8.2.12 for 
instructions.
8.1.3
Screening failures
For screening failures the screening failure form must be completed with the reason for not 
continuing in the trial. The date of informed consent must be transcribed into the eCRF. Only 
serious adverse events (SAEs) from screening failures must be transcribed into the eCRF. Follow-
up of SAEs must be carried out according to section 12.3.
Screening failures experiencing an AE that would otherwise quality for adjudication (see section 
12.7.3) will not be adjudicated as no trial product has been administered. 
A screening failure session must be made in the IV/WRS.
When data has been source data verified and all queries have been resolved, the case book must be 
signed by the investigator in the eCRF.
Re-sampling or re-screening is not allowed if the subject has failed one of the inclusion or exclusion 
criteria related to laboratory parameters.
8.1.4
Randomisation (Visit 2)
All inclusion/exclusion criteria and results from assessments at the screening visit including blood 
sampling, ECG and eye examination results must be available and reviewed by the investigator 
prior to randomisation to ensure subject remains eligible.
To be randomised, subjects must discontinue any OAD treatment except for metformin. Subjects 
will then be randomised to receive IDegLira, IDeg or liraglutide all in combination with metformin. 
Please see the Titration Guideline for initiation of randomised treatment. Also start doses and 
titration of IDegLira and IDeg can be found here. Please see section 5.3 for start dose and escalation 
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of liraglutide. Subjects must be trained in correct use of the pens, and directions for use of the pens 
must be provided in writing to randomised subjects. This must be documented in subjects’ records. 
At Visit 2, prior to leaving the site, subjects should demonstrate to the investigator, that they are 
able to use the pens correctly". The training can be repeated if deemed necessary.
The dose of metformin should remain unchanged throughout the trial. See section 8.2.6.
8.1.5
Treatment period (Visits 2 to 28)
During the treatment period the investigator should ensure that subjects comply with the scheduled 
site visits and telephone contacts and that they record the required source data in the diaries prior to 
every site visit/telephone contact.
If needed a telephone contact may be changed into a site visit. It is the responsibility of the 
investigator to ensure the contact regardless of the format takes place.
At the end of treatment (Visit 28) subjects will be switched from trial product to an appropriate anti-
diabetic treatment at the discretion of the investigator. However, IDeg, insulin detemir (Levemir®) 
or any GLP-1 receptor agonists are not allowed, since they may interfere with antibodies measured
at follow-up (Visit 29). 
8.1.6
Follow-up (Visit 29)
The follow-up visit should be undertaken no earlier than 7 calendar days after Visit 28. Subjects 
must attend this visit having fasted for 2 hours (i.e. no food or drink except water) prior to the blood 
sampling for antibody analysis. Subjects on any type of insulin must not have administered this 
within 12 hours of the blood sampling.
At completion of this visit subjects may again be switched to another suitable marketed product at 
the investigator’s discretion.
8.1.7
Unscheduled visits 
Unscheduled visits can be performed at any time at the discretion of the investigator. An 
unscheduled visit should be performed, if:
!
An AE occurs that needs further attention
!
Additional laboratory sample is needed due to a medical event of special interest (MESI)
!
A confirmatory pregnancy test is needed
!
A confirmatory FPG test for withdrawal criteria #5 is required
!
A blood re-sampling related to a specific visit (if not possible to reschedule blood sampling 
within the visit window)
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For all of the above an unscheduled visit form must be completed in the eCRF, indicating the reason 
for the visit. 
An unscheduled visit form should not be completed, if the subject attends the clinic for a blood re-
sampling within the visit window. Instead a requisition form must be completed with the visit 
number the re-sampling refers to and data must be entered into the eCRF for the corresponding 
visit. Also, additional trial product dispensing does not require the use of the unscheduled visit 
form. Here an additional dispensing session should be made in the IV/WRS.
8.1.8
Subject withdrawal 
If a subject is withdrawn from the trial, the investigator must aim to undertake procedures similar to 
those described for Visits 28 and 29 as soon as possible. The end-of-trial form must be completed, 
and final drug accountability must be performed even if the subject is not able to come to the trial 
site. A withdrawal session must be made in the IV/WRS. The case book must be signed.
Although a subject is not obliged to give his/her reason(s) for withdrawing from a trial, the 
investigator must make a reasonable effort to ascertain the reason(s), while fully respecting the 
subject's rights. Where the reasons are obtained, the primary reason for not completing the trial
must be specified on the end-of-trial form in the eCRF. 
8.2
Subject related information 
8.2.1
Demography 
This is an account of date of birth, sex, race and ethnicity.  
8.2.2
Concomitant illness and medical history
A concomitant illness is any illness that is present at the start of the trial (i.e. at the screening visit). 
Concomitant illness includes any pre-planned procedures/surgeries and any intermittent illness (e.g. 
allergy to food, medication, pollen or others) that is not apparent at the time of screening. 
T2DM should not be recorded as concomitant illness.
Medical history is a medical event that the subject has experienced in the past.
The information collected for concomitant illness and medical history should include diagnosis, 
date of onset and date of resolution or continuation, as applicable.
Any change to a concomitant illness should be recorded during the trial. A clinically significant 
worsening of a concomitant illness must be reported as an AE.
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8.2.3
Adverse events
Adverse events (AEs) will be recorded throughout the trial in accordance with the procedure 
described in section 12.
8.2.4
Diabetes complications and treatment history
The date of diagnosis of T2DM, current diabetes complications, diabetes treatment history, and
family history of diabetes must as a minimum be recorded in the eCRF at screening.
8.2.5
Smoking habits
Details of smoking habit or history must be recorded at Visit 1 and Visit 28. Smoking is defined as 
smoking at least one cigarette, cigar or pipe daily. The collected information should include whether 
or not the subject smokes or has smoked. If the subject smokes or has smoked, record 
approximately when the subject started smoking, and if applicable, when the subject stopped 
smoking.
8.2.6
Concomitant medication
A concomitant medication is any medication including traditional herbal Chinese medicine and 
other local herbal medicine, other than the trial product(s), which is taken during the trial, from 
Visit 1 to Visit 28.
The information collected for each concomitant medication includes trade name or generic name, 
indication, start date and stop date or continuation.
Details of any concomitant medication must be recorded at the first visit. Changes in concomitant 
medication must be recorded at each visit as they occur. 
At each contact with site the subject should confirm that their metformin treatment is unchanged. In 
case of safety concern the dose may be reduced at the discretion of the investigator. The reason, 
date and duration of the change should be documented and transcribed into the eCRF. 
If a change is due to an AE, then this must be reported according to section 12. If the change 
influences the subject's eligibility to continue in the trial, the monitor must be informed.
8.2.7
Body measurements
Height
Height is measured without shoes in centimetres (cm) and recorded to nearest cm.
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Body weight
Body weight should be recorded in kilograms (kg) with one decimal, measured without shoes and 
only wearing light clothing. Subject should be fasting except for body weight assessed at Visit 1. 
The same scale should be used throughout the trial, if possible. 
Body Mass Index 
BMI will be automatically calculated in the eCRF once height and body weight have been entered. 
At the screening visit the BMI must be in accordance with the relevant inclusion criterion, see 
section 6.2. 
Waist circumference
The waist circumference is defined as the minimal abdominal circumferences located midway 
between the lower rib margin and the iliac crest.
The waist circumferences will be measured to the nearest 0.5 cm using a non-stretchable measuring 
tape (provided by Novo Nordisk). Three consecutive measurements should be performed and 
recorded in the eCRF.
The subject should be measured in a standing position with an empty bladder and wearing light 
clothing with accessible waist. The subject should be standing with arms down their side and feet 
together. The tape should touch the skin but not compress soft tissue. Twists in the tape should be 
avoided. The subject should be asked to breathe normally and the measurement should be taken 
when the subject is breathing out gently.
8.2.8
Vital signs (blood pressure and pulse)
Diastolic blood pressure, systolic blood pressure and pulse (beats per minute) should be assessed 
while the subject is in a sitting position. Measurements should be performed after 5 minutes of rest. 
Blood pressure must be measured three times at a visit and all three values should be recorded. The 
mean value will be calculated by the eCRF and must be in accordance with the relevant exclusion 
criterion, see section 6.3.
If the investigator suspects white coat hypertension at the screening visit and/or randomisation visit, 
one re-assessment of the systolic and diastolic blood pressure (as described above) is allowed.
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8.2.9
Physical examination
A physical examination must include:
!
General appearance 
!
Head, ears, eyes, nose, throat, neck
!
Thyroid gland
!
Respiratory system
!
Cardiovascular system
!
Gastrointestinal system including mouth
!
Musculoskeletal system
!
Central and peripheral nervous system
!
Skin
!
Lymph node palpation
The investigator must interpret whether results are normal or abnormal and if abnormal whether this 
is clinically significant or not. Results must be transcribed into the eCRF.
8.2.10
Eye examination
Eye examination (fundoscopy or fundusphotography) must be performed by the investigator, a local 
ophthalmologist or an optometrist according to local practice. 
If an eye examination has been performed within 90 calendar days prior to Visit 2, the procedure 
does not need to be repeated, if the results are available for evaluation at Visit 2 and no worsening 
of visual function since the examination has occurred. If the eye examination is performed before 
the subject consented to participate in the trial, it must also be stated in the subject’s medical 
records that this procedure was not performed in relation to the trial. 
If an eye examination has been performed within 14 calendar days prior to Visit 28, the procedure 
does not need to be repeated, if the results are available for evaluation at Visit 28 and no worsening 
of visual function since the examination has occurred. 
The investigator must interpret whether results are normal or abnormal and if abnormal whether this 
is clinically significant or not. The investigator must sign and date all eye examination results to 
verify that data has been reviewed, and results must be transcribed into the eCRF.
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8.2.11
ECG
A 12-lead ECG must be performed as part of screening procedures and results must be available for 
evaluation at Visit 2 prior to randomisation.
An ECG obtained within 14 calendar days prior to Visit 2 as part of routine practice may replace the 
screening assessment, if results are available for evaluation at Visit 2. If the ECG is performed 
before the subject consented to participate in the trial, it must also be stated in the subject´s medical 
records that this procedure was not performed in relation to the trial. 
An ECG performed within 14 calendar days prior to Visit 28 is acceptable, if the results are 
available for evaluation at Visit 28.
The investigator must interpret whether results are normal or abnormal and if abnormal whether this 
is clinically significant or not. The investigator must sign and date the ECG to verify that data has 
been reviewed, and results must be transcribed into the eCRF.
8.2.12
Self-measured plasma glucose
At the screening visit, subjects should be supplied with a BG-meter which must be used for all 
measurements during the trial. Subjects should be supplied with oral and written directions for use 
of the device including the performance of regular calibrations according to the manufacturer’s 
instructions. Trial site staff should, as necessary, repeat the directions for use to subjects at 
subsequent visits. 
The BG-meter uses test strips calibrated to plasma values. Therefore, all measurements performed 
with capillary blood are automatically calibrated to plasma equivalent glucose values, which will be 
shown on the display and hence recorded in the eCRF as SMPG values.
Subjects should be instructed in how to record the SMPG values in the provided diaries and should 
only record the values based on measurements obtained with the provided BG-meter. See section 
8.6 for source data to be recorded in subject diaries for each treatment arm.
For telephone contacts the investigator or delegated site staff must transcribe the data used for 
titration into the eCRF during/after the telephone contact. Please see the titration guideline.
8.2.13
Self-measured 9-point plasma glucose profile
Subjects will be instructed to perform measurements and record the SMPG values for a 9-point 
profile within one week prior to Visits 2, 14 and 28 on days where subjects do not anticipate 
unusual strenuous exercise. Anti-diabetic medication should be withheld until after the pre-
breakfast measurement.
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SMPG values should be recorded in the diary (including date and actual clock time for the 
measurement) at the following time points, always starting with the measurement before breakfast: 
!
Before breakfast
!
90 min after the start of breakfast
!
Before lunch
!
90 min after the start of lunch
!
Before dinner
!
90 min after the start of dinner
!
At bedtime
!
At 4 am 
!
Before breakfast the following day
8.2.14
Hypoglycaemic episodes
Plasma glucose should always be measured and recorded when a hypoglycaemic episode is 
suspected. 
All plasma glucose values:
!
≤ 3.9 mmol/L or 
!
> 3.9 mmol/L when they occur in conjunction with hypoglycaemic symptoms, 
should be recorded by the subject.These must be transcribed into the eCRF on the hypoglycaemic 
episode form throughout the trial from Visit 2 to Visit 29.
The record should include the following information:
!
Date and time of hypoglycaemic episode
!
The plasma glucose level before treating the episode (if available) 
!
Whether the episode was symptomatic 
!
Whether the subject was able to treat him/herself 
!
Date, time and dose of last trial product (OR other anti-diabetic treatment) administration prior 
to episode 
!
Type of last trial product (OR other anti-diabetic treatment) prior to episode 
!
Date and time of last main meal prior to episode 
!
Whether the episode occurred in relation to physical activity
!
Any sign of fever or other disease 
!
Whether the subject was asleep when the episode occurred
!
Whether the symptoms of the episode woke up the subject
The answer to the question: "Was subject able to treat him/herself?" must be answered "No" for an 
episode requiring assistance of another person to actively administer carbohydrate, glucagon, or 
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take other corrective actions. Plasma glucose concentrations may not be available during an event, 
but neurological recovery following the return of plasma glucose to normal is considered sufficient 
evidence that the event was induced by a low plasma glucose concentration11.
If the question "Was subject able to treat him/herself?" is answered "No", the following information 
should be recorded and transcribed into the eCRF:
!
Who assisted in the treatment of the hypoglycaemic episode (i.e. family/friend/co-worker or 
similar, paramedic, doctor or other, please specify)
!
Where the treatment was administered (i.e. at home/at friends/at work or similar, in an 
ambulance, emergency room/hospital or other, please specify)
!
Type of treatment provided by other person (i.e. oral carbohydrates, glucagon, IV glucose or 
other, please specify)
!
Were symptoms alleviated by the administration of treatment?
!
Factors contributing to the episode (i.e. physical activity, missed meal, diet changed, medication 
error (i.e. overdose, mix-up between products), miscalculation of dose, other factors not listed, 
please specify or none)
!
Did the subject experience seizure?
!
Was the subject unconscious/comatose?    
!
Did the subject experience any of the following symptoms?12
o
Autonomic: sweating, trembling, hunger or palpitations
o
Neuroglycopenic: confusion, drowsiness, speech difficulty, visual disturbances, odd 
behaviour, impaired balance or incoordination
o
General malaise: headache or malaise
!
Did the subject experience other symptoms? Please specify
!
Further description of the episode 
A hypoglycaemic episode form must be filled in for each hypoglycaemic episode. If the 
hypoglycaemic episode fulfils the criteria for an SAE then an AE form and a safety information 
form must also be filled in, see section 12.
8.3
Laboratory assessments
The laboratory analyses will be performed by a central laboratory unless otherwise specified in this 
section. Descriptions of assay methods, laboratory supplies and procedures for obtaining samples, 
handling, labelling and storage of samples along with information regarding who will perform the 
assessments, will be described in a trial-specific laboratory manual, provided by the central 
laboratory. For laboratory details, see Attachment I.
8.3.1
Blood and urine sampling (central laboratory analysis)
The investigator must review all laboratory results, specify on the laboratory report whether any 
values out of range are non-clinically significant or clinically significant, and report concomitant 
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illnesses and AEs according to section 12. Laboratory reports must be signed and dated by the 
investigator on the day of evaluation. The signed laboratory report must be retained at the 
investigator’s site as source documentation. 
Laboratory equipment used may provide analyses not requested in the protocol but produced 
automatically in connection with the requested analyses according to specifications in the laboratory 
standard operating procedures. Such data will not be transferred to the trial database, but abnormal 
values must be reported to the investigator. Laboratory results will be sent by the central laboratory 
to the investigator on an ongoing basis. 
Blood samples analysed by the central laboratory will be destroyed on an ongoing basis. 
Blood sampling performed on subjects throughout the trial will determine levels of the following 
efficacy and safety parameters: 
Efficacy parameters
Glucose metabolism: HbA1c, FPG, Fasting insulin, Fasting glucagon, Fasting C-peptide and 
calculation of HOMA-β (see section 17.4.2.1 for calculation)
Safety parameters
Haematology: Erythrocytes, Haematocrit, Haemoglobin, Leucocytes, Thrombocytes and 
Differential count (eosinophils, neutrophils, basophils, monocytes, and lymphocytes)
Biochemistry: Amylase, Lipase, Aspartate aminotransferase (ASAT/SGOT), Alanine 
aminotransferase (ALAT/SPGT), Alkaline phosphatase, Albumin, Bilirubins (total), Creatinine, 
Potassium, Sodium, Total protein, Urea, Creatine kinase, Calcium and Albumin corrected calcium
Lipids: Cholesterol, HDL cholesterol, LDL cholesterol, Triglycerides, VLDL cholesterol and Free 
fatty acids
Hormones: Calcitonin
Pregnancy test: Serum/plasma hCG
Urine samples: Erythrocytes, Protein, Glucose and Ketones by dipstick. 
8.3.2
Calcitonin sampling (central laboratory analysis)
Blood samples for the measurement of calcitonin concentration will be drawn as per flow chart (see 
section 2). Calcitonin values ≥20 ng/L will be submitted to an independent calcitonin monitoring 
committee of thyroid experts. The committee will provide guidance to the investigator with regards 
to treatment and further investigations. If a subject is screen failed for other reasons than calcitonin 
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exclusion criterion # 11 (calcitonin ≥ 50 ng/L), but has a value of calcitonin ≥10 ng/L, it is 
recommended that they are referred to a thyroid expert for further evaluation. For details see 
appendix D.
8.3.3
Antibody sampling (special laboratory analysis)
Blood samples will be drawn as per flow chart for determination of serum antibodies to IDeg
(including cross reacting antibodies to human insulin) and to liraglutide, dependent on treatment 
arm. Positive anti-liraglutide antibody samples will be further characterised for cross reactivity to 
native GLP-1. 
Visit 29 samples positive for anti-liraglutide antibodies will in addition be analysed for in vitro
neutralising effect in a cell based assay.
Blood sampling for antibody assessment should be performed prior to administering trial product.
Antibody results will not be provided to the investigator as these are not used for clinical evaluation 
during the trial. Instead they will be included in an analytical report after end of trial and retained at 
Novo Nordisk.
Please see section 24.2 for information on storage of antibody samples.
8.3.4
PK blood sampling (special laboratory analysis)
Blood samples for PK will be drawn as per flow chart. Blood sample(s) will be drawn once per 
subject per visit (no PK-profiling required). Samples will be analysed for serum concentrations of 
IDeg and/or plasma concentrations of liraglutide dependent of treatment arm.
The investigator must record the exact time for blood sampling in the eCRF. Blood samples for 
serum IDeg and plasma liraglutide levels will be collected, treated and shipped according to the 
description in a laboratory manual provided by the relevant laboratory.
Subjects must be instructed to write in their diary:
!
Date, dose, injection site and exact clock time for injection from the previous three days of 
dosing and on the day of the visit, if a dose is taken before blood sampling
It is important to explain to the subjects the necessity of accurate diary recording as the investigator 
must transcribe all data into the eCRF subsequently to ensure accurate PK calculation.
The population PK analysis is outlined in section 17.5
The bio-analysis of IDeg and liraglutide will be done at a special laboratory (see attachment I), 
using a specific validated ELISA assay for each component developed by Novo Nordisk. Validation 
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documentation must be provided and a bio-analytical report must be available. PK results will not 
be provided to the investigator as these are not used for clinical evaluation during the trial. Instead 
they will be included in a bio-analytical report that will be available at data base lock and retained at 
Novo Nordisk.
PK samples will be destroyed no later than at the completion of the clinical trial report (CTR).
Destruction of PK samples must only occur with permission from Novo Nordisk.
8.4
Pancreatitis
Confirmed cases of pancreatitis should be followed up with investigations of other potential causes 
(tests such as gallbladder ultrasound, triglycerides, liver enzymes, detailed history of concomitant 
medications or alcohol).
8.5
Thyroid disease
Subjects scheduled for thyroidectomy (partial or total) for any reason during the trial, must be 
instructed to inform the investigator prior to their operation.
8.6
Subject diaries
At each site visit subjects will be provided with a new diary for recording of source data until next 
site visit. Here the diary must be collected and retained at the site as source data in accordance with 
section 14. From handout at a site visit a diary will hence contain source data from e.g. several 
telephone contacts prior to being returned at an upcoming visit.
Subjects are required to record the below source data in their diaries at the timing specified in the 
flow chart in section 2.
!
For all subjects:
o
Date and dose of first trial product
o
Date and dose of last trial product
o
Prior to PK sampling visits: See section 8.3.4 for source data to be recorded
o
9-point profile SMPG values, see section 8.2.13 for source data to be recorded
!
Any AEs, hypoglycaemic episodes and changes in concomitant medication since last site 
visit/telephone contact
!
For subjects on IDeg or IDegLira: 
o
Daily pre-breakfast SMPG values
o
Last trial product dose prior to each titration day
o
Trial product dose to be taken after each titration day
!
For subjects on liraglutide: 
o
Pre-breakfast SMPG values on 3 consecutive days prior to every site visit/telephone 
contact 
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Based on the SMPG values, the investigator/subject will assess whether the trial product dose needs 
adjustment according to the Titration Guideline. 
The diary must be reviewed by the investigator to ensure that AEs, including any overall change in 
health and concomitant medication, are reported. The review of the diary must be documented 
either on the front page of the diary and/or in the subject’s medical records.
The investigator or delegated staff must transcribe data from the diary into the eCRF after each site 
visit/telephone contact according to timelines in section 13.2. 
If clarification of entries or discrepancies in the diaries is needed, the subject should be questioned 
and a conclusion made in the subject’s medical record. Care must be taken not to bias the subject.
8.7
Subject compliance
Throughout the trial the investigator will remind the subjects to follow the trial procedures and 
requirements to ensure subject compliance. 
The investigator should assess the compliance of the subject based on a review of glycaemic 
control, adherence to the visit schedule, completion of the subject’s diary including the 9-point 
profiles. The doses of metformin and the trial product should be assessed at each site visit e.g. by 
reviewing the subject’s diary and by performing drug accountability (see section 9.4). 
If a subject is discovered to be non-compliant, the investigator must inform the subject of the 
importance of taking trial product and metformin as directed. Substantial failure to comply with the 
prescribed trial product dose regimen will lead to withdrawal.
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9
Trial supplies
Trial supplies comprise trial products and auxiliary supplies. Additional details regarding trial 
supplies can be found in the Trial Materials Manual. 
Trial product must not be dispensed to any person not included in the trial. 
Trial product must not be used, if it does not appear clear and colourless. 
9.1
Trial products
The trial products listed in the table below are considered Investigational Medicinal Products 
(IMPs) and will be provided by Novo Nordisk A/S, Denmark:
Table 9–1
Trial products
Trial product (IMP)
Strength
Dosage form
Route of 
administration
Insulin 
degludec/liraglutide 
100 units/mL + 3.6 
mg/mL
Solution for 3 mL pre-
filled pen
Subcutaneous 
injection
Insulin degludec 
100 Units/mL
Liraglutide (Victoza#) 
6 mg/mL
Metformin is a Non-Investigational Medicinal Product. It is not considered a trial product and will 
not be provided by Novo Nordisk.
9.2
Labelling
Labelling of the trial products will be in accordance with Annex 1313, local regulations and trial 
requirements.
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Each investigator site will be supplied with sufficient trial products for the trial on an on-going basis 
controlled by the IV/WRS. The investigator must document that direction for use is given to the 
subject orally and/or in writing at each dispensing visit.
9.3
Storage 
The trial products must be stored according to the instructions in the table below.
Table 9–2
Storage conditions for trial products
Insulin degludec/liraglutide
Storage conditions (not-in-use)
In-use conditions
In-use time*
Store in refrigerator (2°C to 8°C)
Do not freeze
Protect from light
Store below 30∃C 
Protect from light
Use within 3 weeks
Insulin degludec 
Storage conditions (not-in-use)
In-use conditions
In-use time*
Store in refrigerator (2°C to 8°C) 
Do not freeze
Protect from light
Do not refrigerate.
Do not store above 30∃C 
Protect from light
Use within 8 weeks
Liraglutide (Victoza#) 
Storage conditions (not-in-use)
In-use conditions
In-use time*
Store in refrigerator (2°C to 8°C) 
Keep away from the cooling element
Do not freeze 
Protect from light
Store in refrigerator (2°C to 8°C) or
Store below 30∃C 
Keep the cap on the pen in order to 
protect from light
Do not freeze
Use within one 
month
* In-use time starts when first dose is taken.
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The investigator must ensure the availability of proper storage conditions, record and evaluate the 
temperature. The investigator must inform Novo Nordisk immediately if any trial product has been 
stored outside specified conditions (e.g. outside temperature range).
Trial product that has been stored improperly must not be dispensed to any subject before it has 
been re-evaluated and approved for further use by Novo Nordisk. The investigator must take 
appropriate action to ensure correct storage.
9.4
Drug accountability and destruction
Drug accountability is the responsibility of the investigator.
For each subject the IV/WRS allocates trial product by assigning dispensing unit numbers (DUN) 
where each DUN represents a box with a defined number of trial product to be handed out to the 
subject at a dispensing visit.
The investigator or delegated person is responsible for ensuring:
!
The correct DUN is dispensed to the subject
!
The dispense date for any dispensed DUN is confirmed in the IV/WRS drug accountability 
module after each dispensing
!
Subjects are instructed to return all used, partly used and unused trial products including empty 
packaging material at each dispensing visit
!
Drug accountability is performed using the IV/WRS drug accountability module. Only 
dispensed DUNs returned by the subject (used/ partly used or unused) are accounted for
!
Returned trial product (used/partly used or unused including empty packaging material) can be 
stored at room temperature and must be stored separately from non-allocated trial product
Returned trial product destruction will be done according to local procedures after accountability is 
finalised and verified by the monitor. Destruction of trial products must be documented.
9.5
Auxiliary supplies
The following will be provided by Novo Nordisk:
!
Directions for Use of pens
!
Needles for pens
!
BG-meters and BG-meter auxiliaries
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10
Interactive voice/web response system
A trial-specific IV/WRS will be set up and can be accessed at any time via the internet or telephone. 
Access to the IV/WRS must be restricted to and controlled by authorised persons. 
The IV/WRS is used for tracking of subjects throughout the trial i.e. screening, randomisation and 
allocation of trial products according to treatment arm. This is to ensure all subjects receive the 
correct trial product and a sufficient amount according to their dose regimen until end of treatment. 
If a subject withdraws early from the trial, this will also have to be entered into the IV/WRS in 
order to stop trial product allocation to this patient. More specifically the IV/WRS must be used for 
the below tasks in the trial:
!
Screening
!
Screening failure
!
Randomisation
!
Medication arrival
!
Dispensing of trial product
!
Withdrawal
!
Completion
!
Drug accountability
!
Data change
IV/WRS user manuals will be provided to each trial site.
11 Randomisation procedure
Subject will be randomised in a 2:1:1 manner to receive IDegLira, IDeg or liraglutide.
When randomising subjects the IV/WRS is also used to ensure a trial population with a mean HbA1c
level of 8.3%. When the number of subjects with a HbA1c below or equal to 8.3% reach 50% of the 
required number of subjects to be randomised, it will only be possible to randomise subjects with a
HbA1c above 8.3%. Subjects will be stratified with respect to their previous OAD treatment 
(metformin ± one other OAD). Stratification with regards to previous OAD treatment is done to 
ensure an equal proportion of subjects previously on mono therapy and combination therapy in each 
of the three arms. 
The distribution of subjects having a HbA1c above or below 8.3% will be followed closely and 
investigators will be notified in due time before randomisation is closed. Subjects eligible for 
randomisation will be randomised if closing occurs while they are in the screening period.
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12 Adverse events, MESIs, technical complaints and pregnancies
12.1
Definitions
Adverse event (AE)
An AE is any untoward medical occurrence in a subject administered a product, and which does not 
necessarily have a causal relationship with this treatment. 
An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory 
finding), symptom or disease temporally associated with the use of a product, whether or not 
considered related to the product. 
An AE includes:
!
A clinically significant worsening of a concomitant illness.
!
A clinical laboratory adverse event: a clinical laboratory abnormality which is clinically 
significant, i.e. an abnormality that suggests a disease and/or organ toxicity and is of a severity 
that requires active management. Active management includes active treatment or further 
investigations, for example change of medicine dose or more frequent follow-up due to the 
abnormality.
The following should not be reported as AEs:
!
Pre-existing conditions, including those found as a result of screening procedures or baseline 
measurements for lipids (pre-existing conditions should be reported as medical history or 
concomitant illness).
!
Pre-planned procedures unless the condition for which the procedure was planned has worsened 
from the first trial related activity after the subject has signed the informed consent.
!
Non-serious hypoglycaemia is an AE, but is reported on a hypoglycaemic episode form instead 
of on an AE form, see section 8.2.14
The following three definitions are used when assessing severity of an AE:
!
Mild - no or transient symptoms, no interference with the subject's daily activities.
!
Moderate - marked symptoms, moderate interference with the subject's daily activities.
!
Severe - considerable interference with the subject's daily activities; unacceptable.
The following terms are used when assessing the causality between an AE and the relevant trial 
product(s): 
!
Probable - Good reason and sufficient documentation to assume a causal relationship.
!
Possible - A causal relationship is conceivable and cannot be dismissed.
!
Unlikely - The event is most likely related to aetiology other than the trial product.
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Final outcome of an AE
!
Recovered/resolved - The subject has fully recovered, or by medical or surgical treatment the 
condition has returned to the level observed at the first trial-related activity after the subject 
signed the informed consent.
!
Recovering/resolving - The condition is improving and the subject is expected to recover from 
the event. This term is only applicable if the subject has completed the trial or has died from 
another AE.
!
Recovered/resolved with sequelae - The subject has recovered from the condition, but with 
lasting effect due to a disease, injury, treatment or procedure. If a sequela meets an SAE 
criterion, the AE must be reported as an SAE.
!
Not recovered/not resolved - The condition of the subject has not improved and the symptoms 
are unchanged, or the outcome is not known.
!
Fatal - This term is only applicable if the subject died from a condition related to the reported 
AE. Outcomes of other reported AEs in a subject before he/she died should be assessed as 
"recovered/resolved", "recovering/resolving", "recovered/resolved with sequelae" or "not 
recovered/not resolved". An AE with fatal outcome must be reported as an SAE.
!
Unknown - This term is only applicable if the subject is lost to follow-up.
Serious adverse event (SAE)
A SAE is an experience that at any dose results in any of the following:
!
Death.
!
A life-threateninga experience.
!
In-patient hospitalisationb or prolongation of existing hospitalisation.
!
A persistent or significant disability or incapacityc.
!
A congenital anomaly or birth defect.
!
Important medical events that may not result in death, be life threateninga or require 
hospitalisationb may be considered an SAE when - based on appropriate medical judgement -
they may jeopardise the subject and may require medical or surgical intervention to prevent one 
of the outcomes listed in the definition of SAEd. Suspicion of transmission of infectious agents 
via the trial product must always be considered an SAE. 
a. The term "life threatening" in the definition of SAE refers to an event in which the subject was 
at risk of death at the time of the event. It does not refer to an event which hypothetically might 
have caused death if it was more severe.
b. The term "hospitalisation" is used when a subject: 
!
Is admitted to a hospital or in-patient, irrespective of the duration of physical stay, or 
!
Stays at the hospital for treatment or observation for more than 24 hours
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Medical judgement must always be exercised, and when in doubt, the hospital contact should be 
regarded as a hospitalisation. Hospitalisations for administrative, trial related and social 
purposes do not constitute AEs and should therefore not be reported as AEs or SAEs. Hospital 
admissions for surgical procedures, planned before trial inclusion, are not considered AEs or 
SAEs.
c. A substantial disruption of a subject's ability to conduct normal life functions (e.g. following the 
event or clinical investigation the subject has significant, persistent or permanent change, 
impairment, damage or disruption in his/her body function or structure, physical activity and/or 
quality of life).
d. For example intensive treatment in an emergency room or at home of allergic bronchospasm, 
blood dyscrasiasis or convulsions that do not result in hospitalisation or development of drug 
dependency or drug abuse.
Non-serious adverse event
A non-serious AE is any AE which does not fulfil the definition of an SAE.
Medical event of special interest (MESI)
A MESI is an event which, in the evaluation of safety, has a special focus. A MESI is an AE (SAE 
or non-serious AE) which fulfils one or more of the below defined MESI criteria.
1. Acute coronary syndrome (myocardial infarction or hospitalisation for unstable angina)
2. Cerebrovascular event (transient ischemic attack or stroke) 
3. Heart failure requiring hospital admission
4. Revascularisation procedure
5. Pancreatitis or clinical suspicion of pancreatitis
6. Neoplasm
7. Thyroid disease
8. Medication errors concerning trial products:
!
Administration of wrong drug.
!
Wrong route of administration, such as intramuscular instead of subcutaneous.
!
Administration of an overdose with the intention to cause harm (e.g. suicide attempt).
!
Accidental administration of a lower or higher dose than intended. That is a dose that is 
20 % lower or higher than  the intended dose; however the administered dose must 
deviate from the intended dose to an extend where clinical consequences for the trial 
subject were likely to happen as judged by the investigator, although not necessarily did 
happen.
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Technical complaint
A technical complaint is any written, electronic, or oral communication that alleges product 
(medicine or device) defects. The technical complaint may be associated with an AE, but does not 
concern the AE itself.
Examples of technical complaints:
!
The physical or chemical appearance of trial products (e.g. discoloration, particles or 
contamination)
!
The packaging material (e.g. leakage, cracks, rubber membrane issues or errors in labelling text)
!
Problems related to devices (e.g. to the injection mechanism, dose setting mechanism, push 
button or interface between the pen and the needle)
12.2
Reporting of adverse events
All events meeting the definition of an AE must be collected and reported. This includes events 
from the first trial-related activity after the subject has signed the informed consent (screening) until 
Visit 29 which is the end of the post-treatment follow-up period (7 days after end of treatment). 
Exceptions:
!
Non serious events of hypoglycaemic episodes should not be reported before any trial drug is 
given e.g. prior to the randomisation visit
!
Non-serious AEs should not be collected and reported for screening failures
The events must be recorded in the applicable CRF forms in a timely manner, see timelines below.
During each contact with the trial site staff, the subject must be asked about AEs and technical 
complaints, for example by asking: "Have you experienced any problems since the last contact?"
All AEs, observed by the investigator or subject, must be reported by the investigator and evaluated. 
Novo Nordisk assessment of expectedness is performed according to the following reference 
documents: 
IDegLira: NN9068 Investigator’s Brochure edition 6.0 or any updates hereof
IDeg: NN1250 CCDS version 5.0 or any updates hereof
Liraglutide: NN2211 CCDS version 14.0 or any updates hereof
All AEs must be recorded by the investigator on an AE form. The investigator should report the 
diagnosis, if available. If no diagnosis is available, the investigator should record each sign and 
symptom as individual AEs using separate AE forms.  
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For SAEs, a safety information form must be completed in addition to the AE form. If several 
symptoms or diagnoses occur as part of the same clinical picture, one safety information form can 
be used to describe all the SAEs. 
MESIs, regardless of seriousness, must be reported using both the AE form and the safety 
information form and a MESI form. The MESI form is a form tailored to collect specific 
information related to the individual MESI.
Any event confirmed or suspected to be a MESI must be reported as such. In case the sponsor 
identifies potentially missed MESIs through predefined review of available data, the investigator 
will be asked to reconsider if the event is a MESI.
The AE form for a non-serious AE should be signed when the event is resolved or at the end of the 
trial.
Timelines for initial reporting of AEs:
The investigator must complete the following forms in the eCRF within the specified timelines:
!
SAEs: The AE form within 24 hours and the safety information form within 5 calendar days 
of the investigator's first knowledge of the SAE. Both forms must be signed within 7 calendar 
days from the date the information was entered in the eCRF
!
SAEs fulfilling the MESI criteria and/or result in fatal outcome: In addition to above, the 
MESI form and/or the fatal follow up form within 14 calendar days of the investigator's first 
knowledge of the AE
!
Non-serious AE fulfilling the MESI criteria: The AE form, and safety information form and 
MESI form within 14 calendar days of the investigator's first knowledge of the event
!
Events fulfilling the adjudication criteria: Complete the event adjudication collection form 
within 14 calendar days of the investigator's first knowledge of the event
Please see figure Figure 12–1  for timelines. Please see section 12.7.3 for MESIs to be adjudicated. 
If the eCRF is unavailable, the concerned AE information must be reported on paper forms and sent 
to Novo Nordisk by fax, e-mail or courier within the same timelines as stated above. When the 
eCRF becomes available again, the investigator must re-enter the information on the appropriate 
forms in the eCRF. 
Contact details (fax, telephone, e-mail and address) are provided in the investigators trial file. 
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Yes
Yes
No
Fulfilling 
seriousness 
criteria?
Fulfilling MESI 
criteria?
Fatal outcome
or fulfilling 
MESI criteria?
No
Yes
No
Fulfilling 
Adjudication 
criteria?
No
Yes
Complete ≤ 14 calendar 
days:
! MESI and/or
! Fatal FU form
Complete ≤ 14 calendar 
days:
! SIF
! MESI form 
Complete ≤ 14 calendars 
days:
!
Event adjudication 
document collection 
form
An AE is 
observed and 
reported
No additional forms 
to be completed
No additional forms 
to be completed
No additional forms 
to be completed
Complete:
!
AE Form ≤ 24 hours
!
SIF ≤ 5 calendars 
days
Complete:
!
AE Form
Figure 12–1
Initial reporting of AEs
Reporting of trial product-related SUSARs by the sponsor:
Novo Nordisk will notify the investigator of trial product-related suspected unexpected serious 
adverse reactions (SUSARs) in accordance with local requirements and ICH GCP1. In addition, the 
investigator will be informed of any trial-related SAEs that may warrant a change in any trial 
procedure.
In accordance with regulatory requirements, Novo Nordisk will inform the regulatory authorities, 
including EMA, of trial product-related SUSARs. In addition, Novo Nordisk will inform the 
IRBs/IECs of trial product-related SUSARs in accordance with local requirement and ICH GCP1
unless locally this is an obligation of the investigator.
12.3
Follow-up of adverse events
The investigator must record follow-up information by updating the forms in the eCRF.
Follow up information must be reported to Novo Nordisk according to the following:
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!
SAEs: All SAEs must be followed until the outcome of the event is "recovered/resolved", 
"recovered/resolved with sequelae" or "fatal", and until all queries have been resolved. Cases of 
chronic conditions, cancer or AEs ongoing at time of death (where death is due to another AE) 
may be closed with the outcome "recovering/resolving" or "not recovered/not resolved". Cases 
can be closed with the outcome of "recovering/resolving" when the subject has completed the 
follow-up period and is expected by the investigator to recover
The SAE follow-up information should only include new (e.g. corrections or additional) 
information and must be reported within 24 hours of the investigator's first knowledge of the 
information. This is also the case for previously non-serious AEs which subsequently become 
SAEs
!
Non-serious AEs: Non-serious AEs must be followed until the outcome of the event is 
"recovering/resolving", "recovered/resolved" or "recovered/resolved with sequelae" or until the 
end of the follow-up period stated in the protocol, whichever comes first, and until all queries 
related to these AEs have been resolved. Cases of chronic conditions, cancer or AEs ongoing at 
time of death (where death is due to another AE) may be closed with the outcome 
"recovering/resolving" or "not recovered/not resolved". Cases can be closed with the outcome of 
"recovering/resolving" when the subject has completed the follow-up period and is expected by 
the investigator to recover
!
Non-serious AE fulfilling the MESI criteria: Follow-up information on MESIs should only 
include new (e.g. corrections or additional) information and must be reported within 14 
calendar days of the investigator's first knowledge of the information. This is also the case for 
previously reported non-serious AEs which subsequently fulfil the MESI criteria
The investigator must ensure that the worst case severity and seriousness of an event is kept 
throughout the trial. A worsening of an unresolved AE must be reported as follow up with re-
assessment of severity and/or seriousness of the event.
Queries or follow-up requests from Novo Nordisk must be responded to within 14 calendar days
from the date of receipt of the request, unless otherwise specified in the follow-up request.
12.4
Technical complaints and technical complaint samples
12.4.1
Reporting of technical complaints 
All technical complaints on any of the following products: 
!
Insulin degludec/liraglutide 100 units/mL + 3.6 mg/mL(IDegLira), 3 mL pre-filled pen.
!
Insulin degludec 100 Units/mL (IDeg), 3 mL pre-filled pen
!
Liraglutide 6 mg/mL (Victoza®), 3 mL pre-filled pen
!
Novo Nordisk needles for pre-filled pens,
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which occur from the time of first usage of the product until the time of the last usage of the 
product, must be collected and reported to Customer Complaint Center, Novo Nordisk.
Contact details (fax, e-mail and address) are provided in Attachment I to the protocol.
The investigator must assess whether the technical complaint is related to any AEs, SAEs, and/or
MESI.
Technical complaints must be reported on a separate technical complaint form for each product 
listed. If the technical complaint involves more than one batch or lot number or more than one 
DUN, a technical complaint form for each batch or lot number or for each DUN must be completed.
The investigator must complete the technical complaint form in the eCRF within the following 
timelines of the trial site obtaining knowledge of the technical complaint:
Technical complaint assessed as related to an SAE within 24 hours
All other technical complaints within 5 calendar days
If the eCRF is unavailable or when reporting a technical complaint that is not subject related, the 
information must be provided on a paper form by fax, e-mail or courier to Customer Complaint 
Center, Novo Nordisk, within the same timelines as stated above.
12.4.2
Collection, storage and shipment of technical complaint samples
The investigator must collect the technical complaint sample and notify the monitor within 5 
calendar days of obtaining the sample at trial site. The monitor must coordinate the shipment to 
Customer Complaint Center, Novo Nordisk (the address is provided in Attachment I) and ensure 
that the sample is sent as soon as possible. A print of the technical complaint form must be sent with 
the sample.
The investigator must ensure that the technical complaint sample contains the batch or lot number 
and, if available, the DUN.
If the technical complaint sample is unobtainable, the investigator must specify on the technical 
complaint form why it is unobtainable. 
Storage of the technical complaint sample must be done in accordance with the conditions 
prescribed for the product. The shipment of the technical complaint sample should be done in 
accordance with the same conditions as for storage (see section 9.3). 
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12.5
Pregnancies in female subjects
Female subjects must be instructed to notify the investigator immediately if they become pregnant 
during the trial. The investigator must report any pregnancy in subjects who have received trial 
products.
The investigator must follow the pregnancy until the pregnancy outcome and the newborn infant is 
one month of age.
The investigator must report information about the pregnancy, pregnancy outcome, and health of 
the newborn infant(s), as well as AEs in connection with the pregnancy, and AEs in the foetus and 
newborn infant.
The following must be collected and reported by the investigator to Novo Nordisk - electronically 
(e.g. in PDF format), or by fax or courier:
1. Reporting of pregnancy information
Information about the pregnancy and pregnancy outcome/health of the newborn infant(s) has to 
be reported on Maternal Form 1A and 1B, respectively. 
When the pregnancy outcome is abnormal (i.e. congenital anomalies, foetal death including 
spontaneous abortion and/or any anomalies of the foetus observed at gross examination or 
during autopsy), and/or when a congenital anomaly is diagnosed within the first month, further 
information has to be reported for the female subject on Maternal Form 2. In addition, 
information from the male partner has to be reported on the Paternal Form, after an informed 
consent has been obtained from the male partner. 
Initial reporting and follow-up information must be reported within 14 calendar days of the 
investigator's first knowledge of initial or follow-up information. 
2. Reporting of AE information
The investigator has to report AEs in connection with the pregnancy as well as in the foetus and 
newborn infant(s). The SAEs that must be reported include abnormal outcome, such as foetal 
death (including spontaneous abortion), and congenital anomalies (including those observed at 
gross examination or during autopsy of the foetus), as well as other pregnancy complications 
fulfilling the criteria of an SAE.
Forms and timelines for reporting AEs related to pregnancy:
Non-serious AEs: 
!
Paper AE form* within 14 calendar days of the investigator's first knowledge of the initial or 
follow-up information to the non-serious AE
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SAEs: 
!
Paper AE form* within 24 hours of the investigator's first knowledge of the SAE
!
Paper safety information form within 5 calendar days of the investigator's first knowledge of 
the SAE
!
SAE follow-up information to the AE form and/or safety information form within 24 hours of 
the investigator's first knowledge of the follow-up information
*
It must be clearly stated in the AE diagnosis field on the AE form if the event occurred in the 
subject, foetus or newborn infant.
Any queries or follow-up requests from Novo Nordisk to non-serious AEs, SAEs and pregnancy 
forms must be responded to by the investigator within 14 calendar days from the date of receipt of 
the request, unless otherwise specified in the follow-up request.
12.6
Precautions and/or overdose
During treatment with insulin there is a risk of hypoglycaemia. Symptoms of hypoglycaemia 
usually occur suddenly and may include cold sweat, nervousness or tremor, anxious feelings, 
unusual tiredness, confusion, difficulty in concentrating, excessive hunger, temporary vision 
changes, headache, nausea and palpitation. Severe hypoglycaemia may lead to unconsciousness.
Hypoglycaemic episodes should be treated according to best practise at the discretion of the 
investigator. Attention should be given to the fact that the action profile of the insulin component in 
IDegLira and IDeg is long-acting and the prolonged effect may delay recovery from a 
hypoglycaemic episode.
Asymptomatic hypoglycaemia and symptoms of minor hypoglycaemia should be treated by 
ingestion of carbohydrate (for example juice). Severe hypoglycaemia resulting in loss of 
consciousness should be treated with parenteral glucose, glucagon or dextrose at the investigator’s 
discretion.
From clinical trials and marketed use of Liraglutide overdoses up to 40 times the recommended 
maintenance dose (72 mg) have been reported. Events reported included severe nausea and severe 
vomiting. None of the reports included severe hypoglycaemia. All patients recovered without 
complications.
When initiating treatment with IDegLira or Liraglutide, the subject may in some cases experience 
loss of fluids/dehydration, due to vomiting, nausea or diarrhoea. It is important to avoid dehydration
by drinking plenty of fluids. 
For further information on IDeglira, IDeg or liraglutide, please see Investigator’s Brochure, any 
updates hereof, and/or SmPCs/ local labelling, as applicable.
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12.7
Committees related to safety
12.7.1
Novo Nordisk safety committee
Novo Nordisk will constitute an internal IDegLira/NN9068 safety committee to perform ongoing 
safety surveillance. The safety committee will be informed about the results of on-going safety 
surveillance activities for the individual mono components IDeg and liraglutide, respectively.
12.7.2
Calcitonin monitoring committee
An independent committee of thyroid experts is established to perform calcitonin monitoring of all 
calcitonin values ≥20 ng/L in subjects throughout the trial (except for screening failures). The
committee will provide recommendations to investigators with regards to further investigation and 
treatment of the individual subject. The committee will be blinded to trial treatment. 
For further instructions on calcitonin monitoring, see appendix D.
12.7.3
Event adjudication committee
An external event adjudication committee is established to perform qualitative or quantitative 
validation of selected AEs according to pre-defined diagnostic criteria. The validation is based on
review of pre-defined clinical source data related to the specific AE. The events are reviewed by the 
event adjudication committee in an independent and blinded manner.
The following AEs will be adjudicated in this trial:
!
Death
!
Acute coronary syndrome (myocardial infarction or hospitalisation for unstable angina)
!
Cerebrovascular event (transient ischemic attack or stroke) 
!
Heart failure requiring hospital admission
!
Coronary revascularisation
!
Pancreatitis or clinical suspicion of pancreatitis
!
Neoplasm
!
Thyroid disorders requiring thyroidectomy 
AEs for adjudication must be reported according to section 12.2. In addition the specific event 
adjudication document collection form has to be completed and relevant pre-defined documents 
provided within 14 calendar days of the investigator's first knowledge of the AE, according to 
instructions in the event adjudication site manual. The investigator should provide the medical 
documentation within 4 weeks of event identification.
Event adjudication will not be performed for AEs in screening failures. For further information 
regarding definitions, rationales, and events that will be adjudicated, see appendix B.
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13 Case report forms 
Novo Nordisk will provide a system for the eCRF. This system and support services to the system 
will be supplied by a vendor.
When entering data into the eCRF, trial site staff must ensure that all relevant questions are 
answered, and that no empty data field exists. If a test or an assessment has not been done and will 
not be available, or if the question is irrelevant (e.g. is not applicable), indicate this according to the 
data entry guidelines.
The following will be provided as paper CRFs only:
!
Pregnancy forms
In addition paper AE forms, safety information forms and technical complaint forms will be 
provided. These must be used when access to the eCRF is revoked.
On the paper CRF forms print legibly, using a ballpoint pen. Ensure that all questions are answered, 
and that no empty data blocks exist. Ensure that no information is recorded outside the data blocks. 
If a test/assessment has not been done and will not be available, indicate this by writing "ND" (not 
done) in the appropriate answer field in the CRF. If the question is irrelevant (e.g. is not applicable) 
indicate this by writing "NA" (not applicable) in the appropriate answer field. Further guidance can 
be obtained from the instructions in the CRF.
The investigator must ensure that all information is consistent with the source documentation. By 
electronically signing the case book in the eCRF, the investigator confirms that the information in 
the eCRF and related forms is complete and correct.
13.1
Corrections to case report forms 
Corrections to the eCRF data may be made by the investigator or the investigator's authorised staff. 
An audit trail will be maintained in the eCRF application containing as a minimum: the old and the 
new data, identification of the person entering the data, date and time of the entry and reason for the 
correction.
If corrections are made by the investigator's authorised staff after the date the investigator has 
signed the case book, the case book must be signed and dated again by the investigator.
Corrections to the data on paper CRFs may only be made by drawing a straight line through the 
incorrect data and then writing the correct entry next to the data that was crossed out. Each 
correction must be initialled, dated and explained (if necessary). If corrections are made by the 
investigator's authorised staff after the date of the investigator's signature on the affirmation 
statement, the affirmation statement must be signed and dated again by the investigator.
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Corrections necessary after the CRFs have been removed from the trial site must be documented on 
a data clarification form or a monitor-initiated discrepancy form. If the affirmation statement for the 
subject has not yet been signed, any corrections must be approved by the investigator or her/his 
authorised staff. If the affirmation statement for the subject has already been signed, the investigator 
must approve any correction.
13.2
Case report form flow 
The investigator must ensure that data is recorded in the eCRF as soon as possible, preferably 
within 5 days after a site visit/telephone contact. The SMPG values and corresponding insulin 
doses for titration purpose must preferably be entered within 24 hours after the site visit/telephone
contact on week days throughout the trial. 
Once data has been entered, it will be available to Novo Nordisk for data verification and validation 
purposes. Queries will be generated in the eCRF, and the investigator should solve these queries on 
an ongoing basis throughout the trial.
Site specific eCRF data (in an electronic readable format) will be provided to the trial site before 
access to the eCRF is revoked. This data must be retained at the trial site.
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14 Monitoring procedures 
During the course of the trial, the monitor will visit the trial site to ensure that the protocol is 
adhered to, that all issues have been recorded, to perform source data verification and to monitor 
drug accountability. The first monitoring visit will be performed no later than 6 weeks after FPFV. 
The monitoring visit intervals will depend on the outcome of the remote monitoring of the eCRF, 
the trial site's recruitment rate and the compliance of the trial site to the protocol and ICH GCP1, but 
will not exceed 8 weeks.
14.1
Source data verification and source data requirements
The monitor must be given direct access to source documents (original documents, data and 
records). Direct access includes permission to examine, analyse, verify and reproduce any record(s) 
and report(s) that are important to the evaluation of the trial. If the electronic medical record does 
not have a visible audit trail, the investigator must provide the monitor with signed and dated 
printouts. In addition the relevant trial site staff should be available for discussions at monitoring 
visits and between monitoring visits (e.g. by telephone).
Monitors must review the subject's medical records and other source data (e.g. the diaries) to ensure 
consistency and/or identify omissions compared to the CRF. If discrepancies are found, the 
investigator and/or relevant trial site staff should be available for discussion at/between monitoring 
visits.
All data must be verifiable in source documentation other than the CRF. This must be defined in a 
source document agreement at each trial site. There must only be one source defined at any time for 
any data element.
The monitor will collect CRF pages and other trial related forms containing data from screening 
failures. Source data verification requirements for screening failures are described in section 8.1.3.
Source data generated by the trial site can be corrected by another person than the person entering 
the source data if accepted by local regulations; any correction must be explained, signed and dated 
by the person making the correction.
For SMPG values it is accepted that the earliest practically retainable record should be considered 
source data. Therefore, the data recorded by the BG-meter and transcribed into the diary by the 
subject will be considered source data. The diary will be considered the source document with 
respect to:
!
Date and fasting SMPG values
!
Date, time and dose of trial product
!
Date and time for hypoglycaemic episodes
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The original diaries must not be removed from the trial site, unless they form part of the CRF and a 
copy is kept at the site.
A follow-up letter (paper or electronic) will be sent to the investigator following each monitoring 
visit addressing any action to be taken.
15 Data management
Data management is the responsibility of Novo Nordisk. 
Appropriate measures, including encryption of data files containing person identifiable data, will be 
used to ensure confidentiality of subject data, when they are transmitted over open networks. 
Data from central laboratories will be transferred electronically to Novo Nordisk from the 
laboratory performing the analyses. Data from special laboratories may be transferred to Novo 
Nordisk via the central laboratory. In cases where data is transferred via non-secure electronic 
networks, data will be encrypted during transfer. Laboratory reports will be provided directly to the 
investigator for storage at trial site.
The subject and any biological material obtained from the subject will be identified by subject 
number and trial identification number. Appropriate measures such as encryption or leaving out 
certain identifiers will be enforced to protect the identity of subjects in all presentations and 
publications as required by local, regional and national requirements.
16 Computerised systems
Novo Nordisk will capture and process clinical data using computerised systems that are described 
in Novo Nordisk Standard Operating Procedures and IT architecture documentation. The use and 
control of these systems are documented.
Investigators working on the trial may use their own electronic systems to capture source data. 
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17 Statistical considerations
Novo Nordisk will analyse and report data from all sites together.
All analyses of efficacy and safety endpoints will be based on the full analysis set (FAS). The 
analysis of the primary endpoint will be repeated on the per-protocol (PP) analysis set and the 
completer analysis set (CAS) for sensitivity purposes. All efficacy endpoints will be summarised 
using the FAS and safety endpoints will be summarised using the safety analysis set (SAS). 
The impact of protocol deviations and outliers may be investigated further in sensitivity analyses if 
deemed relevant.
Unless otherwise specified, all continuous measurements will be summarised descriptively at each 
visit by treatment using observed data. After 26 weeks of treatment, descriptive statistics will be 
presented based both on observed and last observation carried forward (LOCF) imputed data. 
Endpoints that are analysed untransformed and endpoints that are not formally analysed are 
summarised by the arithmetic mean, standard deviation (SD), median, and minimum and maximum 
value. Endpoints that are analysed log-transformed are supplemented with the geometric mean and 
coefficient of variation (CV).
For measurements over time, mean values will be plotted to explore the trajectory over time. LOCF 
imputed data will be used as the basis for plotting data, if not otherwise specified. For endpoints 
that are analysed log-transformed, the geometric mean values will be plotted.
A standard analysis of covariance (ANCOVA) model will be applied for the continuous primary 
and secondary endpoints. The model includes treatment and previous OAD treatment (metformin or 
metformin in combination with one of the following: AGI, SU, glinides and TZD as fixed effects 
and the corresponding baseline value as covariate. In the following, this model will be referred to as 
the standard ANCOVA model.
Presentation of results from a statistical analysis will include the estimated mean treatment effects 
(Least Square Means [LSMeans]) for absolute values and change from baseline. In addition, 
estimated mean treatment difference (or ratio) will be presented together with the two-sided 95% 
confidence interval and corresponding two-sided 5% p-value.
Handling of missing data
The expected percentage of missing data is around 15%. In accordance with industry guidance14
endpoints will be assessed at frequent visits and also on subjects who withdraw prematurely. This 
will facilitate an analysis in accordance with ITT principles. Also, the combined information on 
frequent outcomes and information on reason for drop-out is assumed to account for the missing 
data anticipated.
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If an assessment has been made both at screening (Visit 1) and randomisation (Visit 2), and if not 
otherwise specified, the value from the randomisation visit will be used as the baseline value. If the 
value measured at the randomisation visit is missing and the assessment also has been made at 
screening, then the screening value will be used as the baseline value.
Missing values (including intermittent missing values) will be imputed using the LOCF method. 
Subjects without data after randomisation will be included by carrying forward their baseline value. 
LOCF has been a standard approach in diabetes trials for many years, and was used as the primary 
analysis in both IDegLira and IDeg phase 3a trials. LOCF is considered to be an appropriate method 
in the context of TTT trials, where subjects after withdrawal typically continue their therapy using 
commercially available insulin. In previous TTT trials with IDegLira and IDeg, LOCF has 
generally provided similar results to alternative methods applied to handle missing data, such as 
repeated measures models and completer analyses. In this trial, similar sensitivity analyses will be 
made to examine the robustness of the LOCF method. The LOCF approach will also be used to 
impute missing values in CAS. 
17.1
Sample size calculation
The primary objective of this trial is to confirm the efficacy of IDegLira in controlling glycaemia as 
assessed by change from baseline in HbA1c after 26 weeks of treatment vs. IDeg and liraglutide,
respectively. This is done by comparing the difference in change from baseline in HbA1c after 26 
weeks of treatment to a non-inferiority margin of 0.4% for IDegLira vs. IDeg and to a superiority 
margin of 0.0% for IDegLira vs. liraglutide. The non-inferiority margin of 0.4% (absolute) was 
chosen in accordance with the Food and Drug Administration (FDA) guidance14. 
A hierarchical testing procedure is applied. This is based on an a priori ordering of the null-
hypotheses and testing them in this order using the two-sided 95% confidence interval approach 
until an insignificant result appears. Non-inferiority and superiority will thus be considered 
confirmed if the upper bound of the two-sided 95% confidence interval is below 0.4% and 0.0% 
respectively. This is equivalent to using a one-sided test of size 2.5%, which means that the type 1 
error rate is controlled at 2.5%.
Formally, let D be the mean difference in change from baseline in HbA1c. The null-hypothesis are 
given as 
!
Non-inferiority: H0 D≥0.40% against HA D<0.40%, with an assumed mean difference in 
treatment of 0.0% and a standard deviation of 1.0%
!
Superiority: H0 D≥0.0% against HA D<0.0%, with an assumed mean difference in treatment of -
0.3% and a standard deviation of 1.0%
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For evaluation of non-inferiority the PP-population is used for the sample size calculations, while 
the FAS is used for evaluation of superiority. It is assumed that 15% of the randomised subjects will 
be excluded from the PP analysis set. The above assumptions are based on experience from the 
phase 3a development programmes for IDegLira and IDeg. The sample size is determined using a t-
statistic under the assumption of a one-sided test of size 2.5% for both the superiority and non-
inferiority testing. Based on these assumptions a sample size of 720 patients results in a non-
inferiority power of 98.1% and a superiority power of 90.7% i.e. the combined power for meeting 
the primary objective is 98.1% * 90.7% = 89.0%. A sample size of 720 patients with a 15% drop-
out rate and a 2:1:1 randomisation results in 306 PP patients in the IDegLira arm.
17.2
Definition of analysis sets
The following analysis sets are defined in accordance with the ICH-E9 guidance15.
!
Full Analysis Set (FAS): includes all randomised subjects. In exceptional cases, subjects may 
be eliminated from the full analysis set. In such cases the elimination will be justified and
documented. The statistical evaluation of the FAS will follow the intention-to-treat (ITT) 
principle and subjects will contribute to the evaluation “as randomised”
!
Per-Protocol (PP) analysis set: includes all subjects in the Full Analysis Set who fulfils the 
following criteria:
o
Have not violated any inclusion criteria
o
Have not fulfilled any exclusion criteria
o
Have a non-missing HbA1c at screening or randomisation
o
Have at least one non-missing HbA1c after 12 weeks of exposure
o
Have at least 12 weeks of exposure
Subjects will contribute to the evaluation “as treated”.
!
Safety Analysis Set (SAS): includes all subjects receiving at least one dose of the 
investigational product or comparator. Subjects in the safety set will contribute to the evaluation 
“as treated”
!
Completer Analysis Set (CAS): includes all randomised subjects who have completed the trial. 
Subjects in the completer analysis set will contribute to the evaluation “as randomised”
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Randomised subjects who are lost to follow up and where no exposure information of the 
investigational product or comparators is available after randomisation will be handled as 
unexposed.
Before data are released for statistical analysis, a review of all data will take place to identify 
protocol deviations that could potentially affect the results. Any decision to exclude any subject or 
observation from the statistical analysis is the joint responsibility of the members of the study 
group. The subjects or observations to be excluded, and the reasons for their exclusion must be
documented and signed by those responsible before database lock. The subjects and observations 
excluded from analysis sets, and the reason for this, will be described in the clinical trial report.
17.3
Primary endpoint
The primary endpoint is defined as change from baseline in HbA1c after 26 weeks of treatment.
The change from baseline in HbA1c after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous OAD treatment (metformin ± one other OAD) as 
fixed effects and baseline HbA1c as covariate. Missing values after 26 weeks of treatment will be 
imputed applying LOCF using HbA1c values at and after baseline.
Non-inferiority of IDegLira vs. IDeg will be considered as confirmed if the 95% confidence interval 
for the mean treatment difference lies entirely below 0.4%; equivalent to a one-sided test with 
significance level of 2.5%. Non-inferiority will be investigated on the FAS. Sensitivity analysis will 
be performed on the PP analysis set.
Superiority of IDegLira vs. liraglutide will be considered as confirmed if the 95% confidence 
interval for the mean treatment difference for change from baseline in HbA1c lies entirely below 
0.0%; equivalent to a one-sided test with significance level of 2.5%. Conclusion of superiority will 
be based on FAS. The primary objective will be fulfilled only if both non-inferiority of IDegLira vs. 
IDeg and superiority of IDegLira vs. liraglutide are confirmed.
In addition to the non-inferiority margin of 0.4% the upper bound of the confidence interval for the 
mean treatment difference of IDegLira vs. IDeg will also be compared to a 0.0% margin. This 
comparison is not part of the hierarchical testing procedure.
17.3.1
Sensitivity analysis
The primary analysis will be repeated on the PP analysis set and the CAS as sensitivity analysis. 
Furthermore, sensitivity analysis will be performed on FAS using the mixed model for repeated 
measurement (MMRM) to evaluate the sensitivity of using LOCF. All HbA1c values available post 
baseline at scheduled measurement times will be analysed in a linear mixed normal model using an 
unstructured residual covariance matrix for HbA1c measurements within the same subject. The 
model will include treatment, visit, and previous OAD treatment as fixed effects and baseline 
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HbA1c as covariate. Interactions between visit and all factors and the covariate are also included in 
the model. The result will be compared to the result of the ANCOVA method using LOCF for 
imputation of missing data. Any marked difference between the MMRM and ANCOVA LOCF 
approach regarding the estimated treatment difference will be commented upon in the CTR.
17.4
Secondary endpoints
17.4.1
Confirmatory secondary endpoints
The following two confirmatory endpoints will be tested for superiority of IDegLira vs. IDeg.
!
Change from baseline in body weight after 26 weeks of treatment. 
!
Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 26 
weeks of treatment.
The tests for superiority of the confirmatory secondary endpoints will be based on the FAS and will 
only be carried out if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. 
liraglutide with regards to the primary endpoint are confirmed. 
In order to control the overall type I error on a 5% level with regards to the secondary endpoints, a 
hierarchical testing procedure will be used. If superiority is confirmed with respect to change from 
baseline in body weight after 26 weeks of treatment the number of treatment emergent severe or BG 
confirmed hypoglycaemic episodes during 26 weeks of treatment will be tested for superiority.
Superiority for change from baseline in body weight will be considered confirmed if the upper 
bound of the two-sided 95% confidence interval for the estimated mean treatment difference 
(IDegLira minus IDeg) is strictly below zero or equivalently if the p-value for the one-sided test of 
H0 D≥0.0% against HA D<0.0%,
is less than 2.5%, where D is the treatment difference.
Superiority for hypoglycaemic episodes will be considered confirmed if the upper bound of the two-
sided 95% confidence interval for the estimated mean treatment ratio (IDegLira vs. IDeg) is strictly 
below one or equivalently if the p-value for the one-sided test of 
H0 RR≥1.0 against HA RR<1.0,
is less than 2.5%, where RR is the estimated rate ratio.
The change from baseline in body weight after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous OAD treatment (metformin ± one other OAD) as 
fixed effect and baseline weight as covariate. 
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Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 26 weeks 
of treatment will be analysed using a negative binominal regression model with a log-link function 
and the logarithm of the time period in which a hypoglycaemic episode is considered treatment 
emergent as offset. The model will include treatment and previous anti-diabetic treatment as fixed 
factors and baseline HbA1c as covariate.
17.4.2
Supportive secondary endpoints
17.4.2.1
Efficacy endpoints
In the following the statistical models will be fitted to all data simultaneously (all treatment groups) 
and from this model the treatment differences for IDegLira vs. IDeg and IDegLira vs. liraglutide 
will be estimated.
Insulin dose after 26 weeks of treatment
The actual daily insulin dose after 26 weeks of treatment will be analysed using an ANCOVA 
model including treatment and previous anti-diabetic treatment as fixed factors and baseline HbA1c
value and baseline insulin dose as covariates.
Responder for HbA1c after 26 weeks of treatment
Two dichotomous endpoints (responder/non-responder) will be defined based on whether a subject 
has met a specific target level after 26 weeks of treatment:
!
ADA HbA1c target (HbA1c < 7.0%)
!
International Diabetes Federation (IDF) HbA1c target (HbA1c ≤ 6.5%)
Analysis of each of the two responder endpoints will be based on a logistic regression model with 
treatment and previous anti-diabetic treatment as fixed factors and baseline HbA1c value as a 
covariate.
HbA1c responder endpoints without weight gain
Responder for HbA1c without weight gain after 26 weeks of treatment will be defined as HbA1c < 
7.0% or ≤ 6.5% at end of treatment and change from baseline in body weight below or equal to 
zero. Analysis of each of the two responder endpoints will be based on a logistic regression model 
with treatment and previous anti-diabetic treatment as fixed factors and baseline HbA1c and body 
weight values as covariates.
HbA1c responder endpoints without hypoglycaemic episodes
Responder for HbA1c without hypoglycaemic episodes after 26 weeks of treatment will be defined 
as HbA1c < 7.0% or ≤ 6.5% at end of treatment and without severe or BG confirmed episodes 
during the last 12 weeks of treatment. Analysis of each of the two responder endpoints will be based 
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on a logistic regression model with treatment and previous anti-diabetic treatment as fixed factors 
and baseline HbA1c values as a covariate.
HbA1c responder endpoints without hypoglycaemic episodes and weight gain
Responder for HbA1c without hypoglycaemic episodes and weight gain after 26 weeks of treatment 
will be defined as HbA1c < 7.0% or ≤ 6.5% at end of treatment, without severe or BG confirmed 
episodes during the last 12 weeks of treatment, and change from baseline in body weight below or 
equal to zero. Analysis of each of the two responder endpoints will be based on a logistic regression 
model with treatment and previous anti-diabetic treatment as fixed factors and baseline HbA1c and 
body weight values as covariates.
Fasting plasma glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment will be analysed using the standard 
ANCOVA model.
Waist circumference
Change from baseline in waist circumference after 26 weeks of treatment will be analysed using the 
standard ANCOVA model.
Beta-cell function (fasting insulin, fasting C-peptide, fasting glucagon, and HOMA-β)
In addition to fasting insulin, fasting C-peptide, and fasting glucagon, one derived parameter will be 
calculated; beta-cell function (HOMA-β).
The calculation of the HOMA endpoint will be done as follows:
!
Beta-cell function (%) = 20·fasting insulin[μU/mL]/(FPG[mmol/L]-3.5)
These endpoints after 26 weeks of treatment will be analysed separately using the standard 
ANCOVA model. In these statistical analyses the endpoint will be log-transformed and so will the 
baseline covariate.
Fasting lipid profile 
Cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, triglycerides, and free fatty 
acids after 26 weeks of treatment will be analysed separately using the standard ANCOVA model. 
In these statistical analyses the endpoint will be log-transformed and so will the baseline covariate.
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Self-measured plasma glucose 9-point profile
Three endpoints from the 9-point profile will be defined: 
!
9-point profile
!
Mean of the 9-point profile, defined as the area under the profile (calculated using the 
trapezoidal method) divided by the measurement time
!
Post-prandial plasma glucose increments (from before meal to 90 min after for breakfast, lunch 
and dinner). The mean increment over all meals will be derived as the mean of all available 
meal increments
A mixed effect model will be fitted to the 9-point profile data. The model will include treatment, 
time, interaction between treatment and time, and previous anti-diabetic treatment as fixed factors 
and the baseline value as a covariate. An unstructured residual covariance matrix within the same 
subject is employed. From the model mean profile by treatment and relevant treatment differences 
will be estimated and explored. 
Change from baseline after 26 weeks of treatment in mean of the 9-point profile and post-prandial 
increment endpoints will be analysed separately using the standard ANCOVA model. 
17.4.2.2
Safety endpoints
Adverse events
AEs will be coded using the most recent version of the Medical Dictionary for Regulatory 
Activities coding.
A TEAE is defined as an event that has onset date on or after the first day of exposure to 
randomised treatment and no later than seven days after the last day of randomised treatment. If the 
event has onset date before the first day of exposure on randomised treatment and increases in 
severity during the treatment period and until 7 days after the last drug date, then this event should 
also be considered as a TEAE.
TEAEs are summarised descriptively, whereas non-TEAEs are presented in listings. TEAE data 
will be displayed in terms of the number of subjects with at least one event (N), the percentage of 
subjects with at least one event (%), the number of events (E) and the event rate per 100 years of 
exposure (R).
Summaries of TEAEs and of serious TEAEs will be presented as an overview including all AEs, 
serious AEs, number of deaths, AEs by severity, AEs by relation to treatment and AEs of special 
interest including AEs leading to withdrawal.
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Furthermore summary tables based on system organ class and preferred terms are made for: 
!
All TEAEs 
!
Serious TEAEs
!
Possibly or probably related TEAEs
!
Severe, moderate and mild TEAEs
!
TEAEs reported by safety areas of interest
!
TEAEs with preferred term that are experienced by at least 5% of the subjects in any treatment 
arm or by at least 5% of all subjects
A listing for non-TEAEs with onset date before the first day of exposure to randomised treatment 
will be presented. A listing will also be presented for non-TEAEs collected after the treatment 
emergent period according to the definition of TEAE.
Classification of Hypoglycaemia
Treatment emergent: hypoglycaemic episodes will be defined as treatment emergent if the onset 
of the episode occurs on or after the first day of trial product administration, and no later than 7 
days after the last day on trial product.
Nocturnal hypoglycaemic episodes: are episodes with time of onset between 00:01 and 05.59 both 
inclusive.
Hypoglycaemic episodes are classified according to the Novo Nordisk classification of 
hypoglycaemia (see Figure 17–1) and the ADA classification of hypoglycaemia (see Figure 17–2).
Novo Nordisk classification of hypoglycaemia
In normal physiology, symptoms of hypoglycaemia occur below a plasma glucose level of 3.1 
mmol/L16. Therefore, Novo Nordisk has included hypoglycaemia with plasma glucose levels below 
this cut-off point in the definition of BG confirmed hypoglycaemia.
Novo Nordisk uses the following classification (in addition to the ADA classification):
!
Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to 
the ADA classification11 or BG confirmed by a plasma glucose value <3.1 mmol/L with
symptoms consistent with hypoglycaemia
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!
Severe or BG confirmed hypoglycaemia: An episode that is severe according to the ADA 
classification11 or BG confirmed by a plasma glucose value <3.1 mmol/L with or without
symptoms consistent with hypoglycaemia
Figure 17–1
Novo Nordisk classification of hypoglycaemia
ADA classification of hypoglycaemia11
!
Severe hypoglycaemia: An episode requiring assistance of another person to actively administer 
carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not 
be available during an event, but neurological recovery following the return of plasma glucose 
to normal is considered sufficient evidence that the event was induced by a low plasma glucose 
concentration
!
Asymptomatic hypoglycaemia: An episode not accompanied by typical symptoms of 
hypoglycaemia, but with a measured plasma glucose concentration ≤ 3.9 mmol/L
!
Documented symptomatic hypoglycaemia: An episode during which typical symptoms of 
hypoglycaemia are accompanied by a measured plasma glucose concentration ≤ 3.9 mmol/L
!
Pseudo-hypoglycaemia: An episode during which the person with diabetes reports any of the 
typical symptoms of hypoglycaemia with a measured plasma glucose concentration > 3.9 
mmol/L but approaching that level
!
Probable symptomatic hypoglycaemia: An episode during which symptoms of hypoglycaemia 
are not accompanied by a plasma glucose determination but that was presumably caused by a 
plasma glucose concentration ≤ 3.9 mmol/L 
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Figure 17–2
ADA classification of hypoglycaemia
Data on treatment emergent hypoglycaemic episodes are presented in terms of the number of 
subjects with at least one event (N), the percentage of subjects with at least one event (%), the 
number of events (E) and the event rate per 100 years (R). 
Separate summaries are made for severe or BG confirmed hypoglycaemic episodes, severe or BG 
confirmed symptomatic hypoglycaemic episodes, nocturnal severe or BG confirmed hypoglycaemic 
episodes, nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes and the ADA 
classification of hypoglycaemia.
All endpoints based on hypoglycaemic episodes will be analysed using the same model as used for 
the treatment emergent severe or BG confirmed hypoglycaemic episodes.
Pulse
Change from baseline in pulse after 26 weeks of treatment will be analysed using the standard 
ANCOVA model.
Systolic and diastolic blood pressure
Change from baseline in systolic and diastolic blood pressure after 26 weeks of treatment will be 
analysed using the standard ANCOVA model.
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Clinical evaluations (physical examination, eye examination and ECG)
Eye examination (fundoscopy/fundusphotography) and ECG findings will be summarised 
descriptively, including:
!
summaries
!
the change from baseline after 26 weeks of treatment
Any findings in the physical examination evaluation at screening will be presented as listings. Any 
clinically significant deterioration of a pre-existing condition after the screening visit, as well as any 
new clinically significant findings will be recorded as adverse events.
Laboratory assessments 
All laboratory parameters will be summarised descriptively.
The following tables will be presented based on both observed and LOCF imputed data:
!
Shift tables from baseline to after 26 weeks of treatment
!
Proportion of subjects with measurements outside reference range by treatment and week
Laboratory values will be presented graphically as box plots by treatment and week.
For each laboratory parameter, individual values outside the reference ranges (abnormal values) 
will be listed.
For lipase and amylase the following rule applies in the evaluation of the result
!
If the amylase or lipase baseline (at screening) value is > 3xUNR the information will be
recorded as medical history for that subject. 
Calcitonin
The purpose of the calcitonin analysis is to evaluate longitudinal changes in calcitonin, with main 
focus on subjects who develop persistently high levels of calcitonin during the trial.
Calcitonin will be displayed in terms of the number of subjects (N), the percentage of subjects (%) 
and the event rate per 100 years of exposure (R). The following criteria are defined for tabulations:
Persistent (all post baseline measurements)
!
From < UNR to persistently ≥ UNR
!
From < UNR to persistently ≥ 1.5 UNR
!
From < UNR to persistently ≥ 20 ng/L
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!
From < UNR to persistently ≥ 50 ng/L
!
From < 20 ng/L to persistently ≥ 20 ng/L
!
From < 50 ng/L to persistently ≥ 50 ng/L
Incidental (at least one post baseline measurements)
!
From < UNR to ≥ UNR
!
From < UNR to ≥ 1.5 UNR
!
From < UNR to ≥ 20 ng/L
!
From < UNR to ≥ 50 ng/L
!
From < 20 ng/L to ≥ 20 ng/L
!
From < 50 ng/L to ≥ 50 ng/L
The distribution of all calcitonin measurements across treatment groups and time will be shown
with histograms and corresponding cumulative plots for actual levels of calcitonin and change from 
baseline. The plots will be presented by treatment group (using EOT measurement - LOCF) and 
within treatment group by week. Plots will be done by each gender, separately.
Summaries tables of calcitonin continuous measurements, will include number and percentage of 
observations < and ≥ LLOQ, minimum, Q25, median, Q75 and maximum. Summaries will be 
presented for all subjects and by gender.
Longitudinal changes for subjects with calcitonin levels ≥ 20 ng/l will be plotted (longitudinal 
plots). The plots will be done by treatment and gender. They will be done for subjects in the 
persistent and incidental categories, separately.
A listing of subjects with at least one post baseline value ≥ 20 ng/l will be done. The listing will 
include age, gender, calcitonin measurements over time and AE history (including preferred term, 
onset and stop dates).
Urinalysis
Categorical urinalysis parameters will be summarised descriptively by:
!
Shift from baseline to EOT (using the number of subjects in the different categories)
!
Subjects with at least one post baseline measurement outside reference range will be listed
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Antibodies towards trial product
Anti-IDeg antibodies, anti-human insulin antibodies, anti-liraglutide antibodies, anti-liraglutide 
antibodies cross reacting with native GLP-1 and in vitro neutralising effect of anti-liraglutide 
antibodies will be summarised and tabulated. The correlation between change from baseline after 26 
weeks of treatment in anti-IDeg and anti-insulin antibodies respectively, to insulin dose after 26 
weeks of treatment, HbA1c after 26 weeks of treatment and change from baseline after 26 weeks of 
treatment in HbA1c will be illustrated using scatter plots.
For the liraglutide component of IDegLira and liraglutide, the number of subjects (N) and the 
percentage of subjects (%) with positive, cross-reacting to native GLP-1 and neutralising antibodies 
will be summarised.
Listing with subjects with liraglutide positive antibody formation will be produced. These listings 
should include efficacy information as minimum HbA1c and body weight over time.
17.5
Pharmacokinetic modelling
Population pharmacokinetic analysis
The objective for this analysis is to compare the pharmacokinetics of IDegLira and its individual 
components at clinically relevant doses during 26 weeks of treatment. Furthermore, dose-
proportionality of IDeg and liraglutide exposures following doses of IDegLira will be evaluated and 
the effects of pre-specified covariates on exposures of IDeg and liraglutide will be investigated.PK 
samples for IDeg and liraglutide sampled at site visits will be included in the analysis. No pre-
defined time of day is specified for the sampling, but the date and exact clock time of sampling will 
be recorded by the Investigator. The subjects must be instructed to write in their diary the date, 
exact clock time, dose, and injection site of the previous three days of dosing as well as the dose on 
the day of the visit, if taken before PK blood sampling.
The population PK analysis will be performed by the Quantitative Clinical Pharmacology 
Department at Novo Nordisk A/S. A more technical and detailed elaboration of the population PK 
analysis will be given in the modelling analysis plan (MAP) which will be finalised before DBL. 
The pre-specified analysis will explore the effects of covariates on the IDeg and liraglutide 
exposure. The structural models and covariate relationships will be predefined in detail in the MAP. 
In brief, previously developed population PK models for IDeg and liraglutide will be used. For both 
PK models, the absorption rate constant (Ka) will be fixed and the apparent clearance (CL/F) and 
the apparent volume of distribution (Vd/F) will be estimated.
The covariates of interest will be evaluated using criteria which will be specified in the MAP.
The following covariates will be tested on the apparent clearance (CL/F):
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!
Dose
!
Treatment (IDegLira, IDeg, liraglutide)
!
Injection site area (Abdomen, Upper arm, Thigh)
!
Body weight
!
Age group (<65, ≥65 years)
!
Gender (Male/Female)
For the categorical variables, it is a requirement to have at least 20 subjects in each category.
Exposure-response analysis
The exposure-response relationship will be investigated for selected response variables, such as 
HbA1c. Individual drug concentration data will be tabulated in the clinical trial report.
The population PK and exposure-response analyses will be reported in a separate modelling report, 
which will not be a part of the clinical trial report.
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18 Ethics
All subjects included in the trial will be treated with IDeglira, IDeg or liraglutide in combination 
with metformin in order to improve their glycaemic control.
Subjects randomised to the trial will be transferred to a treatment regimen anticipated to be better 
than or equal to the treatment they receive at the time they enter the trial. However, they will have
to spend some extra time for trial related visits and some of the assessments performed during the 
trial go beyond normal practice.
When a subject’s participation in the trial ends, the subject will consult his/her investigator to 
decide on the best available marketed treatment. 
18.1
Informed consent 
In seeking and documenting informed consent, the investigator must comply with applicable 
regulatory requirement(s) and adhere to ICH GCP1 and the requirements in the Declaration of 
Helsinki2.
Before any trial-related activity, the investigator must give the subject verbal and written 
information about the trial and the procedures involved in a form that the subject can read and 
understand. 
The subjects must be fully informed of their rights and responsibilities while participating in the 
trial as well as possible disadvantages of being treated with the trial products.
The investigator must ensure the subject has ample time to ask questions and come to a decision 
whether or not to participate in the trial. 
A voluntary, signed and personally dated informed consent must be obtained from the subject 
before any trial-related activity. The subject must be provided with a copy of this.
The responsibility for seeking informed consent must remain with the investigator, but the task may 
be delegated by the investigator to a medically qualified person, in accordance with local 
requirements. The written informed consent must be signed and personally dated by the person who 
seeks the informed consent before any trial-related activity.
If information becomes available that may affect subject's willingness to continue in the trial, the 
investigator must inform the subject in a timely manner. Revised written subject information must 
be provided and a new informed consent must be obtained.
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If a female trial subject becomes pregnant and an abnormality is found in the foetus or newborn 
infant, a separate written information and informed consent form must be given to the subject’s 
male partner for consent to obtain information on paternal health and medical history.
For all of the specific informed consents the subject and/or subject’s partner must have the option to 
abstain from these, while still participating in the trial as per the initial informed consent.
18.2
Data handling
If the subject is withdrawn from the trial or lost to follow up, then the subject's data will be handled 
as follows:
!
Data already collected and data collected at the end-of-trial (Visit 29) will be retained by Novo 
Nordisk, entered into the database and used for the trial report. 
!
Safety events will be reported to Novo Nordisk and regulatory authorities according to 
local/national requirements.
If data is used, it will always be in accordance with local regulations and IRBs/IECs.
18.3
Information to subject during trial
All information provided to the subjects during the trial will be translated to local language and 
submitted to the health authorities and IECs/IRBs for approval according to local regulations.
18.4
Premature termination of the trial and/or trial site
Novo Nordisk, the investigator, the IRBs/IECs or a regulatory authority may decide to stop the trial, 
part of the trial or a trial site at any time, but agreement on procedures to be followed must be 
obtained.
If a trial is suspended or prematurely terminated, the investigator must inform the subjects promptly 
and ensure appropriate therapy and follow-up. The investigator and/or Novo Nordisk must also 
promptly inform the IRBs/IECs and provide a detailed written explanation. The relevant regulatory 
authorities must be informed.
If, after the termination of the trial, the risk/benefit analysis changes, the new evaluation must be 
provided to the IRBs/IECs in case it has an impact on the planned follow-up of subjects who have 
participated in the trial. If it has an impact, the actions needed to inform and protect the subjects 
should be described.
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19 Protocol compliance
Deviations from the protocol should be avoided.
If deviations do occur, the investigator must inform the monitor and the implications of the 
deviation must be reviewed and discussed.
Deviations must be documented and explained in a protocol deviation by stating the reason, date, 
and the action(s) taken. Some deviations, for which corrections are not possible, can be 
acknowledged and confirmed via edit checks in the eCRF or via listings from the clinical database. 
Documentation on protocol deviations must be kept in the investigator's trial file and Novo Nordisk 
trial master file.
20 Audits and inspections
Any aspect of the clinical trial may be subject to audits conducted by Novo Nordisk or inspections 
from domestic or foreign regulatory authorities or from IRBs/IECs. Audits and inspections may 
take place during or after the trial. The investigator and the trial site staff as well as Novo Nordisk 
staff have an obligation to cooperate and assist in audits and inspections. This includes giving 
auditors and inspectors direct access to all source documents and other documents at the trial site 
relevant to the clinical trial. This includes permission to examine, analyse, verify and reproduce any 
record(s) and report(s) that are relevant to the evaluation of the trial.
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21
Critical documents
Before a trial site is allowed to start screening subjects, the following documents must be available 
to Novo Nordisk:
!
Regulatory approval and/or acknowledgement of notification as required 
!
Approval/favourable opinion from IRBs/IECs clearly identifying the documents reviewed as 
follows: protocol, any protocol amendments, subject information/informed consent form, any 
other written information to be provided to the subject and subject recruitment materials
!
List of IRB/IEC members and/or constitution
!
Curricula vitae of investigator and sub-investigator(s) (current, dated and signed - must include 
documented GCP training or a certificate)
!
Signed receipt of Investigator's Brochure
!
SmPC as appropriate
!
Signed and dated agreement on the final protocol
!
Signed and dated agreement on protocol amendment, if applicable
!
Financial agreement(s)
!
Source document agreement
!
Central laboratory certification and normal ranges
!
Insurance statement
!
Signed and dated Investigator Agreement
!
Financial disclosure form from investigator and sub-investigator(s)
Novo Nordisk will analyse and report data from all sites together.
By signing the protocol, each investigator agrees to comply fully with ICH GCP1, applicable 
regulatory requirements and the Declaration of Helsinki2. 
By signing the protocol, each investigator also agrees to allow Novo Nordisk making investigator's 
name and information about site name and address publically available if this is required by 
national or international regulations.
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22 Responsibilities
The investigator is accountable for the conduct of the trial at his/her site. If any tasks are delegated, 
the investigator must maintain a list of appropriately qualified persons to whom he/she has 
delegated specified significant trial-related duties. The investigator must ensure that there is 
adequate training for all staff participating in the conduct of the trial. It is the investigator's 
responsibility to supervise the conduct of the trial and to protect the rights, safety, and well-being of 
the subjects.
A qualified physician, who is an investigator or a sub-investigator for the trial, must be responsible 
for all trial-related medical decisions.
The investigator must ensure adequate supervision of the conduct of the trial at the trial site. 
The investigator will follow instructions from Novo Nordisk when processing data.
22.1
Source data handling
The investigator is responsible for filing essential documents (i.e. those documents which 
individually and collectively permit evaluation of the conduct of a trial and the quality of the data 
produced) in the investigator's trial file. The documents should be kept in a secure locked facility, 
so no unauthorized persons can get access to the data. The subject identification code list must be 
kept securely and separate from the personal data.
The investigator will take all necessary technical and organisational safety measures to prevent 
accidental or wrongful destruction, loss or deterioration of data. The investigator will prevent any 
unauthorised access to data or any other processing of data against applicable law. The investigator 
must be able to provide the necessary information or otherwise demonstrate to Novo Nordisk that 
such technical and organisational safety measures have been taken.
22.2
Delegation of responsibilities
During any period of unavailability, the investigator must delegate responsibility for medical care of 
subjects to a specific qualified physician who will be readily available to subjects during that time.
If the investigator is no longer able to fulfil the role as investigator (e.g. if he/she moves or retires), 
a new investigator will be appointed in consultation with Novo Nordisk. 
The investigator and other site personnel must have sufficient English skills according to their 
assigned tasks.
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23 Reports and publications
The information obtained during the conduct of this trial is considered confidential, and may be 
used by Novo Nordisk for regulatory purposes and for the general development of the trial product. 
All information supplied by Novo Nordisk in connection with this trial shall remain the sole 
property of Novo Nordisk and is to be considered confidential information. No confidential 
information shall be disclosed to others without prior written consent from Novo Nordisk. Such 
information shall not be used except in the performance of this trial. The information obtained 
during this trial may be made available to other physicians who are conducting other clinical trials 
with the trial product, if deemed necessary by Novo Nordisk.
One Principal Investigator will be appointed to review and sign the clinical trial report (signatory 
investigator) on behalf of all participating investigators. The signatory investigator will be 
appointed based upon the criteria defined by the ICMJE for research publications8.
23.1
Communication of results
Novo Nordisk commits to communicating, and otherwise making available for public disclosure, 
results of trials regardless of outcome. Public disclosure includes publication of a paper in a 
scientific journal, abstract submission with a poster or oral presentation at a scientific meeting, or 
disclosure by other means.
The results of this trial will be subject to public disclosure on external web sites according to 
international and national regulations, as reflected in the Novo Nordisk Code of Conduct for 
Clinical Trial Disclosure.
Novo Nordisk reserves the right to defer the release of data until specified milestones are reached, 
for example when the clinical trial report is available. This includes the right not to release the 
results of interim analyses, because the release of such information may influence the results of the 
entire trial.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the 
investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or 
communication for up to 60 days to protect intellectual property.
In all cases the trial results will be reported in an objective, accurate, balanced and complete 
manner, with a discussion of the strengths and limitations. All authors will be given the relevant 
statistical tables, figures, and reports needed to evaluate the planned publication. In the event of any 
disagreement on the content of any publication, both the investigators' and Novo Nordisk opinions 
will be fairly and sufficiently represented in the publication.
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Where required by the journal, the principal investigator from each trial site will be named in an 
acknowledgement or in the supplementary material, as specified by the journal. 
Novo Nordisk maintains the right to be informed of plans by any investigator to publish and to 
review any scientific paper, presentation, communication or other information concerning the 
investigation described in this protocol. Any such communication must be submitted in writing to 
Novo Nordisk before submission for comments. Comments will be given within four weeks from 
receipt of the planned communication. 
23.1.1
Authorship
Authorship of publications should be in accordance with the Uniform Requirements of the ICMJE8
(sometimes referred to as the Vancouver Criteria).
The investigator(s) offered authorship will be asked to comment and approve the publication. The 
authorship of publications of all trial results will be determined by the Publication group.
23.1.2
Site-specific publication(s) by investigator(s)
For a multi-centre clinical trial, analyses based on single-site data usually have significant statistical 
limitations and frequently do not provide meaningful information for healthcare professionals or 
subjects, and therefore may not be supported by Novo Nordisk. It is a Novo Nordisk policy that 
such individual reports do not precede the primary manuscript and should always reference the 
primary manuscript of the trial.
Novo Nordisk reserves the right to prior review of such publications. Further to allow for the 
primary manuscript to be published as the first, Novo Nordisk asks for deferment of publication of 
individual site results until the primary manuscript is accepted for publication. As Novo Nordisk 
wants to live up to the industry publication policy, submission for publication of such primary 
policy will take place no later than 18 months after trial completion.
23.2
Investigator access to data and review of results
As owner of the trial database, Novo Nordisk has the discretion to determine who will have access 
to the database. 
Individual investigators will have access to their own research subjects' data.
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24 Retention of clinical trial documentation and human bio
specimens
24.1
Retention of clinical trial documentation
Subject's medical records must be kept for the maximum period permitted by the hospital, 
institution or private practice.
The investigator must agree to archive the documentation (this includes both electronic and paper-
based records) pertaining to the trial in an archive after completion or discontinuation of the trial if 
not otherwise notified. The investigator should not destroy any documents without prior permission 
from Novo Nordisk. If the investigator cannot archive the documents at the trial site, Novo Nordisk 
can refer the investigator to an independent archive provider that has a system in place to allow only 
the investigator to access the files.
The investigator must be able to access his/her trial documents without involving Novo Nordisk in 
any way. Site-specific CRFs and other subject data (in an electronic readable format or as paper 
copies or prints) will be provided to the investigator before access is revoked to the systems
supplied by Novo Nordisk. These data must be retained by the trial site. If the Novo Nordisk 
provided data (e.g. the CD-ROM) is not readable during the entire storage period, the investigator
can request a new copy. A copy of all data will be stored by Novo Nordisk.
Novo Nordisk will maintain Novo Nordisk documentation pertaining to the trial for as long as the 
product is on the market plus 20 years. 
The files from the investigator site/institution must be retained for 15 years after the completion of 
the trial, or longer if required by local regulations. The deletion process must ensure confidentiality 
of data and must be done in accordance with local regulatory requirements.  
24.2
Retention of human bio specimens
Antibody samples will be analysed and then stored at a special laboratory outside of China until 
final feedback from the Chinese regulatory authorities, but no longer than 15 years from end of trial. 
Only Novo Nordisk will have access to these samples. Further characterisation of the antibody 
response may be requested by the regulatory authorities. 
None of the data will be identified by name. Antibody samples will be identified only by a subject 
number, a visit number and a trial identification number. In the event that the collected antibody 
samples will be used in the future, the investigator will become directly informed by Novo Nordisk 
about the results if the findings are deemed clinically relevant. In such case, a written summary of 
the findings, including listings of subject specific values, will be provided once a firm conclusion 
from the results has been drawn by Novo Nordisk.
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25 Institutional Review Boards/Independent Ethics Committees and 
regulatory authorities
IRB/IEC: Written approval or favourable opinion must be obtained from IRB/IEC prior to 
commencement of the trial.
During the trial, the investigator or sponsor, as applicable, must promptly report the following to the 
IRB/IEC, in accordance with local requirements: updates to Investigator's Brochure, unexpected 
SAEs where a causal relationship cannot be ruled out, protocol amendments according to local 
requirements, deviations to the protocol implemented to eliminate immediate hazards to the 
subjects, new information that may affect adversely the safety of the subjects or the conduct of the 
trial (including new risk/benefit analysis in case it will have an impact on the planned follow-up of 
the subjects), annually written summaries of the trial status, and other documents as required by the 
local IRB/IEC.
The investigator must ensure submission of the clinical trial report synopsis to the IRB/IEC.
Protocol amendments must not be implemented before approval or favourable opinion according to 
local regulations, unless necessary to eliminate immediate hazards to the subjects.
The investigator must maintain an accurate and complete record of all submissions made to the 
IRB/IEC. The records must be filed in the investigator's trial file and copies must be sent to Novo 
Nordisk.
Regulatory Authorities:
Regulatory authorities will receive the clinical trial application, protocol amendments, reports on 
SAEs, and the clinical trial report according to national requirements.
26 Indemnity statement
Novo Nordisk carries product liability for its products, and liability as assumed under the special 
laws, acts and/or guidelines for conducting clinical trials in any country, unless others have shown 
negligence.
Novo Nordisk assumes no liability in the event of negligence, or any other liability of the sites or 
investigators conducting the trial, or by persons for whom the said site or investigator are 
responsible.
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27 References
1 International Conference on Harmonisation (ICH). ICH Harmonised Tripartite Guideline: 
Guideline for Good Clinical Practice. J Postgrad Med 2001; 47(3):199-203.
2 Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. 
Last amended by the 64th WMA General Assembly, Fortaleza, Brazil. World Medical 
Association. 20 A.D.
3 The Diabetes Control and Complications Trial Research Group. The effect of intensive 
treatment of diabetes on the development and progression of long-term complications in 
insulin-dependent diabetes mellitus. New Engl J Med 1993; 329(14):977-986.
4 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with 
sulphonylureas or insulin compared with conventional treatment and risk of complications in 
patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131):837-853.
5 Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M et al. Management 
of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the 
American Diabetes Association (ADA) and the European Association for the Study of 
Diabetes (EASD). Diabetologia 2012; 55(6):1577-1596.
6 Chinese diabetes society. China guideline for type 2 diabetes. Chinese J diabetes mellitus 2, 6-
56. 2010.
7 Novo Nordisk A/S. Investigator's Brochure, insulin degludec/liraglutide (6th Edition).  10-1-
2014. 
8 Recommendations for the conduct, reporting, editing and publication of scholarly work in 
Medical Journals. International Committee of Medical Journal Editors. Dec-2013.
9 Food and Drug Administration. Food and Drug Administration Amendments Act of 2007: 
http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFD
CAct/SignificantAmendmentstotheFDCAct/FoodandDrugAdministrationAmendmentsActof2
007/default.htm. 2007.
10 European Commission Regulation for EudraCT. 
http://www.emea.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_00
0044.jsp&mid=WC0b01ac05800260a3. 2011.
11 Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L et al. Hypoglycemia and 
Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine 
Society. J Clin Endocrinol Metab 2013; 98(5):1845-1859.
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12 McAulay V, Deary IJ, Frier BM. Symptoms of hypoglycaemia in people with diabetes. Diabet 
Med 2001; 18(9):690-705.
13 European Union. The rules governing medicinal products in the European Union, volume 4, 
Annex 13, Manufacture of Investigational Products - Brussels. 2003.
14 Food and Drug Administration. Guidance for Industry. Diabetes Mellitus: Developing Drugs 
and Therapeutic Biologics for Treatment and Prevention .  2008. 
15 International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Statistical 
principles for clinical trials E9. International Conference on Harmonisation E9 Expert 
Working Group.  5-2-1998. 
16 Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose 
counterregulatory systems are higher than the threshold for symptoms. J Clin Invest 1987; 
79(3):777-781.
CONFIDENTIAL


Protocol - Appendix A
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
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Page:
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Appendix A
Titration Guideline
Trial ID: NN9068-4148
DUAL! I - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral anti-diabetic drugs (OADs)
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol - Appendix A
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
2 of 8
Table of Contents
Page
Table of Contents..............................................................................................................................................2
List of in-text tables..........................................................................................................................................2
1
Introduction...............................................................................................................................................3
2
Treatment regimens..................................................................................................................................4
2.1
Injection area..................................................................................................................................4
2.2
Time of injection............................................................................................................................4
3
Initiation and titration ..............................................................................................................................5
3.1
Initiation.........................................................................................................................................5
3.2
Titration .........................................................................................................................................5
3.3
Deviations from the algorithm.......................................................................................................5
4
Data collection ...........................................................................................................................................6
5
Review procedure......................................................................................................................................7
6
References..................................................................................................................................................8
List of in-text tables
Page
Table 1
IDegLira and IDeg dose adjustment ..............................................................................................5
CONFIDENTIAL


Protocol - Appendix A
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Date:
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1
Introduction
The goal of insulin therapy is to achieve near normoglycaemia, i.e. to reach a pre-defined HbA1c
level with a low rate of hypoglycaemic episodes and as little weight gain as possible. Several trials 
have shown that this is difficult to achieve, unless plasma glucose (PG) values are intensively 
monitored and the insulin dose(s) frequently adjusted1-7.
To ensure treatment uniformity between the sites, as well as to ensure that subjects receive an 
optimal treatment, titration algorithms have been developed specifying recommended dose 
adjustments at different PG levels.
It is recognised that treatments differ between different regions and countries. Likewise, specific 
titration guidelines may not be applicable in certain clinical situations. It is important that other 
information, such as symptoms of hypo/hyperglycaemia, previous response to dose adjustments, 
other glucose measurements and other indicators of the subject’s level of glycaemic control, is 
taken into consideration when decisions on dosing are made. The investigator should always use his 
clinical judgement to avoid safety hazards. The investigator is responsible for the treatment of the 
subjects and can therefore overrule the guideline.
To optimise and maintain glycaemic control, the investigator should, throughout the trial be at least 
in weekly contact with the subjects to assist the subjects in adjusting insulin doses and to ensure the 
subjects’ welfare.
CONFIDENTIAL


Protocol - Appendix A
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Date:
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Trial ID: NN9068-4148
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Status:
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2
Treatment regimens
At randomisation all subjects will be randomised in a 2:1:1 manner into three parallel treatment 
groups:
∀
Insulin degludec/liraglutide (IDegLira) OD + metformin
∀
Insulin degludec (IDeg) OD + metformin
∀
Liraglutide OD + metformin 
First dosing should take place on day of randomisation or on the day following randomisation.
Maximum dose for IDegLira is 50 dose steps (50 units of IDeg and 1.8 mg of liraglutide). 
There is no maximum dose for IDeg.
There is no minimum dose for IDeg and IDeglira.
Instructions on the use of liraglutide have not been included in this guideline as no titration will take 
place. Instead, please refer to the protocol section 5.3 for instructions on start dose and dose 
escalation.
2.1
Injection area
IDegLira or IDeg should be injected subcutaneously into the thigh, upper arm (deltoid area) or the 
abdomen. The chosen region should be the same throughout the trial. Rotation of injection sites 
within a given region is recommended.
2.2
Time of injection
IDegLira or IDeg should be injected once daily at any time of the day, but should approximately be 
the same time of the day throughout the trial. 
CONFIDENTIAL


Protocol - Appendix A
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Date:
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Trial ID: NN9068-4148
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3
Initiation and titration
3.1
Initiation
At randomisation (Visit 2), all subjects randomised to IDegLira or IDeg will start on 10 dose steps 
of IDegLira (10 U of IDeg and 0.36 mg of liraglutide) or 10 U of IDeg once daily.
3.2
Titration
Dose will be adjusted twice weekly by the subject 3-4 days apart. The investigator will support 
titration at all contacts. 
Titration should be performed based on the mean of three pre-breakfast self-measured plasma 
glucose (SMPG) values measured two days before and on day of titration. Titration should 
preferably be performed on the same days of the week throughout the trial. The dose adjustment 
will be performed according to Table 1.
Table 1
IDegLira and IDeg dose adjustment
Mean of three pre-breakfast SMPG 
values 
Dose adjustment
mmol/L
U/Dose steps
<4.0
-2
4.0 – 5.0
No adjustment
> 5.0
+ 2
If one or more SMPG values are missing, the adjustment should be performed on the remaining 
SMPG value(s). However, the first time titration is performed after randomisation all three SMPG 
values must be available. If this is not the case, subjects must wait for the next titration day to adjust 
the dose.
3.3
Deviations from the algorithm
It is strongly recommended that the algorithm is followed. However, it is also important that the 
decision to adjust the IDegLira or IDeg doses are based on all relevant information as described in 
Section 1. A reason for deviating from the algorithm should be entered into the eCRF.
CONFIDENTIAL


Protocol - Appendix A
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Date:
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Trial ID: NN9068-4148
Version:
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4
Data collection
The following data must preferably be entered into the eCRF within 24 hours (on week days) after a 
site visit/telephone contact:
∀
Per protocol pre-breakfast SMPG values measured since last visit/telephone contact as 
described in section 3.2
∀
Last IDegLira or IDeg dose taken prior to titration
∀
New IDegLira or IDeg dose to be taken after titration
∀
Reasons for deviation from the titration algorithms, if applicable
∀
Hypoglycaemic episodes
CONFIDENTIAL


Protocol - Appendix A
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671 
Status:
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5
Review procedure
Surveillance of titration data from subjects on IDegLira and IDeg will be performed centrally by 
Novo Nordisk in an unbiased manner. It is important that data regarding dose titration is entered 
into the eCRF within 24 hours (on week days). If delays occur, action cannot be taken in due time 
before the subject’s next site visit/telephone contact. The aim is to reduce the time periods in which 
a subject may receive suboptimal treatment.
The data listed in section 4 will be reviewed by Novo Nordisk within 24 hours (on weekdays). The 
reviewer may contact the investigator to get clarification regarding the reason for deviation or to 
request entry of missing data.
When the investigator receives a query, a response should be received at Novo Nordisk within 24 
hours (on week days). 
During the trial HbA1c will be monitored by Novo Nordisk for additional surveillance of the
glycaemic control. Novo Nordisk may be in contact with sites (visit or telephone contact) to discuss 
progress in glycaemic control and titration of individual subjects based on SMPG values and HbA1c. 
This will be done in an unbiased and whenever possible blinded manner.
CONFIDENTIAL


Protocol - Appendix A
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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6
References 
1 Garber AJ, King AB, Del PS, Sreenan S, Balci MK, Munoz-Torres M et al. Insulin degludec, an 
ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime 
insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-
label, treat-to-target non-inferiority trial. Lancet 2012; 379(9825):1498-1507.
2 Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L et al. Insulin degludec, an ultra-
longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin 
aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-
to-target non-inferiority trial. Lancet 2012; 379(9825):1489-1497.
3 Hermansen K, Davies M, Derezinski T, Martinez RG, Clauson P, Home P. A 26-week, 
randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on 
therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes 
Care 2006; 29(6):1269-1274.
4 Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. 
Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral 
antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther 2006; 28(10):1569-1581.
5 Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or 
human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003; 
26(11):3080-3086.
6 Rosenstock J, Davies M, Home PD, Larsen J, Koenen C, Schernthaner G. A randomised, 52-
week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as 
add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 
2008; 51(3):408-416.
7 Gough S, Buse J, Woo V, Rodbard H, Linjawi S, Poulsen P et al. IDegLira, a novel fixed-ratio 
combination of insulin degludec and liraglutide is efficaious and safe in subjects with type 2 
diabetes: a large randomised phase 3a trial. Diabetologia 2013; 56(Suppl 1):96(abstract 219).
CONFIDENTIAL


Protocol - Appendix B
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671 
Status:
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Appendix B
Medical events of special interest and events requiring 
adjudication
Trial ID: NN9068-4148
DUAL! I - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral anti-diabetic drugs (OADs)
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol - Appendix B
UTN: U1111-1154-6671 
Date:
07 October 2014
Status:
Final
Novo Nordisk
Trial ID: NN9068-4148
     
Version:
2.0
Page:
2 of 5
1
Medical Events of Special Interest (MESI) and events requiring adjudication
Fatal events and MESIs
Definitions
Rationale
Event Adjudication 
Committee
Fatal events
All fatal events should be reported  including all-cause mortality: 
∀
Cardiovascular death 
∀
Non-cardiovascular death
∀
Undetermined cause of death
Fatal events are not considered MESIs as per definition they will always be 
considered SAEs.
An FDA guidance document 1
requests that Sponsors demonstrate 
the cardiovascular safety profile of 
any new therapy for type 2 diabetes in 
order to ensure, that the new therapy 
does not increase the cardiovascular 
risk to an unacceptable extent.
All events will be 
adjudicated
Acute coronary syndrome; 
myocardial infarction (MI) or 
hospitalisation for unstable 
angina
All types of myocardial infarction (MI) must be reported:
∀
Spontaneous MI (including re-infarction and MI associated with stent 
thrombosis)
∀
Percutaneous coronary intervention (PCI) related MI
∀
Coronary artery bypass graft surgery (CABG) related MI 
∀
Silent MI
All events with symptoms of myocardial ischemia requiring hospitalization 
must be reported.
An FDA guidance document1
requests that Sponsors demonstrate 
the cardiovascular safety profile of 
any new therapy for type 2 diabetes in 
order to ensure, that the new therapy 
does not increase the cardiovascular 
risk to an unacceptable extent.
All events will be 
adjudicated
Cerebrovascular event; 
stroke or transient ischemic 
attack
Stroke (ischemic, haemorrhagic or undetermined) is defined as an acute 
episode of neurological dysfunction, caused by focal or global brain, spinal 
cord, or retinal vascular injury as a result of hemorrhage or infarction 2
Transient Ischemic Attack (TIA) is defined as a transient (<24 hours) 
episode of neurological dysfunction caused by focal brain, spinal cord, or 
retinal ischemia, without acute infarction.
An FDA guidance document1
requests that Sponsors demonstrate 
the cardiovascular safety profile of 
any new therapy for type 2 diabetes in 
order to ensure, that the new therapy 
does not increase the cardiovascular 
risk to an unacceptable extent.
All events will be 
adjudicated


Protocol - Appendix B
UTN: U1111-1154-6671 
Date:
07 October 2014
Status:
Final
Novo Nordisk
Trial ID: NN9068-4148
     
Version:
2.0
Page:
3 of 5
Fatal events and MESIs
Definitions
Rationale
Event Adjudication 
Committee
Heart failure requiring 
hospital admission
Clinical manifestations of a new episode or worsening of existing heart 
failure.
An FDA guidance document1
requests that Sponsors demonstrate 
the cardiovascular safety profile of 
any new therapy for type 2 diabetes in 
order to ensure, that the new therapy 
does not increase the cardiovascular 
risk to an unacceptable extent.
All cases of heart 
failure requiring 
hospitalisation,
defined as an 
admission to an 
inpatient unit or a 
visit to an 
emergency 
department that 
results in at least a 
24 hour stay, will 
be adjudicated
Revascularisation procedure
Coronary revascularisation procedure (Coronary Artery Bypass Graft 
Surgery and Percutaneous Coronary Intervention): 
Coronary revascularisation procedure is a catheter-based or open surgical 
procedure designed to improve myocardial blood flow.
Peripheral Arterial Revascularization Procedure (lower extremity, renal, 
mesenteric, iliac, subclavian, aortic etc.):
Peripheral arterial revascularisation procedure is a catheter-based or open 
surgical procedure designed to improve peripheral arterial blood flow. This 
procedure may include thrombectomy, embolectomy, atherectomy, 
dissection repair, angioplasty, and stent placement.
An FDA guidance document1
requests that Sponsors demonstrate 
the cardiovascular safety profile of 
any new therapy for type 2 diabetes in 
order to ensure, that the new therapy 
does not increase the cardiovascular 
risk to an unacceptable extent.
Only coronary 
revascularisation
will be adjudicated
Pancreatitis or clinical 
suspicion of pancreatitis
Two of the following three diagnostic criteria fulfilling the diagnosis of 
acute pancreatitis: 
∀
Severe acute upper abdominal pain 
∀
Elevated blood levels of pancreatic enzymes (lipase, amylase) > 
3xUNR
∀
Characteristic imaging finding (ultrasound, computerised axial 
tomography (CT), magnetic resonance imaging (MRI))
Treatment with GLP-1 receptor 
agonists has been associated with 
acute pancreatitis. Novo Nordisk 
therefore monitors these events 
closely.
All events will be 
adjudicated


Protocol - Appendix B
UTN: U1111-1154-6671 
Date:
07 October 2014
Status:
Final
Novo Nordisk
Trial ID: NN9068-4148
     
Version:
2.0
Page:
4 of 5
Fatal events and MESIs
Definitions
Rationale
Event Adjudication 
Committee
Chronic pancreatitis will be defined by characteristic imaging finding 
(ultrasound, CT, MRI) with abnormal pancreatic function tests or 
characteristic histological findings.
Neoplasm
All types of neoplasms (i.e. all new growth incl. polyps, warts etc.) must be 
reported including:
∀
Malign neoplasm
∀
In situ neoplasm
∀
Benign neoplasm
∀
Neoplasms of uncertain or unknown behaviour
(Please note: for operational reasons thyroid neoplasms will be reported as
thyroid MESI and should not be reported as a Neoplasm MESI)
Fibrosarcomas has been reported in 
rats and mice treated with GLP-1 
receptor agonists in pre-clinical 
studies.
All neoplasm 
events, irrespective 
of malignancy 
stage, will be 
adjudicated
Thyroid disease
All disorders of thyroid gland (incl. thyroid neoplasms) must be reported.
Please refer to the protocol for further details on the assessments.
Thyroid C-cells carcinogenicity has 
been reported in rats and mice treated 
with GLP-1 receptor agonists in non-
clinical studies
Only thyroid 
disorders requiring 
thyroidectomy and 
thyroid neoplasms 
will be adjudicated
Medication errors concerning 
trial products
a.
Administration of wrong drug or use of wrong device
b.
Wrong route of administration, such as intramuscular instead of 
subcutaneous
c.
Administration of a high dose with the intention to cause harm, e.g. 
suicide attempt
d.
Accidental administration of a lower or higher dose than intended. That 
is a dose lower or higher than 20 % of the intended dose; however the 
administered dose must deviate from the intended dose to an extend 
where clinical consequences for the trial subject were likely to happen 
as judged by the investigator, although not necessarily did happen.
Standard MESI in all Novo Nordisk 
clinical trials.
Medication errors are captured to 
collect information which may be 
used to improve the design, name or 
packaging of the product and/or 
information which may have an 
impact on product labelling (for 
example information about substantial 
overdoses)
No adjudication


Protocol - Appendix B
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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2
Reference
1 Standardized Definitions for Endpoint Events Cardiovascular Trials: Draft Recommendations. 
Division: Draft Recommendations. FDA Center for Drug Evaluation and Research (CDER). 20-
Oct-2010.
2 Standardized Definitions for Cardiovascular and Stroke End Point Events in Clinical Trials 
(DRAFT). Karen A. Hicks, H. M. James Hung, Kenneth W. Mahaffey, Roxana Mehran, Steven 
E. Nissen; Norman L. Strockbridge, Shari L. Targum, Robert Temple; on behalf of the 
Standardized Data Collection for Cardiovascular Trials Initiative. November 9, 2012, or any 
updates hereof.
CONFIDENTIAL


Protocol - Appendix C
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
1 of 2
Appendix C
New York Heart Association criteria                                
for functional capacity in heart failure
Trial ID: NN9068-4148
DUAL! I - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral anti-diabetic drugs (OADs)
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol - Appendix C
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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1
Criteria for functional capacity
Functional Capacity 
Objective Assessment 
Class I. Patients with cardiac disease but without resulting limitation 
of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain.
A. No objective evidence 
of cardiovascular disease.
Class II. Patients with cardiac disease resulting in slight limitation of 
physical activity. They are comfortable at rest. Ordinary physical 
activity results in fatigue, palpitation, dyspnea, or anginal pain.
B. Objective evidence of 
minimal cardiovascular 
disease.
Class III. Patients with cardiac disease resulting in marked limitation 
of physical activity. They are comfortable at rest. Less than ordinary 
activity causes fatigue, palpitation, dyspnea, or anginal pain.
C. Objective evidence of 
moderately severe 
cardiovascular disease.
Class IV. Patients with cardiac disease resulting in inability to carry 
on any physical activity without discomfort. Symptoms of heart 
failure or the anginal syndrome may be present even at rest. If any 
physical activity is undertaken, discomfort is increased.
D. Objective evidence of 
severe cardiovascular 
disease.
*The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for 
Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 
1994:253-256.
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
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Appendix D
Monitoring of calcitonin levels 
Trial ID: NN9068-4148
DUAL! I - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral anti-diabetic drugs (OADs)
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
2 of 6
Table of Contents
..............................................................................................................................................................Page
Table of Contents..............................................................................................................................................2
1
Background................................................................................................................................................3
2
Calcitonin and C-cell abnormalities - evaluation and follow-up ..........................................................3
2.1
CT ≥ 100 ng/L................................................................................................................................3
2.2
CT ≥ 50 and < 100 ng/L.................................................................................................................4
2.3
CT ≥ 20 and <50 ng/L....................................................................................................................4
2.4
CT ≥ 10 and < 20 ng/L...................................................................................................................4
3
References..................................................................................................................................................6
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
Page:
3 of 6
1
Background
The approach that follows was developed in collaboration with two leading clinical thyroid experts: 
Dr. 
 of the 
 and 
 and Dr. 
 of 
 and represents a synthesis of the medical 
literature and extensive personal experience. 
All previous calcitonin screening studies in the literature have been performed in patients with 
thyroid nodular disease. The nodular status of the subjects in the current trial will mostly be 
unknown. Nevertheless, for the purpose of follow-up, it will be assumed that the same calcitonin 
cut-offs will apply. Up to 50% of subjects in the age group to be studied in the current trial will 
have clinical or subclinical thyroid nodules1 the majority of which will be clinically apparent. 
Subjects with a known personal or family history of medullar thyroid cancer (MTC) or multiple 
endocrine neoplasia type 2 (MEN 2) and subjects with a screening calcitonin of ≥ 50ng/l will be 
excluded from the trial.
2
Calcitonin and C-cell abnormalities - evaluation and follow-up
A blood sample will be drawn at pre-specified trial visits for measurement of calcitonin. In case a 
subject has an increased calcitonin value ≥ 10 ng/L the algorithm outlined below should be 
followed. The algorithm applies for all calcitonin values including screening values.
All calcitonin values ≥20 ng/L (except for screening failures) will be submitted to an independent 
Calcitonin Monitoring Committee (CMC) of thyroid experts, together with relevant supplementary 
data, i.e. subject’s demographics, diabetes history, concomitant medical history, concomitant 
medications, smoking status as well as information about relevant adverse events reported during 
the trial.
The CMC will provide recommendations to the investigators with regards to further investigation 
and treatment of the individual subject. The CMC will be blinded to trial treatment. 
The summary for the rationale for the use of specific calcitonin values to trigger medical evaluation 
and an overview of the algorithm is provided in the following sections.
2.1
CT ≥ 100 ng/L  
The value will be submitted to the CMC and the subject should be discontinued from trial product. 
If the value is a screening value the subject cannot be randomised and the subject must be referred 
to a thyroid specialist. 
These values were found in 0.15% of the population published by Costante et al1 and in one subject 
(on active comparator) in the liraglutide development program. For a calcitonin value of ≥100 ng/L, 
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4148
Version:
2.0
UTN: U1111-1154-6671 
Status:
Final
     
Page:
4 of 6
the subject should be assumed to have 
 and a high likelihood of having 
 of the 
. Diagnostic evaluation should consist of 
 ultrasound, fine
needle aspiration of any nodules >1 cm and potentially surgery with 
 dissection. Family history 
of MTC or MEN2 should be evoked and a RET proto-oncogene analysis should be performed. 
2.2
CT ≥ 50 and < 100 ng/L
The value will be submitted to the CMC and the investigator will receive guidance from the CMC 
with regards to continuation of trial product. If the value is a screening value the subject cannot be 
randomised and the subject should be referred to a thyroid specialist.
These values were found in 0.18% of a population with thyroid nodular disease published by 
Costante et al1. Diagnostic evaluation will likely include ultrasound examination and if available 
and if there is no contraindication, subjects should undergo a pentagastrin stimulation test. Subjects 
with positive pentagastrin stimulation tests will be considered to undergo surgery. Where 
pentagastrin is not available, thyroid ultrasound and fine needle aspiration biopsy may add 
important clinical information informing the need for surgery. 
2.3
CT ≥20 and <50 ng/L
The value will be submitted to the CMC. If a subject is screen failed for other reasons than 
calcitonin exclusion criterion # 11 (calcitonin ≥ 50 ng/L), but has a value of calcitonin ≥10 ng/L, it 
is recommended that they are referred to a thyroid expert for further evaluation.
These values are expected to be found in up to 1% of subjects. At this level of calcitonin based on 
data from Costante et al1, the predictive value of the level itself for clinically significant C-cell 
disease begins to fall. However, up to 25% of these subjects had a positive pentagastrin stimulation 
test. The likelihood of having a medullary carcinoma >1 cm with calcitonin in this range is 
extremely low. 
2.4
CT ≥ 10 and < 20 ng/L
Confounding factors should be evaluated. If drugs potentially affecting calcitonin can be 
discontinued safely, calcitonin can be repeated after a washout period. Gastrin levels return to the 
normal range by ~ 10 days after stopping proton pump inhibitors.  No further actions are needed 
during the trial if the next calcitonin values remain below 20 ng/L.
If the subject is a screening failure or if the value is the last one taken in the trial, the subject should 
preferably be referred to a thyroid specialist for further evaluation.
These values may be found in ~ 2.5 to 4% of the trial population. Costante et al1 had 216 patients in 
this category. /216 had a subsequent basal (unstimulated) calcitonin of 
 ng/L, and had 
 
. Two other studies used a cutoff of 
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671 
Status:
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CT > 10 ng/L to screen for C-cell disease, but they do not provide sufficient information on patients 
with basal CT >10 and <20 ng/L to allow conclusions2,3.
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Protocol - Appendix D
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Date:
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Trial ID: NN9068-4148
Version:
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Status:
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3
References
1 Costante G, Meringolo D, Durante C, Bianchi D, Nocera M, Tumino S et al. Predictive value of 
serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 
5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 2007; 92(2):450-455.
2 Verga U, Ferrero S, Vicentini L, Brambilla T, Cirello V, Muzza M et al. Histopathological and 
molecular studies in patients with goiter and hypercalcitoninemia: reactive or neoplastic C-cell
hyperplasia? Endocr Relat Cancer 2007; 14(2):393-403.
3 Scheuba C, Kaserer K, Moritz A, Drosten R, Vierhapper H, Bieglmayer C et al. Sporadic 
hypercalcitoninemia: clinical and therapeutic consequences. Endocr Relat Cancer 2009; 
16(1):243-253.
CONFIDENTIAL


Global and country key Novo Nordisk staff
Attachments I and II (if applicable) to the protocol are located in the Trial Master File.
Content: Global key staff and Country key staff
CONFIDENTIAL
Date:
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Version:
Status:
IDegLira
Trial ID: NN9068-4148
Clinical Trial Report
Appendix 16.1.1
16 December 2019
1.0
Final
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Protocol Amendment
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Date:
31 August 2016
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Trial ID: NN9068-4148
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Protocol Amendment
no 1
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin
degludec/liraglutide, insulin degludec, and liraglutide in Chinese
subjects with type 2 diabetes inadequately controlled on oral antidiabetic
drugs (OADs)
Trial phase: 3a
Applicable to China
Amendment originator:
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
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Protocol Amendment
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Date:
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Trial ID: NN9068-4148
Version:
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Status:
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Table of Contents   
Page
Table of Contents..............................................................................................................................................2
1
Introduction including rationale for the protocol amendment.............................................................3
2
Changes......................................................................................................................................................4
2.1.1
Changes to Protocol.....................................................................................................4
2.1.2
Optimisation and standardisation of safety reporting ..................................................4
2.1.2.1
Introducing: “Medication error” and ‘Adverse Events with 
additional data collection’ .....................................................................4
2.1.2.2
Deletion of Medical event of special interest (MESI) definition 
and term.................................................................................................4
2.1.3
Events in scope for adjudication added .......................................................................4
2.1.4
Reporting of adverse events.........................................................................................4
2.1.5
Extra follow-up visit added at the end of trial .............................................................5
2.1.6
Collection of data describing ‘severe hypoglycaemic episodes’ .................................5
2.1.7
Hypoglycaemia unawareness.......................................................................................5
2.1.8
Smoking habits ............................................................................................................5
2.1.9
Eye examination and ECG...........................................................................................5
2.1.10
Laboratory analysis......................................................................................................6
2.1.10.1
Fasting insulin .......................................................................................6
2.1.10.2
Pregnancy test .......................................................................................6
2.1.11
Calcitonin.....................................................................................................................6
2.1.12
Trial product details.....................................................................................................6
2.1.13
IWRS ...........................................................................................................................7
2.1.14
Monitoring procedures more clearly specified ............................................................7
2.1.15
Statistical considerations..............................................................................................7
2.1.16
Ethics ...........................................................................................................................7
2.1.17
Reports and publications..............................................................................................7
2.1.18
Retention of human biosamples...................................................................................8
2.1.19
Flow Chart updates......................................................................................................8
2.1.20
List of abbreviations ....................................................................................................8
2.2
Changes to the SI/IC......................................................................................................................8
2.2.1
Adhering to local regulations and legal requirement...................................................8
2.2.1.1
Blood sample handling & exportation...................................................8
2.2.1.2
Funding of research...............................................................................8
2.2.1.3
Liability information .............................................................................8
2.2.1.4
Subject reimbursement fee....................................................................8
2.2.2
Trial product market availability .................................................................................9
2.2.3
Text describing cardiovascular safety and DEVOTE..................................................9
2.2.3.1
Signal of increased cardiovascular risk.................................................9
2.2.4
Update of section 2.3 If you become pregnant ............................................................9
2.2.5
Other SI/IC updates .....................................................................................................9
2.2.5.1
30 days follow up visit (FU 2) named phone contact 30, added...........9
2.2.5.2
Extra SI/IC version to male partners.....................................................9
2.2.5.3
Extra SI/IC version for genetic testing obsolete....................................9
CONFIDENTIAL


Protocol Amendment
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Date:
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Trial ID: NN9068-4148
Version:
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1
Introduction including rationale for the protocol amendment
The CFDA approved the NN9068-4148 protocol version 2.0, dated 07 October 2014 on 
06 June 2016. Since the preparation of the trial protocol in 2014, some of the Novo Nordisk 
standards and processes have evolved and updated, which is the reason for preparing the 
amendment and updating the protocol. This is in accordance with the feed-back received from 
CFDA; please refer to below text copied from the IDegLira IDL approval letter, optimization of the 
protocol is allowed:
“Before the clinical trial operation, clinical research organization should further refine and 
optimize the protocol, pay attention to the exposed and potential safety risk of the product, and 
make a risk control and management plan.”
While amending the protocol special attention has been on patient safety and reporting, data quality
and GCP compliance. This means that minor refinements have been made throughout the protocol 
with the purpose of improving data quality and clarifying issues, where applicable. Additionally, 
typos and minor formatting corrections have been implemented throughout the protocol.
CONFIDENTIAL


Protocol Amendment
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Date:
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Trial ID: NN9068-4148
Version:
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2
Changes
2.1.1
Changes to Protocol
2.1.2
Optimisation and standardisation of safety reporting
Rationale: Since IB version 6, the identified and potential risks included in the minimum 
mandatory safety text have been updated based on the clinical development of IDegLira. 
Additionally, standardisation and alignment with the current and future internal safety reporting 
processes within Novo Nordisk will result in a more systematic way of colleting safety data and 
improve the quality of data collected. Further, by updating the protocol, the safety processes and 
reporting will be simplified including reporting of medication error as AE requiring additional data 
rather than MESI.
Impact: The impact of the above is mentioned in sections below:
2.1.2.1
Introducing: “Medication error” and ‘Adverse Events with additional data 
collection’
Impact: Section 12 updated with relevant sections, new sections 8.2.3.1 and 8.2.3.2 introduced and 
Appendix B updated.
2.1.2.2
Deletion of Medical event of special interest (MESI) definition and term
Impact: Throughout the protocol MESI has been deleted and medication errors are changed to AE 
requiring additional data collection.
2.1.3
Events in scope for adjudication added
Rationale: All coronary revascularisations (CR) occurring as a result of an Myocardial Infarction 
(MI) will be captured on the specific event form for the corresponding Acute Coronary Syndrome 
(ACS) event and source documents from the procedure will be reviewed by the Event Adjudication 
Committee (EAC) when adjudicating this ACS event.
Impact: Coronary revascularisation (CR) has been removed as event in scope for adjudication as 
only MIs and not the procedure itself will be adjudicated.
2.1.4
Reporting of adverse events
Rationale: This is in order to align with the new Novo Nordisk processes for reporting of adverse 
events.
Impact: Protocol sections 8 and 12 updated.
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Protocol Amendment
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Date:
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Trial ID: NN9068-4148
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2.1.5
Extra follow-up visit added at the end of trial
Rationale: In line with current FDA guidance, an additional follow-up visit (30 days after last dose 
on trial product) was added at the end of trial in order to collect further safety information on 
subject reported SAEs and concomitant antidiabetic treatment.
Impact: This will increase the trial duration with approximately 3 weeks – which has been updated 
in protocol where applicable (e.g. also figure 5.1 updated). Further, the terms 7-days follow up visit 
(FU1) and 30-days follow-up visit FU2 (Phone contact 30) have been introduced throughout the 
protocol – especially Sections 1, 2, 5 and 8.
2.1.6
Collection of data describing ‘severe hypoglycaemic episodes’
Rationale: The protocol was written in 2014 based on 
. Since then the 
hypoglycaemia episode form has been updated to capture additional structured information on 
severe hypoglycaemia symptoms and resource use. Therefore a number of additional questions was
added to the subject diaries.
Impact: The severe hypoglycaemia data being collected in the diaries has been added to protocol 
Sections 8.2.15 and other text corrections made to comply with current standards and improve 
narrative quality.
2.1.7
Hypoglycaemia unawareness
Rationale: Since the protocol was written in 2014 a new section “Hypoglycaemia unawareness” 
has been included in the protocol 
. Because this trial does not exclude 
inclusion of subjects with impaired hypoglycaemia awareness the information about hypoglycaemia 
unawareness will be collected at the screening visit.
Impact: A new section 8.2.5 has been added to the protocol.
2.1.8
Smoking habits
Rationale: The protocol was written in 2014 based on 
 Since then section
“8.2.6 Smoking habits” has been renamed to “Tobacco use” and the question about when the 
subject stopped smoking has been deleted.
Impact: Flowchart and section 8.2.6 updated.
2.1.9
Eye examination and ECG
Rationale: To be aligned with the global DUAL I trial collection of details of an abnormality of eye 
examination and ECG will be collected.
Impact: Section 8.2.11 and 8.2.12 updated.
CONFIDENTIAL


Protocol Amendment
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Date:
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671
Status:
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2.1.10
Laboratory analysis
2.1.10.1
Fasting insulin
Rationale: In line with other DUAL trials the fasting insulin results will not be provided to the 
investigator as these are not used for clinical evaluation during the trial. Instead they will be 
included in an analytical report after end of trial and retained at Novo Nordisk. Also, fasting insulin 
is measured at a special lab and samples are stored until final CTR.
Impact: Section 8.3.1 updated, new section 8.3.5 added and section 24.2 updated.
2.1.10.2
Pregnancy test
Rationale: The text from flowchart foot note i was not mentioned anywhere else in the protocol.
The text reads: “For females of child-bearing potential a urine pregnancy test should be performed 
at site, if pregnancy is suspected or if a menstrual period is missed. If the subject reports missing 
menstrual at a phone contact, the subject must attend the site for an unscheduled visit as soon as 
possible to have a urine test done. If positive, a confirmatory serum hCG sample should be sent to 
the central laboratory”
Impact: Section 8.3.1 updated.
2.1.11
Calcitonin
Rationale: The Calcitonin section in the protocol including an additional withdrawal criteria #7 and 
the Appendix D have been updated to align with the monocomponent of liraglutide based on 
minutes from liraglutide safety committee (SC) Mar 2015 and the IDegLira SC agreed on May-
2015 that:
MTC monitoring set-up (no RET tests will be performed, deletion of the external CMC which is 
replaced by a guideline in the protocol and training of the investigators on handling of elevated 
calcitonin values consistent with the current guideline developed by the CMC) will be implemented 
in the DURABILITY trial (NN9068-4228) and other future NN9068 trials.
Impact: Sections 6.4, 8.3.2 and Appendix D updated.
2.1.12
Trial product details
Rationale: Since the protocol was written in 2014 product information concerning IDegLira, IDeg 
and liraglutide has been updated. Therefore the references to Investigator’s Brochures and local
labelling have been updated to the most updated editions.
Impact: References updated throughout the protocol.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671
Status:
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2.1.13
IWRS
Rationale: Since the protocol was written in 2014 the IWRS system has been upgraded to 
Config. 3.1 to improve drug accountability and drug destruction. Further, dispensing verification 
has been included following introduction of the barcode scanner.
Impact: Updated section 9 and 10.
2.1.14
Monitoring procedures more clearly specified
Rationale: In order to comply with 
 and to ensure subject safety and 
GCP compliance as early as possible at trial sites, the protocol will be updated to define the 
maximum allowed time (4 weeks) from FPFV until the first monitoring at site and 12 weeks for 
subsequent monitoring visits.
Impact: Updated Section 14 Monitoring Procedures.
2.1.15
Statistical considerations
Rationale: To be compliant with the updates made in other sections of the protocol the statistical 
considerations have been updated accordingly. Main update is related to hypoglycaemia definitions.
Impact: Section 17 updated.
2.1.16
Ethics
Rationale: In order to comply with 
 and to ensure subject safety and 
GCP compliance the protocol has been updated with the mandatory SOP template text. Section 18 
of the protocol has been updated to include benefit-risk assessment section, which has previously 
been provided as a separate benefit-risk assessment document. The text in section 18 has been 
updated to align with updates from liraglutide and IDegLira programme
Impact: Section 18 updated.
2.1.17
Reports and publications
Rationale: In order to comply with 
 the protocol has been updated to 
reflect resent disclosure requirements.
Impact: Section 23 updated.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
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Trial ID: NN9068-4148
Version:
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Status:
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2.1.18
Retention of human biosamples
Rationale: In order to comply with 
 and to ensure subject safety and 
GCP compliance the protocol has been updated to more clearly describe which blood samples are 
exported out of China and for how long the samples will be stored.
Impact: Section 24.2 and SI/IC updated.
2.1.19
Flow Chart updates
Rationale: Based on above mentioned changes related to additional FU2 the flowchart has been 
updated displaying what procedures are to be performed at FU1 and FU2. Additionally, the 
flowchart is updated with tobacco use and hypoglycaemia unawareness as described previously.
Impact: Flow chart and footnotes updated accordingly.
2.1.20
List of abbreviations
Rationale: Since protocol preparation back in 2014, new standard abbreviations have been 
implemented and the following terms will be modified throughout the protocol. Also a few new 
terms have been added, refer to below.
Impact: IV/WRS replaced by IWRS, ASAT replaced by AST and ALAT replaced by ALAT
throughout the protocol. Additionally, MESI and SmPC have been deleted throughout the protocol.
2.2
Changes to the SI/IC
2.2.1
Adhering to local regulations and legal requirement
Rationale: Below sections have been added based on experience with EC requested information.
2.2.1.1
Blood sample handling & exportation 
Impact: Section 1.17 about antibody exportation, PK and fasting insulin sampling added.
2.2.1.2
Funding of research
Impact: Section 4.1 is updated.
2.2.1.3
Liability information 
Impact: Section 4.2 updated.
2.2.1.4
Subject reimbursement fee
Impact: Section 4.3 updated.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
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2.2.2
Trial product market availability
Rationale: The description about cardiovascular safety is already included in the market launch 
information for the trial products in section 2.1.
Impact: Last part of section 1.2 about trial product market availability is deleted. 
2.2.3
Text describing cardiovascular safety and DEVOTE
Rationale: In order to present the most recent status on the CV outcome trial initiated based on
FDA request the below section has been updated.
Impact: The previous text in section 2.5.1 has been replaced by updated text in section 2.1.14.
2.2.3.1
Signal of increased cardiovascular risk
Impact: The previous text in safety section 2.0 about CV has been updated.
2.2.4
Update of section 2.3 If you become pregnant
Rationale: Section 2.3 has been updated based on the updated Minimum Mandatory Safety text 
from IDegLira.
2.2.5
Other SI/IC updates
Rationale: Based on updates made to the trial protocol.
2.2.5.1
30 days follow up visit (FU 2) named phone contact 30, added
Impact: Section 1.1, 1.3, 1.4, 1.5.3 and 3.1 updated.
2.2.5.2
Extra SI/IC version to male partners
Impact: The version and date is updated to be aligned with the main SI/IC. Section 3 and 5 
updated.
2.2.5.3
Extra SI/IC version for genetic testing obsolete
Impact: The SI/IC for genetic testing is no longer applicable for IDegLira trials. Therefore it will 
not be resubmitted.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
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Protocol Amendment
no 2
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin
degludec/liraglutide, insulin degludec, and liraglutide in Chinese
subjects with type 2 diabetes inadequately controlled on oral antidiabetic
drugs (OADs)
Trial phase: 3a
Applicable to China
Amendment originator:
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
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Introduction including rationale for the protocol amendment
During the approval process of amendment 01 the below refinement related to improved data 
quality has been discussed in the Biostatistics department. We therefore apply for approval of the
below updates to section 17.4.2.2 to be made in the NN9068-4148 protocol. The reasons for the 
update are:
!
More clearly addresses whether as to an endpoint is of continuous or categorical nature (i.e. 
summary statistics will be on the form {N,mean(SD),min,max,median} or {N,percentage})
!
Specifies scatter plots that are better suited to detect unwanted anti body development
Current text to be deleted in section 17.4.2.2:
Antibodies towards trial product
Anti-insulin degludec antibodies including anti-human insulin antibodies, anti-liraglutide 
antibodies, anti-liraglutide antibodies cross reacting with native GLP-1 and in vitro neutralising 
effect of anti-liraglutide antibodies will be summarised and tabulated. The correlation between 
change from baseline after 26 weeks of treatment in anti-insulin degludec and anti-human insulin 
antibodies respectively, to insulin dose after 26 weeks of treatment, HbA1c after 26 weeks of 
treatment and change from baseline after 26 weeks of treatment in HbA1c will be illustrated using 
scatter plots.
For the liraglutide component of IDegLira and liraglutide, the number of subjects (N) and the 
percentage of subjects (%) with positive, cross-reacting to native GLP-1 and neutralising antibodies 
will be summarised.
Listing with subjects with liraglutide positive antibody formation will be produced. These listings 
should include efficacy information as minimum HbA1c and body weight over time.
New text to be inserted in section 17.4.2.2:
17.4.2.2 Safety endpoints
Insulin and GLP-1 antibodies
Insulin antibodies (IDeg specific, cross-reacting to human insulin and total) will be summarised 
with arithmetic mean, standard deviation (SD), median, and minimum and maximum value by 
treatment and treatment week, and their mean over time will be plotted. Correlations will be 
explored graphically as follows. Insulin antibodies (IDeg specific, cross-reacting to human insulin 
and total) will be plotted against HbA1c after 26 weeks, HbA1c change from baseline after 26 weeks, 
and dose after 26 weeks. Change from baseline to FU1 in insulin antibodies (IDeg specific, cross-
CONFIDENTIAL


Protocol Amendment
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Date:
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Trial ID: NN9068-4148
Version:
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UTN: U1111-1154-6671
Status:
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reacting to human insulin and total) will be plotted against HbA1c after 26 weeks, HbA1c change 
from baseline after 26 weeks, and dose after 26 weeks.
GLP-1 antibodies (liraglutide specific, cross-reacting to native GLP-1, liraglutide in vitro
neutralising and in vitro neutralising to native GLP-1) will be summarised by number of subjects 
(N) and percentage of subjects (%) with positive and negative samples.
Antibody measurements will be listed by subject and visit together with associated age, sex, BMI, 
HbA1c and dose.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
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Protocol Amendment
no 3
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin
degludec/liraglutide, insulin degludec, and liraglutide in Chinese
subjects with type 2 diabetes inadequately controlled on oral antidiabetic
drugs (OADs)
Trial phase: 3a
Applicable to China
Amendment originator:
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
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1
Changes to SI/IC
At the IDegLira safety committee meeting on 30-Aug-2016, it was endorsed to update the MMST 
with the below stated text for the SI/IC. 
Current text to be deleted in section 2.2.5:
1.1.1
Gallstone disease
Cases of gallstones (cholelithiasis) and inflammation of the gallbladder (cholecystitis) have 
been reported from long-term clinical trials with liraglutide (component of IDegLira). These 
events may lead to hospitalisation and removal of the gallbladder. If you experience recurring 
upper abdominal pain, you should contact your trial doctor, who will decide whether you 
should discontinue trial product and/or undergo additional diagnostic procedures.
New text to be inserted in section 2.2.5:
Gallstone disease
Cases of gallstones (cholelithiasis) and inflammation of the gallbladder (cholecystitis) have been 
reported from clinical trials with IDegLira. These events may lead to hospitalisation and removal of 
the gallbladder. If you experience recurring upper abdominal pain, you should contact your trial 
doctor who will decide whether you should discontinue trial medication and/or undergo additional 
diagnostic procedures
New text to be inserted as section 2.2.17
2.2.17 Other adverse events
Feeling tired has been reported with IDegLira in 1 to 10 out of 1000 patients in clinical trials.
Non MMST related update to section 1.5 to be consistent with the protocol
Throughout the trial you must continue your metformin treatment. at the same stable dose and 
frequency as before your trial participation. The dose and frequency should not be changed at any 
time during the trial until the end of treatment visit”.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
28 September 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
EudraCT No.:
Page:
1 of 4
Protocol Amendment
no 4
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin
degludec/liraglutide, insulin degludec, and liraglutide in Chinese
subjects with type 2 diabetes inadequately controlled on oral antidiabetic
drugs (OADs)
Trial phase: 3a
Applicable to China
Amendment originator:
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol Amendment
CONFIDENTIAL
Date:
28 September 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
EudraCT No.:
Page:
2 of 4
Introduction including rationale for the protocol amendment
After finalisation of NN9068-4148 protocol version 3.0 dated 29-Aug-2016 and the subject 
information/informed consent form version 3.0 dated 31-Aug-2016 the following changes have 
been identified why an amendment is needed:
1.1
Update of safety section
The IDegLira safety committee agreed on 30-Aug-2016 to classify ‘acute gallstone disease’ as an 
important identified risk. Section 18 in the protocol has been updated to include ‘acute gallstone 
disease’ as an important identified risk and section 2.2.5 has been updated in the SI/IC.
Updated in SI/IC section 2.2.5:
Gallstone disease
Cases of gallstones (cholelithiasis) and inflammation of the gallbladder (cholecystitis) have been 
reported from clinical trials with IDegLira and liraglutide. These events may lead to hospitalisation 
and removal of the gallbladder. If you experience recurring upper abdominal pain, you should 
contact your trial doctor, who will decide whether you should discontinue the trial medication 
and/or undergo additional diagnostic procedures.
Updated in protocol section 18.1.1.1 Important identified risks:
Acute gallstone disease
Although infrequent, cases of gallstones (cholelithiasis) and inflammation of the gallbladder 
(cholecystitis) have been reported from clinical trials with IDegLira. Both cholelithiasis and 
cholecystitis have possible clinical implications for the patients as the events might lead to 
hospitalisation and cholecystectomy. If cholelithiasis is suspected, treatment should be discontinued 
and gallbladder examination and appropriate clinical follow-up should be initiated. If acute 
gallstone disease is confirmed, the trial product must be permanently discontinued.
1.2
Update of Statistical considerations
The statistical models for the confirmatory secondary endpoints, hypoglycaemic episodes and dose, 
have been updated to be in alignment with the models for the global DUAL trials. In addition, 
clarifications around 1-sided versus 2-sided testing has been added and minor errors corrected.
Updated in protocol section 17:
“Unless otherwise specified, all continuous measurements will be summarised descriptively at each 
visit by treatment using observed data. After 26 weeks of treatment, descriptive statistics will be 
presented based both on observed and last observation carried forward (LOCF) imputed data. 
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
28 September 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
EudraCT No.:
Page:
3 of 4
Endpoints that are analysed untransformed and endpoints that are not formally analysed are 
summarised by the arithmetic mean, standard deviation (SD), median, and minimum and maximum 
value. Endpoints that are analysed log-transformed are summarised by supplemented with the 
geometric mean and coefficient of variation (CV).”
“Presentation of results from a statistical analysis will include the estimated mean treatment effects 
(Least Square Means [LSMeans]) for absolute values and change from baseline. In addition, 
estimated mean treatment difference (or ratio) will be presented together with the two-sided 95% 
confidence interval and corresponding two-sided 5% p-value.”
From section 17.1 Sample size calculation
“A hierarchical testing procedure is applied. This is based on an a priori ordering of the null-
hypotheses and testing them in this order using the two-sided 95% confidence interval approach 
until an insignificant result appears. Non-inferiority and superiority will thus be considered 
confirmed if the upper bound of the two-sided 95% confidence interval is below 0.4% and 0.0% 
respectively. This is equivalent to using a one-sided test of size 2.5%, which means that the type 1 
error rate is controlled at 2.5% (one-sided).”
From section 17.4.1 Confirmatory secondary endpoints
The following two confirmatory endpoints will be tested for superiority of IDegLira vs. IDeg.
Change from baseline in body weight after 26 weeks of treatment.
Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 
26 weeks of treatment.
The tests for superiority of the confirmatory secondary endpoints will be based on the FAS and will 
only be carried out if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. 
liraglutide with regards to the primary endpoint are confirmed.
In order to control the overall type I error on a 2-sided 5% level with regards to the secondary 
endpoints, a hierarchical testing procedure will be used. If superiority is confirmed with respect to 
change from baseline in body weight after 26 weeks of treatment the number of treatment emergent 
severe or BG confirmed hypoglycaemic episodes during 26 weeks of treatment will be tested for 
superiority. Superiority for change from baseline in body weight will be considered confirmed if the 
upper bound of the two-sided 95% confidence interval for the estimated mean treatment difference 
(IDegLira minus IDeg) is strictly below zero or equivalently if the p-value for the one-sided test of
H0 D≥0.0% against HA D<0.0%,
is less than 2.5%, where D is the treatment difference.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
28 September 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
EudraCT No.:
Page:
4 of 4
Superiority for hypoglycaemic episodes will be considered confirmed if the upper bound of the two-
sided 95% confidence interval for the estimated mean treatment ratio (IDegLira vs. IDeg) is strictly 
below one or equivalently if the p-value for the one-sided test of
H0 RR≥1.0 against HA RR<1.0,
is less than 2.5%, where RR is the treatment estimated rate ratio.
The change from baseline in body weight after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous OAD treatment (metformin ± one other OAD) as 
fixed factors and baseline weight as covariate.
Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 26 weeks 
of treatment will be analysed using a negative binominal regression model with a log-link function 
and the logarithm of the time period in which a hypoglycaemic episode is considered treatment 
emergent as offset. The model will include treatment and previous antidiabetic treatment as fixed 
factors and baseline HbA1c as covariate.
From section 17.4.2.1 Efficacy endpoints
In the following the statistical models will be fitted to all data simultaneously (all treatment groups) 
and from this model the treatment differences for IDegLira vs. IDeg and IDegLira vs. liraglutide 
will be estimated.
Insulin dose after 26 weeks of treatment
The actual daily insulin dose after 26 weeks of treatment will be analysed using an ANCOVA 
model including treatment and previous antidiabetic treatment as fixed factors and baseline HbA1c
value and baseline insulin dose as covariate.
From section 17.4.2.2 Safety endpoints, Calcitonin
The distribution of all calcitonin measurements across treatment groups and time will be shown 
with box plots histograms and corresponding cumulative plots for actual levels of calcitonin and 
change from baseline. The plots will be presented by treatment group (using at EOT using
measurement LOCF) imputed values and within treatment group by week. Plots will be done by 
each gender, separately.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
1 of 9
Protocol Amendment
no 5
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4148
DUAL™ I - China
A trial comparing the efficacy and safety of insulin
degludec/liraglutide, insulin degludec, and liraglutide in Chinese
subjects with type 2 diabetes inadequately controlled on oral antidiabetic
drugs (OADs)
Trial phase: 3a
Applicable to China
Amendment originator:
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
CONFIDENTIAL
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
2 of 9
Table of Contents
1
Introduction including rationale for the protocol amendment.............................................................3
2
Changes to protocol version 4.0 dated 28-Sep-2016...............................................................................4
2.1
Affected section 8.3.3: Baseline antibody samples shipped from 
 to Novo Nordisk 
Måløv, Denmark............................................................................................................................4
2.2
Affected section 24.2: Storage time for antibody samples ............................................................5
2.3
Affected section 8.3: Reporting of laboratory results not provided to Investigator.......................5
2.4
Affected sections 9.1 and 12.4.1: Mistake in pen description for Liraglutide in section 9; in 
section 12 this is correctly listed....................................................................................................6
2.5
Affected section 6.4 Withdrawal criteria#5...................................................................................6
3
Changes to Subject information/informed consent form version 4.0 dated 08-Sep-2016...................8
3.1
Affected section 1.7: Baseline antibody samples shipped from 
 to Novo Nordisk 
Måløv, Denmark............................................................................................................................8
3.2
Affected section 3.3: Storage time for antibody samples ..............................................................8
3.3
Affected section 2.1: What are the possible risks if you participate in this trial............................8
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
3 of 9
1
Introduction including rationale for the protocol amendment
After finalisation of NN9068-4148 protocol version 4.0 dated 28-Sep-2016 and the subject 
information/informed consent form version 4.0 dated 28-Sep-2016 the following changes have been 
identified why an amendment is needed:
!
To update with description of shipment of baseline antibody samples from 
, 
, to Novo Nordisk, Denmark
!
To update storage time for antibody samples
!
To align where laboratory results will be reported
!
To correct description of pen to be used for liraglutide arm
!
To align withdrawal criteria #5
!
To update SI/IC risk section with FDA approval of Xultophy
In this substantial protocol amendment global:
!
Any new text is written in italic.
!
Any text deleted from the protocol is written with a strike through
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
4 of 9
2
Changes to protocol version 4.0 dated 28-Sep-2016 
2.1
Affected section 8.3.3: Baseline antibody samples shipped from 
 to Novo 
Nordisk Måløv, Denmark
Rationale: Analysis of in vitro neutralising activity of anti-drug antibodies (ADA) is a requirement 
from the health authorities (FDA, EMA, CFDA) (ref 1, 2, 3). According to the guidelines, antibody 
negative samples/baseline samples from the same population as is investigated for ADA 
development should be used for determining the cut point in the antibody analyses. Therefore, 
commercially obtained human serum samples should not be used to determine the cut point. 
To comply with the recommendations, approximately 30 baseline (visit 2 samples) antibody 
samples will be shipped to a laboratory at Novo Nordisk, Måløv, Denmark to be used for the 
neutralising antibody cut point determination. These samples will consist of visit 2 antibody 
samples from the patients that are ADA positive at the follow up 1visit, as well as an additional 
number of antibody negative visit 2 samples randomly chosen among the antibody negative trial 
subjects. This procedure is in accordance with the previous global trials in the NN9068 phase 3 trial 
programme.
No results from the antibody negative visit 2 samples will be reported to the OC database or the 
investigator as these are only used for calculation of the neutralising cut point and not for any 
clinical relevant results. The only results to be reported in the CTR from the in vitro neutralising 
anti-liraglutide antibody analysis are the results of the antibody positive follow-up visit 1 samples .
1: FDA Draft guidance: Assay Development and Validation for Immunogenicity testing of 
Therapeutic Protein Products. Guidance for Industry. 2016
2: EMA Guideline on Immunogenicity assessment of biotechnology-derived therapeutic proteins 
draft 2015
3: CFDA Guideline for quality control of recombinant DNA products 2003
Updates text section 8.3.3 in protocol version 4.0:
FU1 samples positive for anti-liraglutide antibodies will in addition be analysed for in vitro 
neutralising effect in a cell based assay. In vitro neutralising effect will be analysed by Novo 
Nordisk. Anti-liraglutide antibody positive FU1 samples and baseline(visit 2) samples belonging to 
the same subject will be forwarded by the special lab performing the antibody analysis to Novo 
Nordisk. Additionally, a number of baseline samples from subjects with antibody negative FU1 
samples will also be forwarded to Novo Nordisk to set a cut point for the analysis.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
5 of 9
2.2
Affected section 24.2: Storage time for antibody samples 
Rationale: To be aligned with previous trial NN5401-3598 conducted in China and OHGRA 
guidance on storage time for antibody samples the protocol text has been updated to be aligned with 
the 3598 study protocol section 8.5 (EN version 3.0, dated 27-Aug-2015). 
In section 24.2 storage time for antibody samples and Fasting insulin samples are on purpose 
differently described. The long term storage for antibody samples is requested by the FDA but is 
not applicable for any other parameters or samples. There are no clear rules for retaining samples 
for biomarkers or PK, so it has been decided that Fasting insulin and PK samples are stored until 
final CTR. This is contrary to the regular safety samples at central laboratories which are discarded 
a few days after analysis. Reason for the difference is that sample results are released (and 
considered final) continuously from the central labs whereas the special labs release results at DBL 
due to limitations in the special lab LIMS systems. This keep the option for re-analysis open until 
PK and biomarker data has been evaluated. So it will not be advisable to store the Insulin samples 
as long as the antibody samples.
Updated text section 24.2 in protocol version 4.0:
Antibody samples will be stored until after end of trial and until marketing authorisation approval or 
until the research project terminates, but no longer than 15 years from end of trial after which they 
will be destroyed. Fasting insulin and PK samples will be stored until final CTR after which they 
will be destroyed.
2.3
Affected section 8.3: Reporting of laboratory results not provided to Investigator
Rationale: Based on guidance from the China Human Genetic Resources Administration Office 
(OHGRA) it is a concern that the protocol is not consistent as to where laboratory results that are 
not provided to the investigator will be published (antibody, PK and fasting insulin). . Because all 
results are summarised in the CTR the affected section is updated for consistency.
Updated text section 8.3.5 in protocol version 4.0:
Results from fasting insulin samples will not be provided to the investigator as these are not used 
for clinical evaluation during the trial. Instead they will be included in an analytical report after 
end of trial. The results will be described in the CTR after end of trial.
Updated text section 8.3.4 in protocol version 4.0:
PK results will not be provided to the investigator as these are not used for clinical evaluation 
during the trial. Instead they will be included in a bio-analytical report that will be available at 
data base lock and retained at Novo Nordisk. The results will be described in the CTR after end of 
trial.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
6 of 9
2.4
Affected sections 9.1 and 12.4.1: Mistake in pen description for Liraglutide in section 
9; in section 12 this is correctly listed
Rationale: A discrepancy was discovered in the pen description for liraglutide between table 9-1 
and section 12.4.1. The wrong device was listed for liraglutide in table 9-1 whereas it was correctly 
listed in section 12.4.1. Table 9.1 was updated to specify the dosage form and delivery device for all 
trial products. Furthermore, the brand name for liraglutide (Victoza®) was deleted from both table 9-
1 and section 12.4.1.
Updated table 9-1:
Table 9-1 Trial products (version 4.0 – to be replaced)
Table 9-1 Trial products (protocol version 5.0 – to be inserted)
Updated text section 12.4.1
All technical complaints on any of the following products:
•Insulin degludec/liraglutide 100 units/mL + 3.6 mg/mL (IDegLira), 3 mL pre-filled PDS290 pen
•Insulin degludec 100 units/mL (IDeg), 3 mL pre-filled PDS290 pen
•Liraglutide (Victoza®) 6 mg/mL, 3 mL pre-filled pen injector
•Novo Nordisk needles for pre-filled pens
2.5
Affected section 6.4 Withdrawal criteria#5
Rationale: The week intervals for withdrawal criteria #5 are not clearly defined and not similar to 
Global DUAL I protocol; week 6 and 12 were included in two intervals.
Trial product (IMP)
Strength
Dosage form
Route of 
administration
Insulin 
degludec/liraglutide
100 units/mL +
3.6 mg/mL
Solution for 3 mL pre-
filled PDS290 pen
Subcutaneous injection
Insulin degludec
100 units/mL
Liraglutide (Victoza®)
6 mg/mL
Trial product (IMP)
Strength
Dosage form
Route of 
administration
Delivery device
Insulin 
degludec/liraglutide
100 units/mL +
3.6 mg/mL
Solution for 
injection
Subcutaneous 
injection
3 mL pre-filled 
PDS290 pen
Insulin degludec
100 units/mL
Solution for 
injection
3 mL pre-filled 
PDS290 pen
Liraglutide
6 mg/mL
Solution for 
injection
3 mL pre-filled 
Pen-injector
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
7 of 9
Updated text section 6.4 in protocol version 4.0:
1. If all pre-breakfast SMPG values taken on three consecutive days or if any FPG samples 
analysed by the central laboratory exceeds the limit of:
15.0 mmol/L after baseline to week 6
13.3 mmol/L from week 76 to week 12
11.1 mmol/L from week 132 to last week prior to end of treatment
and given there is no intercurrent cause for the hyperglycaemia, a confirmatory FPG must be 
performed  at the next scheduled visit, or if deemed necessary by the investigator at an unscheduled.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
8 of 9
3
Changes to Subject information/informed consent form version 
4.0 dated 28-Sep-2016 
3.1
Affected section 1.7: Baseline antibody samples shipped from 
 to Novo 
Nordisk Måløv, Denmark
Rationale: To be aligned with the update in the protocol and to delete sentence about NN 
permission as the content is not meaningful and not applicable.
Updated section 1.7 Information about laboratory sampling and exportation:
In order to standardise the sample analysis used in this trial, all serum antibody samples, fasting 
insulin samples and insulin level samples including yours, will be shipped to special laboratories 
outside of China. The antibody samples will be shipped to 
, located in 
, and to 
Novo Nordisk, located in Denmark, for analysis , fFasting insulin samples and one of the insulin 
level samples will be shipped to 
, located in 
. The other insulin level sample 
will be shipped to 
, located in the 
. By involving only two three
special laboratories, comparability of results from subjects at all investigational sites involved in the 
trial will be ensured. 
Further, the serum antibody samples must only be used in relation to this trial, and all samples will 
be destroyed as biological/medical waste at 
and Novo Nordisk, after receiving marketing 
authorisation from the authorities and never shipped back to China.
Similarly, fasting insulin and insulin level samples will be destroyed as biological/medical waste at 
ands
no later than at the completion of the clinical trial report. The insulin 
level samples must only occur with permission from Novo Nordisk.
3.2
Affected section 3.3: Storage time for antibody samples 
Rationale: To be aligned with the update in the protocol.
Updated section 3.3 Will my participation in the trial be kept confidential?
Antibody samples will be stored until marketing authorisation approval or until the research 
project terminates. final feedback from the Chinese health authorities. but no longer than maximum 
15 years from end of trial.
3.3
Affected section 2.1: What are the possible risks if you participate in this trial
Rationale: Xultophy was approved by FDA on 21-Nov-2016. Adding this information to the SI/IC 
will ensure that patients receive the most updated safety information.
Updated section 2.1: What are the possible risks if you participate in this trial
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
05 December 2016
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671
Status:
Final
     
Page:
9 of 9
You must inform the trial staff about any other medications (including over-the-counter drugs and 
herbal remedies) that you are using during the trial. If you are prescribed new medicines or start 
taking a new over-the-counter drug, you should inform the trial staff immediately.
IDegLira, which is approved in EU and US under the names Xultophy® and Xultophy® 100/3.6, 
respectively , is well tolerated. In the clinical development programme IDegLira did not show 
increased incidence of side effects compared to its two monocomponents, Tresiba® (insulin 
degludec) and Victoza® (liraglutide).
CONFIDENTIAL

SAP_001.pdf: 
Cover Page for Statistical Analysis Plan 
Sponsor name: 
Novo Nordisk A/S 
NCT number 
NCT03172494 
Sponsor trial ID: 
NN9068-4148 
Official title of study: 
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral antidiabetic drugs (OADs).  
Document date: 
16 December 2019 


Link
Link
List of contents
Statistical analysis plan......................................................................................................................
Statistical documentation...................................................................................................................
CONFIDENTIAL
Date:
Novo Nordisk
Version:
Status:
IDegLira
Trial ID: NN9068-4148
Clinical Trial Report
Appendix 16.1.9
16 December 2019
1.0
Final
16.1.9 Documentation of statistical methods
CONFIDENTIAL
Redacted VWDWLVWLFDODQDO\VLVSODQ 
Includes redaction of personal identifiable information only. 
. 


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
1 of 23
Statistical Analysis Plan
Trial ID: NN9068-4148
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide, insulin degludec, and liraglutide in 
Chinese subjects with type 2 diabetes inadequately controlled 
on oral antidiabetic drugs (OADs)
Author
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.
This confidential document is the property of Novo Nordisk. No unpublished information contained herein may be 
disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
2 of 23
Table of contents
Page
Table of contents.........................................................................................................................................2
List of abbreviations ...................................................................................................................................3
1
Introduction .........................................................................................................................................5
1.1
Trial information.......................................................................................................................5
1.2
Scope of the statistical analysis plan..........................................................................................5
2
Statistical considerations .....................................................................................................................5
2.1
Sample size calculation............................................................................................................6
2.2
Definition of analysis sets........................................................................................................7
2.3
Primary endpoint ....................................................................................................................8
2.3.1
Sensitivity analysis .................................................................................................9
2.4
Secondary endpoints .............................................................................................................10
2.4.1
Confirmatory secondary endpoints.....................................................................10
2.4.2
Supportive secondary endpoints..........................................................................12
2.4.2.1
Efficacy endpoints ..........................................................................12
2.4.2.2
Safety endpoints .............................................................................14
2.5
Pharmacokinetic modelling ..................................................................................................20
3
Changes to the statistical analyses planned in the protocol..............................................................21
4
References ..........................................................................................................................................23
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
3 of 23
List of abbreviations
ADA
American Diabetes Association
AE
adverse event
AGI
α-glucosidase inhibitors
ANCOVA
analysis of covariance 
BG
blood glucose
BMI
body mass index
CAS
completer analysis set
CTR
clinical trial report
CV
coefficient of variation
DBL
database lock
ECG
electrocardiogram 
EOT
End of treatment
FAS
full analysis set
FDA
U.S. Food and Drug Administration
FPG
fasting plasma glucose
FU
follow-up
GLP-1
glucagon-like peptide-1
HbA1c
glycosylated haemoglobin
HDL
high density lipoprotein
HOMA-β
homeostatic model assessment
IDegLira
insulin degludec/liraglutide
IDeg
insulin degludec
IDF
International Diabetes Federation
ITT
intention-to-treat 
LDL
low density lipoprotein
LLOQ
lower limit of quantification
LOCF
Last Observation Carried Forward
MACE
major adverse cardiovascular event
MAP
modelling analysis plan
MCMC
Markov Chain Monte Carlo
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
mixed model for repeated measurements
OAD
oral antidiabetic drug
PK
pharmacokinetics
PP
per protocol
SAP
statistical analysis plan
SAS
safety analysis set
SD 
standard deviation
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
4 of 23
SU
sulphonylureas
T2DM
type 2 diabetes mellitus
TEAEs
treatment emergent adverse events
TTT
treat-to-target
TZD
thiazolidinedione
UNR
upper normal range
UTN
Universal Trial Number
VLDL
very low density lipoprotein
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
5 of 23
1
Introduction
1.1
Trial information
This is a 26 week, randomised, parallel three-arm, open-label, multi-centre, treat-to-target (TTT) 
confirmatory trial in Chinese subjects with T2DM inadequately controlled with metformin ± one 
other OAD: α-glucosidase inhibitors (AGI), sulphonylureas (SU), glinides and thiazolidinediones 
(TZD). The trial is comparing efficacy and safety of insulin degludec/liraglutide (IDegLira), insulin 
degludec (IDeg) and liraglutide, all in combination with Metformin. For further details please see 
the protocol.
1.2
Scope of the statistical analysis plan
This Statistical Analysis Plan (SAP) is based on final Protocol version 5.0 (05-Dec-2016).
The scope of this SAP is to add one sensitivity analysis for change from baseline in HbA1c after 26 
weeks of treatment and several sensitivity analyses for confirmatory secondary endpoints, and to 
perform other minor changes. For further details on the changes see section 3.
2
Statistical considerations
Novo Nordisk will analyse and report data from all sites together.
All analyses of efficacy and safety endpoints will be based on the full analysis set (FAS). The 
analysis of the primary endpoint and the confirmatory secondary endpoint, change from baseline in 
body weight after 26 weeks of treatment, will be repeated on the per-protocol (PP) analysis set and 
the completer analysis set (CAS) for sensitivity purposes. All efficacy endpoints will be 
summarised using the FAS and safety endpoints will be summarised using the safety analysis set 
(SAS).
The impact of protocol deviations and outliers may be investigated further in sensitivity analyses if 
deemed relevant.
Unless otherwise specified, all continuous measurements will be summarised descriptively at each 
visit by treatment using observed data. After 26 weeks of treatment, descriptive statistics will be 
presented based both on observed and last observation carried forward (LOCF) imputed data. 
Endpoints that are analysed untransformed and endpoints that are not formally analysed are 
summarised by the arithmetic mean, standard deviation (SD), median, and minimum and maximum 
value. Endpoints that are analysed log-transformed are summarised by the geometric mean and 
coefficient of variation (CV).
For measurements over time, mean values will be plotted to explore the trajectory over time. LOCF 
imputed data will be used as the basis for plotting data, if not otherwise specified. For endpoints 
that are analysed log-transformed, the geometric mean values will be plotted.
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Statistical Analysis Plan
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Date:
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Trial ID: NN9068-4148
Version:
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EudraCT No.: N/A
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A standard analysis of covariance (ANCOVA) model will be applied for the continuous primary 
and secondary endpoints. The model includes treatment and previous OAD treatment (metformin or 
metformin in combination with one other OAD) as fixed factors and the corresponding baseline 
value as covariate. In the following, this model will be referred to as the standard ANCOVA model.
Presentation of results from a statistical analysis will include the estimated mean treatment effects 
(Least Square Means [LSMeans]) for absolute values and change from baseline. In addition, 
estimated mean treatment difference (or ratio) will be presented together with the two-sided 95% 
confidence interval and corresponding two-sided p-value.
Handling of missing data
The expected percentage of missing data is around 15%. In accordance with industry guidance1
endpoints will be assessed at frequent visits and also on subjects who withdraw prematurely. This 
will facilitate an analysis in accordance with ITT principles. Also, the combined information on 
frequent outcomes and information on reason for drop-out is assumed to account for the missing 
data anticipated.
If an assessment has been made both at screening (Visit 1) and randomisation (Visit 2), and if not 
otherwise specified, the value from the randomisation visit will be used as the baseline value. If the 
value measured at the randomisation visit is missing and the assessment also has been made at 
screening, then the screening value will be used as the baseline value.
Missing values (including intermittent missing values) will be imputed using the LOCF method. 
Subjects without data after randomisation will be included by carrying forward their baseline value. 
LOCF has been a standard approach in diabetes trials for many years, and was used as the primary 
analysis in both IDegLira and IDeg phase 3a trials. LOCF is considered to be an appropriate method 
in the context of TTT trials, where subjects after withdrawal typically continue their therapy using 
commercially available insulin. In previous TTT trials with IDegLira and IDeg, LOCF has 
generally provided similar results to alternative methods applied to handle missing data, such as 
repeated measures models and completer analyses. In this trial, similar sensitivity analyses will be 
made to examine the robustness of the LOCF method. The LOCF approach will also be used to 
impute missing values in CAS.
2.1
Sample size calculation
The primary objective of this trial is to confirm the efficacy of IDegLira in controlling glycaemia as 
assessed by change from baseline in HbA1c after 26 weeks of treatment vs. IDeg and liraglutide, 
respectively. This is done by comparing the difference in change from baseline in HbA1c after 26 
weeks of treatment to a non-inferiority margin of 0.4% for IDegLira vs. IDeg and to a superiority 
margin of 0.0% for IDegLira vs. liraglutide. The non-inferiority margin of 0.4% (absolute) was 
chosen in accordance with the FDA guidance1.
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Statistical Analysis Plan
CONFIDENTIAL
Date:
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Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
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EudraCT No.: N/A
Page:
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A hierarchical testing procedure is applied. This is based on an a priori ordering of the null-
hypotheses and testing them in this order using the two-sided 95% confidence interval approach 
until an insignificant result appears. Non-inferiority and superiority will thus be considered 
confirmed if the upper bound of the two-sided 95% confidence interval is below 0.4% and 0.0%,
respectively. This is equivalent to using a one-sided test of size 2.5%, which means that the type 1 
error rate is controlled at 2.5% (one-sided).
Formally, let D be the mean difference in change from baseline in HbA1c. The null-hypotheses are 
given as:
!
Non-inferiority: H0 D≥0.40% against HA D<0.40%, with an assumed mean difference in 
treatment of 0.0% and a standard deviation of 1.0%
!
Superiority: H0 D≥0.0% against HA D<0.0%, with an assumed mean difference in treatment of -
0.3% and a standard deviation of 1.0%
For evaluation of non-inferiority the PP-population is used for the sample size calculations, while 
the FAS is used for evaluation of superiority. It is assumed that 15% of the randomised subjects will 
be excluded from the PP analysis set. The above assumptions are based on experience from the 
phase 3a development programmes for IDegLira and IDeg. The sample size is determined using a t-
statistic under the assumption of a one-sided test of size 2.5% for both the superiority and non-
inferiority testing. Based on these assumptions a sample size of 720 patients results in a 
non-inferiority power of 98.1% and a superiority power of 90.7% i.e. the combined power for 
meeting the primary objective is 98.1% * 90.7% = 89.0%. A sample size of 720 patients with a 15% 
drop-out rate and a 2:1:1 randomisation results in 306 PP patients in the IDegLira arm.
2.2
Definition of analysis sets
The following analysis sets are defined in accordance with the ICH-E9 guidance2.
!
Full Analysis Set (FAS): includes all randomised subjects. In exceptional cases, subjects may 
be eliminated from the full analysis set. In such cases the elimination will be justified and 
documented. The statistical evaluation of the FAS will follow the intention-to-treat (ITT) 
principle and subjects will contribute to the evaluation “as randomised”.
!
Per-Protocol (PP) analysis set: includes all subjects in the FAS who fulfils the following 
criteria:
-
Have not violated any inclusion criteria
-
Have not fulfilled any exclusion criteria
-
Have a non-missing HbA1c at screening or randomisation
-
Have at least one non-missing HbA1c after 12 weeks of exposure
-
Have at least 12 weeks of exposure
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Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
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EudraCT No.: N/A
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Subjects will contribute to the evaluation “as treated”.
!
Safety Analysis Set (SAS): includes all subjects receiving at least one dose of the 
investigational product or comparator. Subjects in the safety set will contribute to the evaluation 
“as treated”.
!
Completer Analysis Set (CAS): includes all randomised subjects who have completed the trial. 
Subjects in the completer analysis set will contribute to the evaluation “as randomised”.
Randomised subjects who are lost to follow up and where no exposure information of the 
investigational product or comparators is available after randomisation will be handled as 
unexposed.
Before data are released for statistical analysis, a review of all data will take place to identify 
protocol deviations that could potentially affect the results. Any decision to exclude any subject or 
observation from the statistical analysis is the joint responsibility of the members of the study 
group. The subjects or observations to be excluded, and the reasons for their exclusion must be 
documented and signed by those responsible before database lock. The subjects and observations 
excluded from analysis sets, and the reason for this, will be described in the clinical trial report.
2.3
Primary endpoint
The primary endpoint is defined as change from baseline in HbA1c after 26 weeks of treatment.
The change from baseline in HbA1c after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous OAD treatment (metformin ± one other OAD) as 
fixed factors and baseline HbA1c as covariate. Missing values after 26 weeks of treatment will be 
imputed applying LOCF using HbA1c values at and after baseline.
Non-inferiority of IDegLira vs. IDeg will be considered as confirmed if the 95% confidence interval 
for the mean treatment difference lies entirely below 0.4%; equivalent to a one-sided test with 
significance level of 2.5%. Non-inferiority will be investigated on the FAS. Sensitivity analysis will 
be performed on the PP analysis set.
Superiority of IDegLira vs. liraglutide will be considered as confirmed if the 95% confidence 
interval for the mean treatment difference for change from baseline in HbA1c lies entirely below 
0.0%; equivalent to a one-sided test with significance level of 2.5%. Conclusion of superiority will 
be based on FAS. The primary objective will be fulfilled only if both non-inferiority of IDegLira vs. 
IDeg and superiority of IDegLira vs. liraglutide are confirmed.
In addition to the non-inferiority margin of 0.4% the upper bound of the confidence interval for the 
mean treatment difference of IDegLira vs. IDeg will also be compared to a 0.0% margin. This 
comparison is not part of the hierarchical testing procedure.
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Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
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EudraCT No.: N/A
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2.3.1
Sensitivity analysis
The primary analysis will be repeated on the PP analysis set and the CAS as sensitivity analysis. 
Furthermore, sensitivity analysis will be performed on FAS using the mixed model for repeated 
measurement (MMRM) to evaluate the sensitivity of using LOCF. All HbA1c values available post 
baseline at scheduled measurement times will be analysed in a linear mixed normal model using an 
unstructured residual covariance matrix for HbA1c measurements within the same subject. The 
model will include treatment, visit, and previous OAD treatment as fixed factors and baseline 
HbA1c as covariate. Interactions between visit and all factors and the covariate are also included in 
the model.
Further, a pattern mixture model approach, mimicking an ITT scenario will be applied. The 
imputation will follow the hypothesis being tested. i.e., when deriving the IDegLira vs. IDeg 
contrast the imputation in the IDegLira arm will be based on IDeg values, whereas for the IDegLira 
vs. liraglutide contrast the imputation in the IDegLira arm will be based on liraglutide values. 
Furthermore, 0.4% (absolute) will be added to the imputed values in the IDegLira arm for the non-
inferiority comparison against IDeg to mimic a scenario where subjects discontinued from IDegLira 
treatment are assumed to be switched to a treatment inferior to IDeg. In other words: two 
imputation datasets will be made, one for IDegLira and IDeg and one for IDegLira and liraglutide.
In the analyses, depending on the hypothesis being tested, the respective imputation dataset will be 
used and the third arm (from the other imputation dataset) will be kept in the model. The 
imputations for each hypothesis will be done as follows:
!
In the first step intermittent missing values are imputed using a Markov Chain Monte Carlo 
(MCMC) method, in order to obtain a monotone missing data pattern. This imputation is done 
for each treatment group separately and 1000 copies of the dataset will be generated.
!
In the second step, for each of the 1000 copies of the dataset, an analysis of variance model with 
previous OAD treatment as a fixed factor, and baseline HbA1c as a covariate is fitted to the 
change in HbA1c from baseline to 4 weeks (Visit 6) for a given comparator group only. The 
estimated parameters, and their variances, from this model are used to impute missing values at 
4 weeks for subjects in the comparator and IDegLira treatment groups, based on previous OAD 
treatment and HbA1c at baseline.
!
In the third step, for each of the 1000 copies of the dataset, missing HbA1c values at 8 weeks 
(Visit 10) are imputed in the same way as for 4 weeks. Now the imputations are based on an 
analysis of variance model with the same factors and the HbA1c values at baseline and 4 weeks 
as covariates, fitted to the comparator group.
!
This stepwise procedure is then repeated sequentially over the available planned visits, adding 
one visit in each step until the last planned visit at 26 weeks (Visit 28).
CONFIDENTIAL


Statistical Analysis Plan
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Date:
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Trial ID: NN9068-4148
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!
For the comparison against IDeg, for each subject discontinued from treatment in the IDegLira 
treatment group, a value of 0.4% (absolute; the non-inferiority limit) is added to the change in 
HbA1c at 26 weeks.
For each of the complete data sets, the change from baseline to 26 weeks is analysed using an 
analysis of variance model with treatment and previous OAD treatment as fixed factors and baseline 
HbA1c value as a covariate.
The estimates and standard deviations for the 1000 data sets are pooled to one estimate and 
associated standard deviation using Rubin’s rule3. From these pooled estimates the confidence 
interval for the treatment differences and the associated p-value are calculated.
The results of sensitivity analyses will be compared to the result of the standard ANCOVA method 
using LOCF for imputation of missing data. Any marked difference between the MMRM, the 
pattern mixture approach and ANCOVA LOCF approach regarding the estimated treatment 
difference will be commented upon in the CTR.
2.4
Secondary endpoints
2.4.1
Confirmatory secondary endpoints
The following two confirmatory endpoints will be tested for superiority of IDegLira vs. IDeg.
!
Change from baseline in body weight after 26 weeks of treatment.
!
Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 
26 weeks of treatment.
The tests for superiority of the confirmatory secondary endpoints will be based on the FAS and will 
only be carried out if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. 
liraglutide with regards to the primary endpoint are confirmed.
In order to control the overall type I error on a 2-sided 5% level with regards to the secondary 
endpoints, a hierarchical testing procedure will be used. If superiority is confirmed with respect to 
change from baseline in body weight after 26 weeks of treatment the number of treatment emergent 
severe or BG confirmed hypoglycaemic episodes during 26 weeks of treatment will be tested for 
superiority.
Superiority for change from baseline in body weight will be considered confirmed if the upper 
bound of the two-sided 95% confidence interval for the estimated mean treatment difference 
(IDegLira minus IDeg) is strictly below zero or equivalently if the p-value for the one-sided test of
H0 D≥0.0 against HA D<0.0,
CONFIDENTIAL


Statistical Analysis Plan
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Date:
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Trial ID: NN9068-4148
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is less than 2.5%, where D is the treatment difference.
The change from baseline in body weight after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous OAD treatment (metformin ± one other OAD) as 
fixed factors and baseline weight as covariate.
Similar sensitivity analyses as specified for the primary endpoint (ANCOVA on the PP analysis set 
and CAS; MMRM; the pattern mixture model similar to that described for HbA1c, but without 
added non-inferiority penalty) will be performed.
Superiority for hypoglycaemic episodes will be considered confirmed if the upper bound of the two-
sided 95% confidence interval for the estimated mean treatment ratio (IDegLira vs. IDeg) is strictly 
below one or equivalently if the p-value for the one-sided test of
H0 RR≥1.0 against HA RR<1.0,
is less than 2.5%, where RR is the treatment rate ratio.
Number of treatment emergent severe or BG confirmed hypoglycaemic episodes during 26 weeks 
of treatment will be analysed using a negative binominal regression model with a log-link function 
and the logarithm of the time period in which a hypoglycaemic episode is considered treatment 
emergent as offset. The model will include treatment and previous OAD treatment as fixed factors.
As a sensitivity analysis, for withdrawn subjects, the number of episodes in the missing period (time 
of withdrawal to planned treatment emergent period [max of 27 weeks and longest treatment 
emergent time observed in the trial, in all 3 treatment arms]) will be imputed using a multiple 
imputation technique4. The first step (getting samples from the posterior distribution) is done once,
for all three arms together. In the second step, the imputation will follow the hypothesis being 
tested. When deriving the IDegLira vs. IDeg treatment ratio the imputation will be based on an
assumption that the event rates before and after withdrawal in both arms correspond to the event 
rate in the IDeg group. Similarly for the IDegLira vs liraglutide treatment ratio, the event rate before 
and after withdrawal is assumed to correspond to the event rate in the liraglutide arm. In other 
words: two imputation datasets will be made, one for IDegLira and IDeg and one for IDegLira and 
liraglutide. In the analyses, depending on the hypothesis being tested, the respective imputation 
dataset will be used and the third arm (from the other imputation dataset) will be kept in the model.
The imputation will be done as follows: 
!
As a first step, a Bayes negative binomial model with the same fixed factors used in the original 
confirmatory analysis model is fitted to the event rate data to obtain the posterior distribution of 
model parameters.
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Statistical Analysis Plan
CONFIDENTIAL
Date:
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Trial ID: NN9068-4148
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EudraCT No.: N/A
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!
In the second step, based on the estimated parameters for comparator in this model, the number 
of events in the missing period is imputed for all withdrawn subjects, i.e. pre and post 
withdrawal event rates in the conditional distribution used for imputation are as for a given 
comparator. Multiple copies (1000 copies) of a complete data set are generated by sampling 
from the estimated distribution.
For each of the complete data sets, the number of events is analysed using a negative binomial 
model including the same fixed factors used in the original model.
The estimates and standard deviations for the 1000 data sets are pooled to one estimate and 
associated standard deviation using Rubin’s rule3. From these pooled estimates the confidence 
interval for the treatment ratio and the associated p-value are calculated.
Subjects with missing exposure time will not contribute to the analysis.
2.4.2
Supportive secondary endpoints
2.4.2.1
Efficacy endpoints
In the following the statistical models will be fitted to all data simultaneously (all treatment groups) 
and from this model the treatment differences for IDegLira vs. IDeg and IDegLira vs. liraglutide 
will be estimated. For insulin dose, the model will be fitted only to data from the IDegLira and IDeg 
treatment groups.
Insulin dose after 26 weeks of treatment
The actual daily insulin dose after 26 weeks of treatment will be analysed using an ANCOVA 
model including treatment and previous OAD treatment as fixed factors and baseline HbA1c value 
as covariate.
Responder for HbA1c after 26 weeks of treatment
Two dichotomous endpoints (responder/non-responder) will be defined based on whether a subject 
has met a specific target level after 26 weeks of treatment:
!
ADA HbA1c target (HbA1c < 7.0%)
!
International Diabetes Federation (IDF) HbA1c target (HbA1c ≤ 6.5%)
Analysis of each of the two responder endpoints will be based on a logistic regression model with 
treatment and previous OAD treatment as fixed factors and baseline HbA1c value as a covariate.
HbA1c responder endpoints without weight gain
Responder for HbA1c without weight gain after 26 weeks of treatment will be defined as 
HbA1c< 7.0% or ≤ 6.5% at end of treatment and change from baseline in body weight below or 
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Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
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equal to zero. Analysis of each of the two responder endpoints will be based on a logistic regression 
model with treatment and previous OAD treatment as fixed factors and baseline HbA1c and body 
weight values as covariates.
HbA1c responder endpoints without hypoglycaemic episodes
Responder for HbA1c without hypoglycaemic episodes after 26 weeks of treatment will be defined 
as HbA1c < 7.0% or ≤ 6.5% at end of treatment and without severe or BG confirmed episodes 
during the last 12 weeks of treatment. Analysis of each of the two responder endpoints will be based 
on a logistic regression model with treatment and previous OAD treatment as fixed factors and 
baseline HbA1c values as a covariate.
HbA1c responder endpoints without hypoglycaemic episodes and weight gain
Responder for HbA1c without hypoglycaemic episodes and weight gain after 26 weeks of treatment 
will be defined as HbA1c < 7.0% or ≤ 6.5% at end of treatment, without severe or BG confirmed 
episodes during the last 12 weeks of treatment, and change from baseline in body weight below or 
equal to zero. Analysis of each of the two responder endpoints will be based on a logistic regression 
model with treatment and previous OAD treatment as fixed factors and baseline HbA1c and body 
weight values as covariates.
Fasting plasma glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment will be analysed using the standard 
ANCOVA model.
Waist circumference
Change from baseline in waist circumference after 26 weeks of treatment will be analysed using the 
standard ANCOVA model.
Beta-cell function (fasting insulin, fasting C-peptide, fasting glucagon, and HOMA-β)
In addition to fasting insulin, fasting C-peptide, and fasting glucagon, one derived parameter will be 
calculated; beta-cell function (HOMA-β). The calculation of the HOMA endpoint will be done as 
follows:
!
Beta-cell function (%) = 20·fasting insulin[μU/mL]/(FPG[mmol/L]-3.5)
These endpoints after 26 weeks of treatment will be analysed separately using the standard 
ANCOVA model. In these statistical analyses the endpoint will be log-transformed and so will the 
baseline covariate.
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Statistical Analysis Plan
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Trial ID: NN9068-4148
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Fasting lipid profile
Cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol, triglycerides, and free fatty 
acids after 26 weeks of treatment will be analysed separately using the standard ANCOVA model. 
In these statistical analyses the endpoint will be log-transformed and so will the baseline covariate.
Self-measured plasma glucose 9-point profile
Three endpoints from the 9-point profile will be defined:
!
9-point profile
!
Mean of the 9-point profile, defined as the area under the profile (calculated using the 
trapezoidal method) divided by the measurement time
!
Post-prandial plasma glucose increments (from before meal to 90 min after for breakfast, lunch 
and dinner). The mean increment over all meals will be derived as the mean of all available 
meal increments
A mixed effect model will be fitted to the 9-point profile data. The model will include treatment,
previous OAD treatment, time, interaction between treatment and time, and interaction between 
previous OAD treatment and time as fixed factors, and subject as random effect, where 
measurements within subjects will be assumed correlated with a compound symmetry covariance 
matrix. From the model mean profile by treatment and relevant treatment differences will be 
estimated and explored.
Change from baseline after 26 weeks of treatment in mean of the 9-point profile and post-prandial 
increment endpoints will be analysed separately using the standard ANCOVA model.
2.4.2.2
Safety endpoints
Adverse events
AEs will be coded using the most recent version of the Medical Dictionary for Regulatory 
Activities (MedDRA) coding.
A treatment emergent adverse event (TEAE) is defined as an event that has onset date on or after 
the first day of exposure to randomised treatment and no later than seven days after the last day of 
randomised treatment. If the event has onset date before the first day of exposure on randomised 
treatment and increases in severity during the treatment period and until 7 days after the last drug 
date, then this event should also be considered as a TEAE. Major adverse cardiovascular events 
(MACEs, defined as all cardiovascular deaths, non-fatal myocardial infarctions and non-fatal 
strokes) are considered treatment-emergent until 30 calendar days after the last dose of trial product.
TEAEs are summarised descriptively, whereas non-TEAEs are presented in listings. TEAE data 
will be displayed in terms of the number of subjects with at least one event (N), the percentage of 
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Statistical Analysis Plan
CONFIDENTIAL
Date:
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Trial ID: NN9068-4148
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subjects with at least one event (%), the number of events (E) and the event rate per 100 years of 
exposure (R).
Summaries of TEAEs and of serious TEAEs will be presented as an overview including all AEs, 
AEs by seriousness, AEs by severity, AEs by relation to treatment, technical complaint AEs and 
AEs by outcome (including deaths).
Furthermore, summary tables based on system organ class and preferred terms are made for:
!
All TEAEs
!
TEAEs leading to withdrawal
!
Serious TEAEs
!
Possibly or probably related TEAEs
!
Severe, moderate and mild TEAEs
!
TEAEs reported by safety areas of interest
!
TEAEs with preferred term that are experienced by at least 5% of the subjects in any treatment 
arm or by at least 5% of all subjects
A listing for non-TEAEs with onset date before the first day of exposure to randomised treatment 
will be presented. A listing will also be presented for non-TEAEs collected after the treatment 
emergent period according to the definition of TEAE.
Classification of Hypoglycaemia
Treatment emergent: hypoglycaemic episodes will be defined as treatment emergent if the onset 
of the episode occurs on or after the first day of trial product administration, and no later than 
7 days after the last day on trial product.
Nocturnal hypoglycaemic episodes: are episodes with time of onset between 00:01 and 05.59 both
inclusive.
Hypoglycaemic episodes are classified according to the Novo Nordisk classification of 
hypoglycaemia (see Figure 2–1) and the ADA classification of hypoglycaemia (see Figure 2–2).
Novo Nordisk classification of hypoglycaemia
In normal physiology, symptoms of hypoglycaemia occur below a plasma glucose level of 
3.1 mmol/L.5 Therefore, Novo Nordisk has included hypoglycaemia with plasma glucose levels 
below this cut-off point in the definition of BG confirmed hypoglycaemia.
Novo Nordisk uses the following classification (see Figure 2–1) in addition to the ADA 
classification (see Figure 2–2):
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Statistical Analysis Plan
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!
Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to 
the ADA classification6 or BG confirmed by a plasma glucose value <3.1 mmol/L with
symptoms consistent with hypoglycaemia.
!
Severe or BG confirmed hypoglycaemia: An episode that is severe according to the ADA 
classification6 or BG confirmed by a plasma glucose value <3.1 mmol/L with or without
symptoms consistent with hypoglycaemia.
Hypoglycaemic
episode
PG ≤ 3.9 mmol/L 
(70 mg/dL) 
or 
Alleviation of 
symptoms 
or
Seizure, coma or 
fatal 
SMPG
measurement
PG < 3.1 mmol/L
(56 mg/dL)
with symptoms
PG < 3.1 mmol/L
(56 mg/dL)
without
symptoms
Symptomatic BG 
confirmed 
hypoglycaemia
Asymptomatic BG 
confirmed 
hypoglycaemia
Yes
No
Severe or 
BG confirmed 
symptomatic 
hypoglycaemia
BG confirmed 
hypoglycaemia
Severe or BG 
confirmed 
hypoglycaemia
Note: Glucose measurements are performed with capillary blood calibrated to plasma equivalent glucose values
BG: blood glucose  PG: plasma glucose  SMPG: Self-measured plasma glucose  
Subject 
able to 
treat him/
herself
Severe 
hypoglycaemia
(ADA 2013)
Figure 2–1
Novo Nordisk classification of hypoglycaemia
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ADA classification of hypoglycaemia6
!
Severe hypoglycaemia: An episode requiring assistance of another person to actively administer 
carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not 
be available during an event, but neurological recovery following the return of plasma glucose 
to normal is considered sufficient evidence that the event was induced by a low plasma glucose 
concentration.
!
Asymptomatic hypoglycaemia: An episode not accompanied by typical symptoms of 
hypoglycaemia, but with a measured plasma glucose concentration ≤ 3.9 mmol/L.
!
Documented symptomatic hypoglycaemia: An episode during which typical symptoms of 
hypoglycaemia are accompanied by a measured plasma glucose concentration ≤ 3.9 mmol/L.
!
Pseudo-hypoglycaemia: An episode during which the person with diabetes reports any of the 
typical symptoms of hypoglycaemia with a measured plasma glucose concentration 
> 3.9 mmol/L but approaching that level.
!
Probable symptomatic hypoglycaemia: An episode during which symptoms of hypoglycaemia 
are not accompanied by a plasma glucose determination but that was presumably caused by a 
plasma glucose concentration ≤ 3.9 mmol/L.
Hypoglycaemic 
episode 
PG ≤ 3.9 mmol/L 
(70 mg/dL) 
or 
Alleviation of 
symptoms 
or
Seizure, coma or 
fatal 
SMPG
measurement
Asymptomatic 
hypoglycaemia
Documented 
symptomatic 
hypoglycaemia
Pseudo-
hypoglycaemia
Probable 
symptomatic 
hypoglycaemia
No
Yes
No measurement 
with symptoms
PG > 3.9 mmol/L 
(70 mg/dL)
with symptoms
PG ≤3.9 mmol/L 
(70 mg/dL)
with symptoms
PG ≤3.9 mmol/L 
(70 mg/dL)
without symptoms
No
Yes
Note: Glucose measurements are performed with capillary blood calibrated to plasma equivalent glucose values
PG: plasma glucose  SMPG: Self-measured plasma glucose  
Subject 
able to 
treat him/
herself
Severe 
hypoglycaemia
(ADA 2013)
Figure 2–2
ADA classification of hypoglycaemia
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
18 of 23
Data on treatment emergent hypoglycaemic episodes are presented in terms of the number of 
subjects with at least one event (N), the percentage of subjects with at least one event (%), the 
number of events (E) and the event rate per 100 years (R).
Separate summaries are made for severe or BG confirmed hypoglycaemic episodes, severe or BG 
confirmed symptomatic hypoglycaemic episodes, nocturnal severe or BG confirmed hypoglycaemic 
episodes, nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes and the ADA 
classification of hypoglycaemia.
The number of hypoglycaemic episodes during 26 weeks of treatment will be analysed separately 
for each endpoint using a negative binomial regression model with a log-link function and the 
logarithm of the time period in which a hypoglycaemic episode is considered treatment emergent as 
offset. The model will include treatment and previous OAD treatment at fixed factors.
Pulse
Change from baseline in pulse after 26 weeks of treatment will be analysed using the standard 
ANCOVA model.
Systolic and diastolic blood pressure
Change from baseline in systolic and diastolic blood pressure after 26 weeks of treatment will be 
analysed using the standard ANCOVA model.
Clinical evaluations (physical examination, eye examination and ECG)
Eye examination (dilated fundoscopy/fundus photography) and ECG findings will be summarised 
descriptively, including:
!
Summaries
!
The change from baseline after 26 weeks of treatment
Any clinically significant deterioration of a pre-existing condition after the screening visit, as well 
as any new clinically significant findings will be recorded as adverse events.
Laboratory assessments
All laboratory parameters will be summarised descriptively. The following tables will be presented 
based on both observed and LOCF imputed data:
!
Shift tables from baseline to after 26 weeks of treatment.
!
Proportion of subjects with measurements outside reference range by treatment and week.
Laboratory values for lipase, amylase and calcitonin will be presented graphically as box plots by 
treatment and week.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
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Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
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For each laboratory parameter, individual values outside the reference ranges (abnormal values) 
will be listed.
For lipase and amylase the following rule applies in the evaluation of the result:
!
If the amylase or lipase baseline (at screening) value is > 3xUNR the information will be 
recorded as medical history for that subject.
Calcitonin
The purpose of the calcitonin analysis is to evaluate longitudinal changes in calcitonin, with main 
focus on subjects who develop persistently high levels of calcitonin during the trial.
Calcitonin will be displayed in terms of the number of subjects (N), the percentage of subjects (%) 
and the event rate per 100 years of exposure (R). The following criteria are defined for tabulations:
!
Persistent (all post baseline measurements)
-
From < UNR to persistently ≥ UNR
-
From < UNR to persistently ≥ 1.5 UNR
-
From < UNR to persistently ≥ 20 ng/L
-
From < UNR to persistently ≥ 50 ng/L
-
From < 20 ng/L to persistently ≥ 20 ng/L
-
From < 50 ng/L to persistently ≥ 50 ng/L
!
Incidental (at least one post baseline measurements)
-
From < UNR to ≥ UNR
-
From < UNR to ≥ 1.5 UNR
-
From < UNR to ≥ 20 ng/L
-
From < UNR to ≥ 50 ng/L
-
From < 20 ng/L to ≥ 20 ng/L
-
From < 50 ng/L to ≥ 50 ng/L
The distribution of all calcitonin measurements across treatment groups and time will be shown 
with box plots and corresponding cumulative plots for actual levels of calcitonin and change from 
baseline. The plots will be presented by treatment group at EOT using LOCF imputed values and 
within treatment group by week. Plots will be done by each gender, separately.
Summaries tables of calcitonin continuous measurements, will include number and percentage of 
observations < and ≥ LLOQ, minimum, Q25, median, Q75 and maximum. Summaries will be 
presented for all subjects and by gender.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
20 of 23
Longitudinal changes for subjects with calcitonin levels ≥ 20 ng/l will be plotted (longitudinal 
plots). The plots will be done by treatment and gender. They will be done for subjects in the 
persistent and incidental categories, separately.
A listing of subjects with at least one post baseline value ≥ 20 ng/l will be done. The listing will 
include age, gender, calcitonin measurements over time and AE history (including preferred term, 
onset and stop dates).
Urinalysis
Categorical urinalysis parameters will be summarised descriptively by:
!
Shift from baseline to EOT (using the number of subjects in the different categories).
!
Subjects with at least one post baseline measurement outside reference range will be listed.
Insulin and GLP-1 antibodies
Insulin antibodies (IDeg specific, cross-reacting to human insulin and total) will be summarised 
with arithmetic mean, standard deviation (SD), median, and minimum and maximum value by 
treatment and treatment week, and their mean over time will be plotted. Correlations will be 
explored graphically as follows. Insulin antibodies (IDeg specific, cross-reacting to human insulin 
and total) will be plotted against HbA1c after 26 weeks, HbA1c change from baseline after 26 weeks, 
and dose after 26 weeks. Change from baseline to FU1 in insulin antibodies (IDeg specific, cross-
reacting to human insulin and total) will be plotted against HbA1c after 26 weeks, HbA1c change 
from baseline after 26 weeks, and dose after 26 weeks.
GLP-1 antibodies (liraglutide specific, cross-reacting to native GLP-1, liraglutide in vitro
neutralising and in vitro neutralising to native GLP-1) will be summarised by number of subjects 
(N) and percentage of subjects (%) with positive and negative samples.
2.5
Pharmacokinetic modelling
Population pharmacokinetic analysis
The objective for this analysis is to compare the pharmacokinetics of IDegLira and its individual 
components at clinically relevant doses during 26 weeks of treatment. Furthermore, dose-
proportionality of IDeg and liraglutide exposures following doses of IDegLira will be evaluated and 
the effects of pre-specified covariates on exposures of IDeg and liraglutide will be investigated. 
Pharmacokinetic samples for IDeg and liraglutide sampled at site visits will be included in the 
analysis. No pre-defined time of day is specified for the sampling, but the date and exact clock time 
of sampling will be recorded by the investigator. The subjects must be instructed to write in their 
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
21 of 23
diary the date, exact clock time, dose, and injection site of the previous three days of dosing as well 
as the dose on the day of the visit, if taken before PK blood sampling.
The population PK analysis will be performed by the Quantitative Clinical Pharmacology 
Department at Novo Nordisk. A more technical and detailed elaboration of the population PK 
analysis will be given in the modelling analysis plan (MAP) which will be finalised before DBL.
The pre-specified analysis will explore the effects of covariates on the IDeg and liraglutide 
exposure. The structural models and covariate relationships will be predefined in detail in the MAP. 
In brief, previously developed population PK models for IDeg and liraglutide will be used. For both 
PK models, the absorption rate constant (Ka) will be fixed and the apparent clearance (CL/F) and 
the apparent volume of distribution (Vd/F) will be estimated.
The covariates of interest will be evaluated using criteria which will be specified in the MAP.
The following covariates will be tested on the apparent clearance (CL/F):
!
Dose
!
Treatment (IDegLira, IDeg, liraglutide)
!
Injection site area (Abdomen, Upper arm, Thigh)
!
Body weight
!
Age group (< 65, ≥ 65 years)
!
Gender (Male/Female)
For the categorical variables, it is a requirement to have at least 20 subjects in each category.
Exposure-response analysis
The exposure-response relationship will be investigated for selected response variables, such as 
HbA1c. Individual drug concentration data will be tabulated in the CTR.
The population PK and exposure-response analyses will be reported in a separate modelling report, 
which will not be a part of the CTR.
3
Changes to the statistical analyses planned in the protocol
!
Additional sensitivity analysis was added, using the pattern mixture model, in order to evaluate 
the sensitivity of using LOCF for primary endpoint, change from baseline in HbA1c after 26 
weeks of treatment.
!
Sensitivity analyses for confirmatory secondary endpoint, change from baseline in body weight
after 26 weeks of treatment, were added to evaluate the sensitivity of using LOCF.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
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!
Sensitivity analysis for confirmatory secondary endpoint, number of treatment emergent severe 
or BG confirmed hypoglycaemic episodes during 26 weeks of treatment, was added to evaluate 
the sensitivity of the analysis specified in the protocol.
!
A minor correction regarding the analysis model for the supportive secondary endpoint of 9-
point self-measured plasma glucose was made (baseline value was removed from the model and 
interaction between previous OAD and time was added).
!
Box plots will only be presented for relevant laboratory assessments: lipase, amylase and 
calcitonin.
!
Listings deemed unnecessary were removed: antibody measurements, physical examination 
findings.
!
Minor editorial changes were made, and clarifications were added where considered relevant.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
23 September 2019
Novo Nordisk
Trial ID: NN9068-4148
Version:
1.0
UTN: U1111-1154-6671 
Status:
Final
EudraCT No.: N/A
Page:
23 of 23
4
References
1.
Food and Drug Administration, CDER. Guidance for Industry. Diabetes Mellitus: 
Developing Drugs and Therapeutic Biologics for Treatment and Prevention, Draft Guidance. 
February 2008.
2.
ICH Harmonised Tripartite Guideline. Statistical Principles for Clinical Trials E9, Current 
Step 4 version. 05 Feb 1998.
3.
Little RJA, Rubin DB. Statistical analysis with missing data. New York: Wiley. 1987. xiv, 
278 p.
4.
Keene ON, Roger JH, Hartley BF, Kenward MG. Missing data sensitivity analysis for 
recurrent event data using controlled imputation. Pharmaceutical Statistics. 2014;13(4):258-
64.
5.
Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of 
glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 
1987;79(3):777-81.
6.
Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia 
and diabetes: a report of a workgroup of the American Diabetes Association and the 
Endocrine Society. Diabetes Care. 2013;36(5):1384-95.
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Table of contents
Page
1: Actual daily total insulin dose after 26 weeks of treatment - supportive statistical analysis - full 
analysis set.............................................................................................................................................3
2: HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full 
analysis set.............................................................................................................................................5
3: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per 
protocol analysis set.............................................................................................................................15
4: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set ..........................................................................................................................25
5: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM -
full analysis set ....................................................................................................................................35
6: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set.................................................................................59
7: HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full 
analysis set...........................................................................................................................................87
8: Responder for HbA1c treatment target - supportive statistical analysis - full analysis set .........................97
9: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed 
hypoglycaemic episodes - supportive statistical analysis - full analysis set..........................................101
10: Responder for HbA1c treatment target without weight gain - supportive statistical analysis - full 
analysis set.........................................................................................................................................105
11: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed 
hypoglycaemic episodes and weight gain - supportive statistical analysis - full analysis set ................109
12: Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis -
full analysis set ..................................................................................................................................113
13: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set .....................................................................................................................123
14: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set ........................................................................................................................133
15: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set ..................................................................................................................143
16: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set...............................................................................167
17: Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set...................................................................................................................195
18: Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set...................................................................................................................200
19: 9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical 
analysis - full analysis set...................................................................................................................209
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20: Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from 
baseline - supportive statistical analysis - full analysis set...................................................................277
21: Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set ..............................................287
22: Fasting insulin after 26 weeks of treatment - supportive statistical analysis - full analysis set...............327
23: Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set ..........330
24: Fasting glucagon after 26 weeks of treatment - supportive statistical analysis - full analysis set ...........336
25: HOMA-B after 26 weeks of treatment - supportive statistical analysis - full analysis set......................339
26: HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set............342
27: LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set ............348
28: VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set..........354
29: Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set .................360
30: Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set............366
31: Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set ...............372
32: Hypoglycaemic episodes - treatment emergent - confirmatory statistical analysis - full analysis set .....378
33: Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple imputation 
- full analysis set ................................................................................................................................381
34: Hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full analysis set .........389
35: Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full 
analysis set.........................................................................................................................................392
36: Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full 
analysis set.........................................................................................................................................398
37: Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set...................................................................................................................403
38: Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set...................................................................................................................408
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NN9068
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Version:
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Statistical documentation
1: Actual daily total insulin dose after 26 weeks of treatment - supportive statistical analysis - full 
analysis set
Parameter Code=TOTDDAC
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           2    1 2                           
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             530
          Number of Observations
Number of Observations Read             540
Number of Observations Used             530
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       156.79
           Fit Statistics
-2 Res Log Likelihood          4173.3
AIC (Smaller is Better)        4175.3
AICC (Smaller is Better)       4175.3
BIC (Smaller is Better)        4179.6
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   9.5426     5.5886    526      1.71     0.0883     0.05
trtpn                         1            -5.4917     1.1603    526     -4.73     <.0001     0.05
trtpn                         2                  0                                                
PREOAD2     Metformin                      -0.8080     1.1686    526     -0.69     0.4896     0.05
PREOAD2     Metformin + OAD                      0                                                
HBA1CBL                                     2.5256     0.6569    526      3.84     0.0001     0.05
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NN9068
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Version:
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Statistical document
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Actual daily total insulin dose after 26 weeks of treatment - supportive statistical analysis -
full analysis set
Parameter Code=TOTDDAC
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -1.4362     20.5213
trtpn                         1            -7.7712     -3.2123
trtpn                         2                               
PREOAD2     Metformin                      -3.1038      1.4877
PREOAD2     Metformin + OAD                                   
HBA1CBL                                     1.2352      3.8160
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     526      22.40    <.0001
PREOAD2         1     526       0.48    0.4896
HBA1CBL         1     526      14.78    0.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    24.6139     0.6640     526     37.07     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    30.1057     0.9504     526     31.68     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    23.3095    25.9184        4.894E10        1.328E10        1.804E11
trtpn    LSMeans, IDeg        28.2385    31.9728        1.188E13        1.836E12        7.684E13
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -5.4917     1.1603     526     -4.73
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -7.7712   -3.2123       0.004121
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.000422          0.04027
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2: HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full 
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
TRTPN           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5548
           Fit Statistics
-2 Res Log Likelihood          1635.3
AIC (Smaller is Better)        1637.3
AICC (Smaller is Better)       1637.3
BIC (Smaller is Better)        1641.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.5634     0.2879    715     15.85     <.0001     0.05
TRTPN                         1            -0.6283    0.06796    715     -9.25     <.0001     0.05
TRTPN                         2           -0.03366    0.07869    715     -0.43     0.6690     0.05
TRTPN                         3                  0                                                
PREOAD2     Metformin                      -0.3922    0.05944    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3338    0.03413    715      9.78     <.0001     0.05
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HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   3.9982      5.1287
TRTPN                         1            -0.7618     -0.4949
TRTPN                         2            -0.1882      0.1208
TRTPN                         3                               
PREOAD2     Metformin                      -0.5089     -0.2755
PREOAD2     Metformin + OAD                                   
BASE                                        0.2668      0.4008
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715      95.66    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
TRTPN    LSMeans, IDegLira   WORK.ADATA2     6.5559    0.03921     715    167.18     <.0001     0.05
TRTPN    LSMeans, IDeg       WORK.ADATA2     7.1506    0.05574     715    128.29     <.0001     0.05
TRTPN    LSMeans, Lira       WORK.ADATA2     7.1842   0.05552     715    129.40     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
TRTPN    LSMeans, IDegLira     6.4789     6.6329          703.38          651.26          759.68
TRTPN    LSMeans, IDeg         7.0412     7.2600         1274.85         1142.71         1422.27
TRTPN   LSMeans, Lira         7.0752     7.2933         1318.50         1182.33         1470.34
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.5947    0.06819     715     -8.72
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -0.7286   -0.4608         0.5517
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - IDeg         0.4826           0.6308
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HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -0.6283    0.06796     715     -9.25
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - Lira    <.0001    0.05   -0.7618   -0.4949         0.5335
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - Lira         0.4668           0.6096
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16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
8 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
TRTPN           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      66.2773
           Fit Statistics
-2 Res Log Likelihood          5060.0
AIC (Smaller is Better)        5062.0
AICC (Smaller is Better)       5062.0
BIC (Smaller is Better)        5066.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  34.2233     2.3673    715     14.46     <.0001     0.05
TRTPN                         1            -6.8678     0.7428    715     -9.25     <.0001     0.05
TRTPN                         2            -0.3679     0.8601    715     -0.43     0.6690     0.05
TRTPN                         3                  0                                                
PREOAD2     Metformin                      -4.2869     0.6497    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3338    0.03413    715      9.78     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
9 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  29.5757     38.8709
TRTPN                         1            -8.3262     -5.4094
TRTPN                         2            -2.0566      1.3207
TRTPN                         3                               
PREOAD2     Metformin                      -5.5625     -3.0113
PREOAD2     Metformin + OAD                                   
BASE                                        0.2668      0.4008
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715      95.66    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
TRTPN    LSMeans, IDegLira   WORK.ADATA2    48.1560     0.4286     715    112.35     <.0001     0.05
TRTPN    LSMeans, IDeg       WORK.ADATA2    54.6559     0.6092     715     89.72     <.0001     0.05
TRTPN    LSMeans, Lira       WORK.ADATA2    55.0238     0.6068     715     90.67     <.0001     0.05
                                 Least Squares Means Estimates
                                                                  Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
TRTPN    LSMeans, IDegLira    47.3145    48.9975        8.201E20        3.535E20        1.903E21
TRTPN    LSMeans, IDeg       53.4599    55.8519        5.454E23        1.649E23        1.804E24
TRTPN    LSMeans, Lira        53.8324    56.2152         7.88E23        2.394E23        2.594E24
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -6.4999     0.7453     715     -8.72
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -7.9631   -5.0367       0.001504
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - IDeg       0.000348         0.006495
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
10 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -6.8678     0.7428     715     -9.25
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - Lira    <.0001    0.05   -8.3262   -5.4094       0.001041
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - Lira       0.000242         0.004474
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
11 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
TRTPN           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5548
           Fit Statistics
-2 Res Log Likelihood          1635.3
AIC (Smaller is Better)        1637.3
AICC (Smaller is Better)       1637.3
BIC (Smaller is Better)        1641.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.5634     0.2879    715     15.85     <.0001     0.05
TRTPN                         1            -0.6283    0.06796    715     -9.25     <.0001     0.05
TRTPN                         2           -0.03366    0.07869    715     -0.43     0.6690     0.05
TRTPN                         3                  0                                                
PREOAD2     Metformin                      -0.3922    0.05944    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6662    0.03413    715    -19.52     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
12 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   3.9982      5.1287
TRTPN                         1            -0.7618     -0.4949
TRTPN                         2            -0.1882      0.1208
TRTPN                         3                               
PREOAD2     Metformin                      -0.5089     -0.2755
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7332     -0.5992
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715     380.96    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
TRTPN   Change from baseline, IDegLira  WORK.ADATA2   -1.6769   0.03921    715   -42.76    <.0001
TRTPN   Change from baseline, IDeg      WORK.ADATA2   -1.0822   0.05574    715   -19.42    <.0001
TRTPN   Change from baseline, Lira      WORK.ADATA2   -1.0485   0.05552    715   -18.89    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
TRTPN   Change from baseline, IDegLira    0.05     -1.7539     -1.5999
TRTPN   Change from baseline, IDeg        0.05     -1.1916     -0.9728
TRTPN   Change from baseline, Lira        0.05     -1.1575     -0.9395
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
13 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
TRTPN           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual     66.2773
           Fit Statistics
-2 Res Log Likelihood          5060.0
AIC (Smaller is Better)        5062.0
AICC (Smaller is Better)       5062.0
BIC (Smaller is Better)        5066.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  34.2233     2.3673    715     14.46     <.0001     0.05
TRTPN                         1            -6.8678     0.7428    715     -9.25     <.0001     0.05
TRTPN                         2            -0.3679     0.8601    715     -0.43     0.6690     0.05
TRTPN                         3                  0                                                
PREOAD2     Metformin                      -4.2869     0.6497    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6662    0.03413    715    -19.52     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
14 of 412
HbA1c after 26 weeks of treatment - change from baseline - confirmatory statistical analysis - full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  29.5757     38.8709
TRTPN                         1            -8.3262     -5.4094
TRTPN                         2            -2.0566      1.3207
TRTPN                         3                               
PREOAD2     Metformin                      -5.5625     -3.0113
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7332     -0.5992
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715     380.96    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
TRTPN   Change from baseline, IDegLira  WORK.ADATA2  -18.3282    0.4286    715   -42.76    <.0001
TRTPN   Change from baseline, IDeg      WORK.ADATA2  -11.8284    0.6092    715   -19.42    <.0001
TRTPN   Change from baseline, Lira      WORK.ADATA2  -11.4604    0.6068    715   -18.89    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
TRTPN   Change from baseline, IDegLira    0.05    -19.1697    -17.4868
TRTPN   Change from baseline, IDeg        0.05    -13.0244    -10.6323
TRTPN   Change from baseline, Lira        0.05    -12.6519    -10.2690
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
15 of 412
3: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per 
protocol analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.4940
           Fit Statistics
-2 Res Log Likelihood          1453.8
AIC (Smaller is Better)        1455.8
AICC (Smaller is Better)       1455.8
BIC (Smaller is Better)        1460.3
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.7125     0.2803    669     16.81     <.0001     0.05
trtan                         1            -0.5903    0.06726    669     -8.78     <.0001     0.05
trtan                         2           -0.00164    0.07752    669     -0.02     0.9832     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                      -0.3963    0.05779    669     -6.86     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3060    0.03321    669      9.21     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
16 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   4.1621      5.2628
trtan                         1            -0.7224     -0.4583
trtan                         2            -0.1538      0.1506
trtan                         3                               
PREOAD2     Metformin                      -0.5097     -0.2828
PREOAD2     Metformin + OAD                                   
BASE                                        0.2408      0.3712
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      59.18    <.0001
PREOAD2         1     669      47.01    <.0001
BASE            1     669      84.90    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2     6.5112    0.03790     669    171.78     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2     7.0999    0.05398     669    131.54     <.0001     0.05
trtan    LSMeans, Lira       WORK.ADATA2     7.1016    0.05558     669   127.78     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira     6.4368     6.5856          672.65          624.40          724.62
trtan    LSMeans, IDeg         6.9939     7.2059         1211.88         1090.02         1347.38
trtan    LSMeans, Lira         6.9924     7.2107         1213.87         1088.37         1353.83
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.5887    0.06599     669     -8.92
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -0.7183   -0.4591         0.5550
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg         0.4876           0.6318
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
17 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=C64849B
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -0.5903    0.06726     669     -8.78
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - Lira    <.0001    0.05   -0.7224   -0.4583         0.5541
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - Lira         0.4856           0.6324
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
18 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual     59.0097
           Fit Statistics
-2 Res Log Likelihood          4658.5
AIC (Smaller is Better)        4660.5
AICC (Smaller is Better)       4660.5
BIC (Smaller is Better)        4665.0
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  35.1977     2.3063    669     15.26     <.0001     0.05
trtan                         1            -6.4525     0.7351    669     -8.78     <.0001     0.05
trtan                         2           -0.01787     0.8472    669     -0.02     0.9832     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                      -4.3311     0.6317    669     -6.86     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3060    0.03321    669      9.21     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
19 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  30.6693     39.7261
trtan                         1            -7.8959     -5.0090
trtan                         2            -1.6814      1.6457
trtan                         3                               
PREOAD2     Metformin                      -5.5714     -3.0908
PREOAD2     Metformin + OAD                                   
BASE                                        0.2408      0.3712
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      59.18    <.0001
PREOAD2         1     669      47.01    <.0001
BASE            1     669      84.90    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2    47.6677     0.4143     669    115.06     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2    54.1023     0.5900     669     91.71     <.0001     0.05
trtan    LSMeans, Lira       WORK.ADATA2    54.1201     0.6075     669     89.09     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira    46.8542    48.4811        5.033E20        2.231E20        1.135E21
trtan    LSMeans, IDeg        52.9439    55.2606        3.136E23        9.845E22        9.986E23
trtan    LSMeans, Lira        52.9274    55.3129        3.192E23        9.684E22        1.052E24
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -6.4346     0.7213     669     -8.92
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -7.8508   -5.0183       0.001605
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg       0.000389         0.006615
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
20 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -6.4525     0.7351     669     -8.78
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - Lira    <.0001    0.05   -7.8959   -5.0090       0.001577
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - Lira       0.000372         0.006678
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
21 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.4940
           Fit Statistics
-2 Res Log Likelihood          1453.8
AIC (Smaller is Better)        1455.8
AICC (Smaller is Better)       1455.8
BIC (Smaller is Better)        1460.3
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.7125     0.2803    669     16.81     <.0001     0.05
trtan                         1            -0.5903    0.06726    669     -8.78     <.0001     0.05
trtan                         2           -0.00164    0.07752    669     -0.02     0.9832     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                      -0.3963    0.05779    669     -6.86     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6940    0.03321    669    -20.90     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
22 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   4.1621      5.2628
trtan                         1            -0.7224     -0.4583
trtan                         2            -0.1538      0.1506
trtan                         3                               
PREOAD2     Metformin                      -0.5097     -0.2828
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7592     -0.6288
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      59.18    <.0001
PREOAD2         1     669      47.01    <.0001
BASE            1     669     436.75    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2   -1.7233   0.03790    669   -45.47    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2   -1.1346   0.05398    669   -21.02    <.0001
trtan   Change from baseline, Lira     WORK.ADATA2   -1.1330   0.05558    669   -20.39    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -1.7978     -1.6489
trtan   Change from baseline, IDeg        0.05     -1.2406     -1.0287
trtan   Change from baseline, Lira        0.05     -1.2421     -1.0239
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
23 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      59.0097
           Fit Statistics
-2 Res Log Likelihood          4658.5
AIC (Smaller is Better)        4660.5
AICC (Smaller is Better)       4660.5
BIC (Smaller is Better)        4665.0
                                    Solution for Fixed Effects
                              Actual
                             Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  35.1977     2.3063    669     15.26     <.0001     0.05
trtan                         1            -6.4525     0.7351    669     -8.78     <.0001     0.05
trtan                         2           -0.01787     0.8472    669     -0.02     0.9832     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                      -4.3311     0.6317    669     -6.86     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6940    0.03321    669    -20.90     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
24 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - per
protocol analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  30.6693     39.7261
trtan                         1            -7.8959     -5.0090
trtan                         2            -1.6814      1.6457
trtan                         3                               
PREOAD2     Metformin                      -5.5714     -3.0908
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7592     -0.6288
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      59.18    <.0001
PREOAD2         1     669      47.01    <.0001
BASE            1     669     436.75    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2  -18.8362    0.4143    669   -45.47    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2  -12.4016    0.5900    669   -21.02    <.0001
trtan   Change from baseline, Lira      WORK.ADATA2  -12.3837    0.6075    669   -20.39    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05    -19.6496    -18.0227
trtan   Change from baseline, IDeg        0.05    -13.5600    -11.2432
trtan   Change from baseline, Lira        0.05    -13.5765    -11.1910
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
25 of 412
4: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.4598
           Fit Statistics
-2 Res Log Likelihood          1374.9
AIC (Smaller is Better)        1376.9
AICC (Smaller is Better)       1376.9
BIC (Smaller is Better)        1381.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.8534     0.2736    654     17.74     <.0001    0.05
trtpn                         1            -0.5474    0.06629    654     -8.26     <.0001     0.05
trtpn                         2            0.02449    0.07622    654      0.32     0.7481     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.4131    0.05637    654     -7.33     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.2840    0.03241    654      8.77     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
26 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   4.3162      5.3906
trtpn                         1            -0.6776     -0.4173
trtpn                         2            -0.1252      0.1742
trtpn                         3                               
PREOAD2     Metformin                      -0.5238     -0.3025
PREOAD2     Metformin + OAD                                   
BASE                                        0.2204      0.3477
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      56.18    <.0001
PREOAD2         1     654      53.71    <.0001
BASE            1     654      76.83    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     6.5085    0.03673     654    177.21     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     7.0805    0.05252     654    134.81     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     7.0560    0.05520     654    127.83     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     6.4364     6.5807          670.84          624.16          721.01
trtpn    LSMeans, IDeg         6.9773     7.1836         1188.52         1072.06         1317.64
trtpn    LSMeans, Lira         6.9476     7.1644         1159.77         1040.64         1292.54
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.5719    0.06411     654     -8.92
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -0.6978   -0.4460         0.5644
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4977           0.6402
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
27 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C64849B
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -0.5474    0.06629     654     -8.26
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -0.6776   -0.4173         0.5784
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.5078           0.6588
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
28 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      54.9347
           Fit Statistics
-2 Res Log Likelihood          4507.8
AIC (Smaller is Better)        4509.8
AICC (Smaller is Better)       4509.8
BIC (Smaller is Better)        4514.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  36.2227     2.2522    654     16.08     <.0001     0.05
trtpn                         1            -5.9836     0.7246    654     -8.26     <.0001     0.05
trtpn                         2             0.2677     0.8331    654      0.32     0.7481     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.5157     0.6162    654     -7.33     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.2840    0.03241    654      8.77     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
29 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  31.8002     40.6451
trtpn                         1            -7.4064     -4.5608
trtpn                         2            -1.3682      1.9036
trtpn                         3                               
PREOAD2     Metformin                      -5.7256     -3.3058
PREOAD2     Metformin + OAD                                   
BASE                                        0.2204      0.3477
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      56.18    <.0001
PREOAD2         1     654      53.71    <.0001
BASE            1     654      76.83    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    47.6382     0.4014     654    118.67     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    53.8895     0.5741     654     93.87     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    53.6218     0.6033     654     88.88     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    46.8500    48.4265        4.887E20        2.222E20        1.075E21
trtpn    LSMeans, IDeg        52.7623    55.0167        2.535E23        8.211E22        7.825E23
trtpn    LSMeans, Lira        52.4372    54.8065        1.939E23        5.932E22        6.341E23
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -6.2513     0.7007     654     -8.92
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -7.6272   -4.8753       0.001928
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.000487         0.007633
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
30 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -5.9836     0.7246     654     -8.26
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -7.4064   -4.5608       0.002520
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira       0.000607          0.01045
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
31 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.4598
           Fit Statistics
-2 Res Log Likelihood          1374.9
AIC (Smaller is Better)        1376.9
AICC (Smaller is Better)       1376.9
BIC (Smaller is Better)        1381.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.8534     0.2736    654     17.74     <.0001     0.05
trtpn                         1            -0.5474    0.06629    654     -8.26     <.0001     0.05
trtpn                         2            0.02449    0.07622    654      0.32     0.7481     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.4131    0.05637    654     -7.33     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.7160    0.03241    654    -22.09     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
32 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   4.3162      5.3906
trtpn                         1            -0.6776     -0.4173
trtpn                         2            -0.1252      0.1742
trtpn                         3                               
PREOAD2     Metformin                      -0.5238     -0.3025
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7796     -0.6523
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      56.18    <.0001
PREOAD2         1     654      53.71    <.0001
BASE            1     654     488.10    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -1.7247   0.03673    654   -46.96    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -1.1528   0.05252    654   -21.95    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -1.1773   0.05520    654   -21.33    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -1.7968     -1.6526
trtpn   Change from baseline, IDeg        0.05     -1.2559     -1.0496
trtpn   Change from baseline, Lira        0.05     -1.2856     -1.0689
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
33 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual     54.9347
           Fit Statistics
-2 Res Log Likelihood          4507.8
AIC (Smaller is Better)        4509.8
AICC (Smaller is Better)       4509.8
BIC (Smaller is Better)        4514.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  36.2227     2.2522    654     16.08     <.0001     0.05
trtpn                         1            -5.9836     0.7246    654     -8.26     <.0001     0.05
trtpn                         2             0.2677     0.8331    654      0.32     0.7481     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.5157     0.6162    654     -7.33     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.7160    0.03241    654    -22.09     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
34 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 31.8002     40.6451
trtpn                         1            -7.4064     -4.5608
trtpn                         2            -1.3682      1.9036
trtpn                         3                               
PREOAD2     Metformin                      -5.7256     -3.3058
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7796     -0.6523
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      56.18    <.0001
PREOAD2         1     654      53.71    <.0001
BASE            1     654     488.10    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -18.8510    0.4014    654   -46.96    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -12.5997    0.5741    654   -21.95    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2  -12.8674    0.6033    654   -21.33    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -19.6393    -18.0627
trtpn   Change from baseline, IDeg        0.05    -13.7269    -11.4725
trtpn   Change from baseline, Lira        0.05    -14.0521    -11.6827
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
35 of 412
5: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM 
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
AVISITN         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
36 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
37 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
38 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4041
Number of Observations Not Used         279
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
39 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1      7781.56844929                
        1              3      2512.22254080      0.00036020
        2              1      2511.34737835      0.00000107
        3              1      2511.34477278      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      
UN(2,1)     SUBJID      
UN(2,2)     SUBJID      
UN(3,1)     SUBJID      
UN(3,2)     SUBJID      
UN(3,3)     SUBJID      
UN(4,1)     SUBJID      
UN(4,2)     SUBJID      
UN(4,3)     SUBJID      
UN(4,4)     SUBJID      
UN(5,1)     SUBJID      
UN(5,2)     SUBJID      
UN(5,3)     SUBJID      
UN(5,4)     SUBJID      
UN(5,5)     SUBJID      
UN(6,1)     SUBJID      
UN(6,2)     SUBJID      
UN(6,3)     SUBJID      
UN(6,4)     SUBJID      
UN(6,5)     SUBJID      
UN(6,6)     SUBJID      
           Fit Statistics
-2 Res Log Likelihood          2511.3
AIC (Smaller is Better)        2553.3
AICC (Smaller is Better)       2553.6
BIC (Smaller is Better)        2649.5
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       5270.22          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)      12     828      18.08    <.0001
PREOAD2(AVISITN)       6     668      10.71    <.0001
BASE(AVISITN)          6     670     308.22    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
40 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                                 Least Squares Means Estimates
                                                              Standard
Effect            Label              Margins        Estimate     Error     DF  t Value  Pr > |t|
TRT01PN(AVISITN)  LSMeans, IDegLira  WORK.ANA_DATA    6.5097   0.03704  658.2   175.76    <.0001
TRT01PN(AVISITN)  LSMeans, IDeg      WORK.ANA_DATA    7.1047   0.05281  660.9   134.54    <.0001
TRT01PN(AVISITN)  LSMeans, Lira      WORK.ANA_DATA    7.1015   0.05446  683.2   130.40    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(AVISITN)  LSMeans, IDegLira    0.05      6.4370      6.5825
TRT01PN(AVISITN)  LSMeans, IDeg        0.05      7.0011      7.2084
TRT01PN(AVISITN)  LSMeans, Lira        0.05      6.9946      7.2085
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
41 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
AVISITN         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
42 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
43 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
44 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4041
Number of Observations Not Used         279
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
45 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     26994.97025107                
        1              3     21725.62434258      0.00012195
        2              1     21724.74918014      0.00000036
        3              1     21724.74657456      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID     
UN(2,1)     SUBJID     
UN(2,2)     SUBJID     
UN(3,1)     SUBJID     
UN(3,2)     SUBJID     
UN(3,3)     SUBJID     
UN(4,1)     SUBJID     
UN(4,2)     SUBJID     
UN(4,3)     SUBJID     
UN(4,4)     SUBJID     
UN(5,1)     SUBJID     
UN(5,2)     SUBJID     
UN(5,3)     SUBJID     
UN(5,4)     SUBJID     
UN(5,5)     SUBJID     
UN(6,1)     SUBJID     
UN(6,2)     SUBJID     
UN(6,3)     SUBJID     
UN(6,4)     SUBJID     
UN(6,5)     SUBJID     
UN(6,6)     SUBJID     
           Fit Statistics
-2 Res Log Likelihood         21724.7
AIC (Smaller is Better)       21766.7
AICC (Smaller is Better)      21767.0
BIC (Smaller is Better)       21862.9
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       5270.22          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)      12     828      18.08    <.0001
PREOAD2(AVISITN)       6     668      10.71    <.0001
BASE(AVISITN)          6     670     308.22    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
46 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                                 Least Squares Means Estimates
                                                              Standard
Effect            Label              Margins        Estimate     Error     DF  t Value  Pr > |t|
TRT01PN(AVISITN)  LSMeans, IDegLira  WORK.ANA_DATA   47.6513    0.4048  658.2   117.71    <.0001
TRT01PN(AVISITN)  LSMeans, IDeg      WORK.ANA_DATA   54.1549    0.5772  660.9    93.83    <.0001
TRT01PN(AVISITN)  LSMeans, Lira      WORK.ANA_DATA   54.1197    0.5952  683.2    90.92    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(AVISITN)  LSMeans, IDegLira    0.05     46.8564     48.4462
TRT01PN(AVISITN)  LSMeans, IDeg        0.05     53.0216     55.2882
TRT01PN(AVISITN)  LSMeans, Lira        0.05     52.9510     55.2884
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
47 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           CHG                      
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
AVISITN         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
48 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
49 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
50 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4041
Number of Observations Not Used         279
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
51 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1      7781.56844929                
        1              3      2512.22254080      0.00036020
        2              1      2511.34737835      0.00000107
        3              1      2511.34477278      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      
UN(2,1)     SUBJID      
UN(2,2)     SUBJID      
UN(3,1)     SUBJID      
UN(3,2)     SUBJID      
UN(3,3)     SUBJID      
UN(4,1)     SUBJID      
UN(4,2)     SUBJID      
UN(4,3)     SUBJID      
UN(4,4)     SUBJID      
UN(5,1)     SUBJID      
UN(5,2)     SUBJID      
UN(5,3)     SUBJID      
UN(5,4)     SUBJID      
UN(5,5)     SUBJID      
UN(6,1)     SUBJID      
UN(6,2)     SUBJID      
UN(6,3)     SUBJID      
UN(6,4)     SUBJID      
UN(6,5)     SUBJID      
UN(6,6)     SUBJID      
           Fit Statistics
-2 Res Log Likelihood          2511.3
AIC (Smaller is Better)        2553.3
AICC (Smaller is Better)       2553.6
BIC (Smaller is Better)        2649.5
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       5270.22          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)      12     828      18.08    <.0001
PREOAD2(AVISITN)       6     668      10.71    <.0001
BASE(AVISITN)          6     670      83.04    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
52 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                           Standard
Effect            Label                           Margins        Estimate     Error     DF  t Value
TRT01PN(AVISITN)  Change from baseline, IDegLira  WORK.ANA_DATA   -1.7275   0.03704  658.2   -46.64
TRT01PN(AVISITN)  Change from baseline, IDeg      WORK.ANA_DATA   -1.1325   0.05281  660.9   -21.45
TRT01PN(AVISITN)  Change from baseline, Lira      WORK.ANA_DATA   -1.1357   0.05446  683.2   -20.85
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(AVISITN)  Change from baseline, IDegLira    <.0001      0.05     -1.8002     -1.6548
TRT01PN(AVISITN)  Change from baseline, IDeg        <.0001      0.05     -1.2362     -1.0288
TRT01PN(AVISITN)  Change from baseline, Lira        <.0001      0.05     -1.2426     -1.0288
                                  Least Squares Means Estimates
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -0.5950    0.06453   659.9
TRT01PN(AVISITN)  Treatment contrast, IDegLira - Lira  WORK.ANA_DATA    -0.5918    0.06585   675.3
                                   Least Squares Means Estimates
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg    -9.22    <.0001    0.05   -0.7217   -0.4683
TRT01PN(AVISITN)  Treatment contrast, IDegLira - Lira    -8.99    <.0001    0.05   -0.7211   -0.4625
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           CHG                      
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
AVISITN         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
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NN9068
CONFIDENTIAL
Date:
16 December 2019
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Version:
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
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56 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4041
Number of Observations Not Used         279
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     26994.97025107                
        1              3     21725.62434258      0.00012195
        2              1     21724.74918014      0.00000036
        3              1     21724.74657456      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID     
UN(2,1)     SUBJID     
UN(2,2)     SUBJID     
UN(3,1)     SUBJID     
UN(3,2)     SUBJID     
UN(3,3)     SUBJID     
UN(4,1)     SUBJID     
UN(4,2)     SUBJID     
UN(4,3)     SUBJID     
UN(4,4)     SUBJID     
UN(5,1)     SUBJID     
UN(5,2)     SUBJID     
UN(5,3)     SUBJID     
UN(5,4)     SUBJID     
UN(5,5)     SUBJID     
UN(6,1)     SUBJID     
UN(6,2)     SUBJID     
UN(6,3)     SUBJID     
UN(6,4)     SUBJID     
UN(6,5)     SUBJID     
UN(6,6)     SUBJID     
           Fit Statistics
-2 Res Log Likelihood         21724.7
AIC (Smaller is Better)       21766.7
AICC (Smaller is Better)      21767.0
BIC (Smaller is Better)       21862.9
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       5270.22          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)      12     828      18.08    <.0001
PREOAD2(AVISITN)       6     668      10.71    <.0001
BASE(AVISITN)          6     670      83.04    <.0001
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis - MMRM
- full analysis set
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                           Standard
Effect            Label                           Margins        Estimate     Error     DF  t Value
TRT01PN(AVISITN)  Change from baseline, IDegLira  WORK.ANA_DATA  -18.8815    0.4048  658.2   -46.64
TRT01PN(AVISITN)  Change from baseline, IDeg      WORK.ANA_DATA  -12.3779    0.5772  660.9   -21.45
TRT01PN(AVISITN)  Change from baseline, Lira      WORK.ANA_DATA  -12.4131    0.5952  683.2   -20.85
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(AVISITN)  Change from baseline, IDegLira    <.0001      0.05    -19.6764    -18.0866
TRT01PN(AVISITN)  Change from baseline, IDeg        <.0001      0.05    -13.5112    -11.2446
TRT01PN(AVISITN)  Change from baseline, Lira        <.0001      0.05    -13.5818    -11.2444
                                  Least Squares Means Estimates
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -6.5036     0.7053   659.9
TRT01PN(AVISITN)  Treatment contrast, IDegLira - Lira  WORK.ANA_DATA    -6.4683     0.7197   675.3
                                   Least Squares Means Estimates
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg    -9.22    <.0001    0.05   -7.8885   -5.1186
TRT01PN(AVISITN)  Treatment contrast, IDegLira - Lira    -8.99    <.0001    0.05   -7.8815   -5.0552
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Statistical document
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6: HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000195       0.002826       0.003022   238192
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.069246       0.064770       0.999935
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.103584       0.054969   6.995846   7.211322   238192       7.062800       7.156116
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             129.23     <.0001
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate      0.000084942       0.001399       0.001484   304281
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.060781       0.057305       0.999943
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        6.548286       0.038522   6.472785   6.623788   304281       6.518629       6.575295
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             169.99     <.0001
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000425       0.002804       0.003230    57506
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.151813       0.131833       0.999868
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.107344       0.056832   6.995953   7.218735    57506       7.045183       7.178137
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             125.06     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.023354       0.337598       0.360976   238192
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.069246       0.064770       0.999935
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       54.142174       0.600812   52.96460   55.31975   238192      53.696405      54.716345
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              90.11     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.010148       0.167118       0.177276   304281
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.060781      0.057305       0.999943
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       48.072770       0.421042   47.24754   48.89800   304281      47.748618      48.367977
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             114.18     <.0001
CONFIDENTIAL


NN9068
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.050806       0.334999       0.385856    57506
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.151813       0.131833       0.999868
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       54.183273       0.621173   52.96577   55.40078    57506      53.503846      54.957040
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              87.23     <.0001
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000195       0.002826       0.003022   238192
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.069246       0.064770       0.999935
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.129194       0.054969   -1.23693   -1.02146   238192      -1.169978      -1.076662
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.54     <.0001
CONFIDENTIAL


NN9068
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate      0.000084942       0.001399       0.001484   304281
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.060781       0.057305       0.999943
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.684491       0.038522   -1.75999   -1.60899   304281      -1.714149      -1.657483
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -43.73     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000425       0.002804       0.003230    57506
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.151813       0.131833       0.999868
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.125433       0.056832   -1.23682   -1.01404    57506      -1.187595      -1.054641
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -19.80     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=12 Parameter Code=C64849B Label=Treatment contrast, IDegLira - IDeg 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000265       0.004230       0.004495   286688
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.062734       0.059037       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -0.555298       0.067045   -0.68670   -0.42389   286688      -0.609658      -0.503912
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -8.28     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Final
Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.023354       0.337598       0.360976   238192
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.069246       0.064770       0.999935
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -12.342087       0.600812   -13.5197   -11.1645   238192     -12.787856     -11.767916
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.54     <.0001
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.010148       0.167118       0.177276   304281
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.060781       0.057305       0.999943
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -18.411491       0.421042   -19.2367   -17.5863   304281     -18.735643     -18.116284
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -43.73     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
71 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.050806       0.334999       0.385856    57506
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.151813       0.131833       0.999868
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -12.300988       0.621173   -13.5185   -11.0835    57506     -12.980415     -11.527221
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -19.80     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
72 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=22 Parameter Code=HBA1CONV Label=Treatment contrast, IDegLira - IDeg 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.031667       0.505294       0.536993   286688
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.062734       0.059037       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -6.069404       0.732798   -7.50567   -4.63314   286688      -6.663557      -5.507762
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -8.28     <.0001
CONFIDENTIAL


NN9068
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Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
73 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000194       0.002751       0.002945   229712
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.070602       0.065955       0.999934
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.103029       0.054266   6.996669   7.209389   229712       7.062298       7.155185
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             130.89     <.0001
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
74 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate      0.000072517       0.001362       0.001434   389972
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.053312      0.050618       0.999949
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        6.532857       0.037871   6.458631   6.607083   389972       6.505273       6.557992
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             172.50     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
75 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000425       0.002729       0.003155    54889
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.155948       0.134940       0.999865
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.107487       0.056170   6.997393   7.217581    54889       7.045149       7.178158
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             126.54     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
76 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.023177       0.328601       0.351801   229712
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.070602       0.065955       0.999934
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       54.136108       0.593128   52.97359   55.29862   229712      53.690920      54.706169
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              91.27     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
77 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.008663      0.162664       0.171336   389972
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.053312       0.050618       0.999949
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       47.904126       0.413928   47.09284   48.71541   389972      47.602638      48.178854
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             115.73     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
78 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.050799       0.326071       0.376921    54889
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.155948       0.134940       0.999865
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       54.184834       0.613939   52.98151   55.38816    54889      53.503476      54.957268
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              88.26     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
79 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000194       0.002751       0.002945   229712
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.070602       0.065955       0.999934
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.129749       0.054266   -1.23611   -1.02339   229712      -1.170480      -1.077593
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.82     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
80 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate      0.000072517       0.001362       0.001434   389972
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.053312       0.050618       0.999949
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.699921       0.037871   -1.77415   -1.62570   389972      -1.727504      -1.674786
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -44.89     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
81 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000425       0.002729       0.003155    54889
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.155948      0.134940       0.999865
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.125291       0.056170   -1.23538   -1.01520    54889      -1.187629      -1.054620
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.03     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
82 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=13 Parameter Code=C64849B Label=Treatment contrast, IDegLira - Lira 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000498       0.004090       0.004588    84745
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.121798       0.108595       0.999891
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -0.574630       0.067735   -0.70739   -0.44187    84745      -0.643691      -0.509073
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -8.48     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
83 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.023177       0.328601       0.351801   229712
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.070602       0.065955       0.999934
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -12.348153       0.593128   -13.5107   -11.1856   229712     -12.793341     -11.778092
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.82     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
84 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.008663       0.162664       0.171336   389972
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.053312       0.050618       0.999949
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -18.580135       0.413928   -19.3914   -17.7688   389972     -18.881623     -18.305407
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -44.89     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
85 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.050799       0.326071       0.376921    54889
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.155948       0.134940       0.999865
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -12.299427       0.613939   -13.5028   -11.0961    54889     -12.980785     -11.526993
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -20.03     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
86 of 412
HbA1c after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
PARAM_ANA_SORT=23 Parameter Code=HBA1CONV Label=Treatment contrast, IDegLira - Lira 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.059450       0.488595       0.548105    84745
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.121798       0.108595       0.999891
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -6.280708       0.740341   -7.73177   -4.82965    84745      -7.035540      -5.564170
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -8.48     <.0001
CONFIDENTIAL


NN9068
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16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
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Statistical document
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7: HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full 
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5548
           Fit Statistics
-2 Res Log Likelihood          1635.3
AIC (Smaller is Better)        1637.3
AICC (Smaller is Better)       1637.3
BIC (Smaller is Better)        1641.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.5634     0.2879    715     15.85     <.0001     0.05
trtpn                         1            -0.6283    0.06796    715     -9.25     <.0001     0.05
trtpn                         2           -0.03366    0.07869    715     -0.43     0.6690     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.3922    0.05944    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3338    0.03413    715      9.78     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
88 of 412
HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   3.9982      5.1287
trtpn                         1            -0.7618     -0.4949
trtpn                         2            -0.1882      0.1208
trtpn                         3                               
PREOAD2     Metformin                      -0.5089     -0.2755
PREOAD2     Metformin + OAD                                   
BASE                                        0.2668      0.4008
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715      95.66    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     6.5559    0.03921     715    167.18     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     7.1506    0.05574     715    128.29     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     7.1842    0.05552     715    129.40     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     6.4789     6.6329          703.38          651.26          759.68
trtpn    LSMeans, IDeg         7.0412     7.2600         1274.85         1142.71         1422.27
trtpn    LSMeans, Lira         7.0752     7.2933         1318.50         1182.33         1470.34
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.5947    0.06819    715     -8.72
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -0.7286  -0.4608         0.5517
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4826           0.6308
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analysis set
Parameter Code=C64849B
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -0.6283    0.06796     715     -9.25
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -0.7618   -0.4949         0.5335
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.4668           0.6096
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      66.2773
           Fit Statistics
-2 Res Log Likelihood          5060.0
AIC (Smaller is Better)        5062.0
AICC (Smaller is Better)       5062.0
BIC (Smaller is Better)        5066.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  34.2233     2.3673    715     14.46     <.0001     0.05
trtpn                         1            -6.8678     0.7428    715     -9.25     <.0001     0.05
trtpn                         2            -0.3679     0.8601    715     -0.43     0.6690     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.2869     0.6497    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.3338    0.03413    715      9.78     <.0001     0.05
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 29.5757     38.8709
trtpn                         1            -8.3262     -5.4094
trtpn                         2            -2.0566      1.3207
trtpn                         3                               
PREOAD2     Metformin                      -5.5625     -3.0113
PREOAD2     Metformin + OAD                                   
BASE                                        0.2668      0.4008
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715      95.66    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    48.1560     0.4286     715    112.35     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    54.6559     0.6092     715     89.72     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    55.0238     0.6068     715     90.67     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    47.3145    48.9975        8.201E20        3.535E20        1.903E21
trtpn    LSMeans, IDeg        53.4599    55.8519        5.454E23        1.649E23        1.804E24
trtpn    LSMeans, Lira        53.8324    56.2152         7.88E23        2.394E23        2.594E24
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -6.4999     0.7453     715     -8.72
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -7.9631   -5.0367       0.001504
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.000348         0.006495
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -6.8678     0.7428     715     -9.25
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -8.3262   -5.4094       0.001041
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira       0.000242         0.004474
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NN9068
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5548
           Fit Statistics
-2 Res Log Likelihood          1635.3
AIC (Smaller is Better)        1637.3
AICC (Smaller is Better)       1637.3
BIC (Smaller is Better)        1641.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.5634     0.2879    715     15.85     <.0001     0.05
trtpn                         1            -0.6283    0.06796    715     -9.25     <.0001     0.05
trtpn                         2           -0.03366    0.07869    715     -0.43     0.6690     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.3922    0.05944    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6662    0.03413    715    -19.52     <.0001     0.05
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=C64849B
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   3.9982      5.1287
trtpn                         1            -0.7618     -0.4949
trtpn                         2            -0.1882      0.1208
trtpn                         3                               
PREOAD2     Metformin                      -0.5089     -0.2755
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7332     -0.5992
       Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715     380.96    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -1.6769   0.03921    715   -42.76    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -1.0822   0.05574    715   -19.42    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -1.0485   0.05552    715   -18.89    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -1.7539     -1.5999
trtpn   Change from baseline, IDeg        0.05     -1.1916     -0.9728
trtpn   Change from baseline, Lira        0.05     -1.1575     -0.9395
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NN9068
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      66.2773
           Fit Statistics
-2 Res Log Likelihood          5060.0
AIC (Smaller is Better)        5062.0
AICC (Smaller is Better)       5062.0
BIC (Smaller is Better)        5066.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  34.2233     2.3673    715     14.46     <.0001     0.05
trtpn                         1            -6.8678     0.7428    715     -9.25     <.0001     0.05
trtpn                         2            -0.3679     0.8601    715     -0.43     0.6690     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.2869     0.6497    715     -6.60     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.6662    0.03413    715    -19.52     <.0001     0.05
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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HbA1c after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set
Parameter Code=HBA1CONV
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 29.5757     38.8709
trtpn                         1            -8.3262     -5.4094
trtpn                         2            -2.0566      1.3207
trtpn                         3                               
PREOAD2     Metformin                      -5.5625     -3.0113
PREOAD2     Metformin + OAD                                   
BASE                                       -0.7332     -0.5992
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      60.69    <.0001
PREOAD2         1     715      43.53    <.0001
BASE            1     715     380.96    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -18.3282    0.4286    715   -42.76    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -11.8284    0.6092    715   -19.42    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2  -11.4604    0.6068    715   -18.89    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -19.1697    -17.4868
trtpn   Change from baseline, IDeg        0.05    -13.0244    -10.6323
trtpn   Change from baseline, Lira        0.05    -12.6519    -10.2690
CONFIDENTIAL


NN9068
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Statistical document
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8: Responder for HbA1c treatment target - supportive statistical analysis - full analysis set
Parameter Code=HBA_BL65
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    298
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              298
       2    N              422
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -412.3951                
Full Log Likelihood                    -412.3951                
AIC (smaller is better)                 834.7901                
AICC (smaller is better)                834.8741                
BIC (smaller is better)                 857.6864                
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    3.3360    0.8860    1.5994    5.0726       14.18      0.0002
trtpn      1                 1    1.5276    0.2163    1.1037    1.9514       49.90      <.0001
trtpn      2                 1    0.1533    0.2546   -0.3456    0.6522        0.36      0.5469
CONFIDENTIAL


NN9068
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Responder for HbA1c treatment target - supportive statistical analysis - full analysis set
Parameter Code=HBA_BL65
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    1.1477    0.1809    0.7933    1.5022       40.27      <.0001
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.6000    0.1074   -0.8105   -0.3894       31.19      <.0001
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira   0.4980      0.1204       4.14      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -0.8762      0.1800      -4.87      <.0001      0.05
trtpn   LSMeans frequency, Lira       -1.0295      0.1821      -5.65      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira    0.2621    0.7340         1.6455         1.2997         2.0833
trtpn   LSMeans frequency, IDeg       -1.2289   -0.5235         0.4164         0.2926         0.5925
trtpn   LSMeans frequency, Lira       -1.3864   -0.6727         0.3572         0.2500         0.5103
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.3742     0.2140      6.42     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     1.5276     0.2163      7.06     <.0001     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.9549      1.7936           3.9521
trtpn    Treatment odds ratio, IDegLira / Lira     1.1037      1.9514           4.6070
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          2.5984           6.0111
trtpn    Treatment odds ratio, IDegLira / Lira          3.0154           7.0387
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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Responder for HbA1c treatment target - supportive statistical analysis - full analysis set
Parameter Code=HBA_BL7
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    448
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              448
       2    N              272
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -402.2667                
Full Log Likelihood                    -402.2667                
AIC (smaller is better)                 814.5335                
AICC (smaller is better)                814.6175                
BIC (smaller is better)                 837.4297                
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    5.2013    0.9001    3.4371    6.9654       33.39      <.0001
trtpn      1                 1    1.4327    0.2089    1.0234    1.8420       47.06      <.0001
trtpn      2                 1   -0.0143    0.2262   -0.4576    0.4291        0.00      0.9497
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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Responder for HbA1c treatment target - supportive statistical analysis - full analysis set
Parameter Code=HBA_BL7
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    1.1167    0.1969    0.7307    1.5026       32.16      <.0001
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.6859    0.1082   -0.8979   -0.4739       40.22      <.0001
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira    1.5454      0.1465      10.55      <.0001      0.05
trtpn   LSMeans frequency, IDeg       0.09841      0.1657       0.59      0.5526      0.05
trtpn   LSMeans frequency, Lira        0.1127      0.1628       0.69      0.4889      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira    1.2582    1.8325         4.6897         3.5191         6.2497
trtpn   LSMeans frequency, IDeg       -0.2264    0.4232         1.1034         0.7974         1.5268
trtpn   LSMeans frequency, Lira       -0.2064    0.4317         1.1193         0.8135         1.5399
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.4470     0.2100      6.89     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     1.4327     0.2089      6.86     <.0001     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.0354      1.8585           4.2502
trtpn    Treatment odds ratio, IDegLira / Lira     1.0234      1.8420           4.1900
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          2.8163           6.4142
trtpn    Treatment odds ratio, IDegLira / Lira          2.7825           6.3095
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
101 of 412
9: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed 
hypoglycaemic episodes - supportive statistical analysis - full analysis set
Parameter Code=HB65CHY
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    284
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              284
       2    N              436
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                      
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -415.4484                
Full Log Likelihood                    -415.4484                
AIC (smaller is better)                 840.8968                
AICC (smaller is better)                840.9808                
BIC (smaller is better)                 863.7930                
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    2.7202    0.8796    0.9962    4.4441        9.56      0.0020
trtpn      1                 1    1.4477    0.2161    1.0242    1.8712       44.90      <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
102 of 412
Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes - supportive statistical analysis - full analysis set
Parameter Code=HB65CHY
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
trtpn      2                 1    0.1498    0.2562   -0.3523    0.6519        0.34      0.5587
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    1.0974    0.1785    0.7475    1.4473       37.79      <.0001
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.5290    0.1063   -0.7374   -0.3207       24.77      <.0001
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira    0.3613      0.1179       3.06      0.0022      0.05
trtpn   LSMeans frequency, IDeg       -0.9366      0.1807      -5.18      <.0001      0.05
trtpn   LSMeans frequency, Lira       -1.0864      0.1834      -5.92      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira    0.1302    0.5923         1.4352         1.1390         1.8082
trtpn   LSMeans frequency, IDeg       -1.2908   -0.5825         0.3920         0.2751         0.5585
trtpn   LSMeans frequency, Lira       -1.4458   -0.7270         0.3374         0.2356         0.4833
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2979     0.2134      6.08     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     1.4477     0.2161      6.70     <.0001     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.8796      1.7162           3.6616
trtpn    Treatment odds ratio, IDegLira / Lira     1.0242      1.8712           4.2533
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          2.4099           5.5632
trtpn    Treatment odds ratio, IDegLira / Lira          2.7849           6.4958
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
103 of 412
Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes - supportive statistical analysis - full analysis set
Parameter Code=HB7CHY
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    429
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              429
       2    N              291
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -422.3970                
Full Log Likelihood                    -422.3970                
AIC (smaller is better)                 854.7939                
AICC (smaller is better)                854.8780                
BIC (smaller is better)                 877.6902                
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    4.1765    0.8669    2.4773    5.8757       23.21      <.0001
trtpn      1                 1    1.2638    0.2022    0.8675    1.6600       39.08      <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
104 of 412
Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes - supportive statistical analysis - full analysis set
Parameter Code=HB7CHY
The GENMOD Procedure
                     Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
trtpn      2                 1   -0.0256    0.2239   -0.4644    0.4133        0.01      0.9091
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    1.0552    0.1883    0.6862    1.4243       31.40      <.0001
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.5676    0.1040   -0.7714   -0.3638       29.80      <.0001
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira    1.2949      0.1364       9.49      <.0001      0.05
trtpn   LSMeans frequency, IDeg      0.005601      0.1631       0.03      0.9726      0.05
trtpn   LSMeans frequency, Lira       0.03115      0.1606       0.19      0.8462      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira    1.0275    1.5623         3.6507         2.7941         4.7700
trtpn   LSMeans frequency, IDeg       -0.3142    0.3254         1.0056         0.7304         1.3845
trtpn   LSMeans frequency, Lira       -0.2836    0.3459         1.0316         0.7530         1.4133
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2893     0.2034      6.34     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     1.2638     0.2022      6.25     <.0001     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.8906      1.6881           3.6303
trtpn    Treatment odds ratio, IDegLira / Lira     0.8675      1.6600           3.5387
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          2.4365           5.4090
trtpn    Treatment odds ratio, IDegLira / Lira          2.3810           5.2593
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
105 of 412
10: Responder for HbA1c treatment target without weight gain - supportive statistical analysis - full 
analysis set
Parameter Code=HB65WOWG
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    169
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              169
       2    N              551
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
Prm8            WGTBL                                
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -365.5852                
Full Log Likelihood                    -365.5852                
AIC (smaller is better)                 743.1705                
AICC (smaller is better)                743.2883                
BIC (smaller is better)                 770.6460                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
106 of 412
Responder for HbA1c treatment target without weight gain - supportive statistical analysis - full
analysis set
Parameter Code=HB65WOWG
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    1.8407    1.1171   -0.3489    4.0302        2.71      0.0994
trtpn      1                 1    0.5428    0.2209    0.1097    0.9758        6.04      0.0140
trtpn      2                 1   -0.6440    0.3007   -1.2334   -0.0546        4.59      0.0322
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    0.4953    0.1891    0.1247    0.8660        6.86      0.0088
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.4657    0.1184   -0.6978   -0.2336       15.46      <.0001
WGTBL                        1    0.0056    0.0066   -0.0072    0.0185        0.73      0.3923
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira   -0.7874      0.1214      -6.48      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -1.9742      0.2366      -8.34      <.0001      0.05
trtpn   LSMeans frequency, Lira       -1.3302      0.1898      -7.01      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.0254   -0.5494         0.4550         0.3586         0.5773
trtpn   LSMeans frequency, IDeg       -2.4380   -1.5104         0.1389        0.08734         0.2208
trtpn   LSMeans frequency, Lira       -1.7021   -0.9582         0.2644         0.1823         0.3836
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.1867     0.2630      4.51     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     0.5428     0.2209      2.46     0.0140     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.6713      1.7021           3.2764
trtpn    Treatment odds ratio, IDegLira / Lira     0.1097      0.9758           1.7207
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          1.9569           5.4856
trtpn    Treatment odds ratio, IDegLira / Lira          1.1160           2.6532
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
107 of 412
Responder for HbA1c treatment target without weight gain - supportive statistical analysis - full
analysis set
Parameter Code=HBA7WOWG
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    255
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              255
       2    N              465
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
Prm8            WGTBL                                
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -443.5697                
Full Log Likelihood                    -443.5697                
AIC (smaller is better)                 899.1394                
AICC (smaller is better)                899.2572                
BIC (smaller is better)                 926.6149                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
108 of 412
Responder for HbA1c treatment target without weight gain - supportive statistical analysis - full
analysis set
Parameter Code=HBA7WOWG
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    2.8025    0.9850    0.8719    4.7331        8.09      0.0044
trtpn      1                 1   -0.0231    0.1881   -0.3918    0.3456        0.02      0.9024
trtpn      2                 1   -1.0805    0.2462   -1.5630   -0.5979       19.26      <.0001
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    0.2349    0.1710   -0.1003    0.5701        1.89      0.1696
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.3991    0.1024   -0.5999   -0.1983       15.18      <.0001
WGTBL                        1    0.0004    0.0059   -0.0111    0.0119        0.00      0.9458
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira   -0.3592      0.1129      -3.18      0.0015      0.05
trtpn   LSMeans frequency, IDeg       -1.4167      0.1942      -7.29      <.0001      0.05
trtpn   LSMeans frequency, Lira       -0.3362      0.1562      -2.15      0.0314      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -0.5805   -0.1380         0.6982         0.5596         0.8711
trtpn   LSMeans frequency, IDeg       -1.7973   -1.0360         0.2425         0.1657         0.3549
trtpn   LSMeans frequency, Lira       -0.6423  -0.03007         0.7145         0.5261         0.9704
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.0574     0.2213      4.78     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira   -0.02307     0.1881     -0.12     0.9024     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.6237      1.4911          2.8789
trtpn    Treatment odds ratio, IDegLira / Lira    -0.3918      0.3456           0.9772
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          1.8658           4.4421
trtpn    Treatment odds ratio, IDegLira / Lira          0.6759           1.4129
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
109 of 412
11: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed 
hypoglycaemic episodes and weight gain - supportive statistical analysis - full analysis set
Parameter Code=H65WOCHY
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    160
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              160
       2    N              560
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                      
Prm3            trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
Prm8            WGTBL                                
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -359.6463                
Full Log Likelihood                    -359.6463                
AIC (smaller is better)                 731.2926                
AICC (smaller is better)                731.4104                
BIC (smaller is better)                 758.7681                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
110 of 412
Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes and weight gain - supportive statistical analysis - full analysis set
Parameter Code=H65WOCHY
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    1.4599    1.1291   -0.7530    3.6729        1.67      0.1960
trtpn      1                 1    0.4667    0.2232    0.0292    0.9041        4.37      0.0366
trtpn      2                 1   -0.6089    0.3013   -1.1994   -0.0184        4.08      0.0433
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    0.4783    0.1912    0.1036    0.8531        6.26      0.0124
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.4171    0.1192   -0.6508   -0.1833       12.23      0.0005
WGTBL                        1    0.0051    0.0066   -0.0079    0.0181        0.58      0.4450
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira   -0.8921      0.1233      -7.23      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -1.9677      0.2360      -8.34      <.0001      0.05
trtpn   LSMeans frequency, Lira       -1.3588      0.1911      -7.11      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.1338   -0.6504         0.4098         0.3218         0.5218
trtpn   LSMeans frequency, IDeg       -2.4303   -1.5050         0.1398        0.08801         0.2220
trtpn   LSMeans frequency, Lira       -1.7333   -0.9843         0.2570         0.1767         0.3737
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.0755     0.2634      4.08     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira     0.4667     0.2232      2.09     0.0366     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.5592      1.5919           2.9315
trtpn    Treatment odds ratio, IDegLira / Lira    0.02919      0.9041           1.5947
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          1.7492           4.9129
trtpn    Treatment odds ratio, IDegLira / Lira          1.0296           2.4698
CONFIDENTIAL


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Version:
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Statistical document
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Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes and weight gain - supportive statistical analysis - full analysis set
Parameter Code=HB7WOCHY
The GENMOD Procedure
                      Model Information
Data Set              WORK.ADATA2                             
Distribution             Binomial                             
Link Function               Logit                             
Dependent Variable          AVALC    Analysis Value (C)       
Number of Observations Read         720
Number of Observations Used         720
Number of Events                    241
Number of Trials                    720
             Class Level Information
Class        Levels    Values
trtpn             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              241
       2    N              479
PROC GENMOD is modeling the probability that AVALC='Y'.
                Parameter Information
Parameter       Effect       trtpn    PREOAD2
Prm1            Intercept                            
Prm2            trtpn        1                       
Prm3           trtpn        2                       
Prm4            trtpn        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
Prm7            HBA1CBL                              
Prm8            WGTBL                                
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -438.4315                
Full Log Likelihood                    -438.4315                
AIC (smaller is better)                 888.8631                
AICC (smaller is better)                888.9809                
BIC (smaller is better)                 916.3386                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
112 of 412
Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes and weight gain - supportive statistical analysis - full analysis set
Parameter Code=HB7WOCHY
The GENMOD Procedure
                      Analysis Of Maximum Likelihood Parameter Estimates
                                          Standard       Wald 95%             Wald
Parameter                   DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                    1    2.1921    0.9893    0.2532    4.1311        4.91      0.0267
trtpn      1                 1   -0.1069    0.1890   -0.4774    0.2636        0.32      0.5717
trtpn      2                 1   -1.0692    0.2478   -1.5549   -0.5836       18.62      <.0001
trtpn      3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2    Metformin         1    0.2598    0.1720   -0.0773    0.5968       2.28      0.1309
PREOAD2    Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
HBA1CBL                      1   -0.3417    0.1029   -0.5433   -0.1401       11.03      0.0009
WGTBL                        1    0.0016    0.0059   -0.0100    0.0131        0.07      0.7916
Scale                        0    1.0000    0.0000    1.0000    1.0000                        
NOTE: The scale parameter was held fixed.
                              Least Squares Means Estimates
                                                 Standard
Effect  Label                        Estimate       Error    z Value    Pr > |z|     Alpha
trtpn   LSMeans frequency, IDegLira   -0.4823      0.1139      -4.23      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -1.4447      0.1959      -7.37      <.0001      0.05
trtpn   LSMeans frequency, Lira       -0.3754      0.1564      -2.40      0.0164      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -0.7056   -0.2591         0.6173         0.4938         0.7718
trtpn   LSMeans frequency, IDeg       -1.8286   -1.0607         0.2358         0.1606         0.3462
trtpn   LSMeans frequency, Lira       -0.6820  -0.06891         0.6870         0.5056         0.9334
                                  Least Squares Means Estimates
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     0.9623     0.2234      4.31     <.0001     0.05
trtpn    Treatment odds ratio, IDegLira / Lira    -0.1069     0.1890     -0.57     0.5717     0.05
                            Least Squares Means Estimates
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     0.5244      1.4002           2.6177
trtpn    Treatment odds ratio, IDegLira / Lira    -0.4774      0.2636           0.8986
                         Least Squares Means Estimates
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          1.6894           4.0562
trtpn    Treatment odds ratio, IDegLira / Lira          0.6204           1.3016
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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12: Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis -
full analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.8139
           Fit Statistics
-2 Res Log Likelihood          3434.3
AIC (Smaller is Better)        3436.3
AICC (Smaller is Better)       3436.3
BIC (Smaller is Better)        3440.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -1.9302     0.5566    715     -3.47     0.0006     0.05
trtpn                         1             2.5706     0.2383    715     10.79     <.0001     0.05
trtpn                         2             3.6551     0.2756    715     13.26     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6254     0.2084    715      3.00     0.0028     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9906   0.007083    715    139.86     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
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Version:
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Clinical Trial Report
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Final
Statistical document
Page:
114 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 -3.0230     -0.8375
trtpn                         1             2.1028      3.0384
trtpn                         2             3.1140      4.1961
trtpn                         3                               
PREOAD2     Metformin                       0.2162      1.0347
PREOAD2     Metformin + OAD                                   
BASE                                        0.9767      1.0045
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      95.37    <.0001
PREOAD2         1     715       9.00    0.0028
BASE            1     715    19562.2    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    74.2782     0.1375     715    540.36     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    75.3627     0.1952     715    386.03     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    71.7076     0.1946     715    368.53     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    74.0083    74.5480        1.814E32        1.385E32        2.376E32
trtpn    LSMeans, IDeg        74.9794    75.7460        5.365E32        3.657E32        7.871E32
trtpn    LSMeans, Lira        71.3256    72.0896        1.387E31        9.469E30        2.033E31
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.0845     0.2389     715     -4.54
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.5535   -0.6155         0.3381
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.2115           0.5404
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
Page:
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Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=C25208X
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     2.5706     0.2383     715     10.79
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05    2.1028    3.0384        13.0733
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         8.1888          20.8714
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
116 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      33.1179
           Fit Statistics
-2 Res Log Likelihood          4566.4
AIC (Smaller is Better)        4568.4
AICC (Smaller is Better)       4568.4
BIC (Smaller is Better)        4572.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.2554     1.2271    715     -3.47     0.0006     0.05
trtpn                         1             5.6671     0.5253    715     10.79     <.0001     0.05
trtpn                         2             8.0581     0.6075    715     13.26     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.3789     0.4595    715      3.00     0.0028     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9906   0.007083    715    139.86     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
117 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -6.6645     -1.8463
trtpn                         1             4.6358      6.6985
trtpn                         2             6.8653      9.2509
trtpn                         3                               
PREOAD2     Metformin                       0.4766      2.2811
PREOAD2     Metformin + OAD                                   
BASE                                        0.9767      1.0045
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      95.37    <.0001
PREOAD2         1     715       9.00    0.0028
BASE            1     715    19562.2    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     163.76     0.3030     715    540.36     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     166.15     0.4304     715    386.03     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     158.09     0.4290     715   368.53     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     163.16     164.35        1.312E71        7.238E70        2.379E71
trtpn    LSMeans, IDeg         165.30     166.99        1.434E72        6.158E71        3.337E72
trtpn    LSMeans, Lira         157.25     158.93        4.538E68        1.955E68        1.053E69
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.3909     0.5267     715     -4.54
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -3.4249   -1.3570        0.09154
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        0.03255           0.2574
CONFIDENTIAL


NN9068
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Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
118 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     5.6671     0.5253     715     10.79
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05    4.6358    6.6985         289.21
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         103.11           811.17
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
119 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.8139
           Fit Statistics
-2 Res Log Likelihood          3434.3
AIC (Smaller is Better)        3436.3
AICC (Smaller is Better)       3436.3
BIC (Smaller is Better)        3440.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -1.9302     0.5566    715     -3.47     0.0006     0.05
trtpn                         1             2.5706     0.2383    715     10.79     <.0001     0.05
trtpn                         2             3.6551     0.2756    715     13.26     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6254     0.2084    715      3.00     0.0028     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00938   0.007083    715     -1.32     0.1856     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
120 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -3.0230     -0.8375
trtpn                         1             2.1028      3.0384
trtpn                         2             3.1140      4.1961
trtpn                         3                               
PREOAD2     Metformin                       0.2162      1.0347
PREOAD2     Metformin + OAD                                   
BASE                                      -0.02329    0.004522
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      95.37    <.0001
PREOAD2         1     715       9.00    0.0028
BASE            1     715       1.76    0.1856
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.1480    0.1375    715     1.08    0.2819
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.2325    0.1952    715     6.31    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -2.4226    0.1946    715   -12.45    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira   0.05     -0.1219      0.4179
trtpn   Change from baseline, IDeg        0.05      0.8493      1.6158
trtpn   Change from baseline, Lira        0.05     -2.8046     -2.0405
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
121 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      33.1179
           Fit Statistics
-2 Res Log Likelihood          4566.4
AIC (Smaller is Better)        4568.4
AICC (Smaller is Better)       4568.4
BIC (Smaller is Better)        4572.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.2554     1.2271    715     -3.47     0.0006     0.05
trtpn                         1             5.6671     0.5253    715     10.79     <.0001     0.05
trtpn                         2             8.0581     0.6075    715     13.26     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.3789     0.4595    715      3.00     0.0028     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00938   0.007083    715     -1.32     0.1856     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
122 of 412
Body weight after 26 weeks of treatment - change from baseline - confirmatory statistical analysis
- full analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -6.6645     -1.8463
trtpn                         1             4.6358      6.6985
trtpn                         2             6.8653      9.2509
trtpn                         3                               
PREOAD2     Metformin                       0.4766      2.2811
PREOAD2     Metformin + OAD                                   
BASE                                      -0.02329    0.004522
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      95.37    <.0001
PREOAD2         1     715       9.00    0.0028
BASE            1     715       1.76    0.1856
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.3263    0.3030    715     1.08    0.2819
trtpn   Change from baseline, IDeg      WORK.ADATA2    2.7173    0.4304    715     6.31    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -5.3408    0.4290    715   -12.45    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.2686      0.9213
trtpn   Change from baseline, IDeg        0.05      1.8723      3.5623
trtpn   Change from baseline, Lira        0.05     -6.1830     -4.4986
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
123 of 412
13: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       7.0840
           Fit Statistics
-2 Res Log Likelihood          3241.1
AIC (Smaller is Better)        3243.1
AICC (Smaller is Better)       3243.1
BIC (Smaller is Better)        3247.6
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -2.1023     0.5882    669     -3.57     0.0004    0.05
trtan                         1             2.7218     0.2548    669     10.68     <.0001     0.05
trtan                         2             3.8575     0.2933    669     13.15     <.0001     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                       0.6458     0.2192    669      2.95     0.0033     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9910   0.007451    669    132.99     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
124 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -3.2572     -0.9475
trtan                         1             2.2216      3.2221
trtan                         2             3.2817      4.4334
trtan                         3                               
PREOAD2     Metformin                       0.2154      1.0762
PREOAD2     Metformin + OAD                                   
BASE                                        0.9764      1.0056
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      92.95    <.0001
PREOAD2         1     669       8.68    0.0033
BASE            1     669    17686.7    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2    74.3557     0.1436     669    517.92     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2    75.4914     0.2043     669    369.57     <.0001     0.05
trtan    LSMeans, Lira       WORK.ADATA2    71.6338     0.2104     669    340.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira    74.0738    74.6376         1.96E32        1.479E32        2.598E32
trtan    LSMeans, IDeg        75.0903    75.8924        6.102E32        4.086E32        9.113E32
trtan    LSMeans, Lira        71.2206    72.0471        1.289E31        8.526E30        1.948E31
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.1357     0.2498     669     -4.55
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.6262   -0.6452         0.3212
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg         0.1967           0.5245
CONFIDENTIAL


NN9068
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Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
125 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=C25208X
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - Lira  WORK.ADATA2     2.7218     0.2548     669     10.68
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - Lira    <.0001    0.05    2.2216    3.2221        15.2082
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - Lira         9.2217          25.0810
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
126 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                    
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      34.4308
           Fit Statistics
-2 Res Log Likelihood          4300.5
AIC (Smaller is Better)        4302.5
AICC (Smaller is Better)       4302.5
BIC (Smaller is Better)        4307.0
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.6348     1.2967    669     -3.57     0.0004     0.05
trtan                         1             6.0006     0.5617    669     10.68     <.0001     0.05
trtan                         2             8.5044     0.6465    669     13.15     <.0001     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                       1.4238     0.4832    669      2.95     0.0033     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9910   0.007451    669    132.99     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
127 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -7.1808     -2.0888
trtan                         1             4.8977      7.1035
trtan                         2             7.2349      9.7739
trtan                         3                               
PREOAD2     Metformin                       0.4750      2.3727
PREOAD2     Metformin + OAD                                   
BASE                                        0.9764      1.0056
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      92.95    <.0001
PREOAD2         1     669       8.68    0.0033
BASE            1     669    17686.7    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2     163.93     0.3165     669    517.92     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2     166.43     0.4503     669    369.57     <.0001     0.05
trtan    LSMeans, Lira       WORK.ADATA2     157.93     0.4640     669    340.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira     163.30     164.55        1.557E71        8.363E70        2.898E71
trtan    LSMeans, IDeg         165.55     167.31        1.904E72        7.863E71        4.609E72
trtan    LSMeans, Lira         157.01     158.84        3.857E68        1.551E68        9.591E68
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.5038     0.5507     669     -4.55
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -3.5850   -1.4225        0.08178
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg        0.02774           0.2411
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
128 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - Lira  WORK.ADATA2     6.0006     0.5617     669     10.68
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - Lira    <.0001    0.05    4.8977    7.1035         403.68
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - Lira         133.98          1216.26
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
129 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       7.0840
           Fit Statistics
-2 Res Log Likelihood          3241.1
AIC (Smaller is Better)        3243.1
AICC (Smaller is Better)       3243.1
BIC (Smaller is Better)        3247.6
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -2.1023     0.5882    669     -3.57     0.0004     0.05
trtan                         1             2.7218     0.2548    669     10.68     <.0001     0.05
trtan                         2             3.8575     0.2933    669     13.15     <.0001     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                       0.6458     0.2192    669      2.95     0.0033     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00902   0.007451    669     -1.21     0.2267     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
130 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -3.2572     -0.9475
trtan                         1             2.2216      3.2221
trtan                         2             3.2817      4.4334
trtan                         3                               
PREOAD2     Metformin                       0.2154      1.0762
PREOAD2     Metformin + OAD                                  
BASE                                      -0.02365    0.005614
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      92.95    <.0001
PREOAD2         1     669       8.68    0.0033
BASE            1     669       1.46    0.2267
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2    0.1632    0.1436    669     1.14    0.2559
trtan   Change from baseline, IDeg      WORK.ADATA2    1.2989    0.2043    669     6.36    <.0001
trtan   Change from baseline, Lira      WORK.ADATA2   -2.5586    0.2104    669   -12.16    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -0.1186      0.4451
trtan   Change from baseline, IDeg        0.05      0.8979      1.7000
trtan   Change from baseline, Lira        0.05     -2.9718     -2.1454
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
131 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtan           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             674
          Number of Observations
Number of Observations Read             674
Number of Observations Used             674
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      34.4308
           Fit Statistics
-2 Res Log Likelihood          4300.5
AIC (Smaller is Better)        4302.5
AICC (Smaller is Better)       4302.5
BIC (Smaller is Better)        4307.0
                                    Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.6348     1.2967    669     -3.57     0.0004     0.05
trtan                         1             6.0006     0.5617    669     10.68     <.0001     0.05
trtan                         2             8.5044     0.6465    669     13.15     <.0001     0.05
trtan                         3                  0                                                
PREOAD2     Metformin                       1.4238     0.4832    669      2.95     0.0033     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00902   0.007451    669     -1.21     0.2267     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
132 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
per protocol analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Actual
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -7.1808     -2.0888
trtan                         1             4.8977      7.1035
trtan                         2             7.2349      9.7739
trtan                         3                               
PREOAD2     Metformin                       0.4750      2.3727
PREOAD2     Metformin + OAD                                   
BASE                                      -0.02365    0.005614
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           2     669      92.95    <.0001
PREOAD2         1     669       8.68    0.0033
BASE            1     669       1.46    0.2267
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2    0.3599    0.3165    669     1.14    0.2559
trtan   Change from baseline, IDeg      WORK.ADATA2    2.8637    0.4503    669     6.36    <.0001
trtan   Change from baseline, Lira      WORK.ADATA2   -5.6407    0.4640    669   -12.16    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -0.2616      0.9814
trtan   Change from baseline, IDeg        0.05      1.9794      3.7479
trtan   Change from baseline, Lira        0.05     -6.5517     -4.7297
CONFIDENTIAL


NN9068
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Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
133 of 412
14: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       7.1903
           Fit Statistics
-2 Res Log Likelihood          3178.8
AIC (Smaller is Better)        3180.8
AICC (Smaller is Better)       3180.8
BIC (Smaller is Better)        3185.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -2.0338     0.5997    654     -3.39     0.0007     0.05
trtpn                         1             2.6948     0.2623    654     10.27     <.0001     0.05
trtpn                         2             3.8227     0.3012    654     12.69     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6288     0.2232    654      2.82     0.0050     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9907   0.007605    654    130.26     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
134 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -3.2114     -0.8561
trtpn                         1             2.1797      3.2099
trtpn                         2             3.2313      4.4141
trtpn                         3                               
PREOAD2     Metformin                       0.1905      1.0670
PREOAD2     Metformin + OAD                                   
BASE                                        0.9757      1.0056
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      85.96    <.0001
PREOAD2         1     654       7.94    0.0050
BASE            1     654    16968.0    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    74.3137     0.1453     654    511.41     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    75.4416     0.2076     654    363.33     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    71.6190     0.2183     654    328.11     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    74.0284    74.5991         1.88E32        1.413E32          2.5E32
trtpn    LSMeans, IDeg        75.0339    75.8493        5.806E32        3.862E32        8.729E32
trtpn    LSMeans, Lira        71.1903    72.0476         1.27E31        8.271E30        1.949E31
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.1279     0.2536     654     -4.45
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.6258   -0.6299         0.3237
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.1968           0.5326
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
135 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C25208X
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     2.6948     0.2623     654     10.27
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05    2.1797    3.2099        14.8025
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         8.8438          24.7759
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
136 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      34.9472
           Fit Statistics
-2 Res Log Likelihood          4214.4
AIC (Smaller is Better)        4216.4
AICC (Smaller is Better)       4216.4
BIC (Smaller is Better)        4220.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.4837     1.3222    654     -3.39     0.0007     0.05
trtpn                         1             5.9410     0.5783    654     10.27     <.0001     0.05
trtpn                         2             8.4275     0.6640    654     12.69     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.3862     0.4920    654      2.82     0.0050     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9907   0.007605    654    130.26     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -7.0800     -1.8874
trtpn                         1             4.8055      7.0766
trtpn                         2             7.1237      9.7313
trtpn                         3                               
PREOAD2     Metformin                       0.4201      2.3524
PREOAD2     Metformin + OAD                                   
BASE                                        0.9757      1.0056
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      85.96    <.0001
PREOAD2         1     654       7.94    0.0050
BASE            1     654    16968.0    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     163.83     0.3204     654    511.41     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     166.32     0.4578     654    363.33     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     157.89     0.4812     654    328.11     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     163.20     164.46        1.419E71        7.567E70        2.663E71
trtpn    LSMeans, IDeg         165.42     167.22        1.706E72        6.944E71        4.191E72
trtpn    LSMeans, Lira         156.95     158.84        3.732E68        1.451E68        9.601E68
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.4865     0.5591     654     -4.45
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -3.5843   -1.3887        0.08320
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        0.02776           0.2494
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
138 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     5.9410     0.5783     654     10.27
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05    4.8055    7.0766         380.32
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         122.18          1183.89
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
139 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       7.1903
           Fit Statistics
-2 Res Log Likelihood          3178.8
AIC (Smaller is Better)        3180.8
AICC (Smaller is Better)       3180.8
BIC (Smaller is Better)        3185.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -2.0338     0.5997    654     -3.39     0.0007     0.05
trtpn                         1             2.6948     0.2623    654     10.27     <.0001     0.05
trtpn                         2             3.8227     0.3012    654     12.69     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6288     0.2232    654      2.82     0.0050     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00935   0.007605    654     -1.23     0.2194     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
140 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=C25208X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -3.2114     -0.8561
trtpn                         1             2.1797      3.2099
trtpn                         2             3.2313      4.4141
trtpn                         3                               
PREOAD2     Metformin                       0.1905      1.0670
PREOAD2     Metformin + OAD                                   
BASE                                      -0.02428    0.005584
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      85.96    <.0001
PREOAD2         1     654       7.94    0.0050
BASE            1     654       1.51    0.2194
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.1749    0.1453    654     1.20    0.2292
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.3028    0.2076    654     6.27    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -2.5199    0.2183    654   -11.54    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.1104      0.4602
trtpn   Change from baseline, IDeg        0.05      0.8951      1.7105
trtpn   Change from baseline, Lira        0.05     -2.9485     -2.0913
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
141 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             659
          Number of Observations
Number of Observations Read             659
Number of Observations Used             659
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      34.9472
           Fit Statistics
-2 Res Log Likelihood          4214.4
AIC (Smaller is Better)        4216.4
AICC (Smaller is Better)       4216.4
BIC (Smaller is Better)        4220.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -4.4837     1.3222    654     -3.39     0.0007     0.05
trtpn                         1             5.9410     0.5783    654     10.27     <.0001     0.05
trtpn                         2             8.4275     0.6640    654     12.69     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.3862     0.4920    654      2.82     0.0050     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.00935   0.007605    654     -1.23     0.2194     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
142 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
completer analysis set
Parameter Code=WEIGHTU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -7.0800     -1.8874
trtpn                         1             4.8055      7.0766
trtpn                         2             7.1237      9.7313
trtpn                         3                               
PREOAD2     Metformin                       0.4201      2.3524
PREOAD2     Metformin + OAD                                   
BASE                                      -0.02428    0.005584
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     654      85.96    <.0001
PREOAD2         1     654       7.94    0.0050
BASE            1     654       1.51    0.2194
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.3856    0.3204    654     1.20    0.2292
trtpn   Change from baseline, IDeg      WORK.ADATA2    2.8721    0.4578    654     6.27    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -5.5554    0.4812   654   -11.54    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.2435      1.0146
trtpn   Change from baseline, IDeg        0.05      1.9733      3.7710
trtpn   Change from baseline, Lira        0.05     -6.5003     -4.6105
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NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
143 of 412
15: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
avisitn         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
144 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
145 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
146 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4046
Number of Observations Not Used         274
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
147 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     17548.36814718                
        1              2     13253.73696060      0.00000775
        2              1     13253.71397046      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      
UN(2,1)     SUBJID      
UN(2,2)     SUBJID      
UN(3,1)     SUBJID      
UN(3,2)     SUBJID      
UN(3,3)     SUBJID      
UN(4,1)     SUBJID      
UN(4,2)     SUBJID      
UN(4,3)     SUBJID      
UN(4,4)     SUBJID      
UN(5,1)     SUBJID      
UN(5,2)     SUBJID      
UN(5,3)     SUBJID      
UN(5,4)     SUBJID      
UN(5,5)     SUBJID      
UN(6,1)     SUBJID      
UN(6,2)     SUBJID      
UN(6,3)     SUBJID      
UN(6,4)     SUBJID      
UN(6,5)     SUBJID      
UN(6,6)     SUBJID      
           Fit Statistics
-2 Res Log Likelihood         13253.7
AIC (Smaller is Better)       13295.7
AICC (Smaller is Better)      13295.9
BIC (Smaller is Better)       13391.9
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       4294.65          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)      12     814      20.33    <.0001
PREOAD2(avisitn)       6     674       2.75    0.0120
BASE(avisitn)          6     676    12856.3    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
148 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                                 Least Squares Means Estimates
                                                              Standard
Effect            Label              Margins        Estimate     Error     DF  t Value  Pr > |t|
TRT01PN(avisitn)  LSMeans, IDegLira  WORK.ANA_DATA   74.3474    0.1440  672.4   516.20    <.0001
TRT01PN(avisitn)  LSMeans, IDeg      WORK.ANA_DATA   75.4830    0.2052  675.4   367.88    <.0001
TRT01PN(avisitn)  LSMeans, Lira      WORK.ANA_DATA   71.6194    0.2118  698.6   338.12    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(avisitn)  LSMeans, IDegLira    0.05     74.0646     74.6302
TRT01PN(avisitn)  LSMeans, IDeg        0.05     75.0801     75.8858
TRT01PN(avisitn)  LSMeans, Lira        0.05     71.2035     72.0353
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
149 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
avisitn         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
150 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
151 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
152 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4046
Number of Observations Not Used         274
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
153 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     23907.60340805                
        1              2     19612.97222150      0.00000372
        2              1     19612.94923134      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID     
UN(2,1)     SUBJID     
UN(2,2)     SUBJID     
UN(3,1)     SUBJID     
UN(3,2)     SUBJID     
UN(3,3)     SUBJID     
UN(4,1)     SUBJID     
UN(4,2)     SUBJID     
UN(4,3)     SUBJID     
UN(4,4)     SUBJID     
UN(5,1)     SUBJID     
UN(5,2)     SUBJID     
UN(5,3)     SUBJID     
UN(5,4)     SUBJID     
UN(5,5)     SUBJID     
UN(6,1)     SUBJID     
UN(6,2)     SUBJID     
UN(6,3)     SUBJID     
UN(6,4)     SUBJID     
UN(6,5)     SUBJID     
UN(6,6)     SUBJID     
           Fit Statistics
-2 Res Log Likelihood         19612.9
AIC (Smaller is Better)       19654.9
AICC (Smaller is Better)      19655.2
BIC (Smaller is Better)       19751.1
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       4294.65          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)      12     814      20.33    <.0001
PREOAD2(avisitn)       6     674       2.75    0.0120
BASE(avisitn)          6     676    12856.3    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
154 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                                 Least Squares Means Estimates
                                                              Standard
Effect            Label              Margins        Estimate     Error     DF  t Value  Pr > |t|
TRT01PN(avisitn)  LSMeans, IDegLira  WORK.ANA_DATA    163.91    0.3175  672.4   516.20    <.0001
TRT01PN(avisitn)  LSMeans, IDeg      WORK.ANA_DATA    166.41    0.4524  675.4   367.88    <.0001
TRT01PN(avisitn)  LSMeans, Lira      WORK.ANA_DATA    157.89    0.4670  698.6   338.12    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(avisitn)  LSMeans, IDegLira    0.05      163.28      164.53
TRT01PN(avisitn)  LSMeans, IDeg        0.05      165.52      167.30
TRT01PN(avisitn)  LSMeans, Lira        0.05      156.98      158.81
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
155 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           CHG                      
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
avisitn         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
156 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
157 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
                   
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
158 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4046
Number of Observations Not Used         274
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
159 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     17548.36814717                
        1              2     13253.73696060      0.00000775
        2              1     13253.71397046      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      
UN(2,1)     SUBJID      
UN(2,2)     SUBJID      
UN(3,1)     SUBJID      
UN(3,2)     SUBJID      
UN(3,3)     SUBJID      
UN(4,1)     SUBJID      
UN(4,2)     SUBJID      
UN(4,3)     SUBJID      
UN(4,4)     SUBJID      
UN(5,1)     SUBJID      
UN(5,2)     SUBJID      
UN(5,3)     SUBJID      
UN(5,4)     SUBJID      
UN(5,5)     SUBJID      
UN(6,1)     SUBJID      
UN(6,2)     SUBJID      
UN(6,3)     SUBJID      
UN(6,4)     SUBJID      
UN(6,5)     SUBJID      
UN(6,6)     SUBJID      
           Fit Statistics
-2 Res Log Likelihood         13253.7
AIC (Smaller is Better)       13295.7
AICC (Smaller is Better)      13295.9
BIC (Smaller is Better)       13391.9
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       4294.65          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)      12     814      20.33    <.0001
PREOAD2(avisitn)       6     674       2.75    0.0120
BASE(avisitn)          6     676       6.16    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
160 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                           Standard
Effect            Label                           Margins        Estimate     Error     DF  t Value
TRT01PN(avisitn)  Change from baseline, IDegLira  WORK.ANA_DATA    0.1582    0.1440  672.4     1.10
TRT01PN(avisitn)  Change from baseline, IDeg      WORK.ANA_DATA    1.2938    0.2052  675.4     6.31
TRT01PN(avisitn)  Change from baseline, Lira      WORK.ANA_DATA   -2.5698    0.2118  698.6   -12.13
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(avisitn)  Change from baseline, IDegLira    0.2725      0.05     -0.1246      0.4410
TRT01PN(avisitn)  Change from baseline, IDeg        <.0001      0.05      0.8909      1.6967
TRT01PN(avisitn)  Change from baseline, Lira        <.0001      0.05     -2.9857     -2.1539
                                  Least Squares Means Estimates
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -1.1356     0.2508   674.4
TRT01PN(avisitn)  Treatment contrast, IDegLira - Lira  WORK.ANA_DATA     2.7280     0.2562   690.4
                                   Least Squares Means Estimates
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg    -4.53    <.0001    0.05   -1.6281   -0.6431
TRT01PN(avisitn)  Treatment contrast, IDegLira - Lira    10.65    <.0001    0.05    2.2250    3.2310
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
161 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           CHG                      
Covariance Structure         Unstructured             
Subject Effect               SUBJID                   
Estimation Method            REML                     
Residual Variance Method     None                     
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Satterthwaite            
              Class Level Information
Class      Levels    Values
TRT01PN         3    1 2 3                         
avisitn         6    60 100 140 180 220 280        
PREOAD2         2    Metformin Metformin + OAD     
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
162 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        720   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
163 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
164 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     37
Columns in Z                      0
Subjects                        720
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            4320
Number of Observations Used            4046
Number of Observations Not Used         274
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
165 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     23907.60340805                
        1              2     19612.97222148      0.00000372
        2              1     19612.94923134      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID     
UN(2,1)     SUBJID     
UN(2,2)     SUBJID     
UN(3,1)     SUBJID     
UN(3,2)     SUBJID     
UN(3,3)     SUBJID     
UN(4,1)     SUBJID     
UN(4,2)     SUBJID     
UN(4,3)     SUBJID     
UN(4,4)     SUBJID     
UN(5,1)     SUBJID     
UN(5,2)     SUBJID     
UN(5,3)     SUBJID     
UN(5,4)     SUBJID     
UN(5,5)     SUBJID     
UN(6,1)     SUBJID     
UN(6,2)     SUBJID     
UN(6,3)     SUBJID     
UN(6,4)     SUBJID     
UN(6,5)     SUBJID     
UN(6,6)     SUBJID     
           Fit Statistics
-2 Res Log Likelihood         19612.9
AIC (Smaller is Better)       19654.9
AICC (Smaller is Better)      19655.2
BIC (Smaller is Better)       19751.1
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       4294.65          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)      12     814      20.33    <.0001
PREOAD2(avisitn)       6     674       2.75    0.0120
BASE(avisitn)          6     676       6.16    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
166 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
MMRM - full analysis set
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                           Standard
Effect            Label                           Margins        Estimate     Error     DF  t Value
TRT01PN(avisitn)  Change from baseline, IDegLira  WORK.ANA_DATA    0.3487    0.3175  672.4     1.10
TRT01PN(avisitn)  Change from baseline, IDeg      WORK.ANA_DATA    2.8523   0.4524  675.4     6.31
TRT01PN(avisitn)  Change from baseline, Lira      WORK.ANA_DATA   -5.6654    0.4670  698.6   -12.13
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(avisitn)  Change from baseline, IDegLira    0.2725      0.05     -0.2747      0.9722
TRT01PN(avisitn)  Change from baseline, IDeg        <.0001      0.05      1.9641      3.7405
TRT01PN(avisitn)  Change from baseline, Lira        <.0001      0.05     -6.5822     -4.7486
                                  Least Squares Means Estimates
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -2.5035     0.5530   674.4
TRT01PN(avisitn)  Treatment contrast, IDegLira - Lira  WORK.ANA_DATA     6.0142     0.5648   690.4
                                   Least Squares Means Estimates
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg    -4.53    <.0001    0.05   -3.5893   -1.4177
TRT01PN(avisitn)  Treatment contrast, IDegLira - Lira    10.65    <.0001    0.05    4.9052    7.1231
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
167 of 412
16: Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002049       0.040243       0.042294   424717
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050971       0.048503       0.999951
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       75.432878       0.205654   75.02980   75.83595   424717      75.291050      75.598927
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             366.79     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
168 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000903       0.019951       0.020855   531569
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.045316       0.043355       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       74.335940       0.144413   74.05290   74.61899   531569      74.250861      74.416588
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             514.74     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
169 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005256       0.039976       0.045238    73847
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.131619       0.116334       0.999884
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       71.554362       0.212692   71.13749   71.97124    73847      71.264993      71.786081
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             336.42     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
170 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.009960       0.195593       0.205563   424717
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050971       0.048503       0.999951
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      166.301030       0.453390   165.4124   167.1897   424717     165.988353     166.667105
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             366.79     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
171 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total      DF
Estimate         0.004390       0.096969       0.101364   531569
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.045316       0.043355       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      163.882696       0.318376   163.2587   164.5067   531569     163.695128     164.060492
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             514.74     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
172 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.025548       0.194299       0.219873    73847
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.131619       0.116334       0.999884
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      157.750364       0.468906   156.8313   158.6694    73847     157.112416     158.261218
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             336.42     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
173 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002049       0.040243       0.042294   424717
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050971       0.048503       0.999951
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.302740       0.205654   0.899663   1.705816   424717       1.160912       1.468788
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               6.33     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
174 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000903       0.019951       0.020855   531569
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.045316       0.043355       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.205802       0.144413   -0.07724   0.488847   531569       0.120722       0.286449
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               1.43     0.1541
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
175 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005256      0.039976       0.045238    73847
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.131619       0.116334       0.999884
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -2.575777       0.212692   -2.99265   -2.15890    73847      -2.865146      -2.344058
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -12.11     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
176 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=12 Parameter Code=C25208X Label=Treatment contrast, IDegLira - IDeg 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002813       0.060258       0.063074   501172
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.046733       0.044651       0.999955
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.096938       0.251145   -1.58917   -0.60470   501172      -1.276007      -0.942857
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -4.37     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
177 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.009960       0.195593       0.205563   424717
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050971       0.048503       0.999951
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        2.872049       0.453390   1.983418   3.760680   424717       2.559372       3.238123
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               6.33     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
178 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.004390       0.096969       0.101364   531569
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.045316       0.043355       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.453715       0.318376   -0.17029   1.077723   531569       0.266147       0.631511
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               1.43     0.1541
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
179 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.025548      0.194299       0.219873    73847
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.131619       0.116334       0.999884
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -5.678617       0.468906   -6.59767   -4.75956    73847      -6.316565      -5.167763
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -12.11     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
180 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=22 Parameter Code=WEIGHTU Label=Treatment contrast, IDegLira - IDeg 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI2
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.013673       0.292875       0.306562   501172
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.046733       0.044651       0.999955
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -2.418334       0.553680   -3.50353   -1.33314   501172      -2.813114      -2.078643
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -4.37     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
181 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002050       0.040747       0.042799   434662
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050355       0.047945       0.999952
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       75.434346       0.206879   75.02887   75.83982   434662      75.292957      75.599366
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             364.63     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
182 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000985      0.020201       0.021187   461469
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.048798       0.046532       0.999953
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       74.184327       0.145558   73.89904   74.46962   461469      74.065477      74.270842
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             509.66     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
183 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005262       0.040478       0.045745    75344
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.130133       0.115172       0.999885
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       71.554942       0.213881   71.13574   71.97415    75344      71.265539      71.787147
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             334.56     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
184 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.009963       0.198046       0.208018   434662
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050355       0.047945       0.999952
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      166.304265       0.456090   165.4103   167.1982   434662     165.992557     166.668072
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             364.63     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
185 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.004786       0.098185       0.102976   461469
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.048798       0.046532       0.999953
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      163.548445       0.320899   162.9195   164.1774   461469     163.286426     163.739178
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             509.66     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
186 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=LSMeans, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_ABS_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.025576       0.196735       0.222337    75344
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.130133       0.115172       0.999885
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      157.751645       0.471526   156.8275   158.6758    75344     157.113619     158.263568
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             334.56     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
187 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002050       0.040747       0.042799   434662
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050355       0.047945       0.999952
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.304207       0.206879   0.898730   1.709683   434662       1.162818       1.469227
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               6.30     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
188 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000985       0.020201       0.021187   461469
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.048798       0.046532       0.999953
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.054188       0.145558   -0.23110   0.339476   461469      -0.064662       0.140703
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               0.37     0.7097
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
189 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005262       0.040478       0.045745    75344
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.130133       0.115172       0.999885
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -2.575196       0.213881   -2.99440   -2.15599    75344      -2.864600      -2.342992
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -12.04     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
190 of 412
Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=13 Parameter Code=C25208X Label=Treatment contrast, IDegLira - Lira 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.006210       0.060701       0.066917   115773
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.102405       0.092908       0.999907
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        2.629384       0.258683   2.122370   3.136398   115773       2.405082       2.939673
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              10.16     <.0001
CONFIDENTIAL


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Statistical document
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Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.009963       0.198046       0.208018   434662
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.050355       0.047945       0.999952
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        2.875284       0.456090   1.981361   3.769207   434662       2.563576       3.239091
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               6.30     <.0001
CONFIDENTIAL


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Statistical document
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Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.004786       0.098185       0.102976   461469
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.048798       0.046532       0.999953
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.119464       0.320899   -0.50949   0.748417   461469      -0.142555       0.310196
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               0.37     0.7097
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
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Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=Change from baseline, Lira Statement Number=1
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.025576       0.196735       0.222337    75344
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.130133       0.115172       0.999885
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -5.677336       0.471526   -6.60153   -4.75315    75344      -6.315363      -5.165413
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -12.04     <.0001
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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Body weight after 26 weeks of treatment - change from baseline - statistical sensitivity analysis -
conditional multiple imputation - full analysis set
param_ana_sort=23 Parameter Code=WEIGHTU Label=Treatment contrast, IDegLira - Lira 
The MIANALYZE Procedure
             Model Information
Data Set                  WORK.LSME_CHG_MI3
Number of Imputations     1000             
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.030182       0.295027       0.325239   115773
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.102405       0.092908       0.999907
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        5.796800       0.570298   4.679026   6.914575   115773       5.302299       6.480870
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              10.16     <.0001
CONFIDENTIAL


NN9068
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Statistical document
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17: Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set
Parameter Code=MEANWAIC
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      12.8901
           Fit Statistics
-2 Res Log Likelihood          3873.2
AIC (Smaller is Better)        3875.2
AICC (Smaller is Better)       3875.3
BIC (Smaller is Better)        3879.8
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.4327     1.3030    712      3.40     0.0007     0.05
trtpn                         1             2.4135     0.3281    712      7.36     <.0001     0.05
trtpn                         2             3.8648     0.3795    712     10.18     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6340     0.2863    712      2.21     0.0271     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.9234    0.01353    712     68.27     <.0001     0.05
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=MEANWAIC
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.8746      6.9908
trtpn                         1             1.7693      3.0578
trtpn                         2             3.1197      4.6099
trtpn                         3                               
PREOAD2     Metformin                      0.07184      1.1961
PREOAD2     Metformin + OAD                                  
BASE                                        0.8968      0.9499
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712      53.53    <.0001
PREOAD2         1     712       4.90    0.0271
BASE            1     712    4660.89    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    94.6036     0.1896     712    498.98     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    96.0549     0.2692     712    356.83     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    92.1901     0.2677     712    344.41     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    94.2314    94.9758        1.218E41        8.398E40        1.768E41
trtpn    LSMeans, IDeg        95.5264    96.5834       5.201E41        3.066E41        8.823E41
trtpn    LSMeans, Lira        91.6645    92.7156        1.091E40        6.448E39        1.844E40
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.4513     0.3294     712     -4.41
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -2.0980   -0.8046         0.2343
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.1227           0.4473
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NN9068
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Version:
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Clinical Trial Report
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Statistical document
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Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=MEANWAIC
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     2.4135     0.3281     712      7.36
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05    1.7693    3.0578        11.1735
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         5.8669          21.2799
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
Page:
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Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=MEANWAIC
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      12.8901
           Fit Statistics
-2 Res Log Likelihood          3873.2
AIC (Smaller is Better)        3875.2
AICC (Smaller is Better)       3875.3
BIC (Smaller is Better)        3879.8
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   4.4327     1.3030    712      3.40     0.0007     0.05
trtpn                         1             2.4135     0.3281    712     7.36     <.0001     0.05
trtpn                         2             3.8648     0.3795    712     10.18     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6340     0.2863    712      2.21     0.0271     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                      -0.07661    0.01353    712     -5.66     <.0001     0.05
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
Page:
199 of 412
Waist circumference after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=MEANWAIC
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.8746      6.9908
trtpn                         1             1.7693      3.0578
trtpn                         2             3.1197      4.6099
trtpn                         3                               
PREOAD2     Metformin                      0.07184      1.1961
PREOAD2     Metformin + OAD                                   
BASE                                       -0.1032    -0.05005
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712      53.53    <.0001
PREOAD2         1     712       4.90    0.0271
BASE            1     712      32.08    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.2104    0.1896    712    -1.11    0.2674
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.2408    0.2692    712     4.61    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -2.6240    0.2677    712    -9.80    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.5827      0.1618
trtpn   Change from baseline, IDeg        0.05      0.7123      1.7693
trtpn   Change from baseline, Lira        0.05     -3.1495     -2.0985
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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18: Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set
Parameter Code=C105585P
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2             
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2   Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.7090
           Fit Statistics
-2 Res Log Likelihood          2763.3
AIC (Smaller is Better)        2765.3
AICC (Smaller is Better)       2765.3
BIC (Smaller is Better)        2769.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   6.7293     0.3170    713     21.23     <.0001     0.05
trtpn                         1            -1.8662     0.1503    713    -12.42     <.0001     0.05
trtpn                         2            -1.4011     0.1742    713     -8.04     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.3263     0.1311    713     -2.49     0.0130     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1393    0.03019    713      4.61     <.0001     0.05
CONFIDENTIAL


NN9068
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16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
201 of 412
Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=C105585P
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   6.1069      7.3516
trtpn                         1            -2.1612     -1.5712
trtpn                         2            -1.7431     -1.0591
trtpn                         3                               
PREOAD2     Metformin                      -0.5837    -0.06898
PREOAD2     Metformin + OAD                                   
BASE                                       0.08005      0.1986
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      77.73    <.0001
PREOAD2         1     713       6.20    0.0130
BASE            1     713      21.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     6.1008    0.08676     713     70.32     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     6.5659     0.1235     713     53.17     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     7.9670     0.1227     713     64.92     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect  Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     5.9305     6.2712          446.22          376.34          529.09
trtpn    LSMeans, IDeg         6.3235     6.8084          710.47          557.51          905.40
trtpn    LSMeans, Lira         7.7261     8.2080         2884.34         2266.80         3670.11
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.4651     0.1510     713     -3.08
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0021    0.05   -0.7615   -0.1687         0.6281
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4670           0.8447
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=C105585P
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -1.8662     0.1503     713    -12.42
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -2.1612   -1.5712         0.1547
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.1152           0.2078
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
203 of 412
Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=FPGU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       879.68
           Fit Statistics
-2 Res Log Likelihood          6892.3
AIC (Smaller is Better)        6894.3
AICC (Smaller is Better)       6894.3
BIC (Smaller is Better)        6898.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   121.26     5.7125    713     21.23     <.0001     0.05
trtpn                         1           -33.6294     2.7077    713    -12.42     <.0001     0.05
trtpn                         2           -25.2482     3.1389    713     -8.04     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -5.8804     2.3620    713     -2.49     0.0130     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1393    0.03019    713      4.61     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
204 of 412
Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=FPGU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   110.05      132.48
trtpn                         1           -38.9455    -28.3134
trtpn                         2           -31.4108    -19.0856
trtpn                         3                               
PREOAD2     Metformin                     -10.5177     -1.2431
PREOAD2     Metformin + OAD                                   
BASE                                       0.08005      0.1986
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      77.73    <.0001
PREOAD2         1     713       6.20    0.0130
BASE            1     713      21.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     109.94     1.5634     713     70.32     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     118.32     2.2253     713     53.17     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     143.57     2.2113     713     64.92     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     106.87     113.01        5.558E47        2.582E46        1.197E49
trtpn    LSMeans, IDeg         113.95     122.69        2.426E51        3.072E49        1.916E53
trtpn    LSMeans, Lira         139.22     147.91        2.239E62        2.914E60         1.72E64
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -8.3812     2.7204     713     -3.08
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0021    0.05  -13.7223   -3.0402       0.000229
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       1.098E-6          0.04782
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=FPGU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2   -33.6294     2.7077     713    -12.42
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05  -38.9455  -28.3134       2.48E-15
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira       1.22E-17         5.05E-13
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=C105585P
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.7090
           Fit Statistics
-2 Res Log Likelihood          2763.3
AIC (Smaller is Better)        2765.3
AICC (Smaller is Better)       2765.3
BIC (Smaller is Better)        2769.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   6.7293     0.3170    713     21.23     <.0001     0.05
trtpn                         1            -1.8662     0.1503    713    -12.42     <.0001     0.05
trtpn                         2            -1.4011     0.1742    713     -8.04     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.3263     0.1311    713     -2.49     0.0130     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8607    0.03019    713    -28.50     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=C105585P
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   6.1069      7.3516
trtpn                         1            -2.1612     -1.5712
trtpn                         2            -1.7431     -1.0591
trtpn                         3                               
PREOAD2     Metformin                      -0.5837    -0.06898
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9199     -0.8014
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      77.73    <.0001
PREOAD2         1     713       6.20    0.0130
BASE            1     713     812.50    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                          Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.5461   0.08676    713   -40.87    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -3.0810    0.1235    713   -24.95    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -1.6799    0.1227    713   -13.69    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -3.7164     -3.3758
trtpn   Change from baseline, IDeg        0.05     -3.3235     -2.8386
trtpn   Change from baseline, Lira        0.05     -1.9208     -1.4390
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NN9068
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Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=FPGU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       879.68
           Fit Statistics
-2 Res Log Likelihood          6892.3
AIC (Smaller is Better)        6894.3
AICC (Smaller is Better)       6894.3
BIC (Smaller is Better)        6898.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   121.26     5.7125    713     21.23     <.0001     0.05
trtpn                         1           -33.6294     2.7077    713    -12.42     <.0001     0.05
trtpn                         2           -25.2482     3.1389    713     -8.04     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -5.8804     2.3620    713     -2.49     0.0130     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8607    0.03019    713    -28.50     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
209 of 412
Fasting plasma glucose after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=FPGU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   110.05      132.48
trtpn                         1           -38.9455    -28.3134
trtpn                         2           -31.4108    -19.0856
trtpn                         3                               
PREOAD2     Metformin                     -10.5177     -1.2431
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9199     -0.8014
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      77.73    <.0001
PREOAD2         1     713       6.20    0.0130
BASE            1     713     812.50    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -63.9010    1.5634    713   -40.87    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -55.5197    2.2253    713   -24.95    <.0001
trtpn  Change from baseline, Lira      WORK.ADATA2  -30.2715    2.2113    713   -13.69    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -66.9703    -60.8317
trtpn   Change from baseline, IDeg        0.05    -59.8887    -51.1508
trtpn   Change from baseline, Lira        0.05    -34.6130    -25.9300
19: 9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical 
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Compound Symmetry        
Subject Effect               USUBJID                  
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Kenward-Roger            
Degrees of Freedom Method    Kenward-Roger            
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
              Class Level Information
Class      Levels    Values
USUBJID       720    NN9068-4148/
           
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NN9068
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Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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The Mixed Procedure
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NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
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analysis - full analysis set
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NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
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Statistical document
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
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NN9068
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Date:
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
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analysis - full analysis set
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NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
219 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
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NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
220 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
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TRTPN           3    1 2 3                         
ATPTN           9    1 2 3 4 5 6 7 8 9             
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             2
Columns in X                     49
Columns in Z                      0
Subjects                        720
Max Obs per Subject               9
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
          Number of Observations
Number of Observations Read            6480
Number of Observations Used            6401
Number of Observations Not Used          79
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     28226.72908143                
        1              2     26184.01976519      0.00000000
                   Convergence criteria met.                    
                                   Covariance Parameter Estimates
                                    Standard         Z
Cov Parm     Subject    Estimate       Error     Value        Pr Z     Alpha       Lower       Upper
CS           USUBJID      2.0262      0.1238     16.37      <.0001      0.05      1.7835      2.2688
Residual                  2.7716     0.05215     53.15      <.0001      0.05      2.6721      2.8767
Asymptotic Covariance Matrix of Estimates
Row    Cov Parm        CovP1       CovP2
   1    CS            0.01533    -0.00031
   2    Residual     -0.00031    0.002720
           Fit Statistics
-2 Res Log Likelihood         26184.0
AIC (Smaller is Better)       26188.0
AICC (Smaller is Better)      26188.0
BIC (Smaller is Better)       26197.2
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
     1       2042.71          <.0001
                                    Solution for Fixed Effects
                                 Planned
                                 Treatment
                Pre Trial        for        Analysis
                anti-Diabetic    Period     Timepoint            Standard
Effect          treatment2       01 (N)     (N)        Estimate     Error    DF  t Value  Pr > |t|
Intercept                                                7.1788    0.1737  2673    41.34    <.0001
TRTPN                            1                      -1.6069    0.2005  2664    -8.02    <.0001
TRTPN                            2                      -1.4114    0.2316  2655    -6.09    <.0001
TRTPN                            3                            0                                   
TRTPN(ATPTN)                     1          1           0.05534    0.1385  5650     0.40    0.6895
TRTPN(ATPTN)                     2          1            0.1714    0.1858  5649     0.92    0.3565
TRTPN(ATPTN)                     3          1           0.03570    0.1866  5650     0.19    0.8483
TRTPN(ATPTN)                     1          2            3.7916    0.1387  5650    27.34    <.0001
TRTPN(ATPTN)                     2          2            4.4526   0.1868  5654    23.83    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
222 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                                    Solution for Fixed Effects
                                 Planned
                                 Treatment
                Pre Trial        for        Analysis
                anti-Diabetic    Period     Timepoint            Standard
Effect          treatment2       01 (N)     (N)        Estimate     Error    DF  t Value  Pr > |t|
TRTPN(ATPTN)                     3          2            3.4643    0.1873  5652    18.50    <.0001
TRTPN(ATPTN)                     1          3            1.1290    0.1391  5652     8.12    <.0001
TRTPN(ATPTN)                     2          3            1.6932    0.1867  5654     9.07    <.0001
TRTPN(ATPTN)                     3          3            0.9288    0.1866  5651     4.98    <.0001
TRTPN(ATPTN)                     1          4            3.6173    0.1390  5651    26.03    <.0001
TRTPN(ATPTN)                     2          4            4.7494    0.1869  5655    25.41    <.0001
TRTPN(ATPTN)                     3          4            2.8978    0.1868  5651    15.51    <.0001
TRTPN(ATPTN)                     1          5            1.2618    0.1387  5652     9.10    <.0001
TRTPN(ATPTN)                     2          5            1.9783    0.1860  5652    10.63    <.0001
TRTPN(ATPTN)                     3          5            0.9111    0.1866  5651     4.88    <.0001
TRTPN(ATPTN)                     1          6            4.0292    0.1390  5653    28.99    <.0001
TRTPN(ATPTN)                     2          6            4.8940    0.1861  5652    26.30    <.0001
TRTPN(ATPTN)                     3          6            2.9201    0.1867  5651    15.64    <.0001
TRTPN(ATPTN)                     1          7            2.7960    0.1392  5654    20.08    <.0001
TRTPN(ATPTN)                     2          7            3.4588    0.1873  5655    18.47    <.0001
TRTPN(ATPTN)                     3          7            1.8831    0.1871  5652    10.07    <.0001
TRTPN(ATPTN)                     1          8            0.2813    0.1397  5654     2.01    0.0440
TRTPN(ATPTN)                     2          8            0.6376    0.1880  5657     3.39    0.0007
TRTPN(ATPTN)                     3          8            0.1064    0.1877  5653     0.57    0.5710
TRTPN(ATPTN)                     1          9                 0                                   
TRTPN(ATPTN)                     2          9                 0                                   
TRTPN(ATPTN)                     3          9                 0                                   
PREOAD2(ATPTN)  Metformin                   1           -0.1375    0.1743  2641    -0.79    0.4302
PREOAD2(ATPTN)  Metformin + OAD             1                 0                                   
PREOAD2(ATPTN)  Metformin                   2           -0.7606    0.1750  2671    -4.35    <.0001
PREOAD2(ATPTN)  Metformin + OAD             2                 0                                   
PREOAD2(ATPTN)  Metformin                   3           -0.5825    0.1749  2665    -3.33    0.0009
PREOAD2(ATPTN)  Metformin + OAD             3                 0                                   
PREOAD2(ATPTN)  Metformin                   4           -0.4914    0.1752  2678    -2.80    0.0051
PREOAD2(ATPTN)  Metformin + OAD             4                 0                                   
PREOAD2(ATPTN)  Metformin                   5           -0.6473    0.1749  2664    -3.70    0.0002
PREOAD2(ATPTN)  Metformin + OAD             5                 0                                   
PREOAD2(ATPTN)  Metformin                   6           -0.7595    0.1751  2675    -4.34    <.0001
PREOAD2(ATPTN)  Metformin + OAD             6                 0                                   
PREOAD2(ATPTN)  Metformin                   7           -0.7914    0.1758  2705    -4.50    <.0001
PREOAD2(ATPTN)  Metformin + OAD             7                 0                                   
PREOAD2(ATPTN)  Metformin                   8           -0.3572    0.1766  2738    -2.02    0.0432
PREOAD2(ATPTN)  Metformin + OAD             8                 0                                   
PREOAD2(ATPTN)  Metformin                   9           -0.2029    0.1744  2648    -1.16    0.2449
PREOAD2(ATPTN)  Metformin + OAD             9                 0                                   
           Type 3 Tests of Fixed Effects
                   Num     Den
Effect              DF      DF    F Value    Pr > F
TRTPN                2     716      39.78    <.0001
TRTPN(ATPTN)        16    5652       8.63    <.0001
PREOAD2(ATPTN)       9    5392       5.07    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
223 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                                     Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint                           Standard
Effect        01 (N)     (N)        Margins        Estimate     Error    DF  t Value  Pr > |t|
TRTPN(ATPTN)  1          1          WORK.ANA_DATA    5.5825    0.1153  2641    48.42    <.0001
TRTPN(ATPTN)  2          1          WORK.ANA_DATA    5.8941    0.1637  2641    36.00    <.0001
TRTPN(ATPTN)  3          1          WORK.ANA_DATA    7.1698    0.1633  2641    43.92    <.0001
TRTPN(ATPTN)  1          2          WORK.ANA_DATA    9.1163    0.1155  2655    78.92    <.0001
TRTPN(ATPTN)  2          2          WORK.ANA_DATA    9.9728    0.1650  2697    60.45    <.0001
TRTPN(ATPTN)  3          2          WORK.ANA_DATA   10.3959    0.1638  2669    63.45    <.0001
TRTPN(ATPTN)  1          3          WORK.ANA_DATA    6.5115    0.1158  2676    56.22    <.0001
TRTPN(ATPTN)  2          3          WORK.ANA_DATA    7.2713    0.1647  2683    44.15    <.0001
TRTPN(ATPTN)  3          3          WORK.ANA_DATA    7.9183    0.1633  2641    48.50    <.0001
TRTPN(ATPTN)  1          4          WORK.ANA_DATA    9.0295    0.1157  2669    78.03    <.0001
TRTPN(ATPTN)  2          4          WORK.ANA_DATA   10.3571    0.1650  2697    62.77    <.0001
TRTPN(ATPTN)  3          4          WORK.ANA_DATA    9.9170    0.1636  2655    60.63    <.0001
TRTPN(ATPTN)  1          5          WORK.ANA_DATA    6.6233    0.1156  2662    57.29    <.0001
TRTPN(ATPTN)  2          5          WORK.ANA_DATA    7.5353    0.1641  2654    45.93    <.0001
TRTPN(ATPTN)  3          5          WORK.ANA_DATA    7.8796    0.1633  2641    48.26    <.0001
TRTPN(ATPTN)  1          6          WORK.ANA_DATA    9.3542    0.1159  2683    80.69    <.0001
TRTPN(ATPTN)  2          6          WORK.ANA_DATA   10.4145    0.1641  2654    63.48    <.0001
TRTPN(ATPTN)  3          6          WORK.ANA_DATA    9.8521    0.1633  2641    60.35    <.0001
TRTPN(ATPTN)  1          7          WORK.ANA_DATA    8.1106    0.1163  2704    69.77    <.0001
TRTPN(ATPTN)  2          7          WORK.ANA_DATA    8.9690    0.1653  2712    54.26    <.0001
TRTPN(ATPTN)  3          7          WORK.ANA_DATA    8.8047    0.1636  2655    53.83    <.0001
TRTPN(ATPTN)  1          8          WORK.ANA_DATA    5.7371   0.1167  2733    49.17    <.0001
TRTPN(ATPTN)  2          8          WORK.ANA_DATA    6.2889    0.1659  2741    37.90    <.0001
TRTPN(ATPTN)  3          8          WORK.ANA_DATA    7.1691    0.1644  2697    43.60    <.0001
TRTPN(ATPTN)  1         9          WORK.ANA_DATA    5.5059    0.1155  2655    47.67    <.0001
TRTPN(ATPTN)  2          9          WORK.ANA_DATA    5.7015    0.1637  2641    34.82    <.0001
TRTPN(ATPTN)  3          9          WORK.ANA_DATA    7.1129    0.1638  2669    43.41    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  1          1            0.05      5.3565      5.8086
TRTPN(ATPTN)  2          1            0.05      5.5730      6.2151
TRTPN(ATPTN)  3          1            0.05      6.8497      7.4900
TRTPN(ATPTN)  1          2            0.05      8.8898      9.3428
TRTPN(ATPTN)  2          2            0.05      9.6493     10.2963
TRTPN(ATPTN)  3          2            0.05     10.0746     10.7172
TRTPN(ATPTN)  1          3            0.05      6.2844      6.7387
TRTPN(ATPTN)  2          3            0.05      6.9483      7.5942
TRTPN(ATPTN)  3          3            0.05      7.5982      8.2384
TRTPN(ATPTN)  1          4            0.05      8.8026      9.2564
TRTPN(ATPTN)  2          4            0.05     10.0335     10.6806
TRTPN(ATPTN)  3          4            0.05      9.5962     10.2377
TRTPN(ATPTN)  1          5            0.05      6.3966      6.8500
TRTPN(ATPTN)  2          5            0.05      7.2136      7.8571
TRTPN(ATPTN)  3          5            0.05      7.5594      8.1997
TRTPN(ATPTN)  1          6            0.05      9.1269      9.5815
TRTPN(ATPTN)  2          6            0.05     10.0928     10.7362
TRTPN(ATPTN)  3          6            0.05      9.5320     10.1722
TRTPN(ATPTN)  1          7            0.05      7.8827      8.3386
TRTPN(ATPTN)  2          7            0.05      8.6449      9.2931
TRTPN(ATPTN)  3          7            0.05      8.4840      9.1254
TRTPN(ATPTN)  1          8            0.05      5.5083      5.9660
TRTPN(ATPTN)  2          8            0.05      5.9636      6.6142
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
224 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  3          8            0.05      6.8466      7.4915
TRTPN(ATPTN)  1          9            0.05      5.2795      5.7324
TRTPN(ATPTN)  2          9            0.05      5.3804      6.0225
TRTPN(ATPTN)  3          9            0.05      6.7916      7.4342
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  1          1          2          1          WORK.ANA_DATA   -0.3115    0.2002  2641
TRTPN(ATPTN)  1          1          3          1          WORK.ANA_DATA   -1.5873    0.1999  2641
TRTPN(ATPTN)  1          1          1          2          WORK.ANA_DATA   -3.5338    0.1241  5652
TRTPN(ATPTN)  1          1          2          2          WORK.ANA_DATA   -4.3903    0.2013  2679
TRTPN(ATPTN)  1          1          3          2          WORK.ANA_DATA   -4.8133    0.2003  2660
TRTPN(ATPTN)  1          1          1          3          WORK.ANA_DATA   -0.9290    0.1244  5653
TRTPN(ATPTN)  1          1          2          3          WORK.ANA_DATA   -1.6887    0.2010  2669
TRTPN(ATPTN)  1          1          3          3          WORK.ANA_DATA   -2.3358    0.1999  2641
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  1          1          2          1            -1.56      0.1199      0.05
TRTPN(ATPTN)  1          1          3          1            -7.94      <.0001      0.05
TRTPN(ATPTN)  1          1          1          2           -28.47      <.0001      0.05
TRTPN(ATPTN)  1          1          2          2           -21.81      <.0001      0.05
TRTPN(ATPTN)  1          1          3          2           -24.03      <.0001      0.05
TRTPN(ATPTN)  1          1          1          3            -7.47      <.0001      0.05
TRTPN(ATPTN)  1          1          2          3            -8.40      <.0001      0.05
TRTPN(ATPTN)  1          1          3          3           -11.69      <.0001      0.05
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  1          1          2          1           -0.7042     0.08110
TRTPN(ATPTN)  1          1          3          1           -1.9792     -1.1954
TRTPN(ATPTN)  1          1          1          2           -3.7771     -3.2904
TRTPN(ATPTN)  1          1          2          2           -4.7850     -3.9956
TRTPN(ATPTN)  1          1          3          2           -5.2062     -4.4205
TRTPN(ATPTN)  1          1          1          3           -1.1729     -0.6851
TRTPN(ATPTN)  1          1          2          3           -2.0829     -1.2945
TRTPN(ATPTN)  1          1          3          3           -2.7277     -1.9439
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
225 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  1          1          1          4          WORK.ANA_DATA   -3.4470    0.1243  5653
TRTPN(ATPTN)  1          1          2          4          WORK.ANA_DATA   -4.7745    0.2013  2679
TRTPN(ATPTN)  1          1          3          4          WORK.ANA_DATA   -4.3344    0.2001  2650
TRTPN(ATPTN)  1          1          1          5          WORK.ANA_DATA   -1.0408    0.1242  5652
TRTPN(ATPTN)  1          1          2          5          WORK.ANA_DATA   -1.9528    0.2005  2650
TRTPN(ATPTN)  1          1          3          5          WORK.ANA_DATA   -2.2970    0.1999  2641
TRTPN(ATPTN)  1          1          1          6          WORK.ANA_DATA   -3.7717    0.1245  5653
TRTPN(ATPTN)  1          1          2          6          WORK.ANA_DATA   -4.8320    0.2005  2650
TRTPN(ATPTN)  1          1          3          6          WORK.ANA_DATA   -4.2696    0.1999  2641
TRTPN(ATPTN)  1          1          1          7          WORK.ANA_DATA   -2.5281    0.1248  5654
TRTPN(ATPTN)  1          1          2          7          WORK.ANA_DATA   -3.3864    0.2015  2688
TRTPN(ATPTN)  1          1          3          7          WORK.ANA_DATA   -3.2222    0.2001  2650
TRTPN(ATPTN)  1          1          1          8          WORK.ANA_DATA   -0.1546    0.1252  5656
TRTPN(ATPTN)  1          1          2          8          WORK.ANA_DATA   -0.7064    0.2020  2708
TRTPN(ATPTN)  1          1          3          8          WORK.ANA_DATA   -1.5866    0.2008  2679
TRTPN(ATPTN)  1          1          1          9          WORK.ANA_DATA   0.07658    0.1241  5650
TRTPN(ATPTN)  1          1          2          9          WORK.ANA_DATA   -0.1189    0.2002  2641
TRTPN(ATPTN)  1          1          3          9          WORK.ANA_DATA   -1.5304    0.2003  2660
TRTPN(ATPTN)  2          1          3          1          WORK.ANA_DATA   -1.2758    0.2312 2641
TRTPN(ATPTN)  2          1          1          2          WORK.ANA_DATA   -3.2222    0.2004  2645
TRTPN(ATPTN)  2          1          2          2          WORK.ANA_DATA   -4.0788    0.1772  5656
TRTPN(ATPTN)  2          1          3          2          WORK.ANA_DATA   -4.5018    0.2316  2655
TRTPN(ATPTN)  2          1          1          3          WORK.ANA_DATA   -0.6175    0.2006  2652
TRTPN(ATPTN)  2          1          2          3          WORK.ANA_DATA   -1.3772    0.1769  5656
TRTPN(ATPTN)  2          1          3          3          WORK.ANA_DATA   -2.0242    0.2312  2641
TRTPN(ATPTN)  2          1          1          4          WORK.ANA_DATA   -3.1354    0.2005  2650
TRTPN(ATPTN)  2          1          2          4          WORK.ANA_DATA   -4.4630    0.1772  5656
TRTPN(ATPTN)  2          1          3          4          WORK.ANA_DATA   -4.0229    0.2314  2648
TRTPN(ATPTN)  2          1          1          5          WORK.ANA_DATA   -0.7292    0.2004  2648
TRTPN(ATPTN)  2          1          2          5          WORK.ANA_DATA   -1.6413    0.1763  5653
TRTPN(ATPTN)  2          1          3          5          WORK.ANA_DATA   -1.9855    0.2312  2641
TRTPN(ATPTN)  2          1          1          6          WORK.ANA_DATA   -3.4602    0.2006  2655
TRTPN(ATPTN)  2          1          2          6          WORK.ANA_DATA   -4.5205    0.1763  5653
TRTPN(ATPTN)  2          1          3          6          WORK.ANA_DATA   -3.9580    0.2312  2641
TRTPN(ATPTN)  2          1          1          7          WORK.ANA_DATA   -2.2166    0.2008  2662
TRTPN(ATPTN)  2          1          2          7          WORK.ANA_DATA   -3.0749    0.1774  5656
TRTPN(ATPTN)  2          1          3          7          WORK.ANA_DATA   -2.9106    0.2314  2648
TRTPN(ATPTN)  2          1          1          8          WORK.ANA_DATA    0.1569    0.2011  2672
TRTPN(ATPTN)  2          1          2          8          WORK.ANA_DATA   -0.3948    0.1780  5658
TRTPN(ATPTN)  2          1          3          8          WORK.ANA_DATA   -1.2750    0.2320  2669
TRTPN(ATPTN)  2          1          1          9          WORK.ANA_DATA    0.3881    0.2004  2646
TRTPN(ATPTN)  2          1          2          9          WORK.ANA_DATA    0.1926    0.1760  5649
TRTPN(ATPTN)  2          1          3          9          WORK.ANA_DATA   -1.2188    0.2316  2655
TRTPN(ATPTN)  3          1          1          2          WORK.ANA_DATA   -1.9465    0.2000  2646
TRTPN(ATPTN)  3          1          2          2          WORK.ANA_DATA   -2.8030    0.2321  2669
TRTPN(ATPTN)  3          1          3          2          WORK.ANA_DATA   -3.2260    0.1760  5650
TRTPN(ATPTN)  3          1          1          3          WORK.ANA_DATA    0.6583    0.2002  2653
TRTPN(ATPTN)  3          1          2          3          WORK.ANA_DATA   -0.1014    0.2319  2662
TRTPN(ATPTN)  3          1          3          3          WORK.ANA_DATA   -0.7485    0.1755  5649
TRTPN(ATPTN)  3          1          1          4          WORK.ANA_DATA   -1.8597    0.2001  2650
TRTPN(ATPTN)  3          1          2          4          WORK.ANA_DATA   -3.1872    0.2321  2669
TRTPN(ATPTN)  3          1          3          4          WORK.ANA_DATA   -2.7471    0.1758  5650
TRTPN(ATPTN)  3          1          1          5          WORK.ANA_DATA    0.5465    0.2001  2648
TRTPN(ATPTN)  3          1          2          5          WORK.ANA_DATA   -0.3655    0.2315  2648
TRTPN(ATPTN)  3          1          3          5          WORK.ANA_DATA   -0.7097    0.1755  5649
TRTPN(ATPTN)  3          1          1          6          WORK.ANA_DATA   -2.1844    0.2002  2655
TRTPN(ATPTN)  3          1          2          6          WORK.ANA_DATA   -3.2447    0.2315  2648
TRTPN(ATPTN)  3          1          3          6          WORK.ANA_DATA   -2.6823    0.1755  5649
TRTPN(ATPTN)  3          1          1          7          WORK.ANA_DATA   -0.9408    0.2004  2662
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
226 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  1          1          1          4           -27.73      <.0001      0.05
TRTPN(ATPTN)  1          1          2          4           -23.72      <.0001      0.05
TRTPN(ATPTN)  1          1          3          4           -21.66      <.0001      0.05
TRTPN(ATPTN)  1          1          1          5            -8.38      <.0001      0.05
TRTPN(ATPTN)  1          1          2          5            -9.74      <.0001      0.05
TRTPN(ATPTN)  1          1          3          5           -11.49      <.0001      0.05
TRTPN(ATPTN)  1          1          1          6           -30.29      <.0001      0.05
TRTPN(ATPTN)  1          1          2          6           -24.10      <.0001      0.05
TRTPN(ATPTN)  1          1          3          6           -21.36      <.0001      0.05
TRTPN(ATPTN)  1          1          1          7           -20.25      <.0001      0.05
TRTPN(ATPTN)  1          1          2          7           -16.80      <.0001      0.05
TRTPN(ATPTN)  1          1          3          7           -16.10      <.0001      0.05
TRTPN(ATPTN)  1          1          1          8            -1.23      0.2170      0.05
TRTPN(ATPTN)  1          1          2          8            -3.50      0.0005      0.05
TRTPN(ATPTN)  1          1          3          8            -7.90      <.0001      0.05
TRTPN(ATPTN)  1          1          1          9             0.62      0.5372      0.05
TRTPN(ATPTN)  1          1          2          9            -0.59      0.5526      0.05
TRTPN(ATPTN)  1          1          3          9            -7.64      <.0001      0.05
TRTPN(ATPTN)  2          1          3          1            -5.52      <.0001      0.05
TRTPN(ATPTN)  2          1          1          2           -16.08      <.0001      0.05
TRTPN(ATPTN)  2          1          2          2           -23.02      <.0001      0.05
TRTPN(ATPTN)  2          1          3          2           -19.44      <.0001      0.05
TRTPN(ATPTN)  2          1          1          3            -3.08      0.0021      0.05
TRTPN(ATPTN)  2          1          2          3            -7.79      <.0001      0.05
TRTPN(ATPTN)  2          1          3          3            -8.75      <.0001      0.05
TRTPN(ATPTN)  2          1          1          4           -15.64      <.0001      0.05
TRTPN(ATPTN)  2          1          2          4           -25.19      <.0001      0.05
TRTPN(ATPTN)  2          1          3          4           -17.38      <.0001      0.05
TRTPN(ATPTN)  2          1          1          5            -3.64      0.0003      0.05
TRTPN(ATPTN)  2          1          2          5            -9.31      <.0001      0.05
TRTPN(ATPTN)  2          1          3          5            -8.59      <.0001      0.05
TRTPN(ATPTN)  2          1          1          6           -17.25      <.0001      0.05
TRTPN(ATPTN)  2          1          2          6           -25.64      <.0001      0.05
TRTPN(ATPTN)  2          1          3          6           -17.12      <.0001      0.05
TRTPN(ATPTN)  2          1          1          7           -11.04      <.0001      0.05
TRTPN(ATPTN)  2          1          2          7           -17.33      <.0001      0.05
TRTPN(ATPTN)  2          1          3          7           -12.58      <.0001      0.05
TRTPN(ATPTN)  2          1          1          8             0.78      0.4351      0.05
TRTPN(ATPTN)  2          1          2          8            -2.22      0.0266      0.05
TRTPN(ATPTN)  2          1          3          8            -5.49      <.0001      0.05
TRTPN(ATPTN)  2          1          1          9             1.94      0.0528      0.05
TRTPN(ATPTN)  2          1          2          9             1.09      0.2738      0.05
TRTPN(ATPTN)  2          1          3          9            -5.26      <.0001      0.05
TRTPN(ATPTN)  3          1          1          2            -9.73      <.0001      0.05
TRTPN(ATPTN)  3          1          2          2           -12.08      <.0001      0.05
TRTPN(ATPTN)  3          1          3          2           -18.33      <.0001      0.05
TRTPN(ATPTN)  3          1          1          3             3.29      0.0010      0.05
TRTPN(ATPTN)  3          1          2          3            -0.44      0.6619      0.05
TRTPN(ATPTN)  3          1          3          3            -4.27      <.0001      0.05
TRTPN(ATPTN)  3          1          1          4            -9.29      <.0001      0.05
TRTPN(ATPTN)  3          1          2          4           -13.73      <.0001      0.05
TRTPN(ATPTN)  3          1          3          4           -15.63      <.0001      0.05
TRTPN(ATPTN)  3          1          1          5             2.73      0.0063      0.05
TRTPN(ATPTN)  3          1          2          5            -1.58      0.1144      0.05
TRTPN(ATPTN)  3          1          3          5            -4.04      <.0001      0.05
TRTPN(ATPTN)  3          1          1          6           -10.91      <.0001      0.05
TRTPN(ATPTN)  3          1          2          6           -14.02      <.0001      0.05
TRTPN(ATPTN)  3          1          3          6           -15.28      <.0001      0.05
TRTPN(ATPTN)  3          1          1          7            -4.69      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
227 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  1          1          1          4           -3.6907     -3.2032
TRTPN(ATPTN)  1          1          2          4           -5.1692     -4.3798
TRTPN(ATPTN)  1          1          3          4           -4.7268     -3.9421
TRTPN(ATPTN)  1          1          1          5           -1.2843     -0.7972
TRTPN(ATPTN)  1          1          2          5           -2.3460     -1.5596
TRTPN(ATPTN)  1          1          3          5           -2.6889     -1.9051
TRTPN(ATPTN)  1          1          1          6           -4.0158     -3.5276
TRTPN(ATPTN)  1          1          2          6           -5.2252     -4.4388
TRTPN(ATPTN)  1          1          3          6           -4.6615     -3.8777
TRTPN(ATPTN)  1          1          1          7           -2.7728     -2.2834
TRTPN(ATPTN)  1          1          2          7           -3.7816     -2.9913
TRTPN(ATPTN)  1          1          3          7           -3.6145     -2.8298
TRTPN(ATPTN)  1          1          1          8           -0.4001     0.09088
TRTPN(ATPTN)  1          1          2          8           -1.1025     -0.3102
TRTPN(ATPTN)  1          1          3          8           -1.9804     -1.1928
TRTPN(ATPTN)  1          1          1          9           -0.1667      0.3199
TRTPN(ATPTN)  1          1          2          9           -0.5116      0.2737
TRTPN(ATPTN)  1          1          3          9           -1.9232     -1.1375
TRTPN(ATPTN)  2          1          3          1           -1.7291     -0.8224
TRTPN(ATPTN)  2          1          1          2           -3.6151     -2.8293
TRTPN(ATPTN)  2          1          2          2           -4.4261     -3.7315
TRTPN(ATPTN)  2          1          3          2           -4.9560     -4.0476
TRTPN(ATPTN)  2          1          1          3           -1.0107     -0.2242
TRTPN(ATPTN)  2          1          2          3           -1.7239     -1.0304
TRTPN(ATPTN)  2          1          3          3           -2.4776     -1.5708
TRTPN(ATPTN)  2          1          1          4           -3.5286     -2.7423
TRTPN(ATPTN)  2          1          2          4           -4.8103     -4.1157
TRTPN(ATPTN)  2          1          3          4           -4.4767     -3.5691
TRTPN(ATPTN)  2          1          1          5           -1.1223     -0.3362
TRTPN(ATPTN)  2          1          2          5           -1.9869     -1.2957
TRTPN(ATPTN)  2          1          3          5           -2.4389     -1.5321
TRTPN(ATPTN)  2          1          1          6           -3.8535     -3.0668
TRTPN(ATPTN)  2          1          2          6           -4.8661     -4.1748
TRTPN(ATPTN)  2          1          3          6           -4.4114     -3.5047
TRTPN(ATPTN)  2          1          1          7           -2.6103     -1.8228
TRTPN(ATPTN)  2          1          2          7           -3.4227     -2.7271
TRTPN(ATPTN)  2          1          3          7           -3.3644     -2.4568
TRTPN(ATPTN)  2          1          1          8           -0.2373      0.5512
TRTPN(ATPTN)  2          1          2          8           -0.7438    -0.04583
TRTPN(ATPTN)  2          1          3          8           -1.7300     -0.8200
TRTPN(ATPTN)  2          1          1          9          -0.00476      0.7810
TRTPN(ATPTN)  2          1          2          9           -0.1524      0.5376
TRTPN(ATPTN)  2          1          3          9           -1.6730     -0.7646
TRTPN(ATPTN)  3          1          1          2           -2.3386     -1.5543
TRTPN(ATPTN)  3          1          2          2           -3.2581     -2.3479
TRTPN(ATPTN)  3          1          3          2           -3.5711     -2.8810
TRTPN(ATPTN)  3          1          1          3            0.2658      1.0508
TRTPN(ATPTN)  3          1          2          3           -0.5562      0.3533
TRTPN(ATPTN)  3          1          3          3           -1.0925     -0.4044
TRTPN(ATPTN)  3          1          1          4           -2.2521     -1.4673
TRTPN(ATPTN)  3          1          2          4           -3.6424     -2.7321
TRTPN(ATPTN)  3          1          3          4           -3.0917     -2.4026
TRTPN(ATPTN)  3          1          1         5            0.1542      0.9388
TRTPN(ATPTN)  3          1          2          5           -0.8194     0.08834
TRTPN(ATPTN)  3          1          3          5           -1.0538     -0.3657
TRTPN(ATPTN)  3          1          1          6           -2.5770     -1.7918
TRTPN(ATPTN)  3          1          2          6           -3.6986     -2.7908
TRTPN(ATPTN)  3          1          3          6           -3.0263     -2.3383
TRTPN(ATPTN)  3          1          1          7           -1.3338     -0.5478
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
228 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          1          2          7          WORK.ANA_DATA   -1.7991    0.2323  2676
TRTPN(ATPTN)  3          1          3          7          WORK.ANA_DATA   -1.6349    0.1758  5650
TRTPN(ATPTN)  3          1          1          8          WORK.ANA_DATA    1.4327    0.2007  2672
TRTPN(ATPTN)  3          1          2          8          WORK.ANA_DATA    0.8809    0.2328  2691
TRTPN(ATPTN)  3          1          3          8          WORK.ANA_DATA  0.000731    0.1766  5651
TRTPN(ATPTN)  3          1          1          9          WORK.ANA_DATA    1.6639    0.2000  2646
TRTPN(ATPTN)  3          1          2          9          WORK.ANA_DATA    1.4684    0.2312  2641
TRTPN(ATPTN)  3          1          3          9          WORK.ANA_DATA   0.05695    0.1760  5650
TRTPN(ATPTN)  1          2          2          2          WORK.ANA_DATA   -0.8566    0.2014  2683
TRTPN(ATPTN)  1          2          3          2          WORK.ANA_DATA   -1.2796    0.2005  2664
TRTPN(ATPTN)  1          2          1          3          WORK.ANA_DATA    2.6048    0.1246  5650
TRTPN(ATPTN)  1          2          2          3          WORK.ANA_DATA    1.8450    0.2012  2673
TRTPN(ATPTN)  1          2          3          3          WORK.ANA_DATA    1.1980    0.2000  2646
TRTPN(ATPTN)  1          2          1          4          WORK.ANA_DATA   0.08679    0.1245  5650
TRTPN(ATPTN)  1          2          2          4          WORK.ANA_DATA   -1.2408    0.2014  2683
TRTPN(ATPTN)  1          2          3          4          WORK.ANA_DATA   -0.8007    0.2002  2655
TRTPN(ATPTN)  1          2          1          5          WORK.ANA_DATA    2.4930    0.1244  5651
TRTPN(ATPTN)  1          2          2          5          WORK.ANA_DATA    1.5809    0.2007  2654
TRTPN(ATPTN)  1          2          3          5          WORK.ANA_DATA    1.2367    0.2000  2646
TRTPN(ATPTN)  1          2          1          6          WORK.ANA_DATA   -0.2379    0.1247  5652
TRTPN(ATPTN)  1          2          2          6          WORK.ANA_DATA   -1.2982    0.2007  2654
TRTPN(ATPTN)  1          2          3          6          WORK.ANA_DATA   -0.7358    0.2000  2646
TRTPN(ATPTN)  1          2          1          7          WORK.ANA_DATA    1.0056    0.1250  5653
TRTPN(ATPTN)  1          2          2          7          WORK.ANA_DATA    0.1473    0.2017  2693
TRTPN(ATPTN)  1          2          3          7          WORK.ANA_DATA    0.3116    0.2002  2655
TRTPN(ATPTN)  1          2          1          8          WORK.ANA_DATA    3.3791    0.1254  5653
TRTPN(ATPTN)  1          2          2          8          WORK.ANA_DATA    2.8274    0.2022  2712
TRTPN(ATPTN)  1          2          3          8          WORK.ANA_DATA    1.9472    0.2010  2683
TRTPN(ATPTN)  1          2          1          9          WORK.ANA_DATA    3.6103    0.1243  5651
TRTPN(ATPTN)  1          2          2          9          WORK.ANA_DATA    3.4148    0.2004  2645
TRTPN(ATPTN)  1          2          3          9          WORK.ANA_DATA    2.0034    0.2005  2664
TRTPN(ATPTN)  2          2          3          2          WORK.ANA_DATA   -0.4230    0.2325  2683
TRTPN(ATPTN)  2          2          1          3          WORK.ANA_DATA    3.4613    0.2016  2690
TRTPN(ATPTN)  2          2          2          3          WORK.ANA_DATA    2.7016    0.1778  5652
TRTPN(ATPTN)  2          2          3          3          WORK.ANA_DATA    2.0546    0.2321  2669
TRTPN(ATPTN)  2          2          1          4          WORK.ANA_DATA    0.9433    0.2015  2688
TRTPN(ATPTN)  2          2          2          4          WORK.ANA_DATA   -0.3842    0.1781  5652
TRTPN(ATPTN)  2          2          3          4          WORK.ANA_DATA   0.05589    0.2323  2676
TRTPN(ATPTN)  2          2          1          5          WORK.ANA_DATA    3.3495    0.2015  2685
TRTPN(ATPTN)  2          2          2          5          WORK.ANA_DATA    2.4375    0.1773  5651
TRTPN(ATPTN)  2          2          3          5          WORK.ANA_DATA    2.0933    0.2321  2669
TRTPN(ATPTN)  2          2          1          6          WORK.ANA_DATA    0.6186    0.2016  2692
TRTPN(ATPTN)  2          2          2          6          WORK.ANA_DATA   -0.4417    0.1773  5651
TRTPN(ATPTN)  2          2          3          6          WORK.ANA_DATA    0.1207    0.2321  2669
TRTPN(ATPTN)  2          2          1          7          WORK.ANA_DATA    1.8622    0.2018  2699
TRTPN(ATPTN)  2          2          2          7          WORK.ANA_DATA    1.0039    0.1784  5653
TRTPN(ATPTN)  2          2          3          7          WORK.ANA_DATA    1.1682    0.2323  2676
TRTPN(ATPTN)  2          2          1          8          WORK.ANA_DATA    4.2357    0.2021  2709
TRTPN(ATPTN)  2          2          2          8          WORK.ANA_DATA    3.6840    0.1790  5654
TRTPN(ATPTN)  2          2          3          8          WORK.ANA_DATA    2.8037    0.2329  2697
TRTPN(ATPTN)  2          2          1          9          WORK.ANA_DATA    4.4669    0.2014  2683
TRTPN(ATPTN)  2          2          2          9          WORK.ANA_DATA    4.2714    0.1772  5656
TRTPN(ATPTN)  2          2          3          9          WORK.ANA_DATA    2.8600    0.2325  2683
TRTPN(ATPTN)  3          2          1          3          WORK.ANA_DATA    3.8843    0.2007  2671
TRTPN(ATPTN)  3          2          2          3          WORK.ANA_DATA    3.1246    0.2323  2676
TRTPN(ATPTN)  3          2          3          3          WORK.ANA_DATA    2.4776    0.1760  5650
TRTPN(ATPTN)  3          2          1          4          WORK.ANA_DATA    1.3664    0.2006  2669
TRTPN(ATPTN)  3          2          2          4          WORK.ANA_DATA   0.03882    0.2325  2683
TRTPN(ATPTN)  3          2          3          4          WORK.ANA_DATA    0.4789    0.1763  5651
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
229 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          1          2          7            -7.74      <.0001      0.05
TRTPN(ATPTN)  3          1          3          7            -9.30      <.0001      0.05
TRTPN(ATPTN)  3          1          1          8             7.14      <.0001      0.05
TRTPN(ATPTN)  3          1          2          8             3.78      0.0002      0.05
TRTPN(ATPTN)  3          1          3          8             0.00      0.9967      0.05
TRTPN(ATPTN)  3          1          1          9             8.32      <.0001      0.05
TRTPN(ATPTN)  3          1          2          9             6.35      <.0001      0.05
TRTPN(ATPTN)  3          1          3          9             0.32      0.7463      0.05
TRTPN(ATPTN)  1          2          2          2            -4.25      <.0001      0.05
TRTPN(ATPTN)  1          2          3          2            -6.38      <.0001      0.05
TRTPN(ATPTN)  1          2          1          3            20.91      <.0001      0.05
TRTPN(ATPTN)  1          2          2          3             9.17      <.0001      0.05
TRTPN(ATPTN)  1          2          3          3             5.99      <.0001      0.05
TRTPN(ATPTN)  1          2          1          4             0.70      0.4856      0.05
TRTPN(ATPTN)  1          2          2          4            -6.16      <.0001      0.05
TRTPN(ATPTN)  1          2          3          4            -4.00      <.0001      0.05
TRTPN(ATPTN)  1          2          1          5            20.04      <.0001      0.05
TRTPN(ATPTN)  1          2          2          5             7.88      <.0001      0.05
TRTPN(ATPTN)  1          2          3          5             6.18      <.0001      0.05
TRTPN(ATPTN)  1          2          1          6            -1.91      0.0564      0.05
TRTPN(ATPTN)  1          2          2          6            -6.47      <.0001      0.05
TRTPN(ATPTN)  1          2          3          6            -3.68      0.0002      0.05
TRTPN(ATPTN)  1          2          1          7             8.05      <.0001      0.05
TRTPN(ATPTN)  1          2          2          7             0.73      0.4651      0.05
TRTPN(ATPTN)  1          2          3          7             1.56      0.1198      0.05
TRTPN(ATPTN)  1          2          1          8            26.96      <.0001      0.05
TRTPN(ATPTN)  1          2          2          8            13.99      <.0001      0.05
TRTPN(ATPTN)  1          2          3          8             9.69      <.0001      0.05
TRTPN(ATPTN)  1          2          1          9            29.05      <.0001      0.05
TRTPN(ATPTN)  1          2          2          9            17.04      <.0001      0.05
TRTPN(ATPTN)  1          2          3          9             9.99      <.0001      0.05
TRTPN(ATPTN)  2          2          3          2            -1.82      0.0690      0.05
TRTPN(ATPTN)  2          2          1          3            17.17      <.0001      0.05
TRTPN(ATPTN)  2          2          2          3            15.19      <.0001      0.05
TRTPN(ATPTN)  2          2          3          3             8.85      <.0001      0.05
TRTPN(ATPTN)  2          2          1          4             4.68      <.0001      0.05
TRTPN(ATPTN)  2          2          2          4            -2.16      0.0310      0.05
TRTPN(ATPTN)  2          2          3          4             0.24      0.8099      0.05
TRTPN(ATPTN)  2          2          1          5            16.63      <.0001      0.05
TRTPN(ATPTN)  2          2          2          5            13.75      <.0001      0.05
TRTPN(ATPTN)  2          2          3          5             9.02      <.0001      0.05
TRTPN(ATPTN)  2          2          1          6             3.07      0.0022      0.05
TRTPN(ATPTN)  2          2          2          6            -2.49      0.0128      0.05
TRTPN(ATPTN)  2          2          3          6             0.52      0.6030      0.05
TRTPN(ATPTN)  2          2          1          7             9.23      <.0001      0.05
TRTPN(ATPTN)  2          2          2          7             5.63      <.0001      0.05
TRTPN(ATPTN)  2          2          3          7             5.03      <.0001      0.05
TRTPN(ATPTN)  2          2          1          8            20.96      <.0001      0.05
TRTPN(ATPTN)  2          2          2          8            20.58      <.0001      0.05
TRTPN(ATPTN)  2          2          3          8            12.04      <.0001      0.05
TRTPN(ATPTN)  2          2          1          9            22.18      <.0001      0.05
TRTPN(ATPTN)  2          2          2          9            24.11      <.0001      0.05
TRTPN(ATPTN)  2          2          3          9            12.30      <.0001      0.05
TRTPN(ATPTN)  3          2          1          3            19.36      <.0001      0.05
TRTPN(ATPTN)  3          2          2          3            13.45      <.0001      0.05
TRTPN(ATPTN)  3          2          3          3            14.07      <.0001      0.05
TRTPN(ATPTN)  3          2          1          4             6.81      <.0001      0.05
TRTPN(ATPTN)  3          2          2          4             0.17      0.8674      0.05
TRTPN(ATPTN)  3          2          3          4             2.72      0.0066      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
230 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          1          2          7           -2.2547     -1.3436
TRTPN(ATPTN)  3          1          3          7           -1.9794     -1.2903
TRTPN(ATPTN)  3         1          1          8            1.0392      1.8262
TRTPN(ATPTN)  3          1          2          8            0.4245      1.3374
TRTPN(ATPTN)  3          1          3          8           -0.3454      0.3469
TRTPN(ATPTN)  3          1          1          9            1.2717      2.0560
TRTPN(ATPTN)  3          1          2          9            1.0150      1.9217
TRTPN(ATPTN)  3          1          3          9           -0.2881      0.4020
TRTPN(ATPTN)  1          2          2          2           -1.2515     -0.4616
TRTPN(ATPTN)  1          2          3          2           -1.6727     -0.8865
TRTPN(ATPTN)  1          2          1          3            2.3606      2.8489
TRTPN(ATPTN)  1          2          2          3            1.4506      2.2395
TRTPN(ATPTN)  1          2          3          3            0.8058      1.5902
TRTPN(ATPTN)  1          2          1          4           -0.1572      0.3308
TRTPN(ATPTN)  1          2          2          4           -1.6357     -0.8458
TRTPN(ATPTN)  1          2          3          4           -1.1933     -0.4080
TRTPN(ATPTN)  1          2          1          5            2.2491      2.7368
TRTPN(ATPTN)  1          2          2          5            1.1875      1.9744
TRTPN(ATPTN)  1          2          3          5            0.8446      1.6289
TRTPN(ATPTN)  1          2          1          6           -0.4824    0.006482
TRTPN(ATPTN)  1          2          2          6           -1.6917     -0.9048
TRTPN(ATPTN)  1          2          3          6           -1.1280     -0.3437
TRTPN(ATPTN)  1          2          1          7            0.7606      1.2507
TRTPN(ATPTN)  1          2          2          7           -0.2481      0.5427
TRTPN(ATPTN)  1          2          3          7          -0.08103      0.7042
TRTPN(ATPTN)  1          2          1          8            3.1334      3.6249
TRTPN(ATPTN)  1          2          2          8            2.4310      3.2238
TRTPN(ATPTN)  1          2          3          8            1.5531      2.3412
TRTPN(ATPTN)  1          2          1          9            3.3667      3.8540
TRTPN(ATPTN)  1          2          2          9            3.0219      3.8077
TRTPN(ATPTN)  1          2          3          9            1.6103      2.3965
TRTPN(ATPTN)  2          2          3          2           -0.8790     0.03292
TRTPN(ATPTN)  2          2          1          3            3.0660      3.8566
TRTPN(ATPTN)  2          2          2          3            2.3530      3.0502
TRTPN(ATPTN)  2          2          3          3            1.5994      2.5097
TRTPN(ATPTN)  2          2          1          4            0.5482      1.3385
TRTPN(ATPTN)  2          2          2          4           -0.7334    -0.03505
TRTPN(ATPTN)  2          2          3          4           -0.3996      0.5114
TRTPN(ATPTN)  2          2          1          5            2.9545      3.7446
TRTPN(ATPTN)  2          2          2          5            2.0899      2.7851
TRTPN(ATPTN)  2          2          3          5            1.6381      2.5484
TRTPN(ATPTN)  2          2          1          6            0.2232      1.0140
TRTPN(ATPTN)  2          2          2          6           -0.7893    -0.09404
TRTPN(ATPTN)  2          2          3          6           -0.3344      0.5759
TRTPN(ATPTN)  2          2          1          7            1.4664      2.2580
TRTPN(ATPTN)  2          2          2          7            0.6541      1.3536
TRTPN(ATPTN)  2          2          3          7            0.7126      1.6237
TRTPN(ATPTN)  2          2          1          8            3.8395      4.6319
TRTPN(ATPTN)  2          2          2          8            3.3331      4.0348
TRTPN(ATPTN)  2          2          3          8            2.3470      3.2605
TRTPN(ATPTN)  2          2          1          9            4.0720      4.8618
TRTPN(ATPTN)  2          2          2          9            3.9241      4.6187
TRTPN(ATPTN)  2          2          3          9            2.4040      3.3159
TRTPN(ATPTN)  3          2          1          3            3.4909      4.2778
TRTPN(ATPTN)  3          2          2          3            2.6691      3.5801
TRTPN(ATPTN)  3          2          3          3            2.1325      2.8227
TRTPN(ATPTN)  3          2          1          4            0.9730      1.7597
TRTPN(ATPTN)  3          2          2          4           -0.4171      0.4948
TRTPN(ATPTN)  3          2          3          4            0.1333      0.8245
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
231 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis  for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          2          1          5          WORK.ANA_DATA    3.7726    0.2005  2667
TRTPN(ATPTN)  3          2          2          5          WORK.ANA_DATA    2.8605    0.2319  2662
TRTPN(ATPTN)  3          2          3          5          WORK.ANA_DATA    2.5163    0.1760  5650
TRTPN(ATPTN)  3          2          1          6          WORK.ANA_DATA    1.0416    0.2007  2674
TRTPN(ATPTN)  3          2          2          6          WORK.ANA_DATA  -0.01865    0.2319  2662
TRTPN(ATPTN)  3          2          3          6          WORK.ANA_DATA    0.5438    0.1760  5650
TRTPN(ATPTN)  3          2          1          7          WORK.ANA_DATA    2.2852    0.2009  2681
TRTPN(ATPTN)  3          2          2          7          WORK.ANA_DATA    1.4269    0.2327  2690
TRTPN(ATPTN)  3          2          3          7          WORK.ANA_DATA    1.5912    0.1763  5651
TRTPN(ATPTN)  3          2          1          8          WORK.ANA_DATA    4.6587    0.2012  2690
TRTPN(ATPTN)  3          2          2          8          WORK.ANA_DATA    4.1070    0.2332  2705
TRTPN(ATPTN)  3          2          3          8          WORK.ANA_DATA    3.2268    0.1771  5652
TRTPN(ATPTN)  3          2          1          9          WORK.ANA_DATA    4.8899    0.2005  2664
TRTPN(ATPTN)  3          2          2          9          WORK.ANA_DATA    4.6944    0.2316  2655
TRTPN(ATPTN)  3          2          3          9          WORK.ANA_DATA    3.2830    0.1766  5651
TRTPN(ATPTN)  1          3          2          3          WORK.ANA_DATA   -0.7597    0.2013  2680
TRTPN(ATPTN)  1          3          3          3          WORK.ANA_DATA   -1.4068    0.2002  2653
TRTPN(ATPTN)  1          3          1          4          WORK.ANA_DATA   -2.5180    0.1247  5650
TRTPN(ATPTN)  1          3          2          4          WORK.ANA_DATA   -3.8455    0.2016  2690
TRTPN(ATPTN)  1          3          3          4          WORK.ANA_DATA   -3.4054    0.2004  2662
TRTPN(ATPTN)  1          3          1          5          WORK.ANA_DATA   -0.1118    0.1247  5651
TRTPN(ATPTN)  1          3          2          5          WORK.ANA_DATA   -1.0238    0.2008  2661
TRTPN(ATPTN)  1          3          3          5          WORK.ANA_DATA   -1.3680    0.2002  2653
TRTPN(ATPTN)  1          3          1          6          WORK.ANA_DATA   -2.8427    0.1250  5653
TRTPN(ATPTN)  1          3          2          6          WORK.ANA_DATA   -3.9030    0.2008  2661
TRTPN(ATPTN)  1          3          3          6          WORK.ANA_DATA   -3.3406    0.2002  2653
TRTPN(ATPTN)  1          3          1          7          WORK.ANA_DATA   -1.5991    0.1252  5653
TRTPN(ATPTN)  1          3          2          7          WORK.ANA_DATA   -2.4574    0.2018  2700
TRTPN(ATPTN)  1          3          3          7          WORK.ANA_DATA   -2.2932    0.2004  2662
TRTPN(ATPTN)  1          3          1          8          WORK.ANA_DATA    0.7744    0.1256  5653
TRTPN(ATPTN)  1          3          2          8          WORK.ANA_DATA    0.2226    0.2023  2719
TRTPN(ATPTN)  1          3          3          8          WORK.ANA_DATA   -0.6576    0.2011  2690
TRTPN(ATPTN)  1          3          1          9          WORK.ANA_DATA    1.0056    0.1246  5653
TRTPN(ATPTN)  1          3          2          9          WORK.ANA_DATA    0.8101    0.2006  2652
TRTPN(ATPTN)  1          3          3          9          WORK.ANA_DATA   -0.6013    0.2007  2671
TRTPN(ATPTN)  2          3          3          3          WORK.ANA_DATA   -0.6470    0.2319  2662
TRTPN(ATPTN)  2          3          1          4          WORK.ANA_DATA   -1.7582    0.2013  2678
TRTPN(ATPTN)  2          3          2          4          WORK.ANA_DATA   -3.0858    0.1778  5650
TRTPN(ATPTN)  2          3          3          4          WORK.ANA_DATA   -2.6457    0.2321  2669
TRTPN(ATPTN)  2          3          1          5          WORK.ANA_DATA    0.6480    0.2012  2676
TRTPN(ATPTN)  2          3          2          5          WORK.ANA_DATA   -0.2641    0.1771  5651
TRTPN(ATPTN)  2          3          3          5          WORK.ANA_DATA   -0.6083    0.2319  2662
TRTPN(ATPTN)  2          3          1          6          WORK.ANA_DATA   -2.0830    0.2014  2683
TRTPN(ATPTN)  2          3          2          6          WORK.ANA_DATA   -3.1433    0.1771  5651
TRTPN(ATPTN)  2          3          3          6          WORK.ANA_DATA   -2.5809    0.2319  2662
TRTPN(ATPTN)  2          3          1          7          WORK.ANA_DATA   -0.8394    0.2016  2690
TRTPN(ATPTN)  2          3          2          7          WORK.ANA_DATA   -1.6977    0.1781  5652
TRTPN(ATPTN)  2          3          3          7          WORK.ANA_DATA   -1.5334    0.2321  2669
TRTPN(ATPTN)  2          3          1          8          WORK.ANA_DATA    1.5341    0.2018  2699
TRTPN(ATPTN)  2          3          2          8          WORK.ANA_DATA    0.9824    0.1786  5651
TRTPN(ATPTN)  2          3          3          8          WORK.ANA_DATA    0.1022    0.2327  2690
TRTPN(ATPTN)  2          3          1          9          WORK.ANA_DATA    1.7653    0.2012  2673
TRTPN(ATPTN)  2          3          2          9          WORK.ANA_DATA    1.5698    0.1769  5656
TRTPN(ATPTN)  2          3          3          9          WORK.ANA_DATA    0.1584    0.2323  2676
TRTPN(ATPTN)  3          3          1          4          WORK.ANA_DATA   -1.1112    0.2001  2650
TRTPN(ATPTN)  3          3          2          4          WORK.ANA_DATA   -2.4388    0.2321  2669
TRTPN(ATPTN)  3          3          3          4          WORK.ANA_DATA   -1.9987    0.1758  5650
TRTPN(ATPTN)  3          3          1          5          WORK.ANA_DATA    1.2950    0.2001  2648
TRTPN(ATPTN)  3          3          2          5          WORK.ANA_DATA    0.3829    0.2315  2648
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
232 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          2          1          5            18.81      <.0001      0.05
TRTPN(ATPTN)  3          2          2          5            12.34      <.0001      0.05
TRTPN(ATPTN)  3          2          3          5            14.29      <.0001      0.05
TRTPN(ATPTN)  3          2          1          6             5.19      <.0001      0.05
TRTPN(ATPTN)  3          2          2          6            -0.08      0.9359      0.05
TRTPN(ATPTN)  3          2          3          6             3.09      0.0020      0.05
TRTPN(ATPTN)  3          2          1          7            11.38      <.0001      0.05
TRTPN(ATPTN)  3          2          2          7             6.13      <.0001      0.05
TRTPN(ATPTN)  3          2          3          7             9.03      <.0001      0.05
TRTPN(ATPTN)  3          2          1          8            23.16      <.0001      0.05
TRTPN(ATPTN)  3          2          2          8            17.61      <.0001      0.05
TRTPN(ATPTN)  3          2          3          8            18.22      <.0001      0.05
TRTPN(ATPTN)  3          2          1          9            24.39      <.0001      0.05
TRTPN(ATPTN)  3          2          2          9            20.27      <.0001      0.05
TRTPN(ATPTN)  3          2          3          9            18.59      <.0001      0.05
TRTPN(ATPTN)  1          3          2          3            -3.77      0.0002      0.05
TRTPN(ATPTN)  1          3          3          3            -7.03      <.0001      0.05
TRTPN(ATPTN)  1          3          1          4           -20.19      <.0001      0.05
TRTPN(ATPTN)  1          3          2          4           -19.08      <.0001      0.05
TRTPN(ATPTN)  1          3          3          4           -16.99      <.0001      0.05
TRTPN(ATPTN)  1          3          1          5            -0.90      0.3700      0.05
TRTPN(ATPTN)  1          3          2          5            -5.10      <.0001      0.05
TRTPN(ATPTN)  1          3          3          5            -6.83      <.0001      0.05
TRTPN(ATPTN)  1          3          1          6           -22.75      <.0001      0.05
TRTPN(ATPTN)  1          3          2          6           -19.43      <.0001      0.05
TRTPN(ATPTN)  1          3          3          6           -16.69      <.0001      0.05
TRTPN(ATPTN)  1          3          1          7           -12.77      <.0001      0.05
TRTPN(ATPTN)  1          3          2          7           -12.18      <.0001      0.05
TRTPN(ATPTN)  1          3          3          7           -11.44      <.0001      0.05
TRTPN(ATPTN)  1          3          1          8             6.16      <.0001      0.05
TRTPN(ATPTN)  1          3          2          8             1.10      0.2713      0.05
TRTPN(ATPTN)  1          3          3          8            -3.27      0.0011      0.05
TRTPN(ATPTN)  1          3          1          9             8.07      <.0001      0.05
TRTPN(ATPTN)  1          3          2          9             4.04      <.0001      0.05
TRTPN(ATPTN)  1          3          3          9            -3.00      0.0028      0.05
TRTPN(ATPTN)  2          3          3          3            -2.79      0.0053      0.05
TRTPN(ATPTN)  2          3          1          4            -8.74      <.0001      0.05
TRTPN(ATPTN)  2          3          2          4           -17.36      <.0001      0.05
TRTPN(ATPTN)  2          3          3          4           -11.40      <.0001      0.05
TRTPN(ATPTN)  2          3          1          5             3.22      0.0013      0.05
TRTPN(ATPTN)  2          3          2          5            -1.49      0.1359      0.05
TRTPN(ATPTN)  2          3          3          5            -2.62      0.0088      0.05
TRTPN(ATPTN)  2          3          1          6           -10.34      <.0001      0.05
TRTPN(ATPTN)  2          3          2          6           -17.75      <.0001      0.05
TRTPN(ATPTN)  2          3          3          6           -11.13      <.0001      0.05
TRTPN(ATPTN)  2          3          1          7            -4.16      <.0001      0.05
TRTPN(ATPTN)  2          3          2          7            -9.53      <.0001      0.05
TRTPN(ATPTN)  2          3          3          7            -6.61      <.0001      0.05
TRTPN(ATPTN)  2          3          1          8             7.60      <.0001      0.05
TRTPN(ATPTN)  2          3          2          8             5.50      <.0001      0.05
TRTPN(ATPTN)  2          3          3          8             0.44      0.6607      0.05
TRTPN(ATPTN)  2          3          1          9             8.78      <.0001      0.05
TRTPN(ATPTN)  2          3          2          9             8.87      <.0001      0.05
TRTPN(ATPTN)  2          3          3          9            0.68      0.4955      0.05
TRTPN(ATPTN)  3          3          1          4            -5.55      <.0001      0.05
TRTPN(ATPTN)  3          3          2          4           -10.51      <.0001      0.05
TRTPN(ATPTN)  3          3          3          4           -11.37      <.0001      0.05
TRTPN(ATPTN)  3          3          1          5             6.47      <.0001      0.05
TRTPN(ATPTN)  3          3          2          5             1.65      0.0982      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
233 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          2         1          5            3.3794      4.1658
TRTPN(ATPTN)  3          2          2          5            2.4059      3.3152
TRTPN(ATPTN)  3          2          3          5            2.1712      2.8614
TRTPN(ATPTN)  3          2          1          6            0.6481      1.4352
TRTPN(ATPTN)  3          2          2          6           -0.4733      0.4360
TRTPN(ATPTN)  3          2          3          6            0.1987      0.8889
TRTPN(ATPTN)  3          2          1          7            1.8913      2.6792
TRTPN(ATPTN)  3          2          2          7            0.9705      1.8833
TRTPN(ATPTN)  3          2          3          7            1.2456      1.9368
TRTPN(ATPTN)  3          2          1          8            4.2643      5.0532
TRTPN(ATPTN) 3          2          2          8            3.6498      4.5642
TRTPN(ATPTN)  3          2          3          8            2.8795      3.5740
TRTPN(ATPTN)  3          2          1          9            4.4968      5.2830
TRTPN(ATPTN)  3          2          2          9            4.2402      5.1486
TRTPN(ATPTN)  3          2          3          9            2.9368      3.6292
TRTPN(ATPTN)  1          3          2          3           -1.1545     -0.3649
TRTPN(ATPTN)  1          3          3          3           -1.7993     -1.0142
TRTPN(ATPTN)  1          3          1          4           -2.7625     -2.2734
TRTPN(ATPTN)  1          3          2          4           -4.2408     -3.4502
TRTPN(ATPTN)  1          3          3          4           -3.7984    -3.0124
TRTPN(ATPTN)  1          3          1          5           -0.3562      0.1326
TRTPN(ATPTN)  1          3          2          5           -1.4176     -0.6300
TRTPN(ATPTN)  1          3          3          5           -1.7606     -0.9755
TRTPN(ATPTN)  1          3          1          6           -3.0877     -2.5977
TRTPN(ATPTN)  1          3          2          6           -4.2968     -3.5092
TRTPN(ATPTN)  1          3          3          6           -3.7331     -2.9481
TRTPN(ATPTN)  1          3          1          7           -1.8446     -1.3536
TRTPN(ATPTN)  1          3          2          7           -2.8532     -2.0617
TRTPN(ATPTN)  1          3          3          7           -2.6861     -1.9002
TRTPN(ATPTN)  1          3          1          8            0.5281      1.0207
TRTPN(ATPTN)  1          3          2          8           -0.1741      0.6194
TRTPN(ATPTN)  1          3          3          8           -1.0520     -0.2632
TRTPN(ATPTN)  1          3          1          9            0.7613      1.2498
TRTPN(ATPTN)  1          3          2          9            0.4168      1.2033
TRTPN(ATPTN)  1          3          3          9           -0.9948     -0.2079
TRTPN(ATPTN)  2          3          3          3           -1.1017     -0.1923
TRTPN(ATPTN)  2          3          1          4           -2.1529     -1.3636
TRTPN(ATPTN)  2          3          2          4           -3.4343     -2.7373
TRTPN(ATPTN)  2          3          3          4           -3.1008     -2.1906
TRTPN(ATPTN)  2          3          1          5            0.2534      1.0425
TRTPN(ATPTN)  2          3          2          5           -0.6112     0.08300
TRTPN(ATPTN)  2          3          3          5           -1.0630     -0.1536
TRTPN(ATPTN)  2          3          1          6           -2.4779     -1.6881
TRTPN(ATPTN)  2          3          2          6           -3.4904     -2.7962
TRTPN(ATPTN)  2          3          3          6           -3.0356     -2.1261
TRTPN(ATPTN)  2          3          1          7           -1.2347     -0.4441
TRTPN(ATPTN)  2          3          2          7           -2.0469     -1.3486
TRTPN(ATPTN)  2          3          3          7           -1.9886     -1.0783
TRTPN(ATPTN)  2          3          1          8            1.1383      1.9299
TRTPN(ATPTN)  2          3          2          8            0.6322      1.3325
TRTPN(ATPTN)  2          3          3          8           -0.3542      0.5585
TRTPN(ATPTN)  2          3          1          9            1.3709      2.1597
TRTPN(ATPTN)  2          3          2          9            1.2230      1.9165
TRTPN(ATPTN)  2          3          3          9           -0.2972      0.6139
TRTPN(ATPTN)  3          3          1          4           -1.5036     -0.7188
TRTPN(ATPTN)  3          3          2          4           -2.8939     -1.9836
TRTPN(ATPTN)  3          3          3          4           -2.3432     -1.6541
TRTPN(ATPTN)  3          3          1          5            0.9027      1.6873
TRTPN(ATPTN)  3          3          2          5          -0.07093      0.8368
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
234 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          3          3          5          WORK.ANA_DATA   0.03871    0.1755  5649
TRTPN(ATPTN)  3          3          1          6          WORK.ANA_DATA   -1.4359    0.2002  2655
TRTPN(ATPTN)  3          3          2          6          WORK.ANA_DATA   -2.4962    0.2315  2648
TRTPN(ATPTN)  3          3          3          6          WORK.ANA_DATA   -1.9338    0.1755  5649
TRTPN(ATPTN)  3          3          1          7          WORK.ANA_DATA   -0.1924    0.2004  2662
TRTPN(ATPTN)  3          3          2          7          WORK.ANA_DATA   -1.0507    0.2323  2676
TRTPN(ATPTN)  3          3          3          7          WORK.ANA_DATA   -0.8864    0.1758  5650
TRTPN(ATPTN)  3          3          1          8          WORK.ANA_DATA    2.1811    0.2007  2672
TRTPN(ATPTN)  3          3          2          8          WORK.ANA_DATA    1.6294    0.2328  2691
TRTPN(ATPTN)  3          3          3          8          WORK.ANA_DATA    0.7492    0.1766  5651
TRTPN(ATPTN)  3          3          1          9          WORK.ANA_DATA    2.4123    0.2000  2646
TRTPN(ATPTN)  3          3          2          9          WORK.ANA_DATA    2.2168    0.2312  2641
TRTPN(ATPTN)  3          3          3          9          WORK.ANA_DATA    0.8054    0.1760  5650
TRTPN(ATPTN)  1          4          2          4          WORK.ANA_DATA   -1.3276    0.2015  2688
TRTPN(ATPTN)  1          4          3          4          WORK.ANA_DATA   -0.8875    0.2004  2659
TRTPN(ATPTN)  1          4          1          5          WORK.ANA_DATA    2.4062    0.1246  5652
TRTPN(ATPTN)  1          4          2          5          WORK.ANA_DATA    1.4941    0.2008  2659
TRTPN(ATPTN)  1          4          3          5          WORK.ANA_DATA    1.1499    0.2001  2650
TRTPN(ATPTN)  1          4          1          6          WORK.ANA_DATA   -0.3247    0.1249  5652
TRTPN(ATPTN)  1          4          2          6          WORK.ANA_DATA   -1.3850    0.2008  2659
TRTPN(ATPTN)  1          4          3          6          WORK.ANA_DATA   -0.8226    0.2001  2650
TRTPN(ATPTN)  1          4          1          7          WORK.ANA_DATA    0.9189    0.1252  5654
TRTPN(ATPTN)  1          4          2          7          WORK.ANA_DATA   0.06053    0.2018  2697
TRTPN(ATPTN)  1          4          3          7          WORK.ANA_DATA    0.2248    0.2004  2660
TRTPN(ATPTN)  1          4          1          8          WORK.ANA_DATA    3.2924    0.1255  5653
TRTPN(ATPTN)  1          4          2          8          WORK.ANA_DATA    2.7406    0.2023  2717
TRTPN(ATPTN)  1          4          3          8          WORK.ANA_DATA    1.8604    0.2011  2688
TRTPN(ATPTN)  1          4          1          9          WORK.ANA_DATA    3.5235    0.1245  5652
TRTPN(ATPTN)  1          4          2          9          WORK.ANA_DATA    3.3280    0.2005  2650
TRTPN(ATPTN)  1          4          3          9          WORK.ANA_DATA    1.9166    0.2006  2669
TRTPN(ATPTN)  2          4          3          4          WORK.ANA_DATA    0.4401    0.2323  2676
TRTPN(ATPTN)  2          4          1          5          WORK.ANA_DATA    3.7338    0.2015  2685
TRTPN(ATPTN)  2          4          2          5          WORK.ANA_DATA    2.8217    0.1773  5652
TRTPN(ATPTN)  2          4          3          5          WORK.ANA_DATA    2.4775    0.2321  2669
TRTPN(ATPTN)  2          4          1          6          WORK.ANA_DATA    1.0028    0.2017  2692
TRTPN(ATPTN)  2          4          2          6          WORK.ANA_DATA  -0.05746    0.1773  5652
TRTPN(ATPTN)  2          4          3          6          WORK.ANA_DATA    0.5049    0.2321  2669
TRTPN(ATPTN)  2          4          1          7          WORK.ANA_DATA    2.2464    0.2018  2699
TRTPN(ATPTN)  2          4          2          7          WORK.ANA_DATA    1.3881    0.1784  5653
TRTPN(ATPTN)  2          4          3          7          WORK.ANA_DATA    1.5524    0.2323  2676
TRTPN(ATPTN)  2          4          1          8          WORK.ANA_DATA    4.6199    0.2021  2709
TRTPN(ATPTN)  2          4          2          8          WORK.ANA_DATA    4.0682    0.1789  5652
TRTPN(ATPTN)  2          4          3          8          WORK.ANA_DATA    3.1880    0.2329  2697
TRTPN(ATPTN)  2          4          1          9          WORK.ANA_DATA    4.8511    0.2014  2683
TRTPN(ATPTN)  2          4          2          9          WORK.ANA_DATA    4.6556    0.1772  5656
TRTPN(ATPTN)  2          4          3          9          WORK.ANA_DATA    3.2442    0.2325  2683
TRTPN(ATPTN)  3          4          1          5          WORK.ANA_DATA    3.2936    0.2003  2657
TRTPN(ATPTN)  3          4          2          5          WORK.ANA_DATA    2.3816    0.2317  2655
TRTPN(ATPTN)  3          4          3          5          WORK.ANA_DATA    2.0374    0.1758  5650
TRTPN(ATPTN)  3          4          1          6          WORK.ANA_DATA    0.5627    0.2005  2664
TRTPN(ATPTN)  3          4          2          6          WORK.ANA_DATA   -0.4976    0.2317  2655
TRTPN(ATPTN)  3          4          3          6          WORK.ANA_DATA   0.06484    0.1758  5650
TRTPN(ATPTN)  3          4          1          7          WORK.ANA_DATA    1.8063    0.2007  2671
TRTPN(ATPTN)  3          4          2          7          WORK.ANA_DATA    0.9480    0.2325  2683
TRTPN(ATPTN)  3          4          3          7          WORK.ANA_DATA    1.1123    0.1760  5650
TRTPN(ATPTN)  3          4          1          8          WORK.ANA_DATA    4.1798    0.2009  2681
TRTPN(ATPTN)  3          4          2          8          WORK.ANA_DATA    3.6281    0.2330  2698
TRTPN(ATPTN)  3          4          3          8          WORK.ANA_DATA    2.7479    0.1769  5652
TRTPN(ATPTN)  3          4          1          9          WORK.ANA_DATA    4.4110    0.2002  2655
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
235 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          3          3          5             0.22      0.8254      0.05
TRTPN(ATPTN)  3          3          1          6            -7.17      <.0001      0.05
TRTPN(ATPTN)  3          3          2          6           -10.78      <.0001      0.05
TRTPN(ATPTN)  3          3          3          6           -11.02      <.0001      0.05
TRTPN(ATPTN)  3          3          1          7            -0.96      0.3373      0.05
TRTPN(ATPTN)  3          3          2         7            -4.52      <.0001      0.05
TRTPN(ATPTN)  3          3          3          7            -5.04      <.0001      0.05
TRTPN(ATPTN)  3          3          1          8            10.87      <.0001      0.05
TRTPN(ATPTN)  3          3          2          8             7.00      <.0001      0.05
TRTPN(ATPTN)  3          3          3          8             4.24      <.0001      0.05
TRTPN(ATPTN)  3          3          1          9            12.06      <.0001      0.05
TRTPN(ATPTN)  3          3          2          9             9.59      <.0001      0.05
TRTPN(ATPTN)  3          3          3          9             4.58      <.0001      0.05
TRTPN(ATPTN)  1          4          2          4            -6.59      <.0001      0.05
TRTPN(ATPTN)  1          4          3          4            -4.43      <.0001      0.05
TRTPN(ATPTN)  1          4          1          5            19.31      <.0001      0.05
TRTPN(ATPTN)  1          4          2          5             7.44      <.0001      0.05
TRTPN(ATPTN)  1          4          3          5             5.75      <.0001      0.05
TRTPN(ATPTN)  1          4          1          6            -2.60      0.0093      0.05
TRTPN(ATPTN)  1          4          2          6            -6.90      <.0001      0.05
TRTPN(ATPTN)  1          4          3          6            -4.11      <.0001      0.05
TRTPN(ATPTN)  1          4          1          7             7.34      <.0001      0.05
TRTPN(ATPTN)  1          4          2          7             0.30      0.7642      0.05
TRTPN(ATPTN)  1          4          3          7             1.12      0.2619      0.05
TRTPN(ATPTN)  1          4          1          8            26.23      <.0001      0.05
TRTPN(ATPTN)  1          4          2          8            13.55      <.0001      0.05
TRTPN(ATPTN)  1          4          3          8             9.25      <.0001      0.05
TRTPN(ATPTN)  1          4          1          9            28.30      <.0001      0.05
TRTPN(ATPTN)  1          4          2          9            16.60     <.0001      0.05
TRTPN(ATPTN)  1          4          3          9             9.55      <.0001      0.05
TRTPN(ATPTN)  2          4          3          4             1.89      0.0583      0.05
TRTPN(ATPTN)  2          4          1          5            18.53      <.0001      0.05
TRTPN(ATPTN)  2          4          2          5            15.91      <.0001      0.05
TRTPN(ATPTN)  2          4          3          5            10.67      <.0001      0.05
TRTPN(ATPTN)  2          4          1          6             4.97      <.0001      0.05
TRTPN(ATPTN)  2          4          2          6            -0.32      0.7459      0.05
TRTPN(ATPTN)  2          4          3          6             2.18      0.0297      0.05
TRTPN(ATPTN)  2          4          1         7            11.13      <.0001      0.05
TRTPN(ATPTN)  2          4          2          7             7.78      <.0001      0.05
TRTPN(ATPTN)  2          4          3          7             6.68      <.0001      0.05
TRTPN(ATPTN)  2          4          1          8            22.86      <.0001      0.05
TRTPN(ATPTN)  2          4          2          8            22.74      <.0001      0.05
TRTPN(ATPTN)  2          4          3          8            13.69      <.0001      0.05
TRTPN(ATPTN)  2          4          1          9            24.09      <.0001      0.05
TRTPN(ATPTN)  2          4          2          9            26.28      <.0001      0.05
TRTPN(ATPTN)  2          4          3          9            13.95      <.0001      0.05
TRTPN(ATPTN)  3          4          1          5            16.44      <.0001      0.05
TRTPN(ATPTN)  3          4          2          5            10.28      <.0001      0.05
TRTPN(ATPTN)  3          4          3          5            11.59      <.0001      0.05
TRTPN(ATPTN)  3          4          1          6             2.81      0.0050      0.05
TRTPN(ATPTN)  3          4          2          6            -2.15      0.0318      0.05
TRTPN(ATPTN)  3          4          3          6             0.37      0.7122      0.05
TRTPN(ATPTN)  3          4          1          7             9.00      <.0001      0.05
TRTPN(ATPTN)  3          4          2          7             4.08      <.0001      0.05
TRTPN(ATPTN)  3          4          3          7             6.32      <.0001      0.05
TRTPN(ATPTN)  3          4          1          8            20.80      <.0001      0.05
TRTPN(ATPTN)  3          4          2          8            15.57      <.0001      0.05
TRTPN(ATPTN)  3          4          3          8            15.54      <.0001      0.05
TRTPN(ATPTN)  3          4          1          9            22.03      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
236 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          3          3          5           -0.3053      0.3827
TRTPN(ATPTN)  3          3          1          6           -1.8286     -1.0433
TRTPN(ATPTN)  3          3          2          6           -2.9501     -2.0424
TRTPN(ATPTN)  3          3          3          6           -2.2778     -1.5898
TRTPN(ATPTN)  3          3          1          7          -0.5854      0.2006
TRTPN(ATPTN)  3          3          2          7           -1.5062     -0.5951
TRTPN(ATPTN)  3          3          3          7           -1.2310     -0.5419
TRTPN(ATPTN)  3          3          1          8            1.7876      2.5746
TRTPN(ATPTN)  3          3          2          8            1.1730      2.0858
TRTPN(ATPTN)  3          3          3          8            0.4030      1.0954
TRTPN(ATPTN)  3          3          1          9            2.0202      2.8045
TRTPN(ATPTN)  3          3          2          9            1.7634      2.6702
TRTPN(ATPTN)  3          3          3          9            0.4603      1.1505
TRTPN(ATPTN)  1          4          2          4           -1.7227     -0.9324
TRTPN(ATPTN)  1          4          3          4           -1.2803     -0.4946
TRTPN(ATPTN)  1          4          1          5            2.1620      2.6504
TRTPN(ATPTN)  1          4          2          5            1.1005      1.8878
TRTPN(ATPTN)  1          4          3          5            0.7575      1.5423
TRTPN(ATPTN)  1          4          1          6           -0.5695    -0.07997
TRTPN(ATPTN)  1          4          2          6           -1.7787     -0.9913
TRTPN(ATPTN)  1          4          3          6           -1.2150     -0.4302
TRTPN(ATPTN)  1          4          1          7            0.6735      1.1642
TRTPN(ATPTN)  1          4          2          7           -0.3351      0.4562
TRTPN(ATPTN)  1          4          3          7           -0.1681      0.6177
TRTPN(ATPTN)  1          4          1          8            3.0463      3.5384
TRTPN(ATPTN)  1          4          2          8            2.3440      3.1373
TRTPN(ATPTN)  1          4          3          8            1.4661      2.2547
TRTPN(ATPTN)  1          4          1          9            3.2795      3.7676
TRTPN(ATPTN)  1          4          2          9            2.9349      3.7212
TRTPN(ATPTN)  1          4          3          9            1.5233      2.3100
TRTPN(ATPTN)  2          4          3          4          -0.01544      0.8957
TRTPN(ATPTN)  2          4          1          5            3.3387      4.1288
TRTPN(ATPTN)  2          4          2          5            2.4741      3.1694
TRTPN(ATPTN)  2          4          3          5            2.0223     2.9326
TRTPN(ATPTN)  2          4          1          6            0.6074      1.3982
TRTPN(ATPTN)  2          4          2          6           -0.4051      0.2902
TRTPN(ATPTN)  2          4          3          6           0.04980      0.9601
TRTPN(ATPTN)  2          4          1          7            1.8506      2.6422
TRTPN(ATPTN)  2          4          2          7            1.0384      1.7378
TRTPN(ATPTN)  2          4          3          7            1.0968      2.0079
TRTPN(ATPTN)  2          4          1          8            4.2237      5.0162
TRTPN(ATPTN)  2          4          2          8            3.7175      4.4189
TRTPN(ATPTN)  2          4          3          8            2.7312      3.6447
TRTPN(ATPTN)  2          4          1          9            4.4562      5.2460
TRTPN(ATPTN)  2          4          2          9            4.3083      5.0029
TRTPN(ATPTN)  2          4          3          9            2.7882      3.7001
TRTPN(ATPTN)  3          4          1          5            2.9009      3.6864
TRTPN(ATPTN)  3          4          2          5            1.9273      2.8359
TRTPN(ATPTN)  3          4          3          5            1.6928      2.3819
TRTPN(ATPTN)  3          4          1          6            0.1696      0.9558
TRTPN(ATPTN)  3          4          2          6           -0.9518    -0.04331
TRTPN(ATPTN)  3          4          3          6           -0.2797      0.4094
TRTPN(ATPTN)  3          4          1          7            1.4128      2.1998
TRTPN(ATPTN)  3          4          2          7            0.4920      1.4039
TRTPN(ATPTN)  3          4          3          7            0.7672      1.4573
TRTPN(ATPTN)  3          4          1          8            3.7858      4.5738
TRTPN(ATPTN)  3          4          2          8            3.1712      4.0849
TRTPN(ATPTN)  3          4          3          8            2.4011      3.0946
TRTPN(ATPTN)  3          4          1          9            4.0184      4.8036
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
237 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate    Error    DF
TRTPN(ATPTN)  3          4          2          9          WORK.ANA_DATA    4.2155    0.2314  2648
TRTPN(ATPTN)  3          4          3          9          WORK.ANA_DATA    2.8041    0.1763  5651
TRTPN(ATPTN)  1          5          2          5          WORK.ANA_DATA   -0.9120    0.2007  2657
TRTPN(ATPTN)  1          5          3          5          WORK.ANA_DATA   -1.2563    0.2001  2648
TRTPN(ATPTN)  1          5          1          6          WORK.ANA_DATA   -2.7309    0.1247  5651
TRTPN(ATPTN)  1          5          2          6          WORK.ANA_DATA   -3.7912    0.2007  2657
TRTPN(ATPTN)  1          5          3          6          WORK.ANA_DATA   -3.2288    0.2001  2648
TRTPN(ATPTN)  1          5          1          7          WORK.ANA_DATA   -1.4873    0.1250  5651
TRTPN(ATPTN)  1          5          2          7          WORK.ANA_DATA   -2.3457    0.2017  2695
TRTPN(ATPTN)  1          5          3          7          WORK.ANA_DATA   -2.1814    0.2003  2657
TRTPN(ATPTN)  1          5          1          8          WORK.ANA_DATA    0.8862    0.1254  5653
TRTPN(ATPTN)  1          5          2          8          WORK.ANA_DATA    0.3344    0.2022  2715
TRTPN(ATPTN)  1          5          3          8          WORK.ANA_DATA   -0.5458    0.2010  2685
TRTPN(ATPTN)  1          5          1          9          WORK.ANA_DATA    1.1174    0.1244  5654
TRTPN(ATPTN)  1          5          2          9          WORK.ANA_DATA    0.9218    0.2004  2648
TRTPN(ATPTN)  1          5          3          9          WORK.ANA_DATA   -0.4896    0.2005  2667
TRTPN(ATPTN)  2          5          3          5          WORK.ANA_DATA   -0.3442    0.2315  2648
TRTPN(ATPTN)  2          5          1          6          WORK.ANA_DATA   -1.8189    0.2009  2664
TRTPN(ATPTN)  2          5          2          6          WORK.ANA_DATA   -2.8792    0.1765  5649
TRTPN(ATPTN)  2          5          3          6          WORK.ANA_DATA   -2.3168    0.2315  2648
TRTPN(ATPTN)  2          5          1          7          WORK.ANA_DATA   -0.5753    0.2011  2671
TRTPN(ATPTN)  2          5          2          7          WORK.ANA_DATA   -1.4336    0.1776  5652
TRTPN(ATPTN)  2          5          3          7          WORK.ANA_DATA   -1.2693    0.2317  2655
TRTPN(ATPTN)  2          5          1          8          WORK.ANA_DATA    1.7982    0.2013  2681
TRTPN(ATPTN)  2          5          2          8          WORK.ANA_DATA    1.2465    0.1782  5654
TRTPN(ATPTN)  2          5          3          8          WORK.ANA_DATA    0.3663    0.2323  2676
TRTPN(ATPTN)  2          5          1          9          WORK.ANA_DATA    2.0294    0.2006  2655
TRTPN(ATPTN)  2          5          2          9          WORK.ANA_DATA    1.8339    0.1763  5653
TRTPN(ATPTN)  2          5          3          9          WORK.ANA_DATA    0.4225    0.2319  2662
TRTPN(ATPTN)  3          5          1          6          WORK.ANA_DATA   -1.4747    0.2002  2655
TRTPN(ATPTN)  3          5          2          6          WORK.ANA_DATA   -2.5349    0.2315  2648
TRTPN(ATPTN)  3          5          3          6          WORK.ANA_DATA   -1.9725    0.1755  5649
TRTPN(ATPTN)  3          5          1          7          WORK.ANA_DATA   -0.2311    0.2004  2662
TRTPN(ATPTN)  3          5          2          7          WORK.ANA_DATA   -1.0894    0.2323  2676
TRTPN(ATPTN)  3          5          3          7          WORK.ANA_DATA   -0.9251    0.1758  5650
TRTPN(ATPTN)  3          5          1          8          WORK.ANA_DATA    2.1424    0.2007  2672
TRTPN(ATPTN)  3          5          2          8          WORK.ANA_DATA    1.5907    0.2328  2691
TRTPN(ATPTN)  3          5          3          8          WORK.ANA_DATA    0.7105    0.1766  5651
TRTPN(ATPTN)  3          5          1          9          WORK.ANA_DATA    2.3736    0.2000  2646
TRTPN(ATPTN)  3          5          2          9          WORK.ANA_DATA    2.1781    0.2312  2641
TRTPN(ATPTN)  3          5          3          9          WORK.ANA_DATA    0.7667    0.1760  5650
TRTPN(ATPTN)  1          6          2          6          WORK.ANA_DATA   -1.0603    0.2009  2664
TRTPN(ATPTN)  1          6          3          6          WORK.ANA_DATA   -0.4979    0.2002  2655
TRTPN(ATPTN)  1          6          1          7          WORK.ANA_DATA    1.2436    0.1253  5653
TRTPN(ATPTN)  1          6          2          7          WORK.ANA_DATA    0.3853    0.2019  2702
TRTPN(ATPTN)  1          6          3          7          WORK.ANA_DATA    0.5495    0.2005  2664
TRTPN(ATPTN)  1          6          1          8          WORK.ANA_DATA    3.6171    0.1257  5654
TRTPN(ATPTN)  1          6          2          8          WORK.ANA_DATA    3.0653    0.2024  2722
TRTPN(ATPTN)  1          6          3          8          WORK.ANA_DATA    2.1851    0.2012  2692
TRTPN(ATPTN)  1          6          1          9          WORK.ANA_DATA    3.8483    0.1247  5654
TRTPN(ATPTN)  1          6          2          9          WORK.ANA_DATA    3.6528    0.2006  2655
TRTPN(ATPTN)  1          6          3          9          WORK.ANA_DATA    2.2413    0.2007  2674
TRTPN(ATPTN)  2          6          3          6          WORK.ANA_DATA    0.5624    0.2315  2648
TRTPN(ATPTN)  2          6          1          7          WORK.ANA_DATA    2.3039    0.2011  2671
TRTPN(ATPTN)  2          6          2          7          WORK.ANA_DATA    1.4456    0.1776  5652
TRTPN(ATPTN)  2          6          3          7          WORK.ANA_DATA    1.6098    0.2317  2655
TRTPN(ATPTN)  2          6          1          8          WORK.ANA_DATA    4.6774    0.2013  2681
TRTPN(ATPTN)  2         6          2          8          WORK.ANA_DATA    4.1256    0.1782  5654
TRTPN(ATPTN)  2          6          3          8          WORK.ANA_DATA    3.2454    0.2323  2676
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
238 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          4          2          9            18.22      <.0001      0.05
TRTPN(ATPTN)  3          4          3          9            15.90      <.0001      0.05
TRTPN(ATPTN)  1          5          2          5            -4.54      <.0001      0.05
TRTPN(ATPTN)  1          5          3          5            -6.28      <.0001      0.05
TRTPN(ATPTN)  1          5          1          6           -21.89      <.0001      0.05
TRTPN(ATPTN)  1          5          2          6           -18.89      <.0001      0.05
TRTPN(ATPTN)  1          5          3          6           -16.14      <.0001      0.05
TRTPN(ATPTN)  1          5          1          7           -11.90      <.0001      0.05
TRTPN(ATPTN)  1          5          2          7           -11.63      <.0001      0.05
TRTPN(ATPTN)  1          5          3          7           -10.89      <.0001      0.05
TRTPN(ATPTN)  1          5          1          8             7.06      <.0001      0.05
TRTPN(ATPTN)  1          5          2          8             1.65      0.0983      0.05
TRTPN(ATPTN)  1          5          3          8            -2.72      0.0067      0.05
TRTPN(ATPTN)  1          5          1          9             8.98      <.0001      0.05
TRTPN(ATPTN)  1          5          2          9             4.60      <.0001      0.05
TRTPN(ATPTN) 1          5          3          9            -2.44      0.0147      0.05
TRTPN(ATPTN)  2          5          3          5            -1.49      0.1371      0.05
TRTPN(ATPTN)  2          5          1          6            -9.05      <.0001      0.05
TRTPN(ATPTN)  2          5          2          6           -16.31      <.0001      0.05
TRTPN(ATPTN)  2          5          3          6           -10.01      <.0001      0.05
TRTPN(ATPTN)  2          5          1          7            -2.86      0.0043      0.05
TRTPN(ATPTN)  2          5          2          7            -8.07      <.0001      0.05
TRTPN(ATPTN)  2          5          3          7            -5.48      <.0001      0.05
TRTPN(ATPTN)  2          5          1          8             8.93      <.0001      0.05
TRTPN(ATPTN)  2          5          2          8             6.99      <.0001      0.05
TRTPN(ATPTN)  2          5          3          8             1.58      0.1150      0.05
TRTPN(ATPTN)  2          5          1          9            10.11      <.0001      0.05
TRTPN(ATPTN)  2          5          2          9            10.40      <.0001      0.05
TRTPN(ATPTN)  2          5          3          9             1.82      0.0686      0.05
TRTPN(ATPTN)  3          5          1          6            -7.36      <.0001      0.05
TRTPN(ATPTN)  3          5          2          6           -10.95      <.0001      0.05
TRTPN(ATPTN)  3          5          3          6           -11.24      <.0001      0.05
TRTPN(ATPTN)  3          5          1          7            -1.15      0.2491      0.05
TRTPN(ATPTN)  3          5          2          7            -4.69      <.0001      0.05
TRTPN(ATPTN)  3          5          3          7            -5.26      <.0001      0.05
TRTPN(ATPTN)  3          5          1          8            10.68      <.0001      0.05
TRTPN(ATPTN)  3          5          2          8             6.83      <.0001      0.05
TRTPN(ATPTN)  3          5          3          8             4.02      <.0001      0.05
TRTPN(ATPTN)  3          5          1          9            11.87      <.0001      0.05
TRTPN(ATPTN)  3          5          2          9             9.42      <.0001      0.05
TRTPN(ATPTN)  3          5          3          9             4.36      <.0001      0.05
TRTPN(ATPTN)  1         6          2          6            -5.28      <.0001      0.05
TRTPN(ATPTN)  1          6          3          6            -2.49      0.0130      0.05
TRTPN(ATPTN)  1          6          1          7             9.92      <.0001      0.05
TRTPN(ATPTN)  1          6          2          7             1.91      0.0565      0.05
TRTPN(ATPTN)  1          6          3          7             2.74      0.0062      0.05
TRTPN(ATPTN)  1          6          1          8            28.77      <.0001      0.05
TRTPN(ATPTN)  1          6          2          8            15.14      <.0001      0.05
TRTPN(ATPTN)  1          6          3          8            10.86      <.0001      0.05
TRTPN(ATPTN)  1          6          1          9            30.86      <.0001      0.05
TRTPN(ATPTN)  1          6          2          9            18.21      <.0001      0.05
TRTPN(ATPTN)  1          6          3          9            11.17      <.0001      0.05
TRTPN(ATPTN)  2          6          3          6             2.43      0.0152      0.05
TRTPN(ATPTN)  2          6          1          7            11.46      <.0001      0.05
TRTPN(ATPTN)  2          6          2          7             8.14      <.0001      0.05
TRTPN(ATPTN)  2          6          3          7             6.95      <.0001      0.05
TRTPN(ATPTN)  2          6          1          8            23.23      <.0001      0.05
TRTPN(ATPTN)  2          6          2          8            23.15      <.0001      0.05
TRTPN(ATPTN)  2          6          3          8            13.97      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
239 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          4          2          9            3.7617      4.6693
TRTPN(ATPTN)  3          4          3          9            2.4584      3.1497
TRTPN(ATPTN)  1          5          2          5           -1.3056     -0.5185
TRTPN(ATPTN)  1          5          3          5           -1.6486     -0.8640
TRTPN(ATPTN)  1          5          1          6           -2.9755     -2.4864
TRTPN(ATPTN)  1          5          2          6           -4.1848     -3.3976
TRTPN(ATPTN)  1          5          3          6           -3.6211     -2.8365
TRTPN(ATPTN)  1          5          1          7           -1.7324     -1.2422
TRTPN(ATPTN)  1          5          2          7           -2.7412     -1.9501
TRTPN(ATPTN)  1          5          3          7           -2.5741     -1.7886
TRTPN(ATPTN)  1          5          1          8            0.6403      1.1321
TRTPN(ATPTN)  1          5          2          8          -0.06211      0.7309
TRTPN(ATPTN)  1          5         3          8           -0.9400     -0.1516
TRTPN(ATPTN)  1          5          1          9            0.8734      1.3613
TRTPN(ATPTN)  1          5          2          9            0.5288      1.3149
TRTPN(ATPTN)  1          5          3          9           -0.8828    -0.09636
TRTPN(ATPTN)  2          5          3          5           -0.7981      0.1096
TRTPN(ATPTN)  2          5          1          6           -2.2128     -1.4250
TRTPN(ATPTN)  2          5          2          6           -3.2251     -2.5332
TRTPN(ATPTN)  2          5          3          6           -2.7706     -1.8629
TRTPN(ATPTN)  2          5          1          7           -0.9696     -0.1810
TRTPN(ATPTN)  2          5          2          7           -1.7818     -1.0854
TRTPN(ATPTN) 2          5          3          7           -1.7236     -0.8151
TRTPN(ATPTN)  2          5          1          8            1.4034      2.1930
TRTPN(ATPTN)  2          5          2          8            0.8971      1.5958
TRTPN(ATPTN)  2          5          3          8          -0.08924      0.8217
TRTPN(ATPTN)  2          5          1          9            1.6360      2.4228
TRTPN(ATPTN)  2          5          2          9            1.4883      2.1795
TRTPN(ATPTN)  2          5          3          9          -0.03220      0.8771
TRTPN(ATPTN)  3          5          1          6           -1.8673     -1.0820
TRTPN(ATPTN)  3          5          2          6           -2.9888     -2.0811
TRTPN(ATPTN)  3          5          3          6           -2.3166    -1.6285
TRTPN(ATPTN)  3          5          1          7           -0.6241      0.1619
TRTPN(ATPTN)  3          5          2          7           -1.5449     -0.6338
TRTPN(ATPTN)  3          5          3          7           -1.2697     -0.5806
TRTPN(ATPTN)  3          5          1          8            1.7489      2.5359
TRTPN(ATPTN)  3          5          2          8            1.1343      2.0471
TRTPN(ATPTN)  3          5          3          8            0.3643      1.0567
TRTPN(ATPTN)  3          5          1          9            1.9815      2.7658
TRTPN(ATPTN)  3          5          2          9            1.7247      2.6315
TRTPN(ATPTN)  3          5          3          9            0.4216      1.1118
TRTPN(ATPTN)  1          6          2          6           -1.4542     -0.6664
TRTPN(ATPTN)  1          6          3          6           -0.8905     -0.1053
TRTPN(ATPTN)  1          6          1          7            0.9979      1.4893
TRTPN(ATPTN)  1          6          2          7          -0.01062      0.7811
TRTPN(ATPTN)  1          6          3          7            0.1564      0.9426
TRTPN(ATPTN)  1          6          1          8            3.3706      3.8635
TRTPN(ATPTN)  1          6          2          8            2.6685      3.4622
TRTPN(ATPTN)  1          6          3          8            1.7906      2.5797
TRTPN(ATPTN)  1          6          1          9            3.6038      4.0928
TRTPN(ATPTN)  1          6          2          9            3.2594      4.0461
TRTPN(ATPTN)  1          6          3          9            1.8478      2.6349
TRTPN(ATPTN)  2          6          3          6            0.1085      1.0163
TRTPN(ATPTN)  2          6          1          7            1.9096      2.6982
TRTPN(ATPTN)  2          6          2          7            1.0974      1.7937
TRTPN(ATPTN)  2          6          3          7            1.1556      2.0641
TRTPN(ATPTN)  2          6          1          8            4.2826      5.0722
TRTPN(ATPTN)  2          6          2          8            3.7763      4.4750
TRTPN(ATPTN)  2          6          3          8            2.7899      3.7009
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
240 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  2          6          1          9          WORK.ANA_DATA    4.9086    0.2006  2655
TRTPN(ATPTN)  2          6          2          9          WORK.ANA_DATA    4.7131    0.1763  5653
TRTPN(ATPTN)  2          6          3          9          WORK.ANA_DATA    3.3016    0.2319  2662
TRTPN(ATPTN)  3          6          1          7          WORK.ANA_DATA    1.7415    0.2004  2662
TRTPN(ATPTN)  3          6          2          7          WORK.ANA_DATA    0.8831    0.2323  2676
TRTPN(ATPTN)  3          6          3          7          WORK.ANA_DATA    1.0474    0.1758  5650
TRTPN(ATPTN)  3          6          1          8          WORK.ANA_DATA    4.1150    0.2007  2672
TRTPN(ATPTN)  3          6          2          8          WORK.ANA_DATA    3.5632    0.2328  2691
TRTPN(ATPTN)  3          6          3          8          WORK.ANA_DATA    2.6830    0.1766  5651
TRTPN(ATPTN)  3          6          1          9          WORK.ANA_DATA    4.3462    0.2000  2646
TRTPN(ATPTN)  3          6          2          9          WORK.ANA_DATA    4.1506    0.2312  2641
TRTPN(ATPTN)  3          6          3          9          WORK.ANA_DATA    2.7392    0.1760  5650
TRTPN(ATPTN)  1          7          2          7          WORK.ANA_DATA   -0.8583    0.2021  2709
TRTPN(ATPTN)  1          7          3          7          WORK.ANA_DATA   -0.6940    0.2007  2671
TRTPN(ATPTN)  1          7          1          8          WORK.ANA_DATA    2.3735    0.1260  5654
TRTPN(ATPTN)  1          7          2          8          WORK.ANA_DATA    1.8218    0.2026  2729
TRTPN(ATPTN)  1          7          3          8          WORK.ANA_DATA    0.9415    0.2014  2700
TRTPN(ATPTN)  1          7          1          9          WORK.ANA_DATA    2.6047    0.1250  5655
TRTPN(ATPTN)  1          7          2          9          WORK.ANA_DATA    2.4092    0.2008 2662
TRTPN(ATPTN)  1          7          3          9          WORK.ANA_DATA    0.9978    0.2009  2681
TRTPN(ATPTN)  2          7          3          7          WORK.ANA_DATA    0.1643    0.2325  2683
TRTPN(ATPTN)  2          7          1          8          WORK.ANA_DATA    3.2318    0.2023  2719
TRTPN(ATPTN)  2          7          2          8          WORK.ANA_DATA    2.6801    0.1792  5654
TRTPN(ATPTN)  2          7          3          8          WORK.ANA_DATA    1.7999    0.2332  2704
TRTPN(ATPTN)  2          7          1          9          WORK.ANA_DATA    3.4630    0.2016  2693
TRTPN(ATPTN)  2          7          2          9          WORK.ANA_DATA    3.2675    0.1774  5656
TRTPN(ATPTN)  2          7          3          9          WORK.ANA_DATA    1.8561    0.2327  2690
TRTPN(ATPTN)  3          7          1          8          WORK.ANA_DATA    3.0675    0.2009  2681
TRTPN(ATPTN)  3          7          2          8          WORK.ANA_DATA    2.5158    0.2330  2698
TRTPN(ATPTN)  3          7          3          8          WORK.ANA_DATA    1.6356    0.1769  5652
TRTPN(ATPTN)  3          7          1          9          WORK.ANA_DATA    3.2987    0.2002  2655
TRTPN(ATPTN)  3          7          2          9          WORK.ANA_DATA    3.1032    0.2314  2648
TRTPN(ATPTN)  3          7          3          9          WORK.ANA_DATA    1.6918    0.1763  5651
TRTPN(ATPTN)  1          8          2          8          WORK.ANA_DATA   -0.5517    0.2028  2738
TRTPN(ATPTN)  1          8          3          8          WORK.ANA_DATA   -1.4320    0.2016  2709
TRTPN(ATPTN)  1          8          1          9          WORK.ANA_DATA    0.2312    0.1254  5655
TRTPN(ATPTN)  1          8          2          9          WORK.ANA_DATA   0.03568    0.2011  2672
TRTPN(ATPTN)  1          8          3          9          WORK.ANA_DATA   -1.3757    0.2012  2690
TRTPN(ATPTN)  2          8          3          8          WORK.ANA_DATA   -0.8802    0.2336  2719
TRTPN(ATPTN)  2          8          1          9          WORK.ANA_DATA    0.7829    0.2022  2712
TRTPN(ATPTN)  2          8          2          9          WORK.ANA_DATA    0.5874    0.1780  5658
TRTPN(ATPTN)  2          8          3          9          WORK.ANA_DATA   -0.8240    0.2332  2705
TRTPN(ATPTN)  3          8          1          9          WORK.ANA_DATA    1.6631    0.2010  2683
TRTPN(ATPTN)  3          8          2          9          WORK.ANA_DATA    1.4676    0.2320  2669
TRTPN(ATPTN)  3          8          3          9          WORK.ANA_DATA   0.05621    0.1771  5652
TRTPN(ATPTN)  1          9          2          9          WORK.ANA_DATA   -0.1955    0.2004  2646
TRTPN(ATPTN)  1          9          3          9          WORK.ANA_DATA   -1.6069    0.2005  2664
TRTPN(ATPTN)  2          9          3          9          WORK.ANA_DATA   -1.4114    0.2316  2655
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  2          6          1          9            24.46      <.0001      0.05
TRTPN(ATPTN)  2          6          2          9            26.73      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
241 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  2          6          3          9            14.24      <.0001      0.05
TRTPN(ATPTN)  3          6          1          7             8.69      <.0001      0.05
TRTPN(ATPTN)  3          6          2          7             3.80      0.0001      0.05
TRTPN(ATPTN)  3          6          3          7             5.96      <.0001      0.05
TRTPN(ATPTN)  3          6          1          8            20.51      <.0001      0.05
TRTPN(ATPTN)  3          6          2          8            15.31      <.0001      0.05
TRTPN(ATPTN)  3          6          3          8            15.19      <.0001      0.05
TRTPN(ATPTN)  3          6          1          9            21.73      <.0001      0.05
TRTPN(ATPTN)  3          6          2          9            17.95      <.0001      0.05
TRTPN(ATPTN)  3          6          3          9            15.56      <.0001      0.05
TRTPN(ATPTN)  1          7          2          7           -4.25      <.0001      0.05
TRTPN(ATPTN)  1          7          3          7            -3.46      0.0006      0.05
TRTPN(ATPTN)  1          7          1          8            18.84      <.0001      0.05
TRTPN(ATPTN)  1          7          2          8             8.99      <.0001      0.05
TRTPN(ATPTN)  1          7          3          8             4.68      <.0001      0.05
TRTPN(ATPTN)  1          7          1          9            20.84      <.0001      0.05
TRTPN(ATPTN)  1          7          2          9            12.00      <.0001      0.05
TRTPN(ATPTN)  1          7          3          9             4.97      <.0001      0.05
TRTPN(ATPTN)  2          7          3          7             0.71      0.4800      0.05
TRTPN(ATPTN)  2          7         1          8            15.97      <.0001      0.05
TRTPN(ATPTN)  2          7          2          8            14.95      <.0001      0.05
TRTPN(ATPTN)  2          7          3          8             7.72      <.0001      0.05
TRTPN(ATPTN)  2          7          1          9            17.17      <.0001      0.05
TRTPN(ATPTN)  2          7          2          9            18.41      <.0001      0.05
TRTPN(ATPTN)  2          7          3          9             7.98      <.0001      0.05
TRTPN(ATPTN)  3          7          1          8            15.27      <.0001      0.05
TRTPN(ATPTN)  3          7          2          8            10.80      <.0001      0.05
TRTPN(ATPTN)  3          7          3          8             9.25      <.0001      0.05
TRTPN(ATPTN)  3          7          1          9            16.48      <.0001      0.05
TRTPN(ATPTN)  3          7          2          9            13.41      <.0001      0.05
TRTPN(ATPTN)  3          7          3          9             9.60      <.0001      0.05
TRTPN(ATPTN)  1          8          2          8            -2.72      0.0066      0.05
TRTPN(ATPTN)  1          8          3          8            -7.10      <.0001      0.05
TRTPN(ATPTN)  1          8          1          9             1.84      0.0653      0.05
TRTPN(ATPTN)  1          8          2          9             0.18      0.8592      0.05
TRTPN(ATPTN)  1          8          3          9            -6.84      <.0001      0.05
TRTPN(ATPTN)  2          8          3          8            -3.77      0.0002      0.05
TRTPN(ATPTN)  2          8          1          9             3.87      0.0001      0.05
TRTPN(ATPTN)  2          8          2          9             3.30      0.0010      0.05
TRTPN(ATPTN)  2          8          3          9            -3.53      0.0004      0.05
TRTPN(ATPTN)  3          8          1          9             8.28      <.0001      0.05
TRTPN(ATPTN)  3          8          2          9             6.32      <.0001      0.05
TRTPN(ATPTN)  3          8          3          9             0.32      0.7510      0.05
TRTPN(ATPTN)  1          9          2          9            -0.98      0.3293      0.05
TRTPN(ATPTN)  1          9          3          9            -8.02      <.0001      0.05
TRTPN(ATPTN)  2          9          3          9            -6.09      <.0001      0.05
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
             Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  2          6          1          9            4.5151      5.3020
TRTPN(ATPTN)  2          6          2          9            4.3674      5.0587
TRTPN(ATPTN)  2          6          3          9            2.8470      3.7563
TRTPN(ATPTN)  3          6          1          7            1.3485      2.1345
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
242 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          6          2         7            0.4276      1.3387
TRTPN(ATPTN)  3          6          3          7            0.7029      1.3920
TRTPN(ATPTN)  3          6          1          8            3.7215      4.5085
TRTPN(ATPTN)  3          6          2          8            3.1068      4.0197
TRTPN(ATPTN)  3          6          3          8            2.3368      3.0292
TRTPN(ATPTN)  3          6          1          9            3.9540      4.7383
TRTPN(ATPTN)  3          6          2          9            3.6973      4.6040
TRTPN(ATPTN)  3          6          3          9            2.3941      3.0843
TRTPN(ATPTN)  1          7          2          7           -1.2546     -0.4621
TRTPN(ATPTN)  1          7          3          7           -1.0875     -0.3006
TRTPN(ATPTN)  1         7          1          8            2.1265      2.6205
TRTPN(ATPTN)  1          7          2          8            1.4245      2.2190
TRTPN(ATPTN)  1          7          3          8            0.5467      1.3364
TRTPN(ATPTN)  1          7          1          9            2.3596      2.8498
TRTPN(ATPTN)  1          7          2          9            2.0154      2.8029
TRTPN(ATPTN)  1          7          3          9            0.6038      1.3917
TRTPN(ATPTN)  2          7          3          7           -0.2917      0.6202
TRTPN(ATPTN)  2          7          1          8            2.8351      3.6286
TRTPN(ATPTN)  2          7          2          8            2.3287      3.0315
TRTPN(ATPTN)  2          7          3          8            1.3427      2.2571
TRTPN(ATPTN)  2          7          1          9            3.0676      3.8584
TRTPN(ATPTN)  2          7          2          9            2.9197      3.6154
TRTPN(ATPTN)  2          7          3          9            1.3997      2.3125
TRTPN(ATPTN)  3          7          1          8            2.6736      3.4615
TRTPN(ATPTN)  3          7          2          8            2.0590      2.9726
TRTPN(ATPTN)  3          7          3          8            1.2889      1.9823
TRTPN(ATPTN)  3          7          1          9            2.9061      3.6914
TRTPN(ATPTN)  3          7          2          9            2.6494      3.5570
TRTPN(ATPTN)  3          7          3          9            1.3462      2.0374
TRTPN(ATPTN)  1          8          2          8           -0.9495     -0.1540
TRTPN(ATPTN)  1          8          3          8           -1.8273     -1.0366
TRTPN(ATPTN)  1          8          1          9          -0.01462      0.4770
TRTPN(ATPTN)  1          8          2          9           -0.3586      0.4299
TRTPN(ATPTN)  1          8          3          9           -1.7702     -0.9813
TRTPN(ATPTN)  2          8          3          8           -1.3383     -0.4222
TRTPN(ATPTN)  2          8          1          9            0.3865      1.1793
TRTPN(ATPTN)  2          8          2          9            0.2384      0.9364
TRTPN(ATPTN)  2          8          3          9           -1.2812     -0.3668
TRTPN(ATPTN)  3          8          1          9            1.2691      2.0572
TRTPN(ATPTN)  3          8          2          9            1.0126      1.9226
TRTPN(ATPTN)  3          8          3          9           -0.2910      0.4035
TRTPN(ATPTN)  1          9          2          9           -0.5884      0.1974
TRTPN(ATPTN)  1          9          3          9           -2.0000     -1.2139
TRTPN(ATPTN)  2          9          3          9           -1.8656     -0.9572
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
243 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                  Model Information
Data Set                     WORK.ANA_DATA            
Dependent Variable           AVAL                     
Covariance Structure         Compound Symmetry        
Subject Effect               USUBJID                  
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Kenward-Roger            
Degrees of Freedom Method    Kenward-Roger            
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
244 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
              Class Level Information
Class      Levels    Values
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CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
245 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
246 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
247 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
248 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
249 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
250 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
251 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
252 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
253 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                     NN9068-4148/
           
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                     NN9068-4148/
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
254 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
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TRTPN           3    1 2 3                         
ATPTN           9    1 2 3 4 5 6 7 8 9             
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             2
Columns in X                     49
Columns in Z                      0
Subjects                        720
Max Obs per Subject               9
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
255 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
          Number of Observations
Number of Observations Read            6480
Number of Observations Used            6401
Number of Observations Not Used          79
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     65035.29815169                
        1              2     62992.58883544      0.00000000
                   Convergence criteria met.                    
                                  Covariance Parameter Estimates
                                    Standard         Z
Cov Parm     Subject    Estimate       Error     Value        Pr Z     Alpha       Lower       Upper
CS           USUBJID      657.94     40.2013     16.37      <.0001      0.05      579.15      736.73
Residual                  899.99     16.9343     53.15      <.0001      0.05      867.70      934.12
Asymptotic Covariance Matrix of Estimates
Row    Cov Parm        CovP1       CovP2
   1    CS            1616.14    -32.4580
   2    Residual     -32.4580      286.77
           Fit Statistics
-2 Res Log Likelihood         62992.6
AIC (Smaller is Better)       62996.6
AICC (Smaller is Better)      62996.6
BIC (Smaller is Better)       63005.7
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
     1       2042.71          <.0001
                                    Solution for Fixed Effects
                                 Planned
                                 Treatment
                Pre Trial        for        Analysis
                anti-Diabetic    Period     Timepoint            Standard
Effect          treatment2       01 (N)     (N)        Estimate     Error    DF  t Value  Pr > |t|
Intercept                                                129.36    3.1296  2673    41.34    <.0001
TRTPN                            1                     -28.9569    3.6123  2664    -8.02    <.0001
TRTPN                            2                     -25.4338    4.1740  2655    -6.09    <.0001
TRTPN                            3                            0                                   
TRTPN(ATPTN)                     1          1            0.9972    2.4959  5650     0.40    0.6895
TRTPN(ATPTN)                     2          1            3.0880    3.3486  5649     0.92    0.3565
TRTPN(ATPTN)                     3          1            0.6433    3.3621  5650     0.19    0.8483
TRTPN(ATPTN)                     1          2           68.3246    2.4993  5650    27.34    <.0001
TRTPN(ATPTN)                     2          2           80.2365    3.3670  5654    23.83    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
256 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                                    Solution for Fixed Effects
                                 Planned
                                 Treatment
                Pre Trial        for        Analysis
                anti-Diabetic    Period     Timepoint            Standard
Effect          treatment2       01 (N)     (N)        Estimate     Error    DF  t Value  Pr > |t|
TRTPN(ATPTN)                     3          2           62.4258    3.3750  5652    18.50    <.0001
TRTPN(ATPTN)                     1          3           20.3438    2.5061  5652     8.12    <.0001
TRTPN(ATPTN)                     2          3           30.5109    3.3645  5654     9.07   <.0001
TRTPN(ATPTN)                     3          3           16.7365    3.3632  5651     4.98    <.0001
TRTPN(ATPTN)                     1          4           65.1838    2.5044  5651    26.03    <.0001
TRTPN(ATPTN)                     2          4           85.5833    3.3675  5655    25.41    <.0001
TRTPN(ATPTN)                     3          4           52.2188    3.3660  5651    15.51    <.0001
TRTPN(ATPTN)                     1          5           22.7376    2.4997  5652     9.10    <.0001
TRTPN(ATPTN)                     2          5           35.6495    3.3524  5652    10.63    <.0001
TRTPN(ATPTN)                     3          5           16.4187    3.3632  5651     4.88    <.0001
TRTPN(ATPTN)                     1          6           72.6059    2.5049  5653    28.99    <.0001
TRTPN(ATPTN)                     2          6           88.1892    3.3528  5652    26.30    <.0001
TRTPN(ATPTN)                     3          6           52.6208    3.3636  5651    15.64    <.0001
TRTPN(ATPTN)                     1          7           50.3831    2.5089  5654    20.08    <.0001
TRTPN(ATPTN)                     2          7           62.3271    3.3743  5655    18.47    <.0001
TRTPN(ATPTN)                     3          7           33.9330    3.3706  5652    10.07    <.0001
TRTPN(ATPTN)                     1          8            5.0699    2.5172  5654     2.01    0.0440
TRTPN(ATPTN)                     2          8           11.4891    3.3879  5657     3.39    0.0007
TRTPN(ATPTN)                     3          8            1.9167    3.3824  5653     0.57    0.5710
TRTPN(ATPTN)                     1          9                 0                                   
TRTPN(ATPTN)                     2          9                 0                                   
TRTPN(ATPTN)                     3          9                 0                                   
PREOAD2(ATPTN)  Metformin                   1           -2.4780    3.1407  2641    -0.79    0.4302
PREOAD2(ATPTN)  Metformin + OAD             1                 0                                   
PREOAD2(ATPTN)  Metformin                   2          -13.7059    3.1541  2671    -4.35    <.0001
PREOAD2(ATPTN)  Metformin + OAD             2                 0                                   
PREOAD2(ATPTN)  Metformin                   3          -10.4963    3.1518  2665    -3.33    0.0009
PREOAD2(ATPTN)  Metformin + OAD             3                 0                                   
PREOAD2(ATPTN)  Metformin                   4           -8.8544    3.1571  2678    -2.80    0.0051
PREOAD2(ATPTN)  Metformin + OAD             4                 0                                   
PREOAD2(ATPTN)  Metformin                   5          -11.6645    3.1514  2664    -3.70    0.0002
PREOAD2(ATPTN)  Metformin + OAD             5                 0                                   
PREOAD2(ATPTN)  Metformin                   6          -13.6864    3.1557  2675    -4.34    <.0001
PREOAD2(ATPTN)  Metformin + OAD             6                 0                                   
PREOAD2(ATPTN)  Metformin                   7          -14.2607    3.1682  2705    -4.50    <.0001
PREOAD2(ATPTN)  Metformin + OAD             7                 0                                   
PREOAD2(ATPTN)  Metformin                   8           -6.4367    3.1817  2738    -2.02    0.0432
PREOAD2(ATPTN)  Metformin + OAD             8                 0                                   
PREOAD2(ATPTN)  Metformin                   9           -3.6559    3.1435  2648    -1.16    0.2449
PREOAD2(ATPTN)  Metformin + OAD             9                 0                                   
           Type 3 Tests of Fixed Effects
                   Num     Den
Effect              DF      DF    F Value    Pr > F
TRTPN                2     716      39.78    <.0001
TRTPN(ATPTN)        16    5652       8.63    <.0001
PREOAD2(ATPTN)       9    5392       5.07    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
257 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                                     Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint                           Standard
Effect        01 (N)     (N)        Margins        Estimate     Error    DF  t Value  Pr > |t|
TRTPN(ATPTN)  1          1          WORK.ANA_DATA    100.60    2.0774  2641    48.42    <.0001
TRTPN(ATPTN)  2          1          WORK.ANA_DATA    106.21    2.9502  2641    36.00    <.0001
TRTPN(ATPTN)  3          1          WORK.ANA_DATA    129.20    2.9420  2641    43.92    <.0001
TRTPN(ATPTN)  1          2          WORK.ANA_DATA    164.28    2.0815  2655    78.92    <.0001
TRTPN(ATPTN)  2          2          WORK.ANA_DATA    179.71    2.9730  2697    60.45    <.0001
TRTPN(ATPTN)  3          2          WORK.ANA_DATA    187.33    2.9526  2669    63.45    <.0001
TRTPN(ATPTN)  1          3          WORK.ANA_DATA    117.34    2.0873  2676    56.22    <.0001
TRTPN(ATPTN)  2          3          WORK.ANA_DATA    131.03    2.9677  2683    44.15    <.0001
TRTPN(ATPTN)  3          3          WORK.ANA_DATA    142.69    2.9420  2641    48.50    <.0001
TRTPN(ATPTN)  1          4          WORK.ANA_DATA    162.71    2.0854  2669    78.03    <.0001
TRTPN(ATPTN)  2          4          WORK.ANA_DATA    186.63    2.9732  2697    62.77    <.0001
TRTPN(ATPTN)  3          4          WORK.ANA_DATA    178.70    2.9472  2655    60.63    <.0001
TRTPN(ATPTN)  1          5          WORK.ANA_DATA    119.35    2.0834  2662    57.29    <.0001
TRTPN(ATPTN)  2          5          WORK.ANA_DATA    135.79    2.9565  2654    45.93    <.0001
TRTPN(ATPTN)  3          5          WORK.ANA_DATA    141.99    2.9420  2641    48.26    <.0001
TRTPN(ATPTN)  1          6          WORK.ANA_DATA    168.56    2.0890  2683    80.69    <.0001
TRTPN(ATPTN)  2          6          WORK.ANA_DATA    187.67    2.9565  2654    63.48    <.0001
TRTPN(ATPTN)  3          6          WORK.ANA_DATA    177.54    2.9420  2641    60.35    <.0001
TRTPN(ATPTN)  1          7          WORK.ANA_DATA    146.15    2.0948  2704    69.77    <.0001
TRTPN(ATPTN)  2          7          WORK.ANA_DATA    161.62    2.9785  2712    54.26    <.0001
TRTPN(ATPTN)  3          7          WORK.ANA_DATA    158.66    2.9472  2655    53.83    <.0001
TRTPN(ATPTN)  1          8          WORK.ANA_DATA    103.38    2.1028  2733    49.17    <.0001
TRTPN(ATPTN) 2          8          WORK.ANA_DATA    113.33    2.9898  2741    37.90    <.0001
TRTPN(ATPTN)  3          8          WORK.ANA_DATA    129.19    2.9633  2697    43.60    <.0001
TRTPN(ATPTN)  1          9          WORK.ANA_DATA   99.2172    2.0813  2655    47.67    <.0001
TRTPN(ATPTN)  2          9          WORK.ANA_DATA    102.74    2.9502  2641    34.82    <.0001
TRTPN(ATPTN)  3          9          WORK.ANA_DATA    128.17    2.9526  2669    43.41    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  1          1            0.05     96.5237      104.67
TRTPN(ATPTN)  2          1            0.05      100.43      112.00
TRTPN(ATPTN)  3          1            0.05      123.43      134.97
TRTPN(ATPTN)  1          2            0.05      160.19      168.36
TRTPN(ATPTN)  2          2            0.05      173.88      185.54
TRTPN(ATPTN)  3          2            0.05      181.54      193.12
TRTPN(ATPTN)  1          3            0.05      113.24      121.43
TRTPN(ATPTN)  2          3            0.05      125.21      136.85
TRTPN(ATPTN)  3          3            0.05      136.92      148.46
TRTPN(ATPTN)  1          4            0.05      158.62      166.80
TRTPN(ATPTN)  2          4            0.05      180.80      192.46
TRTPN(ATPTN)  3          4            0.05      172.92      184.48
TRTPN(ATPTN)  1          5            0.05      115.27      123.44
TRTPN(ATPTN)  2          5            0.05      129.99      141.58
TRTPN(ATPTN)  3          5            0.05      136.22      147.76
TRTPN(ATPTN)  1          6            0.05      164.47      172.66
TRTPN(ATPTN)  2         6            0.05      181.87      193.47
TRTPN(ATPTN)  3          6            0.05      171.77      183.30
TRTPN(ATPTN)  1          7            0.05      142.05      150.26
TRTPN(ATPTN)  2          7            0.05      155.78      167.46
TRTPN(ATPTN)  3          7            0.05      152.88      164.44
TRTPN(ATPTN)  1          8            0.05     99.2601      107.51
TRTPN(ATPTN)  2          8            0.05      107.46      119.19
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
258 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  3          8            0.05      123.38      135.00
TRTPN(ATPTN)  1          9            0.05     95.1361      103.30
TRTPN(ATPTN)  2          9            0.05     96.9553      108.53
TRTPN(ATPTN)  3          9            0.05      122.38      133.96
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  1          1          2          1          WORK.ANA_DATA   -5.6140    3.6083  2641
TRTPN(ATPTN)  1          1          3          1          WORK.ANA_DATA  -28.6031    3.6015  2641
TRTPN(ATPTN)  1          1          1          2          WORK.ANA_DATA  -63.6784    2.2368  5652
TRTPN(ATPTN)  1          1          2          2          WORK.ANA_DATA  -79.1134    3.6269  2679
TRTPN(ATPTN)  1          1          3          2          WORK.ANA_DATA  -86.7365    3.6102  2660
TRTPN(ATPTN)  1          1          1          3          WORK.ANA_DATA  -16.7407    2.2422  5653
TRTPN(ATPTN)  1          1          2          3          WORK.ANA_DATA  -30.4309    3.6225  2669
TRTPN(ATPTN)  1          1          3          3          WORK.ANA_DATA  -42.0903    3.6015  2641
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  1          1          2          1            -1.56      0.1199      0.05
TRTPN(ATPTN)  1          1          3          1            -7.94      <.0001      0.05
TRTPN(ATPTN)  1          1          1          2           -28.47      <.0001      0.05
TRTPN(ATPTN)  1          1          2          2           -21.81      <.0001      0.05
TRTPN(ATPTN)  1          1          3          2           -24.03      <.0001      0.05
TRTPN(ATPTN)  1          1          1          3            -7.47      <.0001      0.05
TRTPN(ATPTN)  1          1          2          3            -8.40      <.0001      0.05
TRTPN(ATPTN)  1          1          3          3           -11.69      <.0001      0.05
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  1          1          2          1          -12.6893      1.4614
TRTPN(ATPTN)  1          1          3          1          -35.6651    -21.5411
TRTPN(ATPTN)  1          1          1          2          -68.0634    -59.2934
TRTPN(ATPTN)  1          1          2          2          -86.2253    -72.0016
TRTPN(ATPTN)  1          1          3          2          -93.8155    -79.6575
TRTPN(ATPTN)  1          1          1          3          -21.1361    -12.3452
TRTPN(ATPTN)  1          1          2          3          -37.5342    -23.3276
TRTPN(ATPTN)  1          1          3          3          -49.1524    -35.0283
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
259 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  1          1          1          4          WORK.ANA_DATA  -62.1143    2.2404  5653
TRTPN(ATPTN)  1          1          2          4          WORK.ANA_DATA  -86.0370    3.6271  2679
TRTPN(ATPTN)  1          1          3          4          WORK.ANA_DATA  -78.1063    3.6058  2650
TRTPN(ATPTN)  1          1          1          5          WORK.ANA_DATA  -18.7548    2.2386  5652
TRTPN(ATPTN)  1          1          2          5          WORK.ANA_DATA  -35.1898    3.6134  2650
TRTPN(ATPTN)  1          1          3          5          WORK.ANA_DATA  -41.3928    3.6015  2641
TRTPN(ATPTN)  1          1          1          6          WORK.ANA_DATA  -67.9660    2.2438  5653
TRTPN(ATPTN)  1          1          2          6          WORK.ANA_DATA  -87.0725    3.6134  2650
TRTPN(ATPTN)  1          1          3          6          WORK.ANA_DATA  -76.9379    3.6015  2641
TRTPN(ATPTN)  1          1          1          7          WORK.ANA_DATA  -45.5566    2.2492  5654
TRTPN(ATPTN)  1          1          2          7          WORK.ANA_DATA  -61.0237    3.6314  2688
TRTPN(ATPTN)  1          1          3          7          WORK.ANA_DATA  -58.0633    3.6058  2650
TRTPN(ATPTN)  1          1          1          8          WORK.ANA_DATA   -2.7861    2.2566  5656
TRTPN(ATPTN)  1          1          2          8          WORK.ANA_DATA  -12.7285    3.6407  2708
TRTPN(ATPTN)  1          1          3          8          WORK.ANA_DATA  -28.5899    3.6189  2679
TRTPN(ATPTN)  1          1          1          9          WORK.ANA_DATA    1.3800    2.2365  5650
TRTPN(ATPTN)  1          1          2          9          WORK.ANA_DATA   -2.1432    3.6083  2641
TRTPN(ATPTN)  1          1          3          9          WORK.ANA_DATA  -27.5769    3.6102  2660
TRTPN(ATPTN)  2          1          3          1          WORK.ANA_DATA  -22.9891    4.1665 2641
TRTPN(ATPTN)  2          1          1          2          WORK.ANA_DATA  -58.0644    3.6107  2645
TRTPN(ATPTN)  2          1          2          2          WORK.ANA_DATA  -73.4995    3.1924  5656
TRTPN(ATPTN)  2          1          3          2          WORK.ANA_DATA  -81.1225    4.1739  2655
TRTPN(ATPTN)  2          1          1          3          WORK.ANA_DATA  -11.1267    3.6140  2652
TRTPN(ATPTN)  2          1          2          3          WORK.ANA_DATA  -24.8169    3.1874  5656
TRTPN(ATPTN)  2          1          3          3          WORK.ANA_DATA  -36.4764    4.1664  2641
TRTPN(ATPTN)  2          1          1          4          WORK.ANA_DATA  -56.5004    3.6129  2650
TRTPN(ATPTN)  2          1          2          4          WORK.ANA_DATA  -80.4230    3.1925  5656
TRTPN(ATPTN)  2          1          3          4          WORK.ANA_DATA  -72.4923    4.1702  2648
TRTPN(ATPTN)  2          1          1          5          WORK.ANA_DATA  -13.1408    3.6118  2648
TRTPN(ATPTN)  2          1          2          5          WORK.ANA_DATA  -29.5759    3.1770  5653
TRTPN(ATPTN)  2          1          3          5          WORK.ANA_DATA  -35.7788    4.1664  2641
TRTPN(ATPTN)  2          1          1          6          WORK.ANA_DATA  -62.3520    3.6150  2655
TRTPN(ATPTN)  2          1          2          6          WORK.ANA_DATA  -81.4585    3.1770  5653
TRTPN(ATPTN)  2          1          3          6          WORK.ANA_DATA  -71.3239    4.1664  2641
TRTPN(ATPTN)  2          1          1          7          WORK.ANA_DATA  -39.9426    3.6183  2662
TRTPN(ATPTN)  2          1          2          7          WORK.ANA_DATA  -55.4097    3.1974  5656
TRTPN(ATPTN)  2          1          3          7          WORK.ANA_DATA  -52.4494    4.1702  2648
TRTPN(ATPTN)  2          1          1          8          WORK.ANA_DATA    2.8278    3.6229  2672
TRTPN(ATPTN)  2          1          2          8          WORK.ANA_DATA   -7.1146    3.2079  5658
TRTPN(ATPTN)  2          1          3          8          WORK.ANA_DATA  -22.9760    4.1815  2669
TRTPN(ATPTN)  2          1          1          9          WORK.ANA_DATA    6.9940    3.6105  2646
TRTPN(ATPTN)  2          1          2          9          WORK.ANA_DATA    3.4708    3.1711  5649
TRTPN(ATPTN)  2          1          3          9          WORK.ANA_DATA  -21.9630    4.1739  2655
TRTPN(ATPTN)  3          1          1          2          WORK.ANA_DATA  -35.0753    3.6039  2646
TRTPN(ATPTN)  3          1          2          2          WORK.ANA_DATA  -50.5103    4.1826  2669
TRTPN(ATPTN)  3          1          3          2          WORK.ANA_DATA  -58.1334    3.1721  5650
TRTPN(ATPTN)  3          1          1          3          WORK.ANA_DATA   11.8625    3.6072  2653
TRTPN(ATPTN)  3          1          2          3          WORK.ANA_DATA   -1.8278    4.1788  2662
TRTPN(ATPTN)  3          1          3          3          WORK.ANA_DATA  -13.4872    3.1623  5649
TRTPN(ATPTN)  3          1          1          4          WORK.ANA_DATA  -33.5112    3.6061  2650
TRTPN(ATPTN)  3          1          2          4          WORK.ANA_DATA  -57.4339    4.1827  2669
TRTPN(ATPTN)  3          1          3          4          WORK.ANA_DATA  -49.5032    3.1671  5650
TRTPN(ATPTN)  3          1          1          5          WORK.ANA_DATA    9.8483    3.6050  2648
TRTPN(ATPTN)  3          1          2          5          WORK.ANA_DATA   -6.5867    4.1709  2648
TRTPN(ATPTN)  3          1          3          5          WORK.ANA_DATA  -12.7897    3.1623  5649
TRTPN(ATPTN)  3          1          1          6          WORK.ANA_DATA  -39.3629    3.6082  2655
TRTPN(ATPTN)  3          1          2          6          WORK.ANA_DATA  -58.4694    4.1709  2648
TRTPN(ATPTN)  3          1          3          6          WORK.ANA_DATA  -48.3347    3.1623  5649
TRTPN(ATPTN)  3          1          1          7          WORK.ANA_DATA  -16.9535    3.6116  2662
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
260 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  1          1          1          4           -27.73      <.0001      0.05
TRTPN(ATPTN)  1          1          2          4           -23.72      <.0001      0.05
TRTPN(ATPTN)  1          1          3          4           -21.66      <.0001      0.05
TRTPN(ATPTN)  1          1          1          5            -8.38      <.0001      0.05
TRTPN(ATPTN)  1          1          2          5            -9.74      <.0001      0.05
TRTPN(ATPTN)  1          1          3          5           -11.49      <.0001      0.05
TRTPN(ATPTN)  1          1          1          6           -30.29      <.0001      0.05
TRTPN(ATPTN)  1          1          2          6           -24.10      <.0001      0.05
TRTPN(ATPTN)  1          1          3          6           -21.36      <.0001      0.05
TRTPN(ATPTN)  1          1          1          7           -20.25      <.0001      0.05
TRTPN(ATPTN)  1          1          2          7           -16.80      <.0001      0.05
TRTPN(ATPTN)  1          1          3          7           -16.10      <.0001      0.05
TRTPN(ATPTN)  1          1          1          8            -1.23      0.2170      0.05
TRTPN(ATPTN)  1          1          2          8            -3.50      0.0005      0.05
TRTPN(ATPTN)  1          1          3          8            -7.90      <.0001      0.05
TRTPN(ATPTN)  1          1          1          9             0.62      0.5372      0.05
TRTPN(ATPTN)  1          1          2          9            -0.59      0.5526      0.05
TRTPN(ATPTN)  1          1          3          9            -7.64      <.0001      0.05
TRTPN(ATPTN)  2          1          3          1            -5.52      <.0001      0.05
TRTPN(ATPTN)  2          1          1          2           -16.08      <.0001      0.05
TRTPN(ATPTN)  2          1          2          2           -23.02      <.0001      0.05
TRTPN(ATPTN)  2          1          3          2           -19.44      <.0001      0.05
TRTPN(ATPTN)  2          1          1          3            -3.08      0.0021      0.05
TRTPN(ATPTN)  2          1          2          3            -7.79      <.0001      0.05
TRTPN(ATPTN)  2          1          3          3            -8.75      <.0001      0.05
TRTPN(ATPTN)  2          1          1          4           -15.64      <.0001      0.05
TRTPN(ATPTN)  2          1          2          4           -25.19      <.0001      0.05
TRTPN(ATPTN)  2          1          3          4           -17.38      <.0001      0.05
TRTPN(ATPTN)  2          1          1          5            -3.64      0.0003      0.05
TRTPN(ATPTN)  2          1          2          5            -9.31      <.0001      0.05
TRTPN(ATPTN)  2          1          3          5            -8.59      <.0001      0.05
TRTPN(ATPTN)  2          1          1          6           -17.25      <.0001      0.05
TRTPN(ATPTN)  2          1          2          6           -25.64      <.0001      0.05
TRTPN(ATPTN)  2          1          3          6           -17.12      <.0001      0.05
TRTPN(ATPTN)  2          1          1          7           -11.04      <.0001      0.05
TRTPN(ATPTN)  2          1          2          7           -17.33      <.0001      0.05
TRTPN(ATPTN)  2          1          3          7           -12.58      <.0001      0.05
TRTPN(ATPTN)  2          1          1          8             0.78      0.4351      0.05
TRTPN(ATPTN)  2          1          2          8            -2.22      0.0266      0.05
TRTPN(ATPTN)  2          1          3          8            -5.49      <.0001      0.05
TRTPN(ATPTN)  2          1          1          9             1.94      0.0528      0.05
TRTPN(ATPTN)  2          1          2          9             1.09      0.2738      0.05
TRTPN(ATPTN)  2         1          3          9            -5.26      <.0001      0.05
TRTPN(ATPTN)  3          1          1          2            -9.73      <.0001      0.05
TRTPN(ATPTN)  3          1          2          2           -12.08      <.0001      0.05
TRTPN(ATPTN)  3          1          3          2           -18.33      <.0001      0.05
TRTPN(ATPTN)  3          1          1          3             3.29      0.0010      0.05
TRTPN(ATPTN)  3          1          2          3            -0.44      0.6619      0.05
TRTPN(ATPTN)  3          1          3          3            -4.27      <.0001      0.05
TRTPN(ATPTN)  3          1          1          4            -9.29      <.0001      0.05
TRTPN(ATPTN)  3          1          2          4           -13.73      <.0001      0.05
TRTPN(ATPTN)  3          1          3          4           -15.63      <.0001      0.05
TRTPN(ATPTN)  3          1          1          5             2.73      0.0063      0.05
TRTPN(ATPTN)  3          1          2          5            -1.58      0.1144      0.05
TRTPN(ATPTN)  3          1          3          5            -4.04      <.0001      0.05
TRTPN(ATPTN)  3          1          1          6           -10.91      <.0001      0.05
TRTPN(ATPTN)  3          1          2          6           -14.02      <.0001      0.05
TRTPN(ATPTN)  3          1          3          6           -15.28      <.0001      0.05
TRTPN(ATPTN)  3          1          1          7            -4.69      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
261 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  1          1          1          4          -66.5063    -57.7224
TRTPN(ATPTN)  1          1          2          4          -93.1492    -78.9249
TRTPN(ATPTN)  1          1          3          4          -85.1767    -71.0359
TRTPN(ATPTN)  1          1         1          5          -23.1432    -14.3663
TRTPN(ATPTN)  1          1          2          5          -42.2752    -28.1044
TRTPN(ATPTN)  1          1          3          5          -48.4548    -34.3307
TRTPN(ATPTN)  1          1          1          6          -72.3647    -63.5673
TRTPN(ATPTN)  1          1          2          6          -94.1579    -79.9871
TRTPN(ATPTN)  1          1          3          6          -83.9999    -69.8758
TRTPN(ATPTN)  1          1          1          7          -49.9658    -41.1473
TRTPN(ATPTN)  1          1          2          7          -68.1443    -53.9031
TRTPN(ATPTN)  1          1          3          7          -65.1338    -50.9929
TRTPN(ATPTN)  1          1          1          8           -7.2099      1.6376
TRTPN(ATPTN) 1          1          2          8          -19.8673     -5.5898
TRTPN(ATPTN)  1          1          3          8          -35.6861    -21.4938
TRTPN(ATPTN)  1          1          1          9           -3.0045      5.7645
TRTPN(ATPTN)  1          1          2          9           -9.2185      4.9322
TRTPN(ATPTN)  1          1          3          9          -34.6559    -20.4980
TRTPN(ATPTN)  2          1          3          1          -31.1590    -14.8193
TRTPN(ATPTN)  2          1          1          2          -65.1444    -50.9844
TRTPN(ATPTN)  2          1          2          2          -79.7577    -67.2412
TRTPN(ATPTN)  2          1          3          2          -89.3070    -72.9380
TRTPN(ATPTN)  2          1          1          3          -18.2132    -4.0402
TRTPN(ATPTN)  2          1          2          3          -31.0654    -18.5684
TRTPN(ATPTN)  2          1          3          3          -44.6462    -28.3065
TRTPN(ATPTN)  2          1          1          4          -63.5847    -49.4161
TRTPN(ATPTN)  2          1          2          4          -86.6816    -74.1645
TRTPN(ATPTN)  2          1          3          4          -80.6694    -64.3152
TRTPN(ATPTN)  2          1          1          5          -20.2230     -6.0587
TRTPN(ATPTN)  2          1          2          5          -35.8040    -23.3477
TRTPN(ATPTN)  2          1          3          5          -43.9487    -27.6090
TRTPN(ATPTN)  2          1          1          6          -69.4405    -55.2636
TRTPN(ATPTN)  2          1          2          6          -87.6867    -75.2304
TRTPN(ATPTN)  2          1          3          6          -79.4937    -63.1541
TRTPN(ATPTN)  2          1          1          7          -47.0376    -32.8476
TRTPN(ATPTN)  2          1          2          7          -61.6779    -49.1415
TRTPN(ATPTN)  2          1          3          7          -60.6265    -44.2723
TRTPN(ATPTN)  2          1          1          8           -4.2762      9.9319
TRTPN(ATPTN)  2          1          2          8          -13.4034     -0.8258
TRTPN(ATPTN)  2          1          3          8          -31.1753    -14.7766
TRTPN(ATPTN)  2          1          1          9          -0.08570     14.0736
TRTPN(ATPTN)  2          1          2          9           -2.7459      9.6875
TRTPN(ATPTN)  2          1          3          9          -30.1475    -13.7785
TRTPN(ATPTN)  3          1          1          2          -42.1420    -28.0085
TRTPN(ATPTN)  3          1          2          2          -58.7118    -42.3088
TRTPN(ATPTN)  3          1          3          2          -64.3520    -51.9148
TRTPN(ATPTN)  3          1          1          3            4.7892     18.9357
TRTPN(ATPTN)  3          1          2          3          -10.0218      6.3663
TRTPN(ATPTN)  3          1          3          3          -19.6865     -7.2880
TRTPN(ATPTN)  3          1          1          4          -40.5823    -26.4402
TRTPN(ATPTN)  3          1          2          4          -65.6356    -49.2322
TRTPN(ATPTN)  3          1          3          4          -55.7120    -43.2944
TRTPN(ATPTN)  3          1          1          5            2.7795     16.9172
TRTPN(ATPTN)  3          1          2          5          -14.7653      1.5918
TRTPN(ATPTN)  3          1          3          5          -18.9889     -6.5904
TRTPN(ATPTN)  3          1          1          6          -46.4381    -32.2877
TRTPN(ATPTN)  3          1          2          6          -66.6479    -50.2908
TRTPN(ATPTN)  3          1          3          6          -54.5340    -42.1355
TRTPN(ATPTN)  3          1          1          7          -24.0353     -9.8717
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
262 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          1          2          7          WORK.ANA_DATA  -32.4206    4.1865  2676
TRTPN(ATPTN)  3          1          3         7          WORK.ANA_DATA  -29.4602    3.1672  5650
TRTPN(ATPTN)  3          1          1          8          WORK.ANA_DATA   25.8170    3.6162  2672
TRTPN(ATPTN)  3          1          2          8          WORK.ANA_DATA   15.8746    4.1945  2691
TRTPN(ATPTN)  3          1          3          8          WORK.ANA_DATA   0.01317    3.1821  5651
TRTPN(ATPTN)  3          1          1          9          WORK.ANA_DATA   29.9831    3.6037  2646
TRTPN(ATPTN)  3          1          2          9          WORK.ANA_DATA   26.4599    4.1664  2641
TRTPN(ATPTN)  3          1          3          9          WORK.ANA_DATA    1.0262    3.1721  5650
TRTPN(ATPTN)  1          2          2          2          WORK.ANA_DATA  -15.4350    3.6293  2683
TRTPN(ATPTN)  1          2          3          2          WORK.ANA_DATA  -23.0581    3.6125  2664
TRTPN(ATPTN)  1          2          1          3          WORK.ANA_DATA   46.9377    2.2445  5650
TRTPN(ATPTN)  1          2          2          3          WORK.ANA_DATA   33.2475    3.6249  2673
TRTPN(ATPTN)  1          2          3          3          WORK.ANA_DATA   21.5880    3.6039  2646
TRTPN(ATPTN)  1          2          1          4          WORK.ANA_DATA    1.5640    2.2427  5650
TRTPN(ATPTN)  1          2          2          4          WORK.ANA_DATA  -22.3586    3.6294  2683
TRTPN(ATPTN)  1          2          3          4          WORK.ANA_DATA  -14.4279    3.6082  2655
TRTPN(ATPTN)  1          2          1          5          WORK.ANA_DATA   44.9236    2.2415  5651
TRTPN(ATPTN)  1          2          2          5          WORK.ANA_DATA   28.4885    3.6158  2654
TRTPN(ATPTN)  1          2          3          5          WORK.ANA_DATA   22.2856    3.6039  2646
TRTPN(ATPTN)  1          2          1          6          WORK.ANA_DATA   -4.2876    2.2467  5652
TRTPN(ATPTN)  1          2          2          6          WORK.ANA_DATA  -23.3941    3.6158  2654
TRTPN(ATPTN)  1          2          3          6          WORK.ANA_DATA  -13.2595    3.6039  2646
TRTPN(ATPTN)  1          2          1          7          WORK.ANA_DATA   18.1218    2.2521  5653
TRTPN(ATPTN)  1          2          2          7          WORK.ANA_DATA    2.6547    3.6338  2693
TRTPN(ATPTN)  1          2          3          7          WORK.ANA_DATA    5.6150    3.6082  2655
TRTPN(ATPTN)  1          2          1          8          WORK.ANA_DATA   60.8922    2.2589  5653
TRTPN(ATPTN)  1          2          2          8          WORK.ANA_DATA   50.9498    3.6430  2712
TRTPN(ATPTN)  1          2          3          8          WORK.ANA_DATA   35.0884    3.6213  2683
TRTPN(ATPTN)  1          2          1          9          WORK.ANA_DATA   65.0584    2.2398  5651
TRTPN(ATPTN)  1          2          2          9          WORK.ANA_DATA   61.5352    3.6107  2645
TRTPN(ATPTN)  1          2          3          9          WORK.ANA_DATA   36.1014    3.6125  2664
TRTPN(ATPTN)  2          2          3          2          WORK.ANA_DATA   -7.6231    4.1902  2683
TRTPN(ATPTN)  2          2          1          3          WORK.ANA_DATA   62.3728    3.6326  2690
TRTPN(ATPTN)  2          2          2          3          WORK.ANA_DATA   48.6825    3.2044  5652
TRTPN(ATPTN)  2          2          3          3          WORK.ANA_DATA   37.0231    4.1826  2669
TRTPN(ATPTN)  2          2          1          4          WORK.ANA_DATA   16.9991    3.6315  2688
TRTPN(ATPTN)  2          2          2          4          WORK.ANA_DATA   -6.9236    3.2096  5652
TRTPN(ATPTN)  2          2          3          4          WORK.ANA_DATA    1.0071    4.1863  2676
TRTPN(ATPTN)  2          2          1          5          WORK.ANA_DATA   60.3586    3.6304  2685
TRTPN(ATPTN)  2          2          2          5          WORK.ANA_DATA   43.9236    3.1955  5651
TRTPN(ATPTN)  2          2          3          5          WORK.ANA_DATA   37.7206    4.1826  2669
TRTPN(ATPTN)  2          2          1          6          WORK.ANA_DATA   11.1474    3.6336  2692
TRTPN(ATPTN)  2          2          2          6          WORK.ANA_DATA   -7.9591    3.1955  5651
TRTPN(ATPTN)  2          2          3          6          WORK.ANA_DATA    2.1756    4.1826  2669
TRTPN(ATPTN)  2          2          1          7          WORK.ANA_DATA   33.5568    3.6369  2699
TRTPN(ATPTN)  2          2          2          7          WORK.ANA_DATA   18.0897    3.2148  5653
TRTPN(ATPTN)  2          2          3          7          WORK.ANA_DATA   21.0501    4.1863  2676
TRTPN(ATPTN)  2          2          1          8          WORK.ANA_DATA   76.3273    3.6415  2709
TRTPN(ATPTN)  2          2          2          8          WORK.ANA_DATA   66.3849    3.2250  5654
TRTPN(ATPTN)  2          2          3          8          WORK.ANA_DATA   50.5235    4.1976  2697
TRTPN(ATPTN)  2          2          1          9          WORK.ANA_DATA   80.4934    3.6291  2683
TRTPN(ATPTN)  2          2          2          9          WORK.ANA_DATA   76.9702    3.1924  5656
TRTPN(ATPTN)  2          2          3          9          WORK.ANA_DATA   51.5365    4.1901  2683
TRTPN(ATPTN)  3          2          1          3          WORK.ANA_DATA   69.9958    3.6158  2671
TRTPN(ATPTN)  3          2          2          3          WORK.ANA_DATA   56.3056    4.1863  2676
TRTPN(ATPTN)  3          2          3          3          WORK.ANA_DATA   44.6462    3.1721  5650
TRTPN(ATPTN)  3          2          1          4          WORK.ANA_DATA   24.6221    3.6147  2669
TRTPN(ATPTN)  3          2          2          4          WORK.ANA_DATA    0.6995    4.1902  2683
TRTPN(ATPTN)  3          2          3          4          WORK.ANA_DATA    8.6302    3.1770  5651
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
263 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          1          2          7            -7.74      <.0001      0.05
TRTPN(ATPTN)  3          1          3          7            -9.30      <.0001      0.05
TRTPN(ATPTN)  3          1          1          8             7.14      <.0001      0.05
TRTPN(ATPTN)  3          1          2          8             3.78      0.0002      0.05
TRTPN(ATPTN) 3          1          3          8             0.00      0.9967      0.05
TRTPN(ATPTN)  3          1          1          9             8.32      <.0001      0.05
TRTPN(ATPTN)  3          1          2          9             6.35      <.0001      0.05
TRTPN(ATPTN)  3          1          3          9             0.32      0.7463      0.05
TRTPN(ATPTN)  1          2          2          2            -4.25      <.0001      0.05
TRTPN(ATPTN)  1          2          3          2            -6.38      <.0001      0.05
TRTPN(ATPTN)  1          2          1          3            20.91      <.0001      0.05
TRTPN(ATPTN)  1          2          2          3             9.17      <.0001      0.05
TRTPN(ATPTN)  1          2          3          3             5.99      <.0001      0.05
TRTPN(ATPTN)  1          2          1          4             0.70      0.4856      0.05
TRTPN(ATPTN)  1          2          2          4            -6.16      <.0001      0.05
TRTPN(ATPTN)  1          2          3          4            -4.00      <.0001      0.05
TRTPN(ATPTN)  1          2          1          5            20.04      <.0001      0.05
TRTPN(ATPTN)  1          2          2          5             7.88      <.0001      0.05
TRTPN(ATPTN)  1          2          3          5             6.18      <.0001      0.05
TRTPN(ATPTN)  1          2          1          6            -1.91      0.0564      0.05
TRTPN(ATPTN)  1          2          2          6            -6.47      <.0001      0.05
TRTPN(ATPTN)  1          2          3          6            -3.68      0.0002      0.05
TRTPN(ATPTN)  1          2          1          7             8.05      <.0001      0.05
TRTPN(ATPTN)  1          2          2          7             0.73      0.4651      0.05
TRTPN(ATPTN)  1          2          3          7             1.56      0.1198      0.05
TRTPN(ATPTN)  1          2          1          8            26.96      <.0001      0.05
TRTPN(ATPTN)  1          2          2          8            13.99      <.0001      0.05
TRTPN(ATPTN)  1          2          3          8             9.69      <.0001      0.05
TRTPN(ATPTN)  1          2          1          9            29.05      <.0001      0.05
TRTPN(ATPTN)  1          2          2          9            17.04      <.0001      0.05
TRTPN(ATPTN)  1          2          3          9             9.99      <.0001      0.05
TRTPN(ATPTN)  2          2          3          2            -1.82      0.0690      0.05
TRTPN(ATPTN)  2          2          1          3            17.17      <.0001      0.05
TRTPN(ATPTN)  2          2          2          3            15.19      <.0001      0.05
TRTPN(ATPTN)  2          2          3          3             8.85      <.0001      0.05
TRTPN(ATPTN)  2          2          1          4             4.68      <.0001      0.05
TRTPN(ATPTN) 2          2          2          4            -2.16      0.0310      0.05
TRTPN(ATPTN)  2          2          3          4             0.24      0.8099      0.05
TRTPN(ATPTN)  2          2          1          5            16.63      <.0001      0.05
TRTPN(ATPTN)  2          2          2          5            13.75      <.0001      0.05
TRTPN(ATPTN)  2          2          3          5             9.02      <.0001      0.05
TRTPN(ATPTN)  2          2          1          6             3.07      0.0022      0.05
TRTPN(ATPTN)  2          2          2          6            -2.49      0.0128      0.05
TRTPN(ATPTN)  2          2          3          6             0.52      0.6030      0.05
TRTPN(ATPTN)  2          2          1          7             9.23      <.0001      0.05
TRTPN(ATPTN)  2          2          2          7             5.63      <.0001      0.05
TRTPN(ATPTN)  2          2          3          7             5.03      <.0001      0.05
TRTPN(ATPTN)  2          2          1          8            20.96      <.0001      0.05
TRTPN(ATPTN)  2          2          2          8            20.58      <.0001      0.05
TRTPN(ATPTN)  2          2          3          8            12.04      <.0001      0.05
TRTPN(ATPTN)  2          2          1          9            22.18      <.0001      0.05
TRTPN(ATPTN)  2          2          2          9            24.11      <.0001      0.05
TRTPN(ATPTN)  2          2          3          9            12.30      <.0001      0.05
TRTPN(ATPTN)  3          2          1          3            19.36      <.0001      0.05
TRTPN(ATPTN)  3          2          2          3            13.45      <.0001      0.05
TRTPN(ATPTN)  3          2          3          3            14.07      <.0001      0.05
TRTPN(ATPTN)  3          2          1          4             6.81      <.0001      0.05
TRTPN(ATPTN)  3          2          2          4             0.17      0.8674      0.05
TRTPN(ATPTN)  3          2          3          4             2.72      0.0066      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
264 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
             Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          1          2          7          -40.6297    -24.2115
TRTPN(ATPTN)  3          1          3          7          -35.6691    -23.2514
TRTPN(ATPTN)  3          1          1          8           18.7262     32.9078
TRTPN(ATPTN)  3          1          2          8            7.6498     24.0994
TRTPN(ATPTN)  3          1          3          8           -6.2249      6.2513
TRTPN(ATPTN)  3          1          1          9           22.9167     37.0495
TRTPN(ATPTN)  3          1          2          9           18.2901     34.6298
TRTPN(ATPTN)  3          1          3          9           -5.1924      7.2447
TRTPN(ATPTN)  1          2          2          2          -22.5516     -8.3185
TRTPN(ATPTN)  1          2          3          2          -30.1418    -15.9745
TRTPN(ATPTN)  1          2          1          3           42.5376     51.3378
TRTPN(ATPTN)  1          2          2          3           26.1395     40.3554
TRTPN(ATPTN)  1          2          3          3           14.5213     28.6548
TRTPN(ATPTN)  1          2          1          4           -2.8325      5.9606
TRTPN(ATPTN)  1          2          2          4          -29.4754    -15.2419
TRTPN(ATPTN)  1          2          3          4          -21.5030     -7.3528
TRTPN(ATPTN)  1          2          1          5           40.5294     49.3178
TRTPN(ATPTN)  1          2          2          5           21.3985     35.5786
TRTPN(ATPTN)  1          2          3          5           15.2188     29.3523
TRTPN(ATPTN)  1          2          1          6           -8.6921      0.1168
TRTPN(ATPTN)  1          2          2          6          -30.4842    -16.3041
TRTPN(ATPTN)  1          2          3          6          -20.3262     -6.1928
TRTPN(ATPTN)  1          2          1          7           13.7068     22.5368
TRTPN(ATPTN)  1          2          2          7           -4.4706      9.7799
TRTPN(ATPTN)  1          2          3          7           -1.4601     12.6902
TRTPN(ATPTN)  1          2          1          8           56.4639     65.3206
TRTPN(ATPTN)  1          2          2          8           43.8065     58.0932
TRTPN(ATPTN)  1          2          3          8           27.9876     42.1892
TRTPN(ATPTN)  1          2          1          9           60.6675     69.4493
TRTPN(ATPTN)  1          2          2          9           54.4552     68.6152
TRTPN(ATPTN)  1          2          3          9           29.0178     43.1851
TRTPN(ATPTN)  2          2          3          2          -15.8394      0.5932
TRTPN(ATPTN)  2          2          1          3           55.2498     69.4957
TRTPN(ATPTN)  2          2          2          3           42.4006     54.9645
TRTPN(ATPTN)  2          2          3          3           28.8216     45.2246
TRTPN(ATPTN)  2          2          1          4            9.8783     24.1198
TRTPN(ATPTN)  2          2          2          4          -13.2156     -0.6316
TRTPN(ATPTN)  2          2          3          4           -7.2016      9.2158
TRTPN(ATPTN)  2          2          1          5           53.2400     67.4773
TRTPN(ATPTN)  2          2          2          5           37.6592     50.1880
TRTPN(ATPTN)  2          2          3          5           29.5191     45.9221
TRTPN(ATPTN)  2          2          1          6            4.0225     18.2723
TRTPN(ATPTN)  2          2          2          6          -14.2235     -1.6947
TRTPN(ATPTN)  2          2          3          6           -6.0259     10.3771
TRTPN(ATPTN)  2          2          1          7           26.4254     40.6883
TRTPN(ATPTN)  2          2          2          7           11.7875     24.3920
TRTPN(ATPTN)  2          2          3          7           12.8413     29.2588
TRTPN(ATPTN)  2          2          1          8           69.1869     83.4677
TRTPN(ATPTN)  2          2          2          8           60.0627     72.7070
TRTPN(ATPTN)  2          2          3          8           42.2926     58.7544
TRTPN(ATPTN)  2          2          1          9           73.3773     87.6096
TRTPN(ATPTN)  2          2          2          9           70.7120     83.2285
TRTPN(ATPTN)  2          2          3          9           43.3204     59.7525
TRTPN(ATPTN)  3          2          1          3           62.9057     77.0860
TRTPN(ATPTN)  3          2          2          3           48.0969     64.5143
TRTPN(ATPTN)  3          2          3          3           38.4276     50.8647
TRTPN(ATPTN)  3          2          1          4           17.5342     31.7101
TRTPN(ATPTN)  3          2          2          4           -7.5169      8.9158
TRTPN(ATPTN)  3          2          3          4            2.4021     14.8583
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
265 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          2          1          5          WORK.ANA_DATA   67.9817    3.6136  2667
TRTPN(ATPTN)  3          2          2          5          WORK.ANA_DATA   51.5467    4.1784  2662
TRTPN(ATPTN)  3          2          3          5          WORK.ANA_DATA   45.3437    3.1721  5650
TRTPN(ATPTN)  3          2          1          6          WORK.ANA_DATA   18.7705    3.6169  2674
TRTPN(ATPTN)  3          2          2          6          WORK.ANA_DATA   -0.3360    4.1784  2662
TRTPN(ATPTN)  3          2          3          6          WORK.ANA_DATA    9.7986    3.1721  5650
TRTPN(ATPTN)  3          2          1          7          WORK.ANA_DATA   41.1799    3.6202  2681
TRTPN(ATPTN)  3          2          2          7          WORK.ANA_DATA   25.7128    4.1939  2690
TRTPN(ATPTN)  3          2          3          7          WORK.ANA_DATA   28.6731    3.1770  5651
TRTPN(ATPTN)  3          2          1          8          WORK.ANA_DATA   83.9504    3.6248  2690
TRTPN(ATPTN)  3          2          2          8          WORK.ANA_DATA   74.0080    4.2020  2705
TRTPN(ATPTN)  3          2          3          8          WORK.ANA_DATA   58.1466    3.1919  5652
TRTPN(ATPTN)  3          2          1          9          WORK.ANA_DATA   88.1165    3.6124  2664
TRTPN(ATPTN)  3          2          2          9          WORK.ANA_DATA   84.5933    4.1739  2655
TRTPN(ATPTN)  3          2          3          9          WORK.ANA_DATA   59.1595    3.1820  5651
TRTPN(ATPTN)  1          3          2          3          WORK.ANA_DATA  -13.6902    3.6283  2680
TRTPN(ATPTN)  1          3          3          3          WORK.ANA_DATA  -25.3497    3.6072  2653
TRTPN(ATPTN)  1          3          1          4          WORK.ANA_DATA  -45.3737    2.2477  5650
TRTPN(ATPTN)  1          3          2          4          WORK.ANA_DATA  -69.2964    3.6327  2690
TRTPN(ATPTN)  1          3          3          4          WORK.ANA_DATA  -61.3656    3.6115  2662
TRTPN(ATPTN)  1          3          1          5          WORK.ANA_DATA   -2.0141    2.2463  5651
TRTPN(ATPTN)  1          3          2          5          WORK.ANA_DATA  -18.4492    3.6191  2661
TRTPN(ATPTN)  1          3          3          5          WORK.ANA_DATA  -24.6521    3.6072  2653
TRTPN(ATPTN)  1          3          1          6          WORK.ANA_DATA  -51.2254    2.2521  5653
TRTPN(ATPTN)  1          3          2          6          WORK.ANA_DATA  -70.3318    3.6191  2661
TRTPN(ATPTN)  1          3          3          6          WORK.ANA_DATA  -60.1972    3.6072  2653
TRTPN(ATPTN)  1          3          1          7          WORK.ANA_DATA  -28.8159    2.2569  5653
TRTPN(ATPTN)  1          3          2          7          WORK.ANA_DATA  -44.2830    3.6371  2700
TRTPN(ATPTN)  1          3          3          7          WORK.ANA_DATA  -41.3227    3.6115  2662
TRTPN(ATPTN)  1          3          1          8          WORK.ANA_DATA   13.9545    2.2637  5653
TRTPN(ATPTN)  1          3          2          8          WORK.ANA_DATA    4.0121    3.6463  2719
TRTPN(ATPTN)  1          3          3          8          WORK.ANA_DATA  -11.8493    3.6246  2690
TRTPN(ATPTN)  1          3          1          9          WORK.ANA_DATA   18.1207    2.2451  5653
TRTPN(ATPTN)  1          3          2          9          WORK.ANA_DATA   14.5975    3.6140  2652
TRTPN(ATPTN)  1          3          3          9          WORK.ANA_DATA  -10.8363    3.6158  2671
TRTPN(ATPTN)  2          3          3          3          WORK.ANA_DATA  -11.6594    4.1788  2662
TRTPN(ATPTN)  2          3          1          4          WORK.ANA_DATA  -31.6834    3.6271  2678
TRTPN(ATPTN)  2          3          2          4          WORK.ANA_DATA  -55.6061    3.2032  5650
TRTPN(ATPTN)  2          3          3          4          WORK.ANA_DATA  -47.6754    4.1825  2669
TRTPN(ATPTN)  2          3          1          5          WORK.ANA_DATA   11.6761    3.6260  2676
TRTPN(ATPTN)  2          3          2          5          WORK.ANA_DATA   -4.7589    3.1905  5651
TRTPN(ATPTN)  2          3          3          5          WORK.ANA_DATA  -10.9619    4.1788  2662
TRTPN(ATPTN)  2          3          1          6          WORK.ANA_DATA  -37.5351    3.6292  2683
TRTPN(ATPTN)  2          3          2          6          WORK.ANA_DATA  -56.6416    3.1905  5651
TRTPN(ATPTN)  2          3          3          6          WORK.ANA_DATA  -46.5070    4.1788  2662
TRTPN(ATPTN)  2          3          1          7          WORK.ANA_DATA  -15.1257    3.6326  2690
TRTPN(ATPTN)  2          3          2          7          WORK.ANA_DATA  -30.5928    3.2095  5652
TRTPN(ATPTN)  2          3          3          7          WORK.ANA_DATA  -27.6324    4.1825  2669
TRTPN(ATPTN)  2          3          1          8          WORK.ANA_DATA   27.6448    3.6371  2699
TRTPN(ATPTN)  2          3          2          8          WORK.ANA_DATA   17.7024    3.2186  5651
TRTPN(ATPTN)  2          3          3          8          WORK.ANA_DATA    1.8410    4.1938  2690
TRTPN(ATPTN)  2          3          1          9          WORK.ANA_DATA   31.8109    3.6248  2673
TRTPN(ATPTN)  2          3          2          9          WORK.ANA_DATA   28.2877    3.1874  5656
TRTPN(ATPTN)  2          3          3          9          WORK.ANA_DATA    2.8540    4.1863  2676
TRTPN(ATPTN)  3          3          1          4          WORK.ANA_DATA  -20.0240    3.6061  2650
TRTPN(ATPTN)  3          3          2          4          WORK.ANA_DATA  -43.9467    4.1827  2669
TRTPN(ATPTN)  3          3          3          4          WORK.ANA_DATA  -36.0160    3.1671  5650
TRTPN(ATPTN)  3          3          1          5          WORK.ANA_DATA   23.3356    3.6050  2648
TRTPN(ATPTN)  3          3          2          5          WORK.ANA_DATA    6.9005    4.1709  2648
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
266 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          2          1          5            18.81      <.0001      0.05
TRTPN(ATPTN)  3          2          2          5            12.34      <.0001      0.05
TRTPN(ATPTN)  3          2          3          5            14.29      <.0001      0.05
TRTPN(ATPTN)  3          2          1          6             5.19      <.0001      0.05
TRTPN(ATPTN)  3          2          2          6            -0.08      0.9359      0.05
TRTPN(ATPTN)  3          2          3          6             3.09      0.0020      0.05
TRTPN(ATPTN)  3          2          1          7            11.38      <.0001      0.05
TRTPN(ATPTN)  3          2          2          7             6.13      <.0001      0.05
TRTPN(ATPTN)  3          2          3          7             9.03      <.0001      0.05
TRTPN(ATPTN)  3          2          1          8            23.16      <.0001      0.05
TRTPN(ATPTN)  3          2          2          8            17.61      <.0001      0.05
TRTPN(ATPTN)  3          2          3          8            18.22      <.0001      0.05
TRTPN(ATPTN)  3          2          1          9            24.39      <.0001      0.05
TRTPN(ATPTN)  3          2          2          9            20.27      <.0001      0.05
TRTPN(ATPTN)  3          2          3          9            18.59      <.0001      0.05
TRTPN(ATPTN)  1          3          2          3            -3.77      0.0002      0.05
TRTPN(ATPTN)  1          3          3          3            -7.03      <.0001      0.05
TRTPN(ATPTN)  1          3          1          4           -20.19      <.0001      0.05
TRTPN(ATPTN)  1          3          2          4           -19.08      <.0001      0.05
TRTPN(ATPTN)  1          3          3          4           -16.99      <.0001      0.05
TRTPN(ATPTN)  1          3          1          5            -0.90      0.3700      0.05
TRTPN(ATPTN)  1          3          2          5            -5.10      <.0001      0.05
TRTPN(ATPTN)  1          3          3          5            -6.83      <.0001      0.05
TRTPN(ATPTN)  1          3          1          6           -22.75      <.0001      0.05
TRTPN(ATPTN)  1          3          2          6           -19.43      <.0001      0.05
TRTPN(ATPTN)  1          3          3          6           -16.69      <.0001      0.05
TRTPN(ATPTN)  1          3          1          7           -12.77      <.0001      0.05
TRTPN(ATPTN)  1          3          2          7           -12.18      <.0001      0.05
TRTPN(ATPTN)  1          3          3          7           -11.44      <.0001      0.05
TRTPN(ATPTN)  1          3          1          8             6.16      <.0001      0.05
TRTPN(ATPTN)  1          3          2          8             1.10      0.2713      0.05
TRTPN(ATPTN)  1          3          3          8            -3.27      0.0011      0.05
TRTPN(ATPTN)  1          3          1          9             8.07      <.0001      0.05
TRTPN(ATPTN)  1          3          2          9             4.04      <.0001      0.05
TRTPN(ATPTN)  1          3          3          9            -3.00      0.0028      0.05
TRTPN(ATPTN)  2          3          3          3            -2.79      0.0053      0.05
TRTPN(ATPTN)  2          3          1          4            -8.74      <.0001      0.05
TRTPN(ATPTN)  2          3          2          4           -17.36      <.0001      0.05
TRTPN(ATPTN)  2          3          3          4           -11.40      <.0001      0.05
TRTPN(ATPTN)  2          3          1          5             3.22      0.0013      0.05
TRTPN(ATPTN)  2          3          2          5            -1.49      0.1359      0.05
TRTPN(ATPTN)  2          3          3          5            -2.62      0.0088      0.05
TRTPN(ATPTN)  2          3          1          6           -10.34      <.0001      0.05
TRTPN(ATPTN)  2          3          2          6           -17.75      <.0001      0.05
TRTPN(ATPTN)  2          3          3          6           -11.13      <.0001      0.05
TRTPN(ATPTN)  2          3          1          7            -4.16      <.0001      0.05
TRTPN(ATPTN)  2          3          2          7            -9.53      <.0001      0.05
TRTPN(ATPTN)  2          3          3          7            -6.61      <.0001      0.05
TRTPN(ATPTN) 2          3          1          8             7.60      <.0001      0.05
TRTPN(ATPTN)  2          3          2          8             5.50      <.0001      0.05
TRTPN(ATPTN)  2          3          3          8             0.44      0.6607      0.05
TRTPN(ATPTN)  2          3          1          9             8.78      <.0001      0.05
TRTPN(ATPTN)  2          3          2          9             8.87      <.0001      0.05
TRTPN(ATPTN)  2          3          3          9             0.68      0.4955      0.05
TRTPN(ATPTN)  3          3          1          4            -5.55      <.0001      0.05
TRTPN(ATPTN)  3          3          2          4           -10.51      <.0001      0.05
TRTPN(ATPTN)  3          3          3          4           -11.37      <.0001      0.05
TRTPN(ATPTN)  3          3          1          5             6.47      <.0001      0.05
TRTPN(ATPTN)  3          3          2          5             1.65      0.0982      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
267 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          2          1          5           60.8959     75.0675
TRTPN(ATPTN)  3          2          2          5           43.3535     59.7399
TRTPN(ATPTN)  3          2          3          5           39.1251     51.5623
TRTPN(ATPTN)  3          2         1          6           11.6784     25.8626
TRTPN(ATPTN)  3          2          2          6           -8.5292      7.8572
TRTPN(ATPTN)  3          2          3          6            3.5801     16.0172
TRTPN(ATPTN)  3          2          1          7           34.0812     48.2786
TRTPN(ATPTN)  3          2          2          7           17.4891     33.9365
TRTPN(ATPTN)  3          2          3          7           22.4450     34.9013
TRTPN(ATPTN)  3          2          1          8           76.8427     91.0580
TRTPN(ATPTN)  3          2          2          8           65.7686     82.2473
TRTPN(ATPTN)  3          2          3          8           51.8892     64.4039
TRTPN(ATPTN)  3          2          1          9           81.0332     95.1998
TRTPN(ATPTN) 3          2          2          9           76.4088     92.7778
TRTPN(ATPTN)  3          2          3          9           52.9217     65.3974
TRTPN(ATPTN)  1          3          2          3          -20.8047     -6.5758
TRTPN(ATPTN)  1          3          3          3          -32.4229    -18.2765
TRTPN(ATPTN)  1          3          1          4          -49.7800    -40.9674
TRTPN(ATPTN)  1          3          2          4          -76.4196    -62.1731
TRTPN(ATPTN)  1          3          3          4          -68.4472    -54.2840
TRTPN(ATPTN)  1          3          1          5           -6.4178      2.3896
TRTPN(ATPTN)  1          3          2          5          -25.5457    -11.3526
TRTPN(ATPTN)  1          3          3          5          -31.7254    -17.5789
TRTPN(ATPTN)  1          3          1          6          -55.6402    -46.8105
TRTPN(ATPTN)  1          3          2          6          -77.4284    -63.2353
TRTPN(ATPTN)  1          3          3          6          -67.2704    -53.1240
TRTPN(ATPTN)  1          3          1          7          -33.2404    -24.3914
TRTPN(ATPTN)  1          3          2          7          -51.4147    -37.1513
TRTPN(ATPTN)  1          3          3          7          -48.4043    -34.2411
TRTPN(ATPTN)  1          3          1          8            9.5168     18.3923
TRTPN(ATPTN)  1          3          2          8           -3.1377     11.1619
TRTPN(ATPTN)  1          3          3          8          -18.9565     -4.7420
TRTPN(ATPTN)  1          3          1          9           13.7193     22.5220
TRTPN(ATPTN)  1          3          2          9            7.5110     21.6840
TRTPN(ATPTN)  1          3          3          9          -17.9264     -3.7462
TRTPN(ATPTN)  2          3          3          3          -19.8535     -3.4653
TRTPN(ATPTN)  2          3          1          4          -38.7957    -24.5712
TRTPN(ATPTN)  2          3          2          4          -61.8856    -49.3266
TRTPN(ATPTN)  2          3          3          4          -55.8767    -39.4741
TRTPN(ATPTN)  2          3          1          5            4.5661     18.7862
TRTPN(ATPTN)  2          3          2          5          -11.0136      1.4957
TRTPN(ATPTN)  2          3          3          5          -19.1560     -2.7678
TRTPN(ATPTN)  2          3          1          6          -44.6515    -30.4187
TRTPN(ATPTN)  2          3          2          6          -62.8963    -50.3869
TRTPN(ATPTN)  2          3          3          6          -54.7010    -38.3129
TRTPN(ATPTN)  2          3          1          7          -22.2486     -8.0028
TRTPN(ATPTN)  2          3          2          7          -36.8847    -24.3009
TRTPN(ATPTN)  2          3          3          7          -35.8338    -19.4311
TRTPN(ATPTN)  2          3          1          8           20.5129     34.7766
TRTPN(ATPTN)  2          3          2          8           11.3927     24.0120
TRTPN(ATPTN)  2          3          3          8           -6.3825     10.0644
TRTPN(ATPTN)  2          3          1          9           24.7033     38.9185
TRTPN(ATPTN)  2          3          2          9           22.0392     34.5362
TRTPN(ATPTN)  2          3          3          9           -5.3547     11.0626
TRTPN(ATPTN)  3          3          1          4          -27.0951    -12.9530
TRTPN(ATPTN)  3          3          2          4          -52.1484    -35.7450
TRTPN(ATPTN)  3          3          3          4          -42.2248    -29.8071
TRTPN(ATPTN)  3          3          1          5           16.2667     30.4044
TRTPN(ATPTN)  3          3          2          5           -1.2781     15.0791
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
268 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          3          3          5          WORK.ANA_DATA    0.6975    3.1623  5649
TRTPN(ATPTN)  3          3          1          6          WORK.ANA_DATA  -25.8757    3.6082  2655
TRTPN(ATPTN)  3          3          2          6          WORK.ANA_DATA  -44.9822    4.1709  2648
TRTPN(ATPTN)  3          3          3          6          WORK.ANA_DATA  -34.8475    3.1623  5649
TRTPN(ATPTN)  3          3          1          7          WORK.ANA_DATA   -3.4662    3.6116  2662
TRTPN(ATPTN)  3          3          2          7          WORK.ANA_DATA  -18.9334    4.1865  2676
TRTPN(ATPTN)  3          3          3          7          WORK.ANA_DATA  -15.9730    3.1672  5650
TRTPN(ATPTN)  3          3          1          8          WORK.ANA_DATA   39.3042    3.6162  2672
TRTPN(ATPTN)  3          3          2          8          WORK.ANA_DATA   29.3618    4.1945  2691
TRTPN(ATPTN)  3          3          3          8          WORK.ANA_DATA   13.5004    3.1821  5651
TRTPN(ATPTN)  3          3          1          9          WORK.ANA_DATA   43.4703    3.6037  2646
TRTPN(ATPTN)  3          3          2          9          WORK.ANA_DATA   39.9472    4.1664  2641
TRTPN(ATPTN)  3          3          3          9          WORK.ANA_DATA   14.5134    3.1721  5650
TRTPN(ATPTN)  1          4          2          4          WORK.ANA_DATA  -23.9227    3.6317  2688
TRTPN(ATPTN)  1          4          3          4          WORK.ANA_DATA  -15.9919    3.6104  2659
TRTPN(ATPTN)  1          4          1          5          WORK.ANA_DATA   43.3596    2.2451  5652
TRTPN(ATPTN)  1          4          2          5          WORK.ANA_DATA   26.9245    3.6180  2659
TRTPN(ATPTN)  1          4          3          5          WORK.ANA_DATA   20.7216    3.6061  2650
TRTPN(ATPTN)  1          4          1          6          WORK.ANA_DATA   -5.8517    2.2498  5652
TRTPN(ATPTN)  1          4          2          6          WORK.ANA_DATA  -24.9581    3.6180  2659
TRTPN(ATPTN)  1          4          3          6          WORK.ANA_DATA  -14.8235    3.6061  2650
TRTPN(ATPTN)  1          4          1          7          WORK.ANA_DATA   16.5578    2.2557  5654
TRTPN(ATPTN)  1          4          2          7          WORK.ANA_DATA    1.0907    3.6359  2697
TRTPN(ATPTN)  1          4          3          7          WORK.ANA_DATA    4.0510    3.6104  2660
TRTPN(ATPTN)  1          4          1          8          WORK.ANA_DATA   59.3282    2.2620  5653
TRTPN(ATPTN)  1          4          2          8          WORK.ANA_DATA   49.3858    3.6452  2717
TRTPN(ATPTN)  1          4          3          8          WORK.ANA_DATA   33.5244    3.6235  2688
TRTPN(ATPTN)  1          4          1          9          WORK.ANA_DATA   63.4943    2.2434  5652
TRTPN(ATPTN)  1          4          2          9          WORK.ANA_DATA   59.9712    3.6129  2650
TRTPN(ATPTN)  1          4          3          9          WORK.ANA_DATA   34.5374    3.6147  2669
TRTPN(ATPTN)  2          4          3          4          WORK.ANA_DATA    7.9307    4.1864  2676
TRTPN(ATPTN)  2          4          1          5          WORK.ANA_DATA   67.2822    3.6305  2685
TRTPN(ATPTN)  2          4          2          5          WORK.ANA_DATA   50.8472    3.1957  5652
TRTPN(ATPTN)  2          4          3          5          WORK.ANA_DATA   44.6442    4.1827  2669
TRTPN(ATPTN)  2          4          1          6          WORK.ANA_DATA   18.0710    3.6337  2692
TRTPN(ATPTN)  2          4          2          6          WORK.ANA_DATA   -1.0355    3.1957  5652
TRTPN(ATPTN)  2          4          3          6          WORK.ANA_DATA    9.0992    4.1827  2669
TRTPN(ATPTN)  2          4          1          7          WORK.ANA_DATA   40.4804    3.6371  2699
TRTPN(ATPTN)  2          4          2          7          WORK.ANA_DATA   25.0133    3.2146  5653
TRTPN(ATPTN)  2          4          3          7          WORK.ANA_DATA   27.9737    4.1864  2676
TRTPN(ATPTN)  2          4          1          8          WORK.ANA_DATA   83.2509    3.6417  2709
TRTPN(ATPTN)  2          4          2          8          WORK.ANA_DATA   73.3085    3.2237  5652
TRTPN(ATPTN)  2          4          3          8          WORK.ANA_DATA   57.4471    4.1977  2697
TRTPN(ATPTN)  2          4          1          9          WORK.ANA_DATA   87.4170    3.6293  2683
TRTPN(ATPTN)  2          4          2          9          WORK.ANA_DATA   83.8938    3.1925  5656
TRTPN(ATPTN)  2          4          3          9          WORK.ANA_DATA   58.4601    4.1902  2683
TRTPN(ATPTN)  3          4          1          5          WORK.ANA_DATA   59.3515    3.6093  2657
TRTPN(ATPTN)  3          4          2          5          WORK.ANA_DATA   42.9165    4.1746  2655
TRTPN(ATPTN)  3          4          3          5          WORK.ANA_DATA   36.7135    3.1671  5650
TRTPN(ATPTN)  3          4          1          6          WORK.ANA_DATA   10.1403    3.6125  2664
TRTPN(ATPTN)  3          4          2          6          WORK.ANA_DATA   -8.9662    4.1746  2655
TRTPN(ATPTN)  3          4          3          6          WORK.ANA_DATA    1.1684    3.1671  5650
TRTPN(ATPTN)  3          4          1          7          WORK.ANA_DATA   32.5497    3.6159  2671
TRTPN(ATPTN)  3          4          2          7          WORK.ANA_DATA   17.0826    4.1902  2683
TRTPN(ATPTN)  3          4          3          7          WORK.ANA_DATA   20.0429    3.1720  5650
TRTPN(ATPTN)  3          4          1          8          WORK.ANA_DATA   75.3202    3.6205  2681
TRTPN(ATPTN)  3          4          2          8          WORK.ANA_DATA   65.3778    4.1982  2698
TRTPN(ATPTN)  3          4          3          8          WORK.ANA_DATA   49.5164    3.1870  5652
TRTPN(ATPTN)  3          4          1          9          WORK.ANA_DATA   79.4863    3.6080  2655
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
269 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          3          3          5             0.22      0.8254      0.05
TRTPN(ATPTN)  3          3          1          6            -7.17      <.0001      0.05
TRTPN(ATPTN)  3          3          2          6           -10.78      <.0001      0.05
TRTPN(ATPTN)  3          3          3          6           -11.02      <.0001      0.05
TRTPN(ATPTN)  3          3          1          7            -0.96      0.3373      0.05
TRTPN(ATPTN)  3          3         2          7            -4.52      <.0001      0.05
TRTPN(ATPTN)  3          3          3          7            -5.04      <.0001      0.05
TRTPN(ATPTN)  3          3          1          8            10.87      <.0001      0.05
TRTPN(ATPTN)  3          3          2          8             7.00      <.0001      0.05
TRTPN(ATPTN)  3          3          3          8             4.24      <.0001      0.05
TRTPN(ATPTN)  3          3          1          9            12.06      <.0001      0.05
TRTPN(ATPTN)  3          3          2          9             9.59      <.0001      0.05
TRTPN(ATPTN)  3          3          3          9             4.58      <.0001      0.05
TRTPN(ATPTN)  1          4          2          4            -6.59      <.0001      0.05
TRTPN(ATPTN)  1          4          3          4            -4.43      <.0001      0.05
TRTPN(ATPTN)  1          4          1          5            19.31      <.0001      0.05
TRTPN(ATPTN)  1          4          2          5             7.44      <.0001      0.05
TRTPN(ATPTN)  1          4          3          5             5.75      <.0001      0.05
TRTPN(ATPTN)  1          4          1          6            -2.60      0.0093      0.05
TRTPN(ATPTN)  1          4          2          6            -6.90      <.0001      0.05
TRTPN(ATPTN)  1          4          3          6            -4.11      <.0001      0.05
TRTPN(ATPTN)  1          4          1          7             7.34      <.0001      0.05
TRTPN(ATPTN)  1          4          2          7             0.30      0.7642      0.05
TRTPN(ATPTN)  1          4          3          7             1.12      0.2619      0.05
TRTPN(ATPTN)  1          4          1          8            26.23      <.0001      0.05
TRTPN(ATPTN)  1          4          2          8            13.55      <.0001      0.05
TRTPN(ATPTN)  1          4          3          8             9.25      <.0001      0.05
TRTPN(ATPTN)  1          4          1          9            28.30      <.0001      0.05
TRTPN(ATPTN)  1          4          2          9           16.60      <.0001      0.05
TRTPN(ATPTN)  1          4          3          9             9.55      <.0001      0.05
TRTPN(ATPTN)  2          4          3          4             1.89      0.0583      0.05
TRTPN(ATPTN)  2          4          1          5            18.53      <.0001      0.05
TRTPN(ATPTN)  2          4          2          5            15.91      <.0001      0.05
TRTPN(ATPTN)  2          4          3          5            10.67      <.0001      0.05
TRTPN(ATPTN)  2          4          1          6             4.97      <.0001      0.05
TRTPN(ATPTN)  2          4          2          6            -0.32      0.7459      0.05
TRTPN(ATPTN)  2          4          3          6             2.18      0.0297      0.05
TRTPN(ATPTN)  2          4         1          7            11.13      <.0001      0.05
TRTPN(ATPTN)  2          4          2          7             7.78      <.0001      0.05
TRTPN(ATPTN)  2          4          3          7             6.68      <.0001      0.05
TRTPN(ATPTN)  2          4          1          8            22.86      <.0001      0.05
TRTPN(ATPTN)  2          4          2          8            22.74      <.0001      0.05
TRTPN(ATPTN)  2          4          3          8            13.69      <.0001      0.05
TRTPN(ATPTN)  2          4          1          9            24.09      <.0001      0.05
TRTPN(ATPTN)  2          4          2          9            26.28      <.0001      0.05
TRTPN(ATPTN)  2          4          3          9            13.95      <.0001      0.05
TRTPN(ATPTN)  3          4          1          5            16.44      <.0001      0.05
TRTPN(ATPTN)  3          4          2          5            10.28      <.0001      0.05
TRTPN(ATPTN)  3          4          3          5            11.59      <.0001      0.05
TRTPN(ATPTN)  3          4          1          6             2.81      0.0050      0.05
TRTPN(ATPTN)  3          4          2          6            -2.15      0.0318      0.05
TRTPN(ATPTN)  3          4          3          6             0.37      0.7122      0.05
TRTPN(ATPTN)  3          4          1          7             9.00      <.0001      0.05
TRTPN(ATPTN)  3          4          2          7             4.08      <.0001      0.05
TRTPN(ATPTN)  3          4          3          7             6.32      <.0001      0.05
TRTPN(ATPTN)  3          4          1          8            20.80      <.0001      0.05
TRTPN(ATPTN)  3          4          2          8            15.57      <.0001      0.05
TRTPN(ATPTN)  3          4          3          8            15.54      <.0001      0.05
TRTPN(ATPTN)  3          4          1          9            22.03      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
270 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          3          3          5           -5.5017      6.8968
TRTPN(ATPTN)  3          3          1          6          -32.9509    -18.8005
TRTPN(ATPTN)  3          3          2          6          -53.1607    -36.8036
TRTPN(ATPTN)  3          3          3          6          -41.0468    -28.6483
TRTPN(ATPTN)  3          3          1          7          -10.5480      3.6156
TRTPN(ATPTN)  3          3          2          7          -27.1424    -10.7243
TRTPN(ATPTN)  3          3          3          7          -22.1819     -9.7642
TRTPN(ATPTN)  3          3          1          8           32.2134     46.3950
TRTPN(ATPTN)  3          3          2          8           21.1370     37.5866
TRTPN(ATPTN)  3          3          3          8            7.2623     19.7385
TRTPN(ATPTN)  3          3          1          9           36.4039     50.5367
TRTPN(ATPTN)  3          3          2          9           31.7773     48.1170
TRTPN(ATPTN)  3          3          3          9            8.2948     20.7319
TRTPN(ATPTN)  1          4          2          4          -31.0438    -16.8015
TRTPN(ATPTN)  1          4          3          4          -23.0714     -8.9125
TRTPN(ATPTN)  1          4          1          5           38.9584     47.7607
TRTPN(ATPTN)  1          4          2          5           19.8302     34.0189
TRTPN(ATPTN)  1          4          3          5           13.6505     27.7926
TRTPN(ATPTN)  1          4          1          6          -10.2622     -1.4411
TRTPN(ATPTN)  1          4          2          6          -32.0525    -17.8638
TRTPN(ATPTN)  1          4          3          6          -21.8945     -7.7525
TRTPN(ATPTN)  1          4          1          7           12.1358     20.9797
TRTPN(ATPTN)  1          4          2          7           -6.0389      8.2202
TRTPN(ATPTN)  1          4          3          7           -3.0285     11.1305
TRTPN(ATPTN)  1          4          1          8           54.8938     63.7626
TRTPN(ATPTN)  1          4          2          8           42.2382     56.5334
TRTPN(ATPTN)  1          4          3          8           26.4193     40.6295
TRTPN(ATPTN)  1          4          1          9           59.0965     67.8922
TRTPN(ATPTN)  1          4          2          9           52.8869     67.0555
TRTPN(ATPTN)  1          4          3          9           27.4494     41.6254
TRTPN(ATPTN)  2          4          3          4           -0.2782     16.1396
TRTPN(ATPTN)  2          4          1          5           60.1633     74.4011
TRTPN(ATPTN)  2          4          2          5           44.5824     57.1119
TRTPN(ATPTN)  2          4          3          5           36.4425     52.8460
TRTPN(ATPTN)  2          4          1          6           10.9458     25.1962
TRTPN(ATPTN)  2          4          2          6           -7.3002      5.2293
TRTPN(ATPTN)  2          4          3          6            0.8974     17.3009
TRTPN(ATPTN)  2          4          1          7           33.3487     47.6122
TRTPN(ATPTN)  2          4          2          7           18.7114     31.3153
TRTPN(ATPTN)  2          4          3          7           19.7647     36.1827
TRTPN(ATPTN)  2          4          1          8           76.1102     90.3916
TRTPN(ATPTN)  2          4          2          8           66.9888     79.6281
TRTPN(ATPTN)  2          4          3          8           49.2160     65.6782
TRTPN(ATPTN)  2          4          1          9           80.3006     94.5335
TRTPN(ATPTN)  2          4          2          9           77.6353     90.1524
TRTPN(ATPTN)  2          4          3          9           50.2438     66.6764
TRTPN(ATPTN)  3          4          1          5           52.2743     66.4288
TRTPN(ATPTN)  3          4          2          5           34.7307     51.1023
TRTPN(ATPTN)  3          4          3          5           30.5047     42.9223
TRTPN(ATPTN)  3          4          1          6            3.0567     17.2239
TRTPN(ATPTN)  3          4          2          6          -17.1520     -0.7804
TRTPN(ATPTN)  3          4          3          6           -5.0404      7.3773
TRTPN(ATPTN)  3          4          1          7           25.4596     39.6399
TRTPN(ATPTN)  3          4          2          7            8.8663     25.2989
TRTPN(ATPTN)  3          4          3          7           13.8245     26.2614
TRTPN(ATPTN)  3          4          1          8           68.2210     82.4193
TRTPN(ATPTN)  3          4          2         8           57.1457     73.6098
TRTPN(ATPTN)  3          4          3          8           43.2687     55.7640
TRTPN(ATPTN)  3          4          1          9           72.4115     86.5611
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
271 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  3          4          2          9          WORK.ANA_DATA   75.9631    4.1702  2648
TRTPN(ATPTN)  3          4          3          9          WORK.ANA_DATA   50.5293    3.1770  5651
TRTPN(ATPTN)  1          5          2          5          WORK.ANA_DATA  -16.4351    3.6169  2657
TRTPN(ATPTN)  1          5          3          5          WORK.ANA_DATA  -22.6380    3.6050  2648
TRTPN(ATPTN)  1          5          1          6          WORK.ANA_DATA  -49.2112    2.2480  5651
TRTPN(ATPTN)  1          5          2          6          WORK.ANA_DATA  -68.3177    3.6169  2657
TRTPN(ATPTN)  1          5          3          6          WORK.ANA_DATA  -58.1831    3.6050  2648
TRTPN(ATPTN)  1          5          1          7          WORK.ANA_DATA  -26.8018    2.2529  5651
TRTPN(ATPTN)  1          5          2          7          WORK.ANA_DATA  -42.2689    3.6348  2695
TRTPN(ATPTN)  1          5          3          7          WORK.ANA_DATA  -39.3086    3.6093  2657
TRTPN(ATPTN)  1          5          1          8          WORK.ANA_DATA   15.9686    2.2603  5653
TRTPN(ATPTN)  1          5          2          8          WORK.ANA_DATA    6.0262    3.6441  2715
TRTPN(ATPTN)  1          5          3          8          WORK.ANA_DATA   -9.8352    3.6224  2685
TRTPN(ATPTN)  1          5          1          9          WORK.ANA_DATA   20.1348    2.2422  5654
TRTPN(ATPTN)  1          5          2          9          WORK.ANA_DATA   16.6116    3.6118  2648
TRTPN(ATPTN)  1          5          3          9          WORK.ANA_DATA   -8.8222    3.6136  2667
TRTPN(ATPTN)  2          5          3          5          WORK.ANA_DATA   -6.2030    4.1709  2648
TRTPN(ATPTN)  2          5          1          6          WORK.ANA_DATA  -32.7762    3.6201  2664
TRTPN(ATPTN)  2          5          2          6          WORK.ANA_DATA  -51.8827    3.1802  5649
TRTPN(ATPTN)  2          5          3          6          WORK.ANA_DATA  -41.7480    4.1709  2648
TRTPN(ATPTN)  2          5          1          7          WORK.ANA_DATA  -10.3667    3.6235  2671
TRTPN(ATPTN)  2          5          2          7          WORK.ANA_DATA  -25.8338    3.2006  5652
TRTPN(ATPTN)  2          5          3          7          WORK.ANA_DATA  -22.8735    4.1746  2655
TRTPN(ATPTN)  2          5          1          8          WORK.ANA_DATA   32.4037    3.6280  2681
TRTPN(ATPTN)  2          5          2          8          WORK.ANA_DATA   22.4613    3.2111  5654
TRTPN(ATPTN)  2          5          3          8          WORK.ANA_DATA    6.5999    4.1860  2676
TRTPN(ATPTN)  2          5          1          9          WORK.ANA_DATA   36.5698    3.6156  2655
TRTPN(ATPTN)  2          5          2          9          WORK.ANA_DATA   33.0467    3.1770  5653
TRTPN(ATPTN)  2          5          3          9          WORK.ANA_DATA    7.6129    4.1784  2662
TRTPN(ATPTN)  3          5          1          6          WORK.ANA_DATA  -26.5732    3.6082  2655
TRTPN(ATPTN)  3          5          2          6          WORK.ANA_DATA  -45.6797    4.1709  2648
TRTPN(ATPTN)  3          5          3          6          WORK.ANA_DATA  -35.5451    3.1623  5649
TRTPN(ATPTN)  3          5          1          7          WORK.ANA_DATA   -4.1638    3.6116  2662
TRTPN(ATPTN)  3          5          2          7          WORK.ANA_DATA  -19.6309    4.1865  2676
TRTPN(ATPTN)  3          5          3          7          WORK.ANA_DATA  -16.6706    3.1672  5650
TRTPN(ATPTN)  3          5          1          8          WORK.ANA_DATA   38.6067    3.6162  2672
TRTPN(ATPTN)  3          5          2          8          WORK.ANA_DATA   28.6643    4.1945  2691
TRTPN(ATPTN)  3          5          3          8          WORK.ANA_DATA   12.8029    3.1821  5651
TRTPN(ATPTN)  3          5          1          9          WORK.ANA_DATA   42.7728    3.6037  2646
TRTPN(ATPTN)  3          5          2          9          WORK.ANA_DATA   39.2496    4.1664  2641
TRTPN(ATPTN)  3          5          3          9          WORK.ANA_DATA   13.8158    3.1721  5650
TRTPN(ATPTN)  1          6          2          6          WORK.ANA_DATA  -19.1065    3.6201  2664
TRTPN(ATPTN)  1          6          3          6          WORK.ANA_DATA   -8.9718    3.6082  2655
TRTPN(ATPTN)  1          6          1          7          WORK.ANA_DATA   22.4094    2.2586  5653
TRTPN(ATPTN)  1          6          2          7          WORK.ANA_DATA    6.9423    3.6381  2702
TRTPN(ATPTN)  1          6          3          7          WORK.ANA_DATA    9.9027    3.6125  2664
TRTPN(ATPTN)  1          6          1          8          WORK.ANA_DATA   65.1799    2.2655  5654
TRTPN(ATPTN)  1          6          2          8          WORK.ANA_DATA   55.2375    3.6473  2722
TRTPN(ATPTN)  1          6          3          8          WORK.ANA_DATA   39.3761    3.6256  2692
TRTPN(ATPTN)  1          6          1          9          WORK.ANA_DATA   69.3460    2.2474  5654
TRTPN(ATPTN)  1          6          2          9          WORK.ANA_DATA   65.8228    3.6150  2655
TRTPN(ATPTN)  1          6          3          9          WORK.ANA_DATA   40.3891    3.6169  2674
TRTPN(ATPTN)  2          6          3          6          WORK.ANA_DATA   10.1346    4.1709  2648
TRTPN(ATPTN)  2          6          1          7          WORK.ANA_DATA   41.5159    3.6235  2671
TRTPN(ATPTN)  2          6          2          7          WORK.ANA_DATA   26.0488    3.2006  5652
TRTPN(ATPTN)  2          6          3          7          WORK.ANA_DATA   29.0091    4.1746  2655
TRTPN(ATPTN)  2          6          1          8          WORK.ANA_DATA   84.2864    3.6280  2681
TRTPN(ATPTN)  2          6          2          8          WORK.ANA_DATA   74.3439    3.2111  5654
TRTPN(ATPTN)  2          6          3          8          WORK.ANA_DATA   58.4826    4.1860  2676
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
272 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  3          4          2          9            18.22      <.0001      0.05
TRTPN(ATPTN)  3          4          3          9            15.90      <.0001      0.05
TRTPN(ATPTN)  1          5          2          5            -4.54      <.0001      0.05
TRTPN(ATPTN)  1          5          3          5            -6.28      <.0001      0.05
TRTPN(ATPTN)  1          5          1          6           -21.89      <.0001      0.05
TRTPN(ATPTN)  1          5          2          6           -18.89      <.0001      0.05
TRTPN(ATPTN)  1          5          3          6           -16.14      <.0001      0.05
TRTPN(ATPTN)  1          5          1          7           -11.90      <.0001      0.05
TRTPN(ATPTN)  1          5          2          7           -11.63      <.0001      0.05
TRTPN(ATPTN)  1          5          3          7           -10.89      <.0001      0.05
TRTPN(ATPTN)  1          5          1          8             7.06      <.0001      0.05
TRTPN(ATPTN)  1          5          2          8             1.65      0.0983      0.05
TRTPN(ATPTN)  1          5          3          8            -2.72      0.0067      0.05
TRTPN(ATPTN)  1          5          1          9             8.98      <.0001      0.05
TRTPN(ATPTN)  1          5          2          9             4.60      <.0001      0.05
TRTPN(ATPTN)  1          5          3          9            -2.44      0.0147      0.05
TRTPN(ATPTN)  2          5          3          5            -1.49      0.1371      0.05
TRTPN(ATPTN)  2          5          1          6            -9.05      <.0001      0.05
TRTPN(ATPTN)  2          5          2          6           -16.31      <.0001      0.05
TRTPN(ATPTN)  2          5          3          6           -10.01      <.0001      0.05
TRTPN(ATPTN)  2          5          1          7            -2.86      0.0043      0.05
TRTPN(ATPTN)  2          5          2          7            -8.07      <.0001      0.05
TRTPN(ATPTN)  2          5          3          7            -5.48      <.0001      0.05
TRTPN(ATPTN)  2          5          1          8             8.93      <.0001      0.05
TRTPN(ATPTN)  2          5          2          8             6.99      <.0001      0.05
TRTPN(ATPTN)  2          5          3          8             1.58      0.1150      0.05
TRTPN(ATPTN)  2          5          1          9            10.11      <.0001      0.05
TRTPN(ATPTN)  2          5          2          9            10.40      <.0001      0.05
TRTPN(ATPTN)  2          5          3          9             1.82      0.0686      0.05
TRTPN(ATPTN)  3          5          1          6            -7.36      <.0001      0.05
TRTPN(ATPTN)  3          5          2          6           -10.95      <.0001      0.05
TRTPN(ATPTN)  3          5          3          6           -11.24      <.0001      0.05
TRTPN(ATPTN)  3          5          1          7            -1.15      0.2491      0.05
TRTPN(ATPTN)  3          5          2          7            -4.69      <.0001      0.05
TRTPN(ATPTN)  3          5          3          7            -5.26      <.0001      0.05
TRTPN(ATPTN)  3          5          1          8            10.68      <.0001      0.05
TRTPN(ATPTN)  3          5          2          8             6.83      <.0001      0.05
TRTPN(ATPTN)  3          5          3          8             4.02      <.0001      0.05
TRTPN(ATPTN)  3          5          1          9            11.87      <.0001      0.05
TRTPN(ATPTN)  3          5          2          9             9.42      <.0001      0.05
TRTPN(ATPTN)  3          5          3          9             4.36      <.0001      0.05
TRTPN(ATPTN)  1          6          2          6            -5.28      <.0001      0.05
TRTPN(ATPTN)  1          6          3          6            -2.49      0.0130      0.05
TRTPN(ATPTN)  1          6          1          7             9.92      <.0001      0.05
TRTPN(ATPTN)  1          6          2          7             1.91      0.0565      0.05
TRTPN(ATPTN)  1          6          3          7             2.74      0.0062      0.05
TRTPN(ATPTN)  1          6          1          8            28.77      <.0001      0.05
TRTPN(ATPTN)  1          6          2          8            15.14      <.0001      0.05
TRTPN(ATPTN)  1          6          3          8            10.86      <.0001      0.05
TRTPN(ATPTN)  1          6          1          9            30.86      <.0001      0.05
TRTPN(ATPTN)  1          6          2          9            18.21      <.0001      0.05
TRTPN(ATPTN)  1          6          3          9            11.17      <.0001      0.05
TRTPN(ATPTN)  2          6          3          6             2.43      0.0152      0.05
TRTPN(ATPTN)  2          6          1          7            11.46      <.0001      0.05
TRTPN(ATPTN)  2          6          2          7             8.14      <.0001      0.05
TRTPN(ATPTN)  2          6          3          7             6.95      <.0001      0.05
TRTPN(ATPTN)  2          6          1          8            23.23      <.0001      0.05
TRTPN(ATPTN)  2          6          2          8            23.15      <.0001      0.05
TRTPN(ATPTN)  2          6          3          8            13.97      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
273 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          4          2          9           67.7860     84.1402
TRTPN(ATPTN)  3          4          3          9           44.3012     56.7575
TRTPN(ATPTN)  1          5          2          5          -23.5272     -9.3429
TRTPN(ATPTN)  1          5          3          5          -29.7069    -15.5691
TRTPN(ATPTN)  1          5          1          6          -53.6182    -44.8043
TRTPN(ATPTN)  1          5          2          6          -75.4099    -61.2255
TRTPN(ATPTN)  1          5          3          6          -65.2520    -51.1142
TRTPN(ATPTN)  1          5          1          7          -31.2183    -22.3853
TRTPN(ATPTN)  1          5          2          7          -49.3963    -35.1415
TRTPN(ATPTN)  1          5          3          7          -46.3859    -32.2313
TRTPN(ATPTN)  1          5          1          8           11.5377     20.3996
TRTPN(ATPTN)  1          5          2          8           -1.1192     13.1717
TRTPN(ATPTN)  1          5          3          8          -16.9381     -2.7322
TRTPN(ATPTN)  1          5          1          9           15.7393     24.5303
TRTPN(ATPTN)  1          5          2          9            9.5295     23.6937
TRTPN(ATPTN)  1          5          3          9          -15.9080     -1.7364
TRTPN(ATPTN)  2          5          3          5          -14.3816      1.9757
TRTPN(ATPTN)  2          5          1          6          -39.8747    -25.6777
TRTPN(ATPTN)  2          5          2          6          -58.1170    -45.6483
TRTPN(ATPTN)  2          5          3          6          -49.9266    -33.5695
TRTPN(ATPTN)  2          5          1          7          -17.4718     -3.2617
TRTPN(ATPTN)  2          5          2         7          -32.1082    -19.5595
TRTPN(ATPTN)  2          5          3          7          -31.0594    -14.6877
TRTPN(ATPTN)  2          5          1          8           25.2897     39.5177
TRTPN(ATPTN)  2          5          2          8           16.1663     28.7562
TRTPN(ATPTN)  2          5          3          8           -1.6081     14.8079
TRTPN(ATPTN)  2          5          1          9           29.4801     43.6596
TRTPN(ATPTN)  2          5          2          9           26.8185     39.2748
TRTPN(ATPTN)  2          5          3          9           -0.5803     15.8061
TRTPN(ATPTN)  3          5          1          6          -33.6484    -19.4980
TRTPN(ATPTN)  3          5          2          6          -53.8583    -37.5011
TRTPN(ATPTN)  3         5          3          6          -41.7443    -29.3458
TRTPN(ATPTN)  3          5          1          7          -11.2456      2.9180
TRTPN(ATPTN)  3          5          2          7          -27.8400    -11.4218
TRTPN(ATPTN)  3          5          3          7          -22.8794    -10.4617
TRTPN(ATPTN)  3          5          1          8           31.5159     45.6975
TRTPN(ATPTN)  3          5          2          8           20.4394     36.8891
TRTPN(ATPTN)  3          5          3          8            6.5648     19.0410
TRTPN(ATPTN)  3          5          1          9           35.7064     49.8392
TRTPN(ATPTN)  3          5          2          9           31.0798     47.4195
TRTPN(ATPTN)  3          5          3          9            7.5973     20.0344
TRTPN(ATPTN)  1          6          2          6          -26.2050    -12.0080
TRTPN(ATPTN)  1          6          3          6          -16.0471     -1.8966
TRTPN(ATPTN)  1          6          1          7           17.9818     26.8371
TRTPN(ATPTN)  1          6          2          7           -0.1913     14.0760
TRTPN(ATPTN)  1          6          3          7            2.8190     16.9863
TRTPN(ATPTN)  1          6          1          8           60.7386     69.6212
TRTPN(ATPTN)  1          6          2          8           48.0857     62.3892
TRTPN(ATPTN)  1          6          3          8           32.2668     46.4853
TRTPN(ATPTN)  1          6          1          9           64.9403     73.7517
TRTPN(ATPTN)  1          6          2          9           58.7344     72.9113
TRTPN(ATPTN)  1          6          3          9           33.2969     47.4812
TRTPN(ATPTN)  2          6          3          6            1.9560     18.3133
TRTPN(ATPTN)  2          6         1          7           34.4109     48.6210
TRTPN(ATPTN)  2          6          2          7           19.7744     32.3232
TRTPN(ATPTN)  2          6          3          7           20.8233     37.1950
TRTPN(ATPTN)  2          6          1          8           77.1723     91.4004
TRTPN(ATPTN)  2          6          2          8           68.0490     80.6389
TRTPN(ATPTN)  2          6          3          8           50.2745     66.6906
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
274 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                               Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint                           Standard
Effect        01 (N)     (N)        01 (N)     (N)        Margins        Estimate     Error    DF
TRTPN(ATPTN)  2          6          1          9          WORK.ANA_DATA   88.4525    3.6156  2655
TRTPN(ATPTN)  2          6          2          9          WORK.ANA_DATA   84.9293    3.1770  5653
TRTPN(ATPTN)  2          6          3          9          WORK.ANA_DATA   59.4955    4.1784  2662
TRTPN(ATPTN)  3          6          1          7          WORK.ANA_DATA   31.3813    3.6116  2662
TRTPN(ATPTN)  3          6          2          7          WORK.ANA_DATA   15.9142    4.1865  2676
TRTPN(ATPTN)  3          6          3          7          WORK.ANA_DATA   18.8745    3.1672  5650
TRTPN(ATPTN)  3          6          1          8          WORK.ANA_DATA   74.1517    3.6162  2672
TRTPN(ATPTN)  3          6          2          8          WORK.ANA_DATA   64.2093    4.1945  2691
TRTPN(ATPTN)  3          6          3          8          WORK.ANA_DATA   48.3479    3.1821  5651
TRTPN(ATPTN)  3          6          1          9          WORK.ANA_DATA   78.3179    3.6037  2646
TRTPN(ATPTN)  3          6          2          9          WORK.ANA_DATA   74.7947    4.1664  2641
TRTPN(ATPTN)  3          6          3          9          WORK.ANA_DATA   49.3609    3.1721  5650
TRTPN(ATPTN)  1          7          2          7          WORK.ANA_DATA  -15.4671    3.6413  2709
TRTPN(ATPTN)  1          7          3          7          WORK.ANA_DATA  -12.5068    3.6159  2671
TRTPN(ATPTN)  1          7          1          8          WORK.ANA_DATA   42.7704    2.2704  5654
TRTPN(ATPTN)  1          7          2          8          WORK.ANA_DATA   32.8280    3.6506  2729
TRTPN(ATPTN)  1          7          3          8          WORK.ANA_DATA   16.9666    3.6290  2700
TRTPN(ATPTN)  1          7          1          9          WORK.ANA_DATA   46.9366    2.2528  5655
TRTPN(ATPTN)  1          7          2          9          WORK.ANA_DATA   43.4134    3.6183  2662
TRTPN(ATPTN)  1          7          3          9          WORK.ANA_DATA   17.9796    3.6202  2681
TRTPN(ATPTN)  2          7          3          7          WORK.ANA_DATA    2.9603    4.1903  2683
TRTPN(ATPTN)  2          7          1          8          WORK.ANA_DATA   58.2375    3.6460  2719
TRTPN(ATPTN)  2          7          2          8          WORK.ANA_DATA   48.2951    3.2300  5654
TRTPN(ATPTN)  2          7          3          8          WORK.ANA_DATA   32.4337    4.2015  2704
TRTPN(ATPTN)  2          7          1          9          WORK.ANA_DATA   62.4037    3.6336  2693
TRTPN(ATPTN)  2          7          2          9          WORK.ANA_DATA   58.8805    3.1974  5656
TRTPN(ATPTN)  2          7          3          9          WORK.ANA_DATA   33.4467    4.1939  2690
TRTPN(ATPTN)  3          7          1          8          WORK.ANA_DATA   55.2772    3.6205  2681
TRTPN(ATPTN)  3          7          2          8          WORK.ANA_DATA   45.3348    4.1982  2698
TRTPN(ATPTN)  3          7          3          8          WORK.ANA_DATA   29.4734    3.1870  5652
TRTPN(ATPTN)  3          7          1          9          WORK.ANA_DATA   59.4433    3.6080  2655
TRTPN(ATPTN)  3          7          2          9          WORK.ANA_DATA   55.9202    4.1702  2648
TRTPN(ATPTN)  3          7          3          9          WORK.ANA_DATA   30.4864    3.1770  5651
TRTPN(ATPTN)  1          8          2          8          WORK.ANA_DATA   -9.9424    3.6551  2738
TRTPN(ATPTN)  1          8          3          8          WORK.ANA_DATA  -25.8038    3.6335  2709
TRTPN(ATPTN)  1          8          1          9          WORK.ANA_DATA    4.1661    2.2595  5655
TRTPN(ATPTN)  1          8          2          9          WORK.ANA_DATA    0.6430    3.6229  2672
TRTPN(ATPTN)  1          8          3          9          WORK.ANA_DATA  -24.7908    3.6248  2690
TRTPN(ATPTN)  2          8          3          8          WORK.ANA_DATA  -15.8614    4.2095  2719
TRTPN(ATPTN)  2          8          1          9          WORK.ANA_DATA   14.1085    3.6428  2712
TRTPN(ATPTN)  2          8          2          9          WORK.ANA_DATA   10.5854    3.2079  5658
TRTPN(ATPTN)  2          8          3          9          WORK.ANA_DATA  -14.8484    4.2020  2705
TRTPN(ATPTN)  3          8          1          9          WORK.ANA_DATA   29.9699    3.6211  2683
TRTPN(ATPTN)  3          8          2          9          WORK.ANA_DATA   26.4468    4.1815  2669
TRTPN(ATPTN)  3          8          3          9          WORK.ANA_DATA    1.0130    3.1919  5652
TRTPN(ATPTN)  1          9          2          9          WORK.ANA_DATA   -3.5232    3.6105  2646
TRTPN(ATPTN)  1          9          3          9          WORK.ANA_DATA  -28.9569    3.6123  2664
TRTPN(ATPTN)  2          9          3          9          WORK.ANA_DATA  -25.4338    4.1740  2655
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  2          6          1          9            24.46      <.0001      0.05
TRTPN(ATPTN)  2          6          2          9            26.73      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
275 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                          Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)        t Value    Pr > |t|     Alpha
TRTPN(ATPTN)  2          6          3          9            14.24      <.0001      0.05
TRTPN(ATPTN)  3          6          1          7             8.69      <.0001      0.05
TRTPN(ATPTN)  3          6          2          7             3.80      0.0001      0.05
TRTPN(ATPTN)  3          6          3          7             5.96      <.0001      0.05
TRTPN(ATPTN)  3          6          1          8            20.51      <.0001      0.05
TRTPN(ATPTN)  3          6          2          8            15.31      <.0001      0.05
TRTPN(ATPTN)  3          6          3          8            15.19      <.0001      0.05
TRTPN(ATPTN)  3          6          1          9            21.73      <.0001      0.05
TRTPN(ATPTN)  3          6          2          9            17.95      <.0001      0.05
TRTPN(ATPTN)  3          6          3          9            15.56      <.0001      0.05
TRTPN(ATPTN)  1          7          2          7            -4.25      <.0001      0.05
TRTPN(ATPTN)  1          7          3          7            -3.46      0.0006      0.05
TRTPN(ATPTN)  1          7          1          8            18.84      <.0001      0.05
TRTPN(ATPTN)  1          7          2          8             8.99      <.0001      0.05
TRTPN(ATPTN)  1          7          3          8             4.68      <.0001      0.05
TRTPN(ATPTN)  1          7          1          9            20.84      <.0001      0.05
TRTPN(ATPTN)  1          7          2          9            12.00      <.0001      0.05
TRTPN(ATPTN)  1          7          3          9             4.97      <.0001      0.05
TRTPN(ATPTN)  2          7          3          7             0.71      0.4800      0.05
TRTPN(ATPTN)  2          7          1          8            15.97      <.0001      0.05
TRTPN(ATPTN)  2          7          2          8            14.95      <.0001      0.05
TRTPN(ATPTN)  2          7          3          8             7.72      <.0001      0.05
TRTPN(ATPTN)  2          7          1          9            17.17      <.0001      0.05
TRTPN(ATPTN)  2         7          2          9            18.41      <.0001      0.05
TRTPN(ATPTN)  2          7          3          9             7.98      <.0001      0.05
TRTPN(ATPTN)  3          7          1          8            15.27      <.0001      0.05
TRTPN(ATPTN)  3          7          2          8            10.80      <.0001      0.05
TRTPN(ATPTN)  3          7          3          8             9.25      <.0001      0.05
TRTPN(ATPTN)  3          7          1          9            16.48      <.0001      0.05
TRTPN(ATPTN)  3          7          2          9            13.41      <.0001      0.05
TRTPN(ATPTN)  3          7          3          9             9.60      <.0001      0.05
TRTPN(ATPTN)  1          8          2          8            -2.72      0.0066      0.05
TRTPN(ATPTN)  1          8          3          8            -7.10      <.0001      0.05
TRTPN(ATPTN)  1          8          1          9             1.84      0.0653      0.05
TRTPN(ATPTN)  1          8          2          9             0.18      0.8592      0.05
TRTPN(ATPTN)  1          8          3          9            -6.84      <.0001      0.05
TRTPN(ATPTN)  2          8          3          8            -3.77      0.0002      0.05
TRTPN(ATPTN)  2          8          1          9             3.87      0.0001      0.05
TRTPN(ATPTN)  2          8          2          9             3.30      0.0010      0.05
TRTPN(ATPTN)  2          8          3          9            -3.53      0.0004      0.05
TRTPN(ATPTN)  3          8          1          9             8.28      <.0001      0.05
TRTPN(ATPTN)  3          8          2          9             6.32      <.0001      0.05
TRTPN(ATPTN)  3          8          3          9             0.32      0.7510      0.05
TRTPN(ATPTN)  1          9          2          9            -0.98      0.3293      0.05
TRTPN(ATPTN)  1          9          3          9            -8.02      <.0001      0.05
TRTPN(ATPTN)  2          9          3          9            -6.09      <.0001      0.05
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  2          6          1          9           81.3628     95.5422
TRTPN(ATPTN)  2          6          2          9           78.7012     91.1575
TRTPN(ATPTN)  2          6          3         9           51.3024     67.6887
TRTPN(ATPTN)  3          6          1          7           24.2995     38.4631
CONFIDENTIAL


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Version:
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Statistical document
Page:
276 of 412
9-point self-measured plasma glucose profile after 26 weeks of treatment - supportive statistical
analysis - full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                      Differences of Least Squares Means
              Planned               Planned
              Treatment             Treatment
              for        Analysis   for        Analysis
              Period     Timepoint  Period     Timepoint
Effect        01 (N)     (N)        01 (N)     (N)           Lower       Upper
TRTPN(ATPTN)  3          6          2          7            7.7051     24.1233
TRTPN(ATPTN)  3          6          3          7           12.6657     25.0834
TRTPN(ATPTN)  3          6          1          8           67.0609     81.2425
TRTPN(ATPTN)  3          6          2          8           55.9845     72.4341
TRTPN(ATPTN)  3          6          3          8           42.1098     54.5860
TRTPN(ATPTN)  3          6          1          9           71.2515     85.3842
TRTPN(ATPTN)  3          6          2          9           66.6248     82.9645
TRTPN(ATPTN)  3          6          3          9           43.1423     55.5795
TRTPN(ATPTN)  1          7          2          7          -22.6072     -8.3270
TRTPN(ATPTN)  1          7          3          7          -19.5970     -5.4165
TRTPN(ATPTN)  1          7          1          8           38.3195     47.2214
TRTPN(ATPTN)  1          7          2          8           25.6698     39.9863
TRTPN(ATPTN)  1          7          3          8            9.8508     24.0824
TRTPN(ATPTN)  1          7          1          9           42.5203     51.3529
TRTPN(ATPTN)  1          7          2          9           36.3184     50.5084
TRTPN(ATPTN)  1          7          3          9           10.8809     25.0783
TRTPN(ATPTN)  2          7          3          7           -5.2561     11.1768
TRTPN(ATPTN)  2          7          1          8           51.0884     65.3867
TRTPN(ATPTN)  2          7          2          8           41.9630     54.6272
TRTPN(ATPTN)  2          7          3          8           24.1953     40.6722
TRTPN(ATPTN)  2          7          1          9           55.2788     69.5286
TRTPN(ATPTN)  2          7          2          9           52.6123     65.1487
TRTPN(ATPTN)  2          7          3          9           25.2231     41.6704
TRTPN(ATPTN)  3          7          1          8           48.1780     62.3764
TRTPN(ATPTN)  3          7          2          8           37.1027     53.5669
TRTPN(ATPTN)  3          7          3          8           23.2257     35.7211
TRTPN(ATPTN)  3          7          1          9           52.3685     66.5182
TRTPN(ATPTN)  3          7          2          9           47.7431     64.0973
TRTPN(ATPTN)  3          7          3          9           24.2582     36.7146
TRTPN(ATPTN)  1          8          2          8          -17.1095     -2.7753
TRTPN(ATPTN)  1          8         3          8          -32.9286    -18.6790
TRTPN(ATPTN)  1          8          1          9           -0.2635      8.5957
TRTPN(ATPTN)  1          8          2          9           -6.4611      7.7470
TRTPN(ATPTN)  1          8          3          9          -31.8985    -17.6832
TRTPN(ATPTN)  2          8          3          8          -24.1155     -7.6073
TRTPN(ATPTN)  2          8          1          9            6.9655     21.2516
TRTPN(ATPTN)  2          8          2          9            4.2966     16.8742
TRTPN(ATPTN)  2          8          3          9          -23.0878     -6.6090
TRTPN(ATPTN)  3          8          1          9           22.8695     37.0704
TRTPN(ATPTN)  3          8          2          9           18.2474     34.6461
TRTPN(ATPTN) 3          8          3          9           -5.2444      7.2704
TRTPN(ATPTN)  1          9          2          9          -10.6029      3.5566
TRTPN(ATPTN)  1          9          3          9          -36.0402    -21.8737
TRTPN(ATPTN)  2          9          3          9          -33.6184    -17.2492
CONFIDENTIAL


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CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
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Final
Statistical document
Page:
277 of 412
20: Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from 
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PSMPGM
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             720
Number of Observations Used             708
Number of Observations Not Used          12
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.2712
           Fit Statistics
-2 Res Log Likelihood          2600.9
AIC (Smaller is Better)        2602.9
AICC (Smaller is Better)       2602.9
BIC (Smaller is Better)        2607.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   6.4453     0.3205    703     20.11     <.0001     0.05
trtpn                         1            -1.1247     0.1394    703     -8.07     <.0001     0.05
trtpn                         2            -0.3415     0.1610    703     -2.12     0.0342     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.5115     0.1210    703     -4.23     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.2153    0.02875    703      7.49     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
278 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PSMPGM
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   5.8160      7.0746
trtpn                         1            -1.3983     -0.8511
trtpn                         2            -0.6575    -0.02547
trtpn                         3                               
PREOAD2     Metformin                      -0.7490     -0.2740
PREOAD2     Metformin + OAD                                   
BASE                                        0.1589      0.2718
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703      37.60    <.0001
PREOAD2         1     703      17.88    <.0001
BASE            1     703      56.10    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     7.3919    0.07976     703     92.68     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     8.1751     0.1133     703     72.15     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     8.5166     0.1143     703     74.52     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     7.2353     7.5485        1622.74         1387.52         1897.83
trtpn    LSMeans, IDeg         7.9526     8.3975         3551.30         2843.02         4436.05
trtpn    LSMeans, Lira         8.2922     8.7410         4996.93         3992.62         6253.87
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.7832     0.1386     703     -5.65
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.0552   -0.5112         0.4569
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.3481           0.5998
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
279 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PSMPGM
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -1.1247     0.1394     703     -8.07
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05   -1.3983   -0.8511         0.3247
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.2470           0.4270
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
280 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9SMPGMU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             720
Number of Observations Used             708
Number of Observations Not Used          12
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       737.49
           Fit Statistics
-2 Res Log Likelihood          6672.1
AIC (Smaller is Better)        6674.1
AICC (Smaller is Better)       6674.1
BIC (Smaller is Better)        6678.6
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   116.14     5.7760    703     20.11     <.0001     0.05
trtpn                         1           -20.2673     2.5114    703     -8.07     <.0001     0.05
trtpn                         2            -6.1540     2.9007    703     -2.12     0.0342     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -9.2178     2.1799    703     -4.23     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.2153    0.02875    703      7.49     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
281 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9SMPGMU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   104.80      127.48
trtpn                         1           -25.1980    -15.3365
trtpn                         2           -11.8490     -0.4590
trtpn                         3                               
PREOAD2     Metformin                     -13.4977     -4.9379
PREOAD2     Metformin + OAD                                   
BASE                                        0.1589      0.2718
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703      37.60    <.0001
PREOAD2         1     703      17.88    <.0001
BASE            1     703      56.10    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     133.20     1.4373     703     92.68     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     147.31     2.0417     703     72.15     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     153.47     2.0594     703     74.52     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     130.38     136.02        7.058E57        4.199E56        1.186E59
trtpn    LSMeans, IDeg         143.31     151.32        9.506E63        1.726E62        5.234E65
trtpn    LSMeans, Lira         149.43     157.51        4.473E66        7.846E64         2.55E68
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -14.1133     2.4968     703     -5.65
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05  -19.0154   -9.2112       7.425E-7
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       5.517E-9         0.000100
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
282 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9SMPGMU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2   -20.2673     2.5114     703     -8.07
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    <.0001    0.05  -25.1980  -15.3365       1.578E-9
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira       1.14E-11         2.185E-7
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
283 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PSMPGM
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             720
Number of Observations Used             708
Number of Observations Not Used          12
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.2712
           Fit Statistics
-2 Res Log Likelihood          2600.9
AIC (Smaller is Better)        2602.9
AICC (Smaller is Better)       2602.9
BIC (Smaller is Better)        2607.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   6.4453     0.3205    703     20.11     <.0001     0.05
trtpn                         1            -1.1247     0.1394    703     -8.07     <.0001     0.05
trtpn                         2            -0.3415     0.1610    703     -2.12     0.0342     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.5115     0.1210    703     -4.23     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.7847    0.02875    703    -27.29     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
284 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PSMPGM
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   5.8160      7.0746
trtpn                         1            -1.3983     -0.8511
trtpn                         2            -0.6575    -0.02547
trtpn                         3                               
PREOAD2     Metformin                      -0.7490     -0.2740
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8411     -0.7282
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703      37.60    <.0001
PREOAD2         1     703      17.88    <.0001
BASE            1     703     744.98    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -2.9990   0.07976    703   -37.60    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -2.2158    0.1133    703   -19.56    <.0001
trtpn   Change from baseline, Lira     WORK.ADATA2   -1.8743    0.1143    703   -16.40    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -3.1556     -2.8425
trtpn   Change from baseline, IDeg        0.05     -2.4383     -1.9934
trtpn   Change from baseline, Lira        0.05     -2.0987     -1.6500
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
285 of 412
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9SMPGMU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             720
Number of Observations Used             708
Number of Observations Not Used          12
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       737.49
           Fit Statistics
-2 Res Log Likelihood          6672.1
AIC (Smaller is Better)        6674.1
AICC (Smaller is Better)       6674.1
BIC (Smaller is Better)        6678.6
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   116.14     5.7760    703     20.11     <.0001     0.05
trtpn                         1           -20.2673     2.5114    703     -8.07     <.0001     0.05
trtpn                         2            -6.1540     2.9007    703     -2.12     0.0342     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -9.2178     2.1799    703     -4.23     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.7847    0.02875    703    -27.29     <.0001     0.05
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Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment - change from
baseline - supportive statistical analysis - full analysis set
Parameter Code=P9SMPGMU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   104.80      127.48
trtpn                         1           -25.1980    -15.3365
trtpn                         2           -11.8490     -0.4590
trtpn                         3                               
PREOAD2     Metformin                     -13.4977     -4.9379
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8411     -0.7282
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703      37.60    <.0001
PREOAD2         1     703      17.88    <.0001
BASE            1     703     744.98    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -54.0429    1.4373    703   -37.60    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -39.9296    2.0417    703   -19.56    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2  -33.7756    2.0594    703   -16.40    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -56.8648    -51.2210
trtpn   Change from baseline, IDeg        0.05    -43.9381    -35.9210
trtpn   Change from baseline, Lira        0.05    -37.8188    -29.7323
CONFIDENTIAL


NN9068
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NN9068-4148
Version:
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Clinical Trial Report
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Final
Statistical document
Page:
287 of 412
21: Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIBU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             709
          Number of Observations
Number of Observations Read             718
Number of Observations Used             709
Number of Observations Not Used           9
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      1902.47
           Fit Statistics
-2 Res Log Likelihood          7349.6
AIC (Smaller is Better)        7351.6
AICC (Smaller is Better)       7351.6
BIC (Smaller is Better)        7356.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  50.3800     4.2937    704     11.73     <.0001     0.05
trtpn                         1             5.6651     4.0320    704      1.41     0.1604     0.05
trtpn                         2            14.1118     4.6635    704      3.03     0.0026     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -10.8133     3.5012    704     -3.09     0.0021     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1397    0.02911    704      4.80     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
288 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIBU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  41.9500     58.8101
trtpn                         1            -2.2510     13.5813
trtpn                         2             4.9558     23.2678
trtpn                         3                               
PREOAD2     Metformin                     -17.6874     -3.9393
PREOAD2     Metformin + OAD                                   
BASE                                       0.08260      0.1969
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     704       4.67    0.0096
PREOAD2         1     704       9.54    0.0021
BASE            1     704      23.05    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    63.9851     2.3037     704     27.77     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    72.4317     3.2899     704     22.02     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    58.3200     3.3073     704     17.63     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    59.4621    68.5081        6.143E27        6.669E25        5.658E29
trtpn    LSMeans, IDeg        65.9725    78.8910        2.862E31        4.482E28        1.828E34
trtpn    LSMeans, Lira        51.8266    64.8133        2.128E25        3.221E22        1.406E28
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -8.4466     4.0189     704     -2.10
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0359    0.05  -16.3372   -0.5561       0.000215
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       8.033E-8           0.5734
CONFIDENTIAL


NN9068
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Date:
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Version:
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Clinical Trial Report
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Statistical document
Page:
289 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIBU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     5.6651     4.0320     704      1.41
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.1604    0.05   -2.2510   13.5813         288.63
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.1053           791207
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NN9068
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Version:
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Clinical Trial Report
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Final
Statistical document
Page:
290 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIEU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             707
          Number of Observations
Number of Observations Read             718
Number of Observations Used             707
Number of Observations Not Used          11
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2035.95
           Fit Statistics
-2 Res Log Likelihood          7376.4
AIC (Smaller is Better)        7378.4
AICC (Smaller is Better)       7378.4
BIC (Smaller is Better)        7382.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  28.2369     3.8281    702      7.38     <.0001     0.05
trtpn                         1            13.7323     4.1645    702      3.30     0.0010     0.05
trtpn                         2            15.3706     4.7970    702      3.20     0.0014     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -2.5249     3.6263    702     -0.70     0.4865     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1860    0.03057    702      6.08     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
291 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIEU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  20.7210     35.7529
trtpn                         1             5.5560     21.9086
trtpn                         2             5.9524     24.7888
trtpn                         3                               
PREOAD2     Metformin                      -9.6446      4.5948
PREOAD2     Metformin + OAD                                   
BASE                                        0.1259      0.2460
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     702       6.70    0.0013
PREOAD2         1     702       0.48    0.4865
BASE            1     702      37.00    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    49.6516     2.4018     702     20.67     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    51.2899     3.3822     702     15.16     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    35.9193     3.4016     702     10.56     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    44.9360    54.3671        3.659E21        3.277E19        4.087E23
trtpn    LSMeans, IDeg        44.6494    57.9303        1.883E22         2.46E19        1.442E25
trtpn    LSMeans, Lira        29.2407    42.5979        3.977E15        5.001E12        3.162E18
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.6383     4.1484     702     -0.39
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.6930    0.05   -9.7830    6.5065         0.1943
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.000056           669.48
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
292 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIEU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    13.7323     4.1645     702      3.30
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.0010    0.05    5.5560   21.9086         920162
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         258.79         3.2717E9
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
293 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGILU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             718
Number of Observations Used             708
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2006.21
           Fit Statistics
-2 Res Log Likelihood          7376.7
AIC (Smaller is Better)        7378.7
AICC (Smaller is Better)       7378.7
BIC (Smaller is Better)        7383.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  31.7807     3.6382    703      8.74     <.0001     0.05
trtpn                         1             6.7797     4.1349    703     1.64     0.1015     0.05
trtpn                         2            16.6127     4.7770    703      3.48     0.0005     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.7065     3.5950    703      0.47     0.6352     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1446    0.02759    703      5.24     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
294 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGILU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  24.6377     38.9237
trtpn                         1            -1.3385     14.8979
trtpn                         2             7.2337     25.9916
trtpn                         3                               
PREOAD2     Metformin                      -5.3517      8.7648
PREOAD2     Metformin + OAD                                   
BASE                                       0.09041      0.1987
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703       6.15    0.0022
PREOAD2         1     703       0.23    0.6352
BASE            1     703      27.46    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    44.9642     2.3828     703     18.87     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    54.7972     3.3775     703     16.22     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    38.1846     3.3702     703     11.33     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    40.2859    49.6426        3.371E19        3.133E17        3.627E21
trtpn    LSMeans, IDeg        48.1661    61.4284        6.283E23        8.284E20        4.765E26
trtpn    LSMeans, Lira        31.5677    44.8015        3.831E16        5.125E13        2.864E19
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -9.8330     4.1312     703     -2.38
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0176    0.05  -17.9439   -1.7221       0.000054
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       1.611E-8           0.1787
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
295 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGILU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     6.7797     4.1349     703      1.64
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.1015    0.05   -1.3385   14.8979         879.78
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.2622          2951642
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
296 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINC
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2.6091
           Fit Statistics
-2 Res Log Likelihood          2736.5
AIC (Smaller is Better)        2738.5
AICC (Smaller is Better)       2738.5
BIC (Smaller is Better)        2743.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   2.0022     0.1527    713     13.12     <.0001     0.05
trtpn                         1             0.4424     0.1479    713      2.99     0.0029     0.05
trtpn                         2             0.8538     0.1710    713      4.99     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.2348     0.1288    713     -1.82     0.0688     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1750    0.02899    713      6.04     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
297 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINC
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.7025      2.3019
trtpn                         1             0.1521      0.7327
trtpn                         2             0.5180      1.1895
trtpn                         3                               
PREOAD2     Metformin                      -0.4876     0.01811
PREOAD2     Metformin + OAD                                   
BASE                                        0.1181      0.2319
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      12.47    <.0001
PREOAD2         1     713       3.32    0.0688
BASE            1     713      36.43    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     2.9129    0.08514     713     34.21     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    3.3242     0.1208     713     27.52     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     2.4705     0.1209     713     20.44     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.7457     3.0800         18.4094         15.5757         21.7585
trtpn    LSMeans, IDeg         3.0871     3.5614         27.7781         21.9128         35.2134
trtpn    LSMeans, Lira         2.2332     2.7077         11.8280          9.3295         14.9955
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.4114     0.1478     713     -2.78
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0055    0.05   -0.7015   -0.1213         0.6627
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4958           0.8858
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
298 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINC
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     0.4424     0.1479     713      2.99
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.0029    0.05    0.1521    0.7327         1.5564
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         1.1643           2.0807
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
299 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCB
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             709
          Number of Observations
Number of Observations Read             718
Number of Observations Used             709
Number of Observations Not Used           9
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      5.8588
           Fit Statistics
-2 Res Log Likelihood          3272.6
AIC (Smaller is Better)        3274.6
AICC (Smaller is Better)       3274.6
BIC (Smaller is Better)        3279.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   2.7958     0.2383    704     11.73     <.0001     0.05
trtpn                         1             0.3144     0.2238    704      1.41     0.1604     0.05
trtpn                         2             0.7831     0.2588    704      3.03     0.0026     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.6001     0.1943    704     -3.09     0.0021     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1397    0.02911    704      4.80     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
300 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCB
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   2.3280      3.2636
trtpn                         1            -0.1249      0.7537
trtpn                         2             0.2750      1.2912
trtpn                         3                               
PREOAD2     Metformin                      -0.9815     -0.2186
PREOAD2     Metformin + OAD                                   
BASE                                       0.08260      0.1969
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     704       4.67    0.0096
PREOAD2         1     704       9.54    0.0021
BASE            1     704      23.05    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.5508     0.1278     704     27.77     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    4.0195     0.1826     704     22.02     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     3.2364     0.1835     704     17.63     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.2998     3.8018         34.8406         27.1067         44.7809
trtpn    LSMeans, IDeg         3.6611     4.3780         55.6743         38.9029         79.6761
trtpn    LSMeans, Lira         2.8761     3.5967         25.4420         17.7442         36.4793
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.4687     0.2230     704     -2.10
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0359    0.05   -0.9066  -0.03086         0.6258
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4039           0.9696
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
301 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCB
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     0.3144     0.2238     704      1.41
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.1604    0.05   -0.1249    0.7537         1.3694
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.8826           2.1248
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
302 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCE
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            707
          Number of Observations
Number of Observations Read             718
Number of Observations Used             707
Number of Observations Not Used          11
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.2699
           Fit Statistics
-2 Res Log Likelihood          3311.0
AIC (Smaller is Better)        3313.0
AICC (Smaller is Better)       3313.0
BIC (Smaller is Better)        3317.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.5670     0.2124    702      7.38     <.0001     0.05
trtpn                         1             0.7621     0.2311    702      3.30     0.0010     0.05
trtpn                         2             0.8530     0.2662    702      3.20     0.0014     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1401     0.2012    702     -0.70     0.4865     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1860    0.03057    702      6.08     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
303 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCE
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.1499      1.9841
trtpn                         1             0.3083      1.2158
trtpn                         2             0.3303      1.3756
trtpn                         3                               
PREOAD2     Metformin                      -0.5352      0.2550
PREOAD2     Metformin + OAD                                   
BASE                                        0.1259      0.2460
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     702       6.70    0.0013
PREOAD2         1     702       0.48    0.4865
BASE            1     702      37.00    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     2.7554     0.1333     702     20.67     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    2.8463     0.1877     702     15.16     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     1.9933     0.1888     702     10.56     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.4937     3.0170         15.7267         12.1057         20.4308
trtpn    LSMeans, IDeg         2.4778     3.2148         17.2235         11.9146         24.8978
trtpn    LSMeans, Lira         1.6227     2.3639          7.3397          5.0666         10.6326
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -0.09091     0.2302     702     -0.39
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.6930    0.05   -0.5429    0.3611         0.9131
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.5811           1.4349
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
304 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCE
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     0.7621     0.2311     702      3.30
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.0010    0.05    0.3083    1.2158         2.1427
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         1.3611           3.3730
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
305 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCL
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             718
Number of Observations Used             708
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      6.1783
           Fit Statistics
-2 Res Log Likelihood          3305.5
AIC (Smaller is Better)        3307.5
AICC (Smaller is Better)       3307.5
BIC (Smaller is Better)        3312.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.7636     0.2019    703      8.74     <.0001     0.05
trtpn                         1             0.3762     0.2295    703      1.64     0.1015     0.05
trtpn                         2             0.9219     0.2651    703      3.48     0.0005     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.09470     0.1995    703      0.47     0.6352     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1446    0.02759    703      5.24     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
306 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCL
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.3672      2.1600
trtpn                         1           -0.07428      0.8267
trtpn                         2             0.4014      1.4424
trtpn                         3                               
PREOAD2     Metformin                      -0.2970      0.4864
PREOAD2     Metformin + OAD                                   
BASE                                       0.09041      0.1987
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703       6.15    0.0022
PREOAD2         1     703       0.23    0.6352
BASE            1     703      27.46    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     2.4952     0.1322     703     18.87     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    3.0409     0.1874     703     16.22     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     2.1190     0.1870     703     11.33     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.2356     2.7549         12.1247          9.3523         15.7188
trtpn    LSMeans, IDeg         2.6729     3.4089         20.9243         14.4822         30.2320
trtpn    LSMeans, Lira         1.7518     2.4862          8.3229          5.7650         12.0156
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.5457     0.2293     703     -2.38
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0176    0.05   -0.9958  -0.09557         0.5795
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.3694           0.9089
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
307 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCL
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     0.3762     0.2295     703      1.64
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.1015    0.05  -0.07428    0.8267         1.4568
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.9284           2.2859
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
308 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject            718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       847.22
           Fit Statistics
-2 Res Log Likelihood          6865.6
AIC (Smaller is Better)        6867.6
AICC (Smaller is Better)       6867.6
BIC (Smaller is Better)        6872.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  36.0789     2.7508    713     13.12     <.0001     0.05
trtpn                         1             7.9719     2.6645    713      2.99     0.0029     0.05
trtpn                         2            15.3852     3.0818    713      4.99     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.2304     2.3209    713     -1.82     0.0688     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.1750    0.02899    713      6.04     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
309 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  30.6782     41.4796
trtpn                         1             2.7408     13.2031
trtpn                         2             9.3347     21.4356
trtpn                         3                               
PREOAD2     Metformin                      -8.7870      0.3263
PREOAD2     Metformin + OAD                                   
BASE                                        0.1181      0.2319
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      12.47    <.0001
PREOAD2         1     713       3.32    0.0688
BASE            1     713      36.43    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    52.4897     1.5341     713     34.21     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    59.9030     2.1769     713     27.52     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    44.5178     2.1779     713     20.44     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    49.4777    55.5017        6.252E22        3.075E21        1.271E24
trtpn    LSMeans, IDeg        55.6290    64.1769        1.036E26        1.443E24        7.442E27
trtpn    LSMeans, Lira        40.2420    48.7936        2.157E19        2.998E17        1.552E21
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -7.4132     2.6629     713     -2.78
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0055    0.05  -12.6413   -2.1852       0.000603
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       3.236E-6           0.1125
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
310 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIU
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     7.9719     2.6645     713      2.99
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.0029    0.05    2.7408   13.2031        2898.47
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira        15.4998           542016
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
311 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIBU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             709
          Number of Observations
Number of Observations Read             718
Number of Observations Used             709
Number of Observations Not Used           9
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      1902.47
           Fit Statistics
-2 Res Log Likelihood          7349.6
AIC (Smaller is Better)        7351.6
AICC (Smaller is Better)       7351.6
BIC (Smaller is Better)        7356.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  50.3800     4.2937    704     11.73     <.0001     0.05
trtpn                         1             5.6651     4.0320    704      1.41     0.1604     0.05
trtpn                         2            14.1118     4.6635    704      3.03     0.0026     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -10.8133     3.5012    704     -3.09     0.0021     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8603    0.02911    704    -29.56     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
312 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIBU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  41.9500     58.8101
trtpn                         1            -2.2510     13.5813
trtpn                         2             4.9558     23.2678
trtpn                         3                               
PREOAD2     Metformin                     -17.6874     -3.9393
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9174     -0.8031
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     704       4.67    0.0096
PREOAD2         1     704       9.54    0.0021
BASE            1     704     873.62    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -17.9360    2.3037    704    -7.79    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -9.4894    3.2899    704    -2.88    0.0040
trtpn   Change from baseline, Lira      WORK.ADATA2  -23.6011    3.3073    704    -7.14    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -22.4590    -13.4130
trtpn   Change from baseline, IDeg        0.05    -15.9486     -3.0301
trtpn   Change from baseline, Lira        0.05    -30.0945    -17.1078
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
313 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIEU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             707
          Number of Observations
Number of Observations Read             718
Number of Observations Used             707
Number of Observations Not Used          11
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2035.95
           Fit Statistics
-2 Res Log Likelihood          7376.4
AIC (Smaller is Better)        7378.4
AICC (Smaller is Better)       7378.4
BIC (Smaller is Better)        7382.9
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  28.2369     3.8281    702      7.38     <.0001     0.05
trtpn                         1            13.7323     4.1645    702      3.30     0.0010     0.05
trtpn                         2            15.3706     4.7970    702      3.20     0.0014     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -2.5249     3.6263    702     -0.70     0.4865     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8140    0.03057    702    -26.62     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
314 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIEU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  20.7210     35.7529
trtpn                         1             5.5560     21.9086
trtpn                         2             5.9524     24.7888
trtpn                         3                               
PREOAD2     Metformin                      -9.6446      4.5948
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8741     -0.7540
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     702       6.70    0.0013
PREOAD2         1     702       0.48    0.4865
BASE            1     702     708.88    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    3.9262    2.4018    702     1.63    0.1026
trtpn   Change from baseline, IDeg      WORK.ADATA2    5.5644    3.3822    702     1.65    0.1004
trtpn   Change from baseline, Lira      WORK.ADATA2   -9.8061    3.4016    702    -2.88    0.0041
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.7894      8.6417
trtpn   Change from baseline, IDeg        0.05     -1.0761     12.2049
trtpn   Change from baseline, Lira        0.05    -16.4847     -3.1275
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
315 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGILU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             718
Number of Observations Used             708
Number of Observations Not Used         10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2006.21
           Fit Statistics
-2 Res Log Likelihood          7376.7
AIC (Smaller is Better)        7378.7
AICC (Smaller is Better)       7378.7
BIC (Smaller is Better)        7383.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  31.7807     3.6382    703      8.74     <.0001     0.05
trtpn                         1             6.7797     4.1349    703      1.64     0.1015     0.05
trtpn                         2            16.6127     4.7770    703      3.48     0.0005     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       1.7065     3.5950    703      0.47     0.6352     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8554    0.02759   703    -31.01     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
316 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGILU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  24.6377     38.9237
trtpn                         1            -1.3385     14.8979
trtpn                         2             7.2337     25.9916
trtpn                         3                               
PREOAD2     Metformin                      -5.3517      8.7648
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9096     -0.8013
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703       6.15    0.0022
PREOAD2         1     703       0.23    0.6352
BASE            1     703     961.45    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    4.5032    2.3828    703     1.89    0.0592
trtpn   Change from baseline, IDeg      WORK.ADATA2   14.3362    3.3775    703     4.24    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -2.2764    3.3702    703    -0.68    0.4996
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.1751      9.1816
trtpn   Change from baseline, IDeg        0.05      7.7051     20.9674
trtpn   Change from baseline, Lira        0.05     -8.8933      4.3405
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
317 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINC
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.6091
           Fit Statistics
-2 Res Log Likelihood          2736.5
AIC (Smaller is Better)        2738.5
AICC (Smaller is Better)       2738.5
BIC (Smaller is Better)        2743.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   2.0022     0.1527    713     13.12     <.0001     0.05
trtpn                         1             0.4424     0.1479    713      2.99     0.0029     0.05
trtpn                         2             0.8538     0.1710    713      4.99     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.2348     0.1288    713     -1.82     0.0688     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8250    0.02899    713    -28.46     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
318 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINC
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.7025      2.3019
trtpn                         1             0.1521      0.7327
trtpn                         2             0.5180      1.1895
trtpn                         3                               
PREOAD2     Metformin                      -0.4876     0.01811
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8819     -0.7681
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      12.47    <.0001
PREOAD2         1     713       3.32    0.0688
BASE            1     713     809.82    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.1987   0.08514    713    -2.33    0.0199
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.2127    0.1208    713     1.76    0.0787
trtpn   Change from baseline, Lira      WORK.ADATA2   -0.6411    0.1209    713    -5.30    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.3658    -0.03153
trtpn   Change from baseline, IDeg        0.05    -0.02447      0.4499
trtpn   Change from baseline, Lira        0.05     -0.8784     -0.4038
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
319 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCB
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             709
          Number of Observations
Number of Observations Read             718
Number of Observations Used             709
Number of Observations Not Used           9
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      5.8588
           Fit Statistics
-2 Res Log Likelihood          3272.6
AIC (Smaller is Better)        3274.6
AICC (Smaller is Better)       3274.6
BIC (Smaller is Better)        3279.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   2.7958     0.2383    704     11.73     <.0001     0.05
trtpn                         1             0.3144     0.2238    704      1.41     0.1604     0.05
trtpn                         2             0.7831     0.2588    704      3.03     0.0026     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.6001     0.1943    704     -3.09     0.0021     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8603    0.02911    704    -29.56     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
320 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCB
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   2.3280      3.2636
trtpn                         1            -0.1249      0.7537
trtpn                         2             0.2750      1.2912
trtpn                         3                               
PREOAD2     Metformin                      -0.9815     -0.2186
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9174     -0.8031
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     704       4.67    0.0096
PREOAD2         1     704       9.54    0.0021
BASE            1     704     873.62    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.9953    0.1278    704    -7.79    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -0.5266    0.1826    704    -2.88    0.0040
trtpn   Change from baseline, Lira      WORK.ADATA2   -1.3097    0.1835    704    -7.14    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -1.2463     -0.7443
trtpn   Change from baseline, IDeg        0.05     -0.8851     -0.1682
trtpn   Change from baseline, Lira        0.05     -1.6701     -0.9494
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
321 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCE
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             707
          Number of Observations
Number of Observations Read             718
Number of Observations Used             707
Number of Observations Not Used          11
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.2699
           Fit Statistics
-2 Res Log Likelihood          3311.0
AIC (Smaller is Better)        3313.0
AICC (Smaller is Better)       3313.0
BIC (Smaller is Better)        3317.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.5670     0.2124    702      7.38     <.0001     0.05
trtpn                         1             0.7621     0.2311    702     3.30     0.0010     0.05
trtpn                         2             0.8530     0.2662    702      3.20     0.0014     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1401     0.2012    702     -0.70     0.4865     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8140    0.03057    702    -26.62     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
322 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCE
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.1499      1.9841
trtpn                         1             0.3083      1.2158
trtpn                         2             0.3303      1.3756
trtpn                         3                               
PREOAD2     Metformin                      -0.5352      0.2550
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8741     -0.7540
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     702       6.70    0.0013
PREOAD2         1     702       0.48    0.4865
BASE            1     702     708.88    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.2179    0.1333    702     1.63    0.1026
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.3088    0.1877    702     1.65    0.1004
trtpn   Change from baseline, Lira      WORK.ADATA2   -0.5442    0.1888    702    -2.88    0.0041
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -0.04381      0.4796
trtpn   Change from baseline, IDeg        0.05    -0.05972      0.6773
trtpn   Change from baseline, Lira        0.05     -0.9148     -0.1736
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
323 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCL
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             708
          Number of Observations
Number of Observations Read             718
Number of Observations Used             708
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.1783
           Fit Statistics
-2 Res Log Likelihood          3305.5
AIC (Smaller is Better)        3307.5
AICC (Smaller is Better)       3307.5
BIC (Smaller is Better)        3312.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.7636     0.2019    703      8.74     <.0001     0.05
trtpn                         1             0.3762     0.2295    703     1.64     0.1015     0.05
trtpn                         2             0.9219     0.2651    703      3.48     0.0005     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.09470     0.1995    703      0.47     0.6352     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8554    0.02759    703    -31.01     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
324 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGINCL
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.3672      2.1600
trtpn                         1           -0.07428      0.8267
trtpn                         2             0.4014      1.4424
trtpn                         3                               
PREOAD2     Metformin                      -0.2970      0.4864
PREOAD2     Metformin + OAD                                   
BASE                                       -0.9096     -0.8013
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     703       6.15    0.0022
PREOAD2         1     703       0.23    0.6352
BASE            1     703     961.45    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.2499    0.1322    703     1.89    0.0592
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.7956    0.1874    703     4.24    <.0001
trtpn   Change from baseline, Lira      WORK.ADATA2   -0.1263    0.1870    703    -0.68    0.4996
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -0.00972      0.5095
trtpn   Change from baseline, IDeg        0.05      0.4276      1.1636
trtpn   Change from baseline, Lira        0.05     -0.4935      0.2409
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
325 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       847.22
           Fit Statistics
-2 Res Log Likelihood          6865.6
AIC (Smaller is Better)        6867.6
AICC (Smaller is Better)       6867.6
BIC (Smaller is Better)        6872.1
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  36.0789     2.7508    713     13.12     <.0001     0.05
trtpn                         1             7.9719     2.6645    713      2.99     0.0029     0.05
trtpn                         2            15.3852     3.0818    713      4.99     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -4.2304     2.3209    713     -1.82     0.0688     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.8250    0.02899    713    -28.46     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
326 of 412
Prandial increment after 26 weeks of treatment - 9-point self-measured plasma glucose profile -
change from baseline - supportive statistical analysis - full analysis set
Parameter Code=P9PGIU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  30.6782     41.4796
trtpn                         1             2.7408     13.2031
trtpn                         2             9.3347     21.4356
trtpn                         3                               
PREOAD2     Metformin                      -8.7870      0.3263
PREOAD2     Metformin + OAD                                   
BASE                                       -0.8819     -0.7681
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713      12.47    <.0001
PREOAD2         1     713       3.32    0.0688
BASE            1     713     809.82    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.5802    1.5341    713    -2.33    0.0199
trtpn   Change from baseline, IDeg      WORK.ADATA2    3.8331    2.1769    713     1.76    0.0787
trtpn   Change from baseline, Lira      WORK.ADATA2  -11.5521    2.1779    713    -5.30    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -6.5921     -0.5682
trtpn   Change from baseline, IDeg        0.05     -0.4409      8.1070
trtpn   Change from baseline, Lira        0.05    -15.8279     -7.2763
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
327 of 412
22: Fasting insulin after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=INS_TO_S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             690
          Number of Observations
Number of Observations Read             720
Number of Observations Used             690
Number of Observations Not Used          30
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3923
           Fit Statistics
-2 Res Log Likelihood          1329.8
AIC (Smaller is Better)        1331.8
AICC (Smaller is Better)       1331.8
BIC (Smaller is Better)        1336.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   0.7793     0.1511    685      5.16     <.0001    0.05
trtpn                         1            -0.6006    0.05867    685    -10.24     <.0001     0.05
trtpn                         2            -0.8995    0.06772    685    -13.28     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.1397    0.05082    685      2.75     0.0061     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.7857    0.03686    685     21.32     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
328 of 412
Fasting insulin after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=INS_TO_S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   0.4825      1.0760
trtpn                         1            -0.7158     -0.4854
trtpn                         2            -1.0325     -0.7666
trtpn                         3                               
PREOAD2     Metformin                      0.03996      0.2395
PREOAD2     Metformin + OAD                                   
base_log                                    0.7133      0.8581
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     685      92.97    <.0001
PREOAD2         1     685       7.56    0.0061
base_log        1     685     454.43    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.3323    0.03368     685     98.94     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.0334    0.04766     685     63.65     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     3.9329    0.04800     685     81.94     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.2662     3.3984         28.0031         26.2112         29.9174
trtpn    LSMeans, IDeg         2.9398     3.1270         20.7677         18.9125         22.8049
trtpn    LSMeans, Lira         3.8387     4.0272         51.0568         46.4650         56.1022
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.2989   0.05834    685     5.12    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.1844      0.4135           1.3484
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.2025           1.5120
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
329 of 412
Fasting insulin after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=INS_TO_S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error    DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2   -0.6006   0.05867    685   -10.24    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.7158     -0.4854           0.5485
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.4888           0.6154
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
330 of 412
23: Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74736S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2604
           Fit Statistics
-2 Res Log Likelihood          1088.9
AIC (Smaller is Better)        1090.9
AICC (Smaller is Better)       1090.9
BIC (Smaller is Better)        1095.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -0.1787    0.04809    712     -3.72     0.0002     0.05
trtpn                         1            -0.5435    0.04666    712    -11.65     <.0001     0.05
trtpn                         2            -0.8717    0.05399    712    -16.15     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.1591    0.04070    712      3.91     0.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.8438    0.04307    712     19.59     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
331 of 412
Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74736S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -0.2731    -0.08427
trtpn                         1            -0.6351     -0.4519
trtpn                         2            -0.9777     -0.7657
trtpn                         3                               
PREOAD2     Metformin                      0.07922      0.2391
PREOAD2     Metformin + OAD                                   
base_log                                    0.7592      0.9283
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn          2     712     134.44    <.0001
PREOAD2         1     712      15.28    0.0001
base_log        1     712     383.88    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -1.1571    0.02694     712    -42.95     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -1.4853    0.03825     712    -38.83     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    -0.6136    0.03808     712    -16.12     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -1.2100    -1.1042          0.3144          0.2982          0.3315
trtpn    LSMeans, IDeg        -1.5604    -1.4102          0.2264          0.2100          0.2441
trtpn    LSMeans, Lira        -0.6884    -0.5389          0.5414          0.5024          0.5834
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.3282   0.04678    712     7.02    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.2364      0.4200           1.3885
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.2666           1.5220
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
332 of 412
Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74736S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2   -0.5435   0.04666    712   -11.65    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.6351     -0.4519           0.5807
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.5299           0.6364
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
333 of 412
Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=CPEPTI_U
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2604
           Fit Statistics
-2 Res Log Likelihood          1088.9
AIC (Smaller is Better)        1090.9
AICC (Smaller is Better)       1090.9
BIC (Smaller is Better)        1095.4
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                 -0.00601    0.04562    712     -0.13     0.8952     0.05
trtpn                         1            -0.5435    0.04666    712    -11.65     <.0001     0.05
trtpn                         2            -0.8717    0.05399    712    -16.15     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.1591    0.04070    712      3.91     0.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.8438    0.04307    712     19.59     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
334 of 412
Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=CPEPTI_U
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                             Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 -0.09558     0.08356
trtpn                         1            -0.6351     -0.4519
trtpn                         2            -0.9777     -0.7657
trtpn                         3                               
PREOAD2     Metformin                      0.07922      0.2391
PREOAD2     Metformin + OAD                                   
base_log                                    0.7592      0.9283
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712     134.44    <.0001
PREOAD2         1     712      15.28    0.0001
base_log        1     712     383.88    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2   -0.05188    0.02694     712     -1.93     0.0545     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -0.3801    0.03825     712     -9.94     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     0.4917    0.03808     712     12.91     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -0.1048   0.001007          0.9494          0.9005          1.0010
trtpn    LSMeans, IDeg        -0.4552    -0.3050          0.6838          0.6343          0.7371
trtpn    LSMeans, Lira         0.4169     0.5664          1.6350          1.5172          1.7619
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.3282   0.04678    712     7.02    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.2364      0.4200           1.3885
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.2666           1.5220
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
335 of 412
Fasting C-peptide after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=CPEPTI_U
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2   -0.5435   0.04666    712   -11.65    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.6351     -0.4519           0.5807
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.5299           0.6364
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
336 of 412
24: Fasting glucagon after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74859P
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             716
          Number of Observations
Number of Observations Read             720
Number of Observations Used             716
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2508
           Fit Statistics
-2 Res Log Likelihood          1061.4
AIC (Smaller is Better)        1063.4
AICC (Smaller is Better)       1063.4
BIC (Smaller is Better)        1068.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.8063    0.09730    711     18.56     <.0001     0.05
trtpn                         1           -0.03470    0.04578    711     -0.76     0.4487     0.05
trtpn                         2            0.02292    0.05309    711      0.43     0.6661     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.06368    0.04004    711      1.59     0.1122     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.4190    0.02777    711     15.09     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
337 of 412
Fasting glucagon after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74859P
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.6153      1.9973
trtpn                         1            -0.1246     0.05519
trtpn                         2           -0.08132      0.1272
trtpn                         3                               
PREOAD2     Metformin                     -0.01494      0.1423
PREOAD2     Metformin + OAD                                   
base_log                                    0.3645      0.4736
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn          2     711       0.85    0.4276
PREOAD2         1     711       2.53    0.1122
base_log        1     711     227.65    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.1465    0.02643     711    119.04     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.2042    0.03766     711     85.08     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     3.1812    0.03737     711     85.13     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.0946     3.1984         23.2554         22.0793         24.4942
trtpn    LSMeans, IDeg         3.1302     3.2781         24.6348         22.8790         26.5253
trtpn    LSMeans, Lira         3.1079     3.2546         24.0766         22.3734         25.9094
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.05762   0.04601    711    -1.25    0.2108
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1479     0.03270           0.9440
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8625           1.0332
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
338 of 412
Fasting glucagon after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C74859P
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.03470   0.04578    711    -0.76    0.4487
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1246     0.05519           0.9659
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8829           1.0567
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
339 of 412
25: HOMA-B after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HOMA_BCS
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             690
          Number of Observations
Number of Observations Read             720
Number of Observations Used             690
Number of Observations Not Used          30
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3530
           Fit Statistics
-2 Res Log Likelihood          1257.7
AIC (Smaller is Better)        1259.7
AICC (Smaller is Better)       1259.7
BIC (Smaller is Better)        1264.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.9156     0.1653    685     11.59     <.0001     0.05
trtpn                         1           -0.02107    0.05561    685     -0.38     0.7049     0.05
trtpn                         2            -0.3761    0.06411    685     -5.87     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.2495    0.04821    685      5.18     <.0001     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6704    0.03092    685     21.68     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
340 of 412
HOMA-B after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HOMA_BCS
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.5911      2.2402
trtpn                         1            -0.1303     0.08811
trtpn                         2            -0.5020     -0.2503
trtpn                         3                               
PREOAD2     Metformin                       0.1549      0.3442
PREOAD2     Metformin + OAD                                   
base_log                                    0.6097      0.7311
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     685      24.13    <.0001
PREOAD2         1     685      26.79    <.0001
base_log        1     685     470.21    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     5.4547    0.03195     685    170.72     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     5.0996    0.04518     685    112.88     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     5.4757    0.04548     685    120.41     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     5.3919     5.5174          233.85          219.63          248.99
trtpn    LSMeans, IDeg         5.0109     5.1883          163.96          150.04          179.16
trtpn    LSMeans, Lira         5.3865     5.5650          238.83          218.43          261.13
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.3551   0.05533    685     6.42    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.2464      0.4637           1.4263
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.2795           1.5900
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
341 of 412
HOMA-B after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HOMA_BCS
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.02107   0.05561    685    -0.38    0.7049
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1303     0.08811           0.9791
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8779           1.0921
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
342 of 412
26: HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105587S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02087
           Fit Statistics
-2 Res Log Likelihood          -710.3
AIC (Smaller is Better)        -708.3
AICC (Smaller is Better)       -708.3
BIC (Smaller is Better)        -703.8
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  0.04221    0.01193    713      3.54     0.0004     0.05
trtpn                         1           -0.00377    0.01320    713     -0.29     0.7751     0.05
trtpn                         2           0.006356    0.01529    713      0.42     0.6777     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -0.03054    0.01155    713     -2.64     0.0084     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.8509    0.02184    713     38.97     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
343 of 412
HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105587S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  0.01879     0.06564
trtpn                         1           -0.02970     0.02215
trtpn                         2           -0.02365     0.03637
trtpn                         3                               
PREOAD2     Metformin                     -0.05321    -0.00787
PREOAD2     Metformin + OAD                                   
base_log                                    0.8080      0.8937
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       0.29    0.7458
PREOAD2         1     713       7.00    0.0084
base_log        1     713    1518.36    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     0.1331   0.007616     713     17.47     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     0.1432    0.01083     713     13.22     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     0.1368    0.01078     713     12.69     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     0.1181     0.1480          1.1423          1.1254          1.1595
trtpn    LSMeans, IDeg         0.1219     0.1644          1.1539          1.1297          1.1787
trtpn    LSMeans, Lira         0.1157     0.1580          1.1466          1.1226          1.1712
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01013   0.01324    713    -0.77    0.4444
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.03612     0.01586           0.9899
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9645           1.0160
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
344 of 412
HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105587S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.00377   0.01320    713    -0.29    0.7751
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05    -0.02970     0.02215           0.9962
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9707           1.0224
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
345 of 412
HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HDL_SU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02087
           Fit Statistics
-2 Res Log Likelihood          -710.3
AIC (Smaller is Better)        -708.3
AICC (Smaller is Better)       -708.3
BIC (Smaller is Better)        -703.8
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   0.5871    0.08405    713      6.99     <.0001     0.05
trtpn                         1           -0.00377    0.01320    713     -0.29     0.7751     0.05
trtpn                         2           0.006356    0.01529    713      0.42     0.6777     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -0.03054    0.01155    713     -2.64     0.0084     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.8509    0.02184    713     38.97     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
346 of 412
HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HDL_SU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                             Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   0.4221      0.7521
trtpn                         1           -0.02970     0.02215
trtpn                         2           -0.02365     0.03637
trtpn                         3                               
PREOAD2     Metformin                     -0.05321    -0.00787
PREOAD2     Metformin + OAD                                   
base_log                                    0.8080      0.8937
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       0.29    0.7458
PREOAD2         1     713       7.00    0.0084
base_log        1     713    1518.36    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.7866   0.007616     713    497.19     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    3.7967    0.01083     713    350.56     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     3.7903    0.01078     713    351.64     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.7716     3.8015         44.1045         43.4500         44.7690
trtpn    LSMeans, IDeg         3.7754     3.8180         44.5536         43.6163         45.5111
trtpn    LSMeans, Lira         3.7692     3.8115         44.2713         43.3443         45.2182
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01013   0.01324    713    -0.77    0.4444
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.03612     0.01586           0.9899
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9645           1.0160
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
347 of 412
HDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=HDL_SU
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.00377   0.01320    713    -0.29    0.7751
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05    -0.02970     0.02215           0.9962
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9707           1.0224
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
348 of 412
27: LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105588S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                    
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn          3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.09670
           Fit Statistics
-2 Res Log Likelihood           383.1
AIC (Smaller is Better)         385.1
AICC (Smaller is Better)        385.1
BIC (Smaller is Better)         389.7
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   0.2751    0.03638    712      7.56     <.0001     0.05
trtpn                         1           -0.04478    0.02840    712     -1.58     0.1153     0.05
trtpn                         2            0.01832    0.03293    712      0.56     0.5783     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     0.001663    0.02477    712      0.07     0.9465     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6341    0.03134    712     20.24     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
349 of 412
LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105588S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   0.2037      0.3465
trtpn                         1            -0.1005     0.01098
trtpn                         2           -0.04634     0.08297
trtpn                         3                               
PREOAD2     Metformin                     -0.04697     0.05030
PREOAD2     Metformin + OAD                                   
base_log                                    0.5726      0.6956
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712       2.84    0.0593
PREOAD2         1     712       0.00    0.9465
base_log        1     712     409.47    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     0.7677    0.01642     712     46.75     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    0.8308    0.02336     712     35.57     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     0.8125    0.02318     712     35.05     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     0.7354     0.7999          2.1548          2.0864          2.2254
trtpn    LSMeans, IDeg         0.7849     0.8766          2.2951          2.1922          2.4028
trtpn    LSMeans, Lira         0.7669     0.8580          2.2534          2.1532          2.3584
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.06309   0.02858    712    -2.21    0.0276
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1192    -0.00698           0.9389
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8876           0.9930
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
350 of 412
LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105588S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.04478   0.02840    712    -1.58    0.1153
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1005     0.01098           0.9562
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                    Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9044           1.0110
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
351 of 412
LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=LDL_SU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.09670
           Fit Statistics
-2 Res Log Likelihood           383.1
AIC (Smaller is Better)         385.1
AICC (Smaller is Better)        385.1
BIC (Smaller is Better)         389.7
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.6119     0.1434    712     11.24     <.0001     0.05
trtpn                         1           -0.04478    0.02840    712     -1.58     0.1153     0.05
trtpn                         2            0.01832    0.03293    712      0.56     0.5783     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     0.001663    0.02477   712      0.07     0.9465     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6341    0.03134    712     20.24     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
352 of 412
LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=LDL_SU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
           Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.3303      1.8935
trtpn                         1            -0.1005     0.01098
trtpn                         2           -0.04634     0.08297
trtpn                         3                               
PREOAD2     Metformin                     -0.04697     0.05030
PREOAD2     Metformin + OAD                                   
base_log                                    0.5726      0.6956
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712       2.84    0.0593
PREOAD2         1     712       0.00    0.9465
base_log        1     712     409.47    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     4.4212    0.01642     712    269.25     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     4.4843    0.02336     712    191.97     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     4.4660    0.02318     712    192.65     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     4.3889     4.4534         83.1951         80.5558         85.9209
trtpn    LSMeans, IDeg         4.4384     4.5301        88.6134         84.6413         92.7718
trtpn    LSMeans, Lira         4.4205     4.5115         87.0051         83.1340         91.0566
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.06309   0.02858    712    -2.21    0.0276
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1192    -0.00698           0.9389
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8876           0.9930
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
353 of 412
LDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=LDL_SU
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.04478   0.02840    712    -1.58    0.1153
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1005     0.01098           0.9562
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9044           1.0110
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
354 of 412
28: VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105589S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.1590
           Fit Statistics
-2 Res Log Likelihood           739.1
AIC (Smaller is Better)         741.1
AICC (Smaller is Better)        741.1
BIC (Smaller is Better)         745.6
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -0.1589    0.03205    713     -4.96     <.0001     0.05
trtpn                         1           -0.05191    0.03644    713     -1.42     0.1547     0.05
trtpn                         2            -0.1175    0.04219    713     -2.79     0.0055     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.07176    0.03185    713      2.25     0.0246     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6564    0.02753    713     23.84     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
355 of 412
VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105589S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -0.2218    -0.09595
trtpn                         1            -0.1235     0.01963
trtpn                         2            -0.2003    -0.03468
trtpn                         3                               
PREOAD2     Metformin                     0.009229      0.1343
PREOAD2     Metformin + OAD                                   
base_log                                    0.6024      0.7105
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.90    0.0206
PREOAD2         1     713       5.08    0.0246
base_log        1     713     568.38    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -0.3405    0.02102     713    -16.20     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -0.4061    0.02989     713   -13.58     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    -0.2885    0.02975     713     -9.70     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -0.3817    -0.2992          0.7114          0.6827          0.7414
trtpn    LSMeans, IDeg        -0.4647    -0.3474          0.6663          0.6283          0.7065
trtpn    LSMeans, Lira        -0.3470    -0.2301          0.7493          0.7068          0.7944
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.06560   0.03654    713     1.80    0.0730
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.00614      0.1373           1.0678
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9939           1.1472
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
356 of 412
VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105589S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.05191   0.03644    713    -1.42    0.1547
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1235     0.01963           0.9494
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8839           1.0198
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
357 of 412
VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=VLDL_SU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2   Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.1590
           Fit Statistics
-2 Res Log Likelihood           739.1
AIC (Smaller is Better)         741.1
AICC (Smaller is Better)        741.1
BIC (Smaller is Better)         745.6
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.0964    0.09974    713     10.99     <.0001     0.05
trtpn                         1           -0.05191    0.03644    713     -1.42     0.1547     0.05
trtpn                         2           -0.1175    0.04219    713     -2.79     0.0055     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.07176    0.03185    713      2.25     0.0246     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6564    0.02753    713     23.84     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
358 of 412
VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=VLDL_SU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   0.9006      1.2922
trtpn                         1            -0.1235     0.01963
trtpn                         2            -0.2003    -0.03468
trtpn                         3                               
PREOAD2     Metformin                     0.009229      0.1343
PREOAD2     Metformin + OAD                                   
base_log                                    0.6024      0.7105
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.90    0.0206
PREOAD2         1     713       5.08    0.0246
base_log        1     713     568.38    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.3131    0.02102     713    157.61     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.2475    0.02989     713    108.63     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     3.3650    0.02975     713    113.11     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.2718     3.3543         27.4688         26.3583         28.6262
trtpn    LSMeans, IDeg         3.1888     3.3061         25.7247         24.2584         27.2797
trtpn    LSMeans, Lira         3.3066     3.4234         28.9324         27.2909         30.6726
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.06560   0.03654    713     1.80    0.0730
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.00614      0.1373           1.0678
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9939           1.1472
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
359 of 412
VLDL cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=VLDL_SU
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.05191   0.03644    713    -1.42    0.1547
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1235     0.01963           0.9494
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8839          1.0198
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
360 of 412
29: Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C64812S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2   Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.1843
           Fit Statistics
-2 Res Log Likelihood           844.6
AIC (Smaller is Better)         846.6
AICC (Smaller is Better)        846.6
BIC (Smaller is Better)         851.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   0.1162    0.03729    713      3.12     0.0019     0.05
trtpn                         1           -0.05449    0.03922    713     -1.39     0.1652     0.05
trtpn                         2            -0.1254    0.04541    713     -2.76     0.0059     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.07324    0.03435    713      2.13     0.0333     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6416    0.02615    713     24.54     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
361 of 412
Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C64812S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  0.04296      0.1894
trtpn                         1            -0.1315     0.02252
trtpn                         2            -0.2145    -0.03622
trtpn                         3                               
PREOAD2     Metformin                     0.005797      0.1407
PREOAD2     Metformin + OAD                                   
base_log                                    0.5902      0.6929
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.84    0.0219
PREOAD2         1     713       4.55    0.0333
base_log        1     713     601.98    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|   Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     0.4647    0.02263     713     20.53     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     0.3938    0.03218     713     12.24     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     0.5191    0.03202     713     16.21     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     0.4202     0.5091          1.5915          1.5223          1.6638
trtpn    LSMeans, IDeg         0.3306     0.4570          1.4826          1.3918          1.5793
trtpn    LSMeans, Lira         0.4563     0.5820          1.6806          1.5782          1.7896
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.07089   0.03934    713     1.80    0.0720
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.00635      0.1481           1.0735
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9937           1.1597
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
362 of 412
Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C64812S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.05449   0.03922    713    -1.39    0.1652
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1315     0.02252           0.9470
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8768           1.0228
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
363 of 412
Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=TRIG_SU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.1843
           Fit Statistics
-2 Res Log Likelihood           844.6
AIC (Smaller is Better)         846.6
AICC (Smaller is Better)        846.6
BIC (Smaller is Better)         851.2
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.7251     0.1372    713     12.58     <.0001     0.05
trtpn                         1           -0.05449    0.03922    713     -1.39     0.1652     0.05
trtpn                         2            -0.1254    0.04541    713     -2.76     0.0059     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.07324    0.03435    713      2.13     0.0333     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6416    0.02615    713     24.54     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
364 of 412
Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=TRIG_SU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.4558      1.9944
trtpn                         1            -0.1315     0.02252
trtpn                         2            -0.2145    -0.03622
trtpn                         3                               
PREOAD2     Metformin                     0.005797      0.1407
PREOAD2     Metformin + OAD                                   
base_log                                    0.5902      0.6929
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.84    0.0219
PREOAD2         1     713       4.55    0.0333
base_log        1     713     601.98    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     4.9533    0.02263     713    218.87     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     4.8824    0.03218     713    151.71     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     5.0078    0.03202     713    156.38     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     4.9089     4.9977          141.64          135.49          148.08
trtpn    LSMeans, IDeg         4.8192     4.9456          131.95          123.87          140.55
trtpn    LSMeans, Lira         4.9449     5.0707          149.57          140.46          159.28
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.07089   0.03934    713     1.80    0.0720
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.00635      0.1481           1.0735
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9937           1.1597
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
365 of 412
Triglycerides after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=TRIG_SU
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.05449   0.03922    713    -1.39    0.1652
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.1315     0.02252           0.9470
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.8768           1.0228
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
366 of 412
30: Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105586S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02679
           Fit Statistics
-2 Res Log Likelihood          -532.6
AIC (Smaller is Better)        -530.6
AICC (Smaller is Better)       -530.6
BIC (Smaller is Better)        -526.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   0.4849    0.04556    713     10.64     <.0001     0.05
trtpn                         1           -0.03161    0.01495    713     -2.11     0.0348     0.05
trtpn                         2           0.003833    0.01736    713      0.22     0.8253     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.01028    0.01304    713      0.79     0.4307     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6563    0.02899    713     22.64     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
367 of 412
Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105586S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   0.3955      0.5744
trtpn                         1           -0.06095    -0.00226
trtpn                         2           -0.03025     0.03791
trtpn                         3                               
PREOAD2     Metformin                     -0.01533     0.03590
PREOAD2     Metformin + OAD                                   
base_log                                    0.5994      0.7133
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.78    0.0232
PREOAD2         1     713       0.62    0.4307
base_log        1     713     512.47    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     1.4372   0.008628     713    166.58     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     1.4727    0.01230     713    119.76     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     1.4688    0.01221     713    120.27     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     1.4203     1.4542          4.2090          4.1383          4.2809
trtpn    LSMeans, IDeg         1.4485     1.4968          4.3609          4.2569          4.4674
trtpn    LSMeans, Lira         1.4449     1.4928          4.3442          4.2413          4.4496
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.03544   0.01503    713    -2.36    0.0186
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.06495    -0.00593           0.9652
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9371           0.9941
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
368 of 412
Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C105586S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.03161   0.01495    713    -2.11    0.0348
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05    -0.06095    -0.00226           0.9689
                     Least Squares Means Estimates
                                          Exponentiated   Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9409           0.9977
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
369 of 412
Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=T_CHOL_U
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             718
          Number of Observations
Number of Observations Read             720
Number of Observations Used             718
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02679
           Fit Statistics
-2 Res Log Likelihood          -532.6
AIC (Smaller is Better)        -530.6
AICC (Smaller is Better)       -530.6
BIC (Smaller is Better)        -526.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.7405     0.1502    713     11.59     <.0001     0.05
trtpn                         1           -0.03161    0.01495    713     -2.11     0.0348     0.05
trtpn                         2           0.003833    0.01736    713      0.22     0.8253     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      0.01028    0.01304    713      0.79     0.4307     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.6563    0.02899    713     22.64     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
370 of 412
Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=T_CHOL_U
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.4457      2.0354
trtpn                         1           -0.06095    -0.00226
trtpn                         2           -0.03025     0.03791
trtpn                         3                               
PREOAD2     Metformin                     -0.01533     0.03590
PREOAD2     Metformin + OAD                                   
base_log                                    0.5994      0.7133
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     713       3.78    0.0232
PREOAD2         1     713       0.62    0.4307
base_log        1     713     512.47    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     5.0907   0.008628     713    590.03     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     5.1262    0.01230     713    416.87     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     5.1224    0.01221     713    419.42     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     5.0738     5.1077          162.51          159.78          165.29
trtpn    LSMeans, IDeg         5.1020     5.1503          168.37          164.36          172.49
trtpn    LSMeans, Lira         5.0984     5.1463          167.73          163.76          171.80
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.03544   0.01503    713    -2.36    0.0186
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.06495    -0.00593           0.9652
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9371           0.9941
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
371 of 412
Total cholesterol after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=T_CHOL_U
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2  -0.03161   0.01495    713    -2.11    0.0348
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05    -0.06095    -0.00226           0.9689
                     Least Squares Means Estimates
                                          Exponentiated   Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.9409           0.9977
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
372 of 412
31: Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C80200S
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3464
           Fit Statistics
-2 Res Log Likelihood          1291.7
AIC (Smaller is Better)        1293.7
AICC (Smaller is Better)       1293.7
BIC (Smaller is Better)        1298.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  -0.7292    0.06369    712    -11.45     <.0001     0.05
trtpn                         1            -0.3934    0.05383    712     -7.31     <.0001     0.05
trtpn                         2            -0.4788    0.06237    712     -7.68     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -0.03614    0.04688    712     -0.77     0.4410     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.2984    0.05385    712      5.54     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
373 of 412
Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C80200S
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  -0.8542     -0.6041
trtpn                         1            -0.4991     -0.2877
trtpn                         2            -0.6013     -0.3564
trtpn                         3                               
PREOAD2     Metformin                      -0.1282     0.05590
PREOAD2     Metformin + OAD                                   
base_log                                    0.1927      0.4042
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712      35.68    <.0001
PREOAD2         1     712       0.59    0.4410
base_log        1     712      30.71    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -1.3691    0.03102     712    -44.14     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -1.4546    0.04415     712    -32.95     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    -0.9757    0.04400     712    -22.17     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -1.4300    -1.3082          0.2543          0.2393          0.2703
trtpn    LSMeans, IDeg        -1.5413    -1.3679          0.2335          0.2141          0.2546
trtpn    LSMeans, Lira        -1.0621    -0.8894          0.3769          0.3457          0.4109
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.08544   0.05397    712     1.58    0.1138
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.02052      0.1914           1.0892
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9797           1.2109
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
374 of 412
Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=C80200S
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2   -0.3934   0.05383    712    -7.31    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.4991     -0.2877           0.6748
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.6071           0.7500
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
375 of 412
Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=FFAU
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           aval_log                 
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             717
          Number of Observations
Number of Observations Read             720
Number of Observations Used             717
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3464
           Fit Statistics
-2 Res Log Likelihood          1291.7
AIC (Smaller is Better)        1293.7
AICC (Smaller is Better)       1293.7
BIC (Smaller is Better)        1298.3
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                   1.6135     0.1442    712     11.19     <.0001     0.05
trtpn                         1            -0.3934    0.05383    712     -7.31     <.0001     0.05
trtpn                         2            -0.4788    0.06237    712     -7.68     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                     -0.03614    0.04688    712     -0.77     0.4410     0.05
PREOAD2     Metformin + OAD                      0                                                
base_log                                    0.2984    0.05385    712      5.54     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
376 of 412
Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=FFAU
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                   1.3304      1.8966
trtpn                         1            -0.4991     -0.2877
trtpn                         2            -0.6013     -0.3564
trtpn                         3                               
PREOAD2     Metformin                      -0.1282     0.05590
PREOAD2     Metformin + OAD                                   
base_log                                    0.1927      0.4042
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     712      35.68    <.0001
PREOAD2         1     712       0.59    0.4410
base_log        1     712      30.71    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     1.9702    0.03102     712     63.51     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     1.8847    0.04415     712     42.69     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     2.3636    0.04400     712     53.71     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     1.9093     2.0311          7.1720          6.7482          7.6223
trtpn    LSMeans, IDeg         1.7981     1.9714          6.5847          6.0380          7.1809
trtpn    LSMeans, Lira         2.2772     2.4500         10.6289          9.7492         11.5880
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2   0.08544   0.05397    712     1.58    0.1138
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.02052      0.1914           1.0892
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9797           1.2109
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Free fatty acid after 26 weeks of treatment - supportive statistical analysis - full analysis set
Parameter Code=FFAU
The Mixed Procedure
                                   Least Squares Means Estimates
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - Lira  WORK.ADATA2   -0.3934   0.05383    712    -7.31    <.0001
                              Least Squares Means Estimates
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - Lira    0.05     -0.4991     -0.2877           0.6748
                     Least Squares Means Estimates
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - Lira         0.6071           0.7500
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32: Hypoglycaemic episodes - treatment emergent - confirmatory statistical analysis - full analysis set
Parameter Code=HYCNFSE
The GENMOD Procedure
                         Model Information
Data Set                  WORK.ANA_DATA                             
Distribution          Negative Binomial                             
Link Function                       Log                             
Dependent Variable                 AVAL    Analysis Value           
Offset Variable                  logoff                             
Number of Observations Read         720
Number of Observations Used         713
Missing Values                        7
             Class Level Information
Class        Levels    Values
TRTPN             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
                Parameter Information
Parameter       Effect       TRTPN    PREOAD2
Prm1            Intercept                            
Prm2            TRTPN        1                       
Prm3            TRTPN        2                       
Prm4            TRTPN        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
                          Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm3         Prm5    Dispersion
   0        0    -380.13843    4.8306049    -0.036595    -0.104861    -0.051602     0.8802336
   1       16    -302.60682    4.5389129      -0.1549    -0.175903    -0.142035     0.9183973
   2       16    -255.22114    4.2626473    -0.251412    -0.242057    -0.226961     0.9503451
   3        1    -206.65271    2.8432976    0.1567368     -0.10993    -0.427447     0.0358785
   4        1     -202.3443    2.5892984    0.6980844    0.2589648    -0.555308     0.0395708
   5        1    -200.99292    2.3670321    0.9318901    0.5113944    -0.588845      0.043325
   6        1    -200.22341     2.198899    1.1100727    0.7072959    -0.596857     0.0478977
   7        1    -199.73835    2.0671899     1.247524    0.8581409     -0.59647     0.0535168
   8        1    -199.39683    1.9622075    1.3560667    0.9762753    -0.593838     0.0605805
   9        1    -199.12347    1.8774354     1.443274     1.070397    -0.590982     0.0697204
  10        1    -198.86994    1.8082494    1.5142491    1.1464569    -0.588478     0.0819888
  11        1    -198.59526     1.751282    1.5725976    1.2086072    -0.586426     0.0992653
  12        1   -198.24946    1.7040306    1.6209577    1.2598201    -0.584788     0.1252315
  13        1    -197.74733    1.6646022    1.6613144     1.302261    -0.583503     0.1680471
  14        1    -196.90293    1.6315452     1.695204    1.3374889    -0.582535     0.2491751
  15        1    -195.23725     1.603746    1.7238705    1.3664613    -0.581914     0.4401437
  16        1    -191.68986    1.5804119    1.7484509     1.389049    -0.581882     1.0431561
  17        1    -187.56845    1.5611562    1.7700432    1.4034058    -0.582981     2.7017295
  18        0    -186.76627    1.4976435    1.8401498    1.4556977    -0.585191     6.8888986
  19        0    -186.39066    1.4866145    1.8515736    1.4690204    -0.584467     5.1881713
  20        0    -186.38768    1.4871635    1.8506212    1.4690617    -0.584092     5.0432744
  21        0    -186.38768    1.4871611    1.8506254    1.4690662    -0.584093     5.0416978
  22        0    -186.38768    1.4871611    1.8506254    1.4690662    -0.584093     5.0416978
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Hypoglycaemic episodes - treatment emergent - confirmatory statistical analysis - full analysis set
Parameter Code=HYCNFSE
The GENMOD Procedure
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     709        178.6787          0.2520
Scaled Deviance              709        178.6787          0.2520
Pearson Chi-Square           709        910.8445          1.2847
Scaled Pearson X2            709        910.8445          1.2847
Log Likelihood                         -186.3877                
Full Log Likelihood                    -197.5958                
AIC (smaller is better)                 405.1916                
AICC (smaller is better)                405.2765                
BIC (smaller is better)                 428.0391                
             Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm3           Prm5      Dispersion
Gradient        4.5021E-9        8.37E-9      7.528E-10      -1.755E-9       5.4659E-8
Prm1            39.194138      26.152514      10.311714      9.5802638       0.0027883
Prm2            26.152514     26.152514              0      6.9340316       -0.018622
Prm3            10.311714              0      10.311714        2.00561       0.0446241
Prm5            9.5802638      6.9340316        2.00561      9.5802638       0.0038538
Dispersion      0.0027883      -0.018622      0.0446241      0.0038538       0.2835077
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                           Standard       Wald 95%             Wald
Parameter                    DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                     1    1.4872    0.6117    0.2882    2.6861        5.91      0.0151
TRTPN       1                 1    1.8506    0.6363    0.6035    3.0978        8.46      0.0036
TRTPN       2                 1    1.4691    0.6812    0.1338    2.8043        4.65      0.0310
TRTPN       3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2     Metformin         1   -0.5841    0.3726   -1.3145    0.1463        2.46      0.1170
PREOAD2     Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
Dispersion                    1    5.0417    1.8794    2.4281   10.4686                        
NOTE: The negative binomial dispersion parameter was estimated by maximum likelihood.
                                     TRTPN Least Squares Means
Planned
Treatment              Standard
(N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper   Exponentiated
1             3.0457     0.2142     14.22     <.0001     0.05     2.6258     3.4656         21.0256
2             2.6642     0.3317      8.03     <.0001     0.05     2.0141     3.3143         14.3562
3             1.1951     0.6135      1.95     0.0514     0.05   -0.00724     2.3975          3.3039
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                 13.8162          31.9969
2                  7.4940          27.5020
3                  0.9928          10.9953
CONFIDENTIAL


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Hypoglycaemic episodes - treatment emergent - confirmatory statistical analysis - full analysis set
Parameter Code=HYCNFSE
The GENMOD Procedure
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2             0.3816     0.3688      1.03     0.3008     0.05    -0.3412     1.1044
1           3             1.8506     0.6363      2.91     0.0036     0.05     0.6035     3.0978
2           3             1.4691     0.6812      2.16     0.0310     0.05     0.1338     2.8043
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  1.4646           0.7109           3.0173
1           3                  6.3638           1.8285          22.1486
2           3                  4.3452           1.1432          16.5153
                                  Least Squares Means Estimates
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg     0.3816     0.3688      1.03     0.3008     0.05    -0.3412     1.1044
TRTPN    IDegLira / Lira     1.8506     0.6363      2.91     0.0036     0.05     0.6035     3.0978
                      Least Squares Means Estimates
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          1.4646           0.7109           3.0173
TRTPN    IDegLira / Lira          6.3638           1.8285          22.1486
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33: Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple imputation 
- full analysis set
ANA_SORT=2 Parameter Code=HYCNFSE Planned Treatment (N)=1 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI2
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000963       0.044886       0.045849   2.26E6
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.021473       0.021022       0.999979
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        3.038074       0.214125   2.618397   3.457751   2.26E6       2.986481       3.203014
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              14.19     <.0001
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=2 Parameter Code=HYCNFSE Planned Treatment (N)=2 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI2
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002318       0.107840       0.110161   2.25E6
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.021518       0.021065       0.999979
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        2.665038       0.331905   2.014517   3.315560   2.25E6       2.592518       2.921904
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               8.03     <.0001
CONFIDENTIAL


NN9068
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=2 Parameter Code=HYCNFSE Planned Treatment (N)=3 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI2
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.039026       0.334826       0.373891    91512
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.116673       0.104502       0.999896
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.177674       0.611466   -0.02079   2.376142    91512       1.003454       2.309467
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               1.93     0.0541
CONFIDENTIAL


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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=2 Parameter Code=HYCNFSE Label=IDegLira / IDeg Statement Number=1
The MIANALYZE Procedure
           Model Information
Data Set                  WORK.LSME_MI2
Number of Imputations     1000         
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002478       0.133550       0.136031      3E6
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.018575       0.018237       0.999982
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.373036       0.368824   -0.34985   1.095918      3E6       0.121602       0.511817
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               1.01     0.3118
CONFIDENTIAL


NN9068
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
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ANA_SORT=3 Parameter Code=HYCNFSE Planned Treatment (N)=1 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI3
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000309       0.045685       0.045994   2.22E7
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.006760       0.006715       0.999993
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        3.020836       0.214463   2.600497   3.441176   2.22E7       2.985600       3.127575
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              14.09     <.0001
CONFIDENTIAL


NN9068
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=3 Parameter Code=HYCNFSE Planned Treatment (N)=2 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI3
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002102       0.108684       0.110788   2.77E6
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.019355       0.018989       0.999981
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        2.662611       0.332848   2.010241   3.314982   2.77E6       2.602009       2.921904
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               8.00     <.0001
CONFIDENTIAL


NN9068
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=3 Parameter Code=HYCNFSE Planned Treatment (N)=3 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI3
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.038929       0.335631       0.374599    92316
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.116104       0.104046       0.999896
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.175999       0.612045   -0.02360   2.375601    92316       1.005759       2.300105
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               1.92     0.0547
CONFIDENTIAL


NN9068
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Statistical document
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Hypoglycaemic episodes - treatment emergent - statistical sensitivity analysis - multiple
imputation - full analysis set
ANA_SORT=3 Parameter Code=HYCNFSE Label=IDegLira / Lira Statement Number=1
The MIANALYZE Procedure
           Model Information
Data Set                  WORK.LSME_MI3
Number of Imputations     1000         
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.038461       0.363910       0.402410   109140
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.105795       0.095690       0.999904
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.844837       0.634358   0.601505   3.088170   109140       0.750524       2.067895
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0               2.91     0.0036
CONFIDENTIAL


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34: Hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full analysis set
Parameter Code=HYCNFSES
The GENMOD Procedure
                         Model Information
Data Set                  WORK.ANA_DATA                             
Distribution          Negative Binomial                             
Link Function                       Log                             
Dependent Variable                 AVAL    Analysis Value           
Offset Variable                  logoff                             
Number of Observations Read         720
Number of Observations Used         713
Missing Values                        7
             Class Level Information
Class        Levels    Values
TRTPN             3    1 2 3                     
PREOAD2           2    Metformin Metformin + OAD 
                Parameter Information
Parameter       Effect       TRTPN    PREOAD2
Prm1            Intercept                            
Prm2            TRTPN        1                       
Prm3            TRTPN        2                       
Prm4            TRTPN        3                       
Prm5            PREOAD2               Metformin      
Prm6            PREOAD2               Metformin + OAD
                          Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm3         Prm5    Dispersion
   0        0    -353.06722    4.8066601    -0.074818    -0.131729    -0.020934      0.861409
   1       16    -266.30919      4.49535    -0.204286    -0.209027    -0.112915     0.8962711
   2       16    -210.74259    4.1900096    -0.317233    -0.284518    -0.199872     0.9218333
   3       16    -173.55805    3.8503107    -0.415706    -0.366987    -0.291605     0.9418687
   4        1     -143.6538    3.0355129    -0.140169    -0.327641    -0.370119     0.8064204
   5        1    -135.39985    2.4869883    0.2781764    -0.163044    -0.420301     1.5551127
   6        1    -131.14278    2.0944005    0.6753206    0.0960382    -0.432245      3.435585
   7        0    -128.32846    1.2717192    1.5420922    1.0071474     -0.38109     8.3037715
   8        0    -127.62792    0.5784988    2.2398711    1.7079566    -0.362035     6.2854472
   9        0    -127.59326    0.3486607     2.469668     1.937593    -0.365232      6.226675
  10        0    -127.59288    0.3209942    2.4973578    1.9652698    -0.365305     6.2291019
  11        0   -127.59288    0.3206337    2.4977184    1.9656304    -0.365306     6.2291245
  12        0    -127.59288    0.3206337    2.4977184    1.9656304    -0.365306     6.2291245
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     709        123.9740          0.1749
Scaled Deviance              709        123.9740          0.1749
Pearson Chi-Square           709       1089.6976          1.5370
Scaled Pearson X2            709       1089.6976          1.5370
Log Likelihood                         -127.5929                
Full Log Likelihood                    -132.8504                
AIC (smaller is better)                 275.7008                
AICC (smaller is better)                275.7856                
BIC (smaller is better)                 298.5482                
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full analysis set
Parameter Code=HYCNFSES
The GENMOD Procedure
             Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm3           Prm5      Dispersion
Gradient        5.7947E-8      -5.49E-13       7.89E-13      1.6345E-8       -6.43E-10
Prm1            25.276692      18.132024      6.1824107      6.7687429       0.0081878
Prm2            18.132024      18.132024              0      5.2170454       -0.004494
Prm3            6.1824107              0      6.1824107      1.2857398       0.0171082
Prm5            6.7687429      5.2170454      1.2857398      6.7687429       -0.006032
Dispersion      0.0081878      -0.004494      0.0171082      -0.006032       0.1016866
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                           Standard       Wald 95%             Wald
Parameter                    DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                     1    0.3206    1.0271   -1.6924    2.3337        0.10      0.7549
TRTPN       1                 1    2.4977    1.0462    0.4472    4.5483        5.70      0.0170
TRTPN       2                 1    1.9656    1.0966   -0.1836    4.1148        3.21      0.0730
TRTPN       3                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2     Metformin         1   -0.3653    0.4505   -1.2484    0.5178        0.66      0.4175
PREOAD2     Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
Dispersion                    1    6.2291    3.1372    2.3213   16.7154                        
NOTE: The negative binomial dispersion parameter was estimated by maximum likelihood.
                                     TRTPN Least Squares Means
Planned
Treatment              Standard
(N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper   Exponentiated
1             2.6357     0.2536     10.39     <.0001     0.05     2.1387     3.1327         13.9531
2             2.1036     0.4232      4.97     <.0001     0.05     1.2741     2.9331          8.1957
3             0.1380     1.0245      0.13     0.8929     0.05    -1.8700     2.1460          1.1480
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  8.4884          22.9357
2                  3.5755          18.7858
3                  0.1541           8.5504
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2             0.5321     0.4672      1.14     0.2547     0.05    -0.3836     1.4478
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  1.7025           0.6814           4.2537
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Statistical document
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Parameter Code=HYCNFSES
The GENMOD Procedure
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           3             2.4977     1.0462      2.39     0.0170     0.05     0.4472     4.5483
2           3             1.9656     1.0966      1.79     0.0730     0.05    -0.1836     4.1148
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           3                 12.1547           1.5639          94.4701
2           3                  7.1394           0.8323          61.2429
                                  Least Squares Means Estimates
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg     0.5321     0.4672      1.14     0.2547     0.05    -0.3836     1.4478
TRTPN    IDegLira / Lira     2.4977     1.0462      2.39     0.0170     0.05     0.4472     4.5483
                      Least Squares Means Estimates
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          1.7025           0.6814           4.2537
TRTPN    IDegLira / Lira         12.1547           1.5639          94.4701
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35: Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full 
analysis set
Parameter Code=HYNOCSE
The GENMOD Procedure
                         Model Information
Data Set                  WORK.ANA_DATA                             
Distribution          Negative Binomial                             
Link Function                       Log                             
Dependent Variable                 AVAL    Analysis Value           
Offset Variable                  logoff                             
Number of Observations Read         540
Number of Observations Used         533
Missing Values                        7
             Class Level Information
Class        Levels    Values
TRTPN             2    1 2                       
PREOAD2           2    Metformin Metformin + OAD 
                Parameter Information
Parameter       Effect       TRTPN    PREOAD2
Prm1            Intercept                            
Prm2            TRTPN        1                       
Prm3            TRTPN        2                       
Prm4            PREOAD2               Metformin      
Prm5            PREOAD2               Metformin + OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -243.64107     4.637979    0.0194619    0.0260575     0.8386892
   1       16    -184.26619    4.3981381      -0.1288    -0.045806     0.8662332
   2        1    -68.411958     2.935821    -0.434955    -0.206637     0.0121826
   3     0.06    -58.692105    2.1873247    -0.320872    -0.130925     0.0128597
   4     0.06    -57.230315    1.7003907    -0.150367    -0.025395     0.0151914
   5     0.06     -57.13682    1.5241268    -0.041456    0.0331984     0.0206355
   6     0.06    -57.110943    1.4998604    -0.020569    0.0424738     0.0343106
   7     0.06    -56.971669    1.4982316    -0.018939    0.0431973     0.1151813
   8        1    -56.947602    1.4981784    -0.018898    0.0432318     0.1298369
   9        1    -56.917385    1.4981527    -0.018879    0.0432527     0.1485335
  10        1    -56.878466    1.4981399    -0.018875    0.0432673     0.1731113
  11        1    -56.826753    1.4981338    -0.018879    0.0432803     0.2066582
  12        1    -56.755364    1.4981313    -0.018892     0.043295        0.2547
  13        1    -56.652094     1.498131    -0.018915    0.0433146       0.32794
  14        1    -56.494193    1.4981321    -0.018952    0.0433443     0.4491921
  15        1    -56.238368    1.4981344    -0.019017     0.043395     0.6726469
  16        1    -55.810424    1.4981378    -0.019144    0.0434916     1.1394896
  17        1    -55.147082    1.4981417    -0.019409    0.0436941     2.2055893
  18        1    -54.385791     1.498142    -0.019956    0.0441147     4.4431574
  19        0    -54.054726     1.498489    -0.023739    0.0471084     38.111462
  20        0    -53.520173    1.4987877     -0.02712    0.0502384     19.488384
  21        0    -53.506363    1.4984434     -0.02461    0.0479554     17.083396
  22        0    -53.506335    1.4984612    -0.024704    0.0480491     16.976997
  23        0    -53.506335    1.4984612    -0.024704    0.0480488     16.976758
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Statistical document
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Parameter Code=HYNOCSE
The GENMOD Procedure
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     530         45.8965          0.0866
Scaled Deviance              530         45.8965          0.0866
Pearson Chi-Square           530        488.5132          0.9217
Scaled Pearson X2            530        488.5132          0.9217
Log Likelihood                          -53.5063                
Full Log Likelihood                     -54.8926                
AIC (smaller is better)                 117.7853                
AICC (smaller is better)                117.8610                
BIC (smaller is better)                 134.8993                
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        1.703E-12      3.889E-12      -2.15E-12        5.95E-12
Prm1            8.6322112      5.7634921      2.8522502       0.0009603
Prm2            5.7634921      5.7634921      2.1928143       0.0011125
Prm4            2.8522502      2.1928143      2.8522502       -0.000068
Dispersion      0.0009603      0.0011125      -0.000068       0.0048804
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                           Standard       Wald 95%             Wald
Parameter                    DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                     1    1.4985    0.6139    0.2952    2.7017        5.96      0.0147
TRTPN       1                 1   -0.0247    0.7309   -1.4573    1.4079        0.00      0.9730
TRTPN       2                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2     Metformin         1    0.0480    0.7320   -1.3866    1.4827        0.00      0.9477
PREOAD2     Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
Dispersion                    1   16.9768   14.3149    3.2518   88.6320                        
NOTE: The negative binomial dispersion parameter was estimated by maximum likelihood.
                                     TRTPN Least Squares Means
Planned
Treatment              Standard
(N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper   Exponentiated
1             1.4978     0.4256      3.52     0.0004     0.05     0.6635     2.3320          4.4718
2             1.5225     0.6226      2.45     0.0145     0.05     0.3021     2.7428          4.5836
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  1.9417          10.2987
2                  1.3527          15.5312
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Statistical document
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Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full
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Parameter Code=HYNOCSE
The GENMOD Procedure
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2           -0.02470     0.7309     -0.03     0.9730     0.05    -1.4573     1.4079
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.9756           0.2329           4.0873
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg   -0.02470     0.7309     -0.03     0.9730     0.05    -1.4573     1.4079
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.9756           0.2329           4.0873
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full
analysis set
Parameter Code=HYNOCSES
The GENMOD Procedure
                         Model Information
Data Set                  WORK.ANA_DATA                             
Distribution          Negative Binomial                             
Link Function                       Log                             
Dependent Variable                 AVAL    Analysis Value           
Offset Variable                  logoff                             
Number of Observations Read         540
Number of Observations Used         533
Missing Values                        7
             Class Level Information
Class        Levels    Values
TRTPN             2    1 2                       
PREOAD2           2    Metformin Metformin + OAD 
                Parameter Information
Parameter       Effect       TRTPN    PREOAD2
Prm1            Intercept                            
Prm2            TRTPN        1                       
Prm3            TRTPN        2                       
Prm4            PREOAD2               Metformin      
Prm5            PREOAD2               Metformin + OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -239.38395    4.6320803    0.0130252    0.0267412     0.8307234
   1       16     -178.5201    4.3885276    -0.137679    -0.045836     0.8568435
   2        1       -52.915    2.7724072    -0.477285    -0.213908     0.0055764
   3     0.06    -43.169463    1.9833211    -0.422206    -0.099201     0.0055064
   4        0    -41.402752    1.4086308    -0.303289    0.0916114     0.0000105
   5        0    -41.279967    1.1755251     -0.21786    0.2104166     3.6292E-6
   6        0    -41.278755    1.1467312    -0.202954    0.2269668     1.4011E-6
   7        0    -41.278755    1.1463672    -0.202723     0.227155     4.7003E-7
   8        0    -41.278755    1.1463672    -0.202723     0.227155     4.7001E-7
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     530         66.5575          0.1256
Scaled Deviance              530         66.5575          0.1256
Pearson Chi-Square           530        506.8188          0.9563
Scaled Pearson X2            530        506.8188          0.9563
Log Likelihood                          -41.2788                
Full Log Likelihood                     -41.2788                
AIC (smaller is better)                  90.5575                
AICC (smaller is better)                 90.6333                
BIC (smaller is better)                 107.6716                
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full
analysis set
Parameter Code=HYNOCSES
The GENMOD Procedure
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        1.7262E-7      3.2856E-8      1.7575E-8       0.0300508
Prm1            8.0000001              5              3       -0.000228
Prm2                    5              5      1.8918351       0.0041442
Prm4                    3      1.8918351              3       -0.004008
Dispersion      -0.000228      0.0041442      -0.004008       141409.99
Algorithm converged.                                                       
                      Analysis Of Maximum Likelihood Parameter Estimates
                                           Standard       Wald 95%             Wald
Parameter                    DF  Estimate     Error   Confidence Limits  Chi-Square  Pr > ChiSq
Intercept                     1    1.1464    0.6373   -0.1027    2.3954        3.24      0.0720
TRTPN       1                 1   -0.2027    0.7303   -1.6341    1.2287        0.08      0.7813
TRTPN       2                 0    0.0000    0.0000    0.0000    0.0000                        
PREOAD2     Metformin         1    0.2272    0.7303   -1.2043    1.6586        0.10      0.7558
PREOAD2     Metformin + OAD   0    0.0000    0.0000    0.0000    0.0000                        
Dispersion                    1    0.0000    0.0027                                            
NOTE: The negative binomial dispersion parameter was estimated by maximum likelihood.
                                     TRTPN Least Squares Means
Planned
Treatment              Standard
(N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper   Exponentiated
1             1.0572     0.4560      2.32     0.0204     0.05     0.1636     1.9509          2.8784
2             1.2599     0.5852      2.15     0.0313     0.05     0.1130     2.4069          3.5252
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  1.1777           7.0348
2                  1.1197          11.0992
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2            -0.2027     0.7303     -0.28     0.7813     0.05    -1.6341     1.2287
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.8165           0.1951           3.4168
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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Nocturnal hypoglycaemic episodes - treatment emergent - supportive statistical analysis - full
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Parameter Code=HYNOCSES
The GENMOD Procedure
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg    -0.2027     0.7303     -0.28     0.7813     0.05    -1.6341     1.2287
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label            Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.8165           0.1951           3.4168
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NN9068
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36: Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full 
analysis set
Parameter Code=C49676X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      61.0988
           Fit Statistics
-2 Res Log Likelihood          5001.9
AIC (Smaller is Better)        5003.9
AICC (Smaller is Better)       5003.9
BIC (Smaller is Better)        5008.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  39.7507     2.4558    715     16.19     <.0001     0.05
trtpn                         1            -1.1609     0.7136    715     -1.63     0.1042     0.05
trtpn                         2            -5.4522     0.8252    715     -6.61     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1803     0.6226    715     -0.29     0.7722     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.5538    0.03075    715     18.01     <.0001     0.05
CONFIDENTIAL


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Statistical document
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Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full
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Parameter Code=C49676X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  34.9293     44.5720
trtpn                         1            -2.5619      0.2401
trtpn                         2            -7.0723     -3.8322
trtpn                         3                               
PREOAD2     Metformin                      -1.4025      1.0420
PREOAD2     Metformin + OAD                                   
BASE                                        0.4934      0.6142
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      25.41    <.0001
PREOAD2         1     715       0.08    0.7722
BASE            1     715     324.30    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    81.2475     0.4115     715    197.44     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    76.9561     0.5843     715    131.71     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    82.4084     0.5828     715    141.41     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    80.4396    82.0554        1.929E35         8.6E34        4.327E35
trtpn    LSMeans, IDeg        75.8090    78.1032         2.64E33        8.384E32        8.314E33
trtpn    LSMeans, Lira        81.2642    83.5525        6.159E35        1.962E35        1.934E36
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2     4.2914     0.7147     715      6.00
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05    2.8882    5.6945        73.0660
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        17.9611           297.23
CONFIDENTIAL


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Clinical Trial Report
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Statistical document
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Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full
analysis set
Parameter Code=C49676X
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -1.1609     0.7136     715     -1.63
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.1042    0.05   -2.5619    0.2401         0.3132
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira        0.07716           1.2714
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Final
Statistical document
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Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full
analysis set
Parameter Code=C49676X
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      61.0988
           Fit Statistics
-2 Res Log Likelihood          5001.9
AIC (Smaller is Better)        5003.9
AICC (Smaller is Better)       5003.9
BIC (Smaller is Better)        5008.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  39.7507     2.4558    715     16.19     <.0001     0.05
trtpn                         1            -1.1609     0.7136    715     -1.63     0.1042     0.05
trtpn                         2            -5.4522     0.8252    715     -6.61     <.0001     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1803     0.6226    715     -0.29     0.7722     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.4462    0.03075    715    -14.51     <.0001     0.05
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
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402 of 412
Pulse after 26 weeks of treatment - change from baseline - supportive statistical analysis - full
analysis set
Parameter Code=C49676X
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  34.9293     44.5720
trtpn                         1            -2.5619      0.2401
trtpn                         2            -7.0723     -3.8322
trtpn                         3                               
PREOAD2     Metformin                      -1.4025      1.0420
PREOAD2     Metformin + OAD                                   
BASE                                       -0.5066     -0.3858
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715      25.41    <.0001
PREOAD2         1     715       0.08    0.7722
BASE            1     715     210.49    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    4.1169    0.4115    715    10.00    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -0.1744    0.5843    715    -0.30    0.7654
trtpn   Change from baseline, Lira      WORK.ADATA2    5.2778    0.5828    715     9.06    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05      3.3090      4.9248
trtpn   Change from baseline, IDeg        0.05     -1.3215      0.9727
trtpn   Change from baseline, Lira        0.05      4.1337      6.4220
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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NN9068-4148
Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
403 of 412
37: Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set
Parameter Code=SYSBPMEA
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       112.91
           Fit Statistics
-2 Res Log Likelihood          5441.9
AIC (Smaller is Better)        5443.9
AICC (Smaller is Better)       5443.9
BIC (Smaller is Better)        5448.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  54.8951     3.5822    715     15.32     <.0001     0.05
trtpn                         1             0.3202     0.9699    715      0.33     0.7414     0.05
trtpn                         2             2.3622     1.1218    715      2.11     0.0356     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1735     0.8456    715     -0.21     0.8375     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.5459    0.02725    715     20.03     <.0001     0.05
CONFIDENTIAL


NN9068
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Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
404 of 412
Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=SYSBPMEA
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  47.8622     61.9280
trtpn                         1            -1.5840      2.2244
trtpn                         2             0.1598      4.5646
trtpn                         3                               
PREOAD2     Metformin                      -1.8337      1.4867
PREOAD2     Metformin + OAD                                   
BASE                                        0.4924      0.5994
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715       2.80    0.0613
PREOAD2         1     715       0.04    0.8375
BASE            1     715     401.30    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     125.34     0.5593     715    224.09     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     127.38     0.7942     715    160.38     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2     125.02     0.7922     715    157.81     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     124.24     126.44        2.717E54         9.06E53        8.147E54
trtpn    LSMeans, IDeg         125.82     128.94        2.094E55        4.402E54        9.956E55
trtpn    LSMeans, Lira         123.46     126.57        1.972E54        4.164E53        9.342E54
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.0420     0.9715     715     -2.10
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0359    0.05   -3.9492   -0.1347         0.1298
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        0.01927           0.8739
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
405 of 412
Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=SYSBPMEA
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2     0.3202     0.9699     715      0.33
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha    Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.7414    0.05   -1.5840    2.2244         1.3774
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.2052           9.2480
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
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NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
406 of 412
Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=SYSBPMEA
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       112.91
           Fit Statistics
-2 Res Log Likelihood          5441.9
AIC (Smaller is Better)        5443.9
AICC (Smaller is Better)       5443.9
BIC (Smaller is Better)        5448.5
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  54.8951     3.5822    715     15.32     <.0001     0.05
trtpn                         1             0.3202     0.9699    715      0.33     0.7414     0.05
trtpn                         2             2.3622     1.1218    715      2.11     0.0356     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                      -0.1735     0.8456    715     -0.21     0.8375     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.4541    0.02725    715    -16.66     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
407 of 412
Systolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical
analysis - full analysis set
Parameter Code=SYSBPMEA
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  47.8622     61.9280
trtpn                         1            -1.5840      2.2244
trtpn                         2             0.1598      4.5646
trtpn                         3                               
PREOAD2     Metformin                      -1.8337      1.4867
PREOAD2     Metformin + OAD                                   
BASE                                       -0.5076     -0.4006
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715       2.80    0.0613
PREOAD2         1     715       0.04    0.8375
BASE            1     715     277.68    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.2197    0.5593    715    -5.76    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -1.1778    0.7942    715    -1.48    0.1386
trtpn   Change from baseline, Lira      WORK.ADATA2   -3.5399    0.7922   715    -4.47    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -4.3179     -2.1216
trtpn   Change from baseline, IDeg        0.05     -2.7371      0.3816
trtpn   Change from baseline, Lira        0.05     -5.0953     -1.9846
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
408 of 412
38: Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive statistical 
analysis - full analysis set
Parameter Code=DIABPMEA
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           AVAL                     
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class     Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      50.4183
           Fit Statistics
-2 Res Log Likelihood          4864.5
AIC (Smaller is Better)        4866.5
AICC (Smaller is Better)       4866.5
BIC (Smaller is Better)        4871.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  33.7874     2.3740    715     14.23     <.0001     0.05
trtpn                         1            -0.2455     0.6479    715     -0.38     0.7049     0.05
trtpn                         2            -0.8356     0.7496    715     -1.11     0.2653     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6531     0.5681    715      1.15     0.2507     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                        0.5735    0.02907    715     19.73     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
409 of 412
Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive
statistical analysis - full analysis set
Parameter Code=DIABPMEA
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                 29.1266     38.4483
trtpn                         1            -1.5175      1.0265
trtpn                         2            -2.3072      0.6360
trtpn                         3                               
PREOAD2     Metformin                      -0.4622      1.7685
PREOAD2     Metformin + OAD                                   
BASE                                        0.5165      0.6306
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715       0.67    0.5102
PREOAD2         1     715       1.32    0.2507
BASE            1     715     389.16    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    79.6002     0.3737     715    212.99     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    79.0100     0.5308     715    148.86     <.0001     0.05
trtpn    LSMeans, Lira       WORK.ADATA2    79.8456     0.5293     715    150.86     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    78.8664    80.3339        3.715E34        1.783E34        7.737E34
trtpn    LSMeans, IDeg        77.9680    80.0521        2.059E34        7.262E33        5.837E34
trtpn    LSMeans, Lira        78.8066    80.8847        4.748E34         1.68E34        1.342E35
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2     0.5901     0.6492     715      0.91
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.3636    0.05   -0.6844    1.8646         1.8042
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.5044           6.4535
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
410 of 412
Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive
statistical analysis - full analysis set
Parameter Code=DIABPMEA
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - Lira  WORK.ADATA2    -0.2455     0.6479     715     -0.38
                                 Least Squares Means Estimates
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - Lira    0.7049    0.05   -1.5175    1.0265         0.7823
                       Least Squares Means Estimates
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - Lira         0.2193           2.7913
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
411 of 412
Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive
statistical analysis - full analysis set
Parameter Code=DIABPMEA
The Mixed Procedure
                  Model Information
Data Set                     WORK.ADATA2              
Dependent Variable           CHG                      
Covariance Structure         Diagonal                 
Estimation Method            REML                     
Residual Variance Method     Profile                  
Fixed Effects SE Method      Model-Based              
Degrees of Freedom Method    Residual                 
              Class Level Information
Class      Levels    Values
trtpn           3    1 2 3                         
PREOAD2         2    Metformin Metformin + OAD     
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             720
          Number of Observations
Number of Observations Read             720
Number of Observations Used             720
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      50.4183
           Fit Statistics
-2 Res Log Likelihood          4864.5
AIC (Smaller is Better)        4866.5
AICC (Smaller is Better)       4866.5
BIC (Smaller is Better)        4871.0
                                    Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period                 Standard
Effect      treatment2        01 (N)      Estimate      Error     DF   t Value   Pr > |t|    Alpha
Intercept                                  33.7874     2.3740    715     14.23     <.0001     0.05
trtpn                         1            -0.2455     0.6479    715     -0.38     0.7049     0.05
trtpn                         2            -0.8356     0.7496    715     -1.11     0.2653     0.05
trtpn                         3                  0                                                
PREOAD2     Metformin                       0.6531     0.5681    715      1.15     0.2507     0.05
PREOAD2     Metformin + OAD                      0                                                
BASE                                       -0.4265    0.02907    715    -14.67     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
16 December 2019
Novo Nordisk
NN9068-4148
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
412 of 412
Diastolic blood pressure after 26 weeks of treatment - change from baseline - supportive
statistical analysis - full analysis set
Parameter Code=DIABPMEA
The Mixed Procedure
                  Solution for Fixed Effects
                              Planned
                              Treatment
            Pre Trial         for
            anti-Diabetic     Period
Effect      treatment2        01 (N)         Lower       Upper
Intercept                                  29.1266     38.4483
trtpn                         1            -1.5175      1.0265
trtpn                         2            -2.3072      0.6360
trtpn                         3                               
PREOAD2     Metformin                      -0.4622      1.7685
PREOAD2     Metformin + OAD                                   
BASE                                       -0.4835     -0.3694
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           2     715       0.67    0.5102
PREOAD2         1     715       1.32    0.2507
BASE            1     715     215.17    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.3360    0.3737    715    -0.90    0.3690
trtpn   Change from baseline, IDeg      WORK.ADATA2   -0.9261    0.5308    715    -1.74    0.0815
trtpn   Change from baseline, Lira     WORK.ADATA2  -0.09047    0.5293    715    -0.17    0.8643
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -1.0697      0.3978
trtpn   Change from baseline, IDeg        0.05     -1.9681      0.1160
trtpn   Change from baseline, Lira        0.05     -1.1295      0.9486
CONFIDENTIAL