Conditions: Diabetes Diabetes Mellitus, Type 2
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 453
Healthy volunteers: no

Brief summary:
This trial is conducted in Asia. The aim of this trial is to confirm the superiority of insulin degludec/liraglutide versus insulin degludec in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus after 26 weeks of treatment

Detailed description:

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Insulin degludec/liraglutide intervention 2: Insulin degludec
Intervention descriptions: intervention 1: Administered subcutaneously (s.c., under the skin) once daily in combination with metformin for the treatment duration of 26 weeks. intervention 2: Administered subcutaneously (s.c., under the skin) once daily in combination with metformin for the treatment duration of 26 weeks.

Protocol document:
Prot_001.pdf: 
Cover Page for Protocol 
 
Sponsor name: 
Novo Nordisk A/S 
NCT number 
NCT03175120  
Sponsor trial ID: 
NN9068-4166 
Official title of study: 
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD. DUAL™ II China 
Document date: 
04 December 2019 
 
 
 
 
 
 
Redacted protocol 
Includes redaction of personal identifiable information only. 
 
 
 
. 
 
 


Link
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List of contents
Protocol - version 2.............................................................................................................................
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: NN9068-4166
Clinical Trial Report
Appendix 16.1.1
04 December 2019
1.0
Final
16.1.1 Protocol and protocol amendments
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Trial ID: NN9068-4166
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Protocol
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in 
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately 
controlled with basal insulin therapy and metformin ± one other OAD
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: NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
Page:
2 of 88
Table of Contents   
Page
Table of Contents..............................................................................................................................................2
Table of Figures................................................................................................................................................6
Table of Tables..................................................................................................................................................6
List of abbreviations.........................................................................................................................................7
1
Summary..................................................................................................................................................10
2
Flow chart ................................................................................................................................................14
3
Background information and rationale for the trial............................................................................17
3.1
Background information..............................................................................................................17
3.2
Rationale for the Trial..................................................................................................................17
4
Objectives and endpoints........................................................................................................................18
4.1
Objectives ....................................................................................................................................18
4.1.1
Primary objective.......................................................................................................18
4.1.2
Secondary objectives .................................................................................................18
4.2
Endpoints .....................................................................................................................................18
4.2.1
Primary endpoint........................................................................................................18
4.2.2
Secondary endpoints..................................................................................................18
4.2.2.1
Confirmatory secondary endpoints .....................................................18
4.2.2.2
Supportive secondary efficacy endpoints............................................19
4.2.2.3
Supportive secondary safety endpoints...............................................19
5
Trial design ..............................................................................................................................................21
5.1
Type of trial .................................................................................................................................21
5.2
Rationale for trial design..............................................................................................................22
5.3
Treatment of subjects...................................................................................................................22
5.4
Treatment in follow-up period.....................................................................................................23
5.5
Treatment after end of trial ..........................................................................................................23
5.6
Rationale for treatment ................................................................................................................23
6
Trial population.......................................................................................................................................25
6.1
Number of subjects......................................................................................................................25
6.2
Inclusion criteria ..........................................................................................................................25
6.3
Exclusion criteria.........................................................................................................................26
6.4
Withdrawal criteria ......................................................................................................................27
6.5
Subject replacement.....................................................................................................................28
6.6
Rationale for trial population.......................................................................................................28
7
Milestones.................................................................................................................................................29
8
Methods and assessments .......................................................................................................................30
8.1
Visit procedures...........................................................................................................................30
8.1.1
Fasting requirements for blood sampling ..................................................................30
8.1.2
Screening (Visit 1).....................................................................................................30
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8.1.3
Screening Failures......................................................................................................31
8.1.4
Randomisation (Visit 2).............................................................................................31
8.1.5
Treatment period (Visit 2 -Visit 33) ..........................................................................32
8.1.6
Follow-up visit (Visit 34) ..........................................................................................32
8.1.7
Unscheduled visit(s) ..................................................................................................32
8.1.8
Subject withdrawal ....................................................................................................33
8.2
Subject related information..........................................................................................................33
8.2.1
Demography...............................................................................................................33
8.2.2
Concomitant illness and medical history...................................................................33
8.2.3
Adverse events...........................................................................................................33
8.2.4
Diabetes complications and treatment history...........................................................34
8.2.5
Smoking habits ..........................................................................................................34
8.2.6
Concomitant medication............................................................................................34
8.2.7
Body measurements...................................................................................................34
8.2.8
Vital Signs (blood pressure and pulse) ......................................................................35
8.2.9
Physical Examination ................................................................................................35
8.2.10
Eye examination ........................................................................................................36
8.2.11
ECG ...........................................................................................................................36
8.2.12
Self-measured plasma glucose (SMPG) ....................................................................36
8.2.13
Self measured 9-point blood glucose profile .............................................................37
8.2.14
Hypoglycaemic episodes ...........................................................................................38
8.3
Laboratory assessments ...............................................................................................................39
8.3.1
Blood and urine sampling (central laboratory analysis) ............................................39
8.3.2
Calcitonin sampling (central laboratory analysis) .....................................................40
8.3.3
Antibodies sampling ..................................................................................................41
8.4
Pancreatitis...................................................................................................................................41
8.5
Thyroid disease............................................................................................................................41
8.6
Subject diaries..............................................................................................................................41
8.7
Subject compliance......................................................................................................................42
9
Trial supplies ...........................................................................................................................................43
9.1
Trial product ................................................................................................................................43
9.2
Non-Investigational Medicinal Product.......................................................................................43
9.3
Labelling......................................................................................................................................43
9.4
Storage .........................................................................................................................................44
9.5
Drug accountability and destruction............................................................................................44
9.6
Auxiliary supplies........................................................................................................................45
10 Interactive voice/web response system ..................................................................................................46
11 Randomisation procedure and breaking of blinded codes..................................................................47
11.1
Breaking of blinded codes ...........................................................................................................47
12 Adverse events, technical complaints, and pregnancies ......................................................................48
12.1
Definitions ...................................................................................................................................48
12.2
Reporting of adverse events.........................................................................................................51
12.3
Follow-up of adverse events........................................................................................................53
12.4
Technical complaints and technical complaint samples ..............................................................54
12.4.1
Reporting of technical complaints .............................................................................54
12.4.2
Collection, storage and shipment of technical complaint samples ............................55
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12.5
Pregnancies..................................................................................................................................56
12.5.1
Pregnancies in female subjects ..................................................................................56
12.6
Precautions and/or overdose ........................................................................................................57
12.7
Committees related to safety........................................................................................................58
12.7.1
Novo Nordisk safety committee ................................................................................58
12.7.2
Calcitonin monitoring committee ..............................................................................58
12.7.3
Event adjudication committee....................................................................................58
13 Case report forms....................................................................................................................................60
13.1
Corrections to case report forms..................................................................................................60
13.2
Case report form flow..................................................................................................................61
14 Monitoring procedures ...........................................................................................................................62
14.1
Source data verification and source data requirements................................................................62
15 Data management....................................................................................................................................63
16 Computerised systems.............................................................................................................................63
17 Statistical considerations ........................................................................................................................63
17.1
Sample size calculation................................................................................................................65
17.2
Definition of analysis sets............................................................................................................65
17.3
Primary endpoint..........................................................................................................................66
17.3.1
Sensitivity analysis ....................................................................................................67
17.4
Secondary endpoints....................................................................................................................67
17.4.1
Confirmatory secondary endpoints............................................................................67
17.4.2
Supportive secondary endpoints ................................................................................68
17.4.2.1
Efficacy endpoints...............................................................................68
17.4.2.2
Safety endpoints..................................................................................70
18 Ethics........................................................................................................................................................77
18.1
Informed consent .........................................................................................................................77
18.2
Data handling...............................................................................................................................78
18.3
Information to subject during trial...............................................................................................78
18.4
Premature termination of the trial and/or trial site.......................................................................78
19 Protocol compliance................................................................................................................................79
20 Audits and inspections ............................................................................................................................79
21 Critical documents ..................................................................................................................................80
22 Responsibilities........................................................................................................................................81
23 Reports and publications........................................................................................................................82
23.1
Communication of results............................................................................................................82
23.1.1
Authorship .................................................................................................................83
23.1.2
Site-specific publication(s) by investigator(s) ...........................................................83
23.2
Investigator access to data and review of results.........................................................................83
24 Retention of clinical trial documentation and human biospecimens..................................................84
24.1
Retention of clinical trial documentation.....................................................................................84
24.2
Retention of human biospecimens...............................................................................................84
25 Institutional Review Boards/Independent Ethics Committees and regulatory authorities..............85
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26 Indemnity statement ...............................................................................................................................86
27 References................................................................................................................................................87
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 – Global list of key staff and relevant departments and vendors
Attachment II – Country list of key staff and relevant departments
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Table of Figures   
Page
Figure 5–1
Trial design.............................................................................................................................21
Figure 12–1
Initial reporting of AEs...........................................................................................................53
Figure 17–1
Novo Nordisk classification of hypoglycaemia......................................................................72
Figure 17–2
ADA classification of hypoglycaemia....................................................................................73
Table of Tables
Page
Table 9–1
Trial products..........................................................................................................................43
Table 9–2
Storage conditions for IMPs...................................................................................................44
Table 9–1
Trial products..........................................................................................................................43
Table 9–2
Storage conditions for IMPs...................................................................................................44
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Date:
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Trial ID: NN9068-4166
Version:
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List of abbreviations
ADA
American Diabetes Association
AE
adverse event
AGI
α-glucose inhibitors
ALAT
alanine transaminase
ANCOVA
standard analysis of covariance 
ASAT
aspartate transaminase
BG
blood glucose
BMI
body mass index
CAS
completer analysis set
CRF
case report form
DPP-4
dipeptidyl peptidase-4 
DUN
dispensing unit number
EASD
European Association for the Study of Diabetes
ECG
electrocardiogram
eCRF
electronic case report form
EOT
end of treatment
FAS
full analysis set
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
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation 
IDeg
insulin degludec
IDegLira
insulin degludec/liraglutide
CONFIDENTIAL


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Date:
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Trial ID: NN9068-4166
Version:
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Status:
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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
MEN2
multiple endocrine neoplasia type 2
MESI
medical event of special interest
MMRM
mixed model for repeated measurement 
NYHA
New York Heart Association
OAD
oral anti-diabetic drug
OD
once daily
PP
per protocol
SAE
serious adverse event
SAS
safety analysis set 
SmPC
summary of product characteristics
SIF
safety information form
SMPG
self-measured plasma glucose
SU
sulphonylureas
SUSAR
suspected unexpected serious adverse reaction
T2DM
type 2 diabetes
TEAE
treatment emergent adverse event 
TMM
trial materials manual
TTT
treat-to-target
TZD
thiazolidinediones
U
Unit
UNR 
upper normal range 
UTN
universal trial number
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Trial ID: NN9068-4166
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VLDL
very low-density lipoprotein
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1
Summary
Primary objective
To confirm the superiority of insulin degludec/liraglutide versus insulin degludec in controlling 
glycaemia in Chinese subjects with type 2 diabetes mellitus after 26 weeks of treatment.
Primary endpoint
Change from baseline in HbA1c after 26 weeks of treatment. 
Secondary objective
!
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 the overall efficacy and safety of insulin degludec/liraglutide to insulin 
degludec after 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
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Trial ID: NN9068-4166
Version:
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Trial design
This is a 26 week, randomised, parallel two-arm, double-blind, multi-centre, treat-to-target trial in 
Chinese subjects with type 2 diabetes inadequately controlled with basal insulin therapy and 
metformin ± one other oral anti-diabetic agent: α-glucosidase inhibitors, sulphonylureas, glinides or 
thiazolidinediones.
Subjects will be randomised in a 2:1 manner to receive insulin degludec/liraglutide or insulin 
degludec once daily with metformin. The randomisation of subjects will be stratified with respect to 
their previous anti-diabetic treatment (basal insulin and metformin or basal insulin, metformin and
one other oral anti-diabetic agent).
The total trial duration for the individual subject will be approximately 29 weeks. 
Trial population:
A total of 450 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 procedures to determine suitability 
for the trial
!
Male or female, age ≥ 18 years at the time of signing inform consent
!
Type 2 diabetes mellitus (clinically diagnosed)
!
HbA1c ≥ 7.5% by central laboratory analysis, with the aim of a median of 8.5%. When 
approximately 50% of the randomised subjects have an HbA1c above 8.5%, the remaining 
subjects randomised must have an HbA1c below or equal to 8.5% or when approximately 50% 
of the subjects randomised have an HbA1c below or equal to 8.5%, the remaining subjects 
randomised must have an HbA1c above 8.5%
!
Current treatment for at least 90 calendar days prior to screening with basal insulin + metformin 
± α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. Subjects should be on 
a stable dose for at least 60 calendar days prior to screening of: 
Basal insulin 20-50 units (U)/day (both inclusive)* on the day of screening in combination with
i. Metformin (≥1500 mg or max tolerated dose) or
ii. Metformin (≥1500 mg or max tolerated dose) and sulphonylureas (≥half of 
the max approved dose according to local label) or
iii. Metformin (≥1500 mg or max tolerated dose) and glinide (≥half of the max 
approved dose according to local label) or
iv. Metformin (≥1500 mg or max tolerated dose) and α-glucosidase inhibitors 
(AGI) (≥half of the max approved dose according to local label) or
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v. Metformin (≥1500 mg or max tolerated dose) and thiazolidinediones (≥half 
of the max approved dose according to local label)
*Individual fluctuations of ± 5U during the 60 day period prior to the day of screening are 
acceptable
!
Body mass index (BMI) ≥24 kg/m2
Key exclusion criteria
!
Current use of any anti-diabetic drug (except for basal insulin, metformin, α-glucosidase 
inhibitors, sulphonylureas, glinides or thiazolidinediones) or anticipated change in concomitant 
medication, that in the investigator´s opinion could interfere with glucose level (e.g. systemic 
corticosteroids)
!
Treatment with glucagon like peptide -1 receptor agonists, or dipeptidyl peptidase -4 inhibitors 
or insulin (except for basal insulin) within 90 days prior to Visit 1
!
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 (MTC) 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
!
Severe uncontrolled treated or untreated hypertension (systolic blood pressure ≥180 mm Hg or 
diastolic blood pressure ≥100 mm Hg)
!
Proliferative retinopathy or maculopathy (macular oedema) requiring acute treatment
!
History of pancreatitis (acute or chronic)
Key efficacy assessments
!
HbA1c
!
Weight
!
Fasting plasma glucose
Key safety assessments
!
Hypoglycaemic episodes
!
Adverse events
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Trial product(s)
The trial products for subcutaneous injection in the 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
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2
Flow chart
Screening (S)
Randomisation (R)
Visit (V)
Telephone contact (T)
Follow up visit (FU)
S
R
T
V
T
V
T
V
T
V
T
V
T
V
T
V
T
V
FU
Visit/Contact 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
30
31
32
33
34
Timing of visit (weeks)1
- 22
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
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)
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
+3
SUBJECT RELATED INFO/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
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
X
X
Smoking Habits
X
X
Demography
X
Diagnosis of diabetes
X
Diabetes treatment history
X
Family history of diabetes
X
Diabetes complications
X
Body measurements
Height
X
Body weight
X
X
X
X
X
X
X
X
BMI
X
X
Waist circumference
X
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
Self measured plasma 
glucose
9-point profile
X
X
X
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Protocol
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Trial ID: NN9068-4166
Version:
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EudraCT no.:
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Screening (S)
Randomisation (R)
Visit (V)
Telephone contact (T)
Follow up visit (FU)
S
R
T
V
T
V
T
V
T
V
T
V
T
V
T
V
T
V
FU
Visit/Contact 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
30
31
32
33
34
Timing of visit (weeks)1
- 22
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
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)
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
+3
Once daily
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SAFETY
Adverse events 
X
X
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
X
X
Hypoglycaemic episodes
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ECG
X3
X4
Eye examination
X5
X6
Physical examination
X
X
Vital signs
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 7
X
X
TRIAL MATERIAL
IV/WRS call 
X
X
X
X
X
X
X
X
Administration of trial 
product
X
X
X
X
X
X
Drug accountability 
X
X
X
X
X
X
X
REMINDERS
Hand out ID card
X
Handout and instruct in 
BG meter use
X
Training in trial product 
and pen handling 
X
Attend visit fasting
X
X
X
X
X
X
X
X8
Hand out and instruct in
diary
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
Dose of trial product to be 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CONFIDENTIAL


Protocol
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT no.:
Page:
16 of 88
Screening (S)
Randomisation (R)
Visit (V)
Telephone contact (T)
Follow up visit (FU)
S
R
T
V
T
V
T
V
T
V
T
V
T
V
T
V
T
V
FU
Visit/Contact 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
30
31
32
33
34
Timing of visit (weeks)1
- 22
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
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)
±1
±1
±1
±1
±1
±1
±1
±3
±3
±3
±3
±3
±3
±3
±3
±3
+3
taken after titration 
Confirmation of 
unchanged metformin 
dose
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
End of trial and sign off 
case book
X
1 A 0.5 week interval is corresponding to previous visit plus three calendar days
2 Screening must take place within 14 calendar days prior to randomisation
3 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
4 ECG obtained within 14 calendar days prior to Visit 33 is acceptable, if the results are available for evaluation at Visit 33. See section 8.2.11
5 Eye examination performed within 90 calendar days prior to visit 2 as part of routine practise may replace the screening assessment if results are 
available for Visit 2. See section 8.2.10
6 Eye examination performed within 14 calendar days prior to Visit 33 is acceptable, if the results are available for evaluation at Visit 33. See section 
8.2.10
7 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 period at a phone contact, the subject must attend the site for an unscheduled visit as soon as possible to have 
a urine pregnancy test done. If positive a confirmatory serum hCG test should be sent to the central laboratory
8 For fasting requirements prior to Visit 34 see section 8.1.6
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Trial ID: NN9068-4166
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3
Background information and rationale for the trial
The trial will be conducted in compliance with this protocol, ICH GCP1 and 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 
diabetes 3 4 . Given the progressive nature of T2DM, current anti-diabetic therapies, including 
treatment with basal insulin in combination 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 and American Diabetes Association (ADA)/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 progresses 5 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 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 human 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 confirmatory trial will be used for registration purposes in China to document the efficacy and 
safety of treatment with IDegLira OD in combination with metformin in Chinese subjects with 
T2DM. For detailed information on IDeg or IdegLira, see the Investigator´s Brochure, any updates 
hereof, and/or SmPC, as applicable. 
CONFIDENTIAL


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Trial ID: NN9068-4166
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4
Objectives and endpoints
4.1
Objectives
4.1.1
Primary objective 
To confirm the superiority of IDegLira versus IDeg in controlling glycaemia in Chinese subjects 
with T2DM after 26 weeks of treatment.
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. 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 the overall efficacy and safety of IDegLira to IDeg after 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
!
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
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 efficacy endpoints
!Insulin dose after 26 weeks of treatment
!Responder for HbA1c after 26 weeks of treatment (Yes/No)
o
HbA1c < 7.0%
o
HbA1c ≤ 6.5% 
o
HbA1c < 7.0% and change from baseline in body weight below or equal to zero
o
HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero
o
HbA1c <7.0% without severe or blood glucose (BG) confirmed hypoglycaemic episodes 
during the last 12 weeks of treatment
o
HbA1c ≤ 6.5% without severe or BG confirmed hypoglycaemic episodes during the last 12 
weeks of treatment
o
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
o
HbA1c ≤ 6.5% of treatment 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:
o
Fasting plasma glucose (FPG)
o
Waist circumference
o
Mean of the 9-point profile
!Mean post prandial increment (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 
incrementsFasting 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
4.2.2.3
Supportive secondary safety endpoints
!
Number of treatment emergent adverse events (TEAEs) during 26 weeks of treatment
!
Number of treatment emergent nocturnal severe or blood glucose (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
!
Number of treatment emergent hypoglycaemic episodes according to ADA definition
!
Change from baseline in clinical evaluations after 26 weeks of treatment
o
Physical examination
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Trial ID: NN9068-4166
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o
Fundoscopy or fundus photography
o
Electrocardiogram (ECG)
o
Pulse
o
Blood pressure
!Change from baseline in laboratory assessments during 26 weeks of treatment
o
Biochemistry
o
Haematology 
o
Calcitonin
!Urinalysis (dipstick for erythrocytes, protein, glucose and ketones)
!Antibodies towards trial product
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Protocol
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Trial ID: NN9068-4166
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5
Trial design
5.1
Type of trial
This is a 26 week, randomised, parallel two-arm, double-blind, multi-centre, treat-to-target (TTT)
trial in Chinese subjects with T2DM inadequately controlled with basal insulin therapy and 
metformin ± one other OAD: α-glucosidase inhibitors (AGI), sulphonylureas (SU), glinides or
thiazolidinediones (TZD). Inadequately controlled diabetes will be defined as HbA1c level of ≥ 
7.5%.
Subjects will be randomised in a 2:1 manner, using a centralised allocation via interactive 
voice/web response system (IV/WRS) to receive IDegLira or IDeg both once daily in combination 
with metformin. Other pre-trial OAD treatment will be discontinued at randomisation. Subjects will 
be stratified with respect to their previous anti-diabetic treatment (basal insulin and metformin or 
basal insulin, metformin and one other OAD).
A total of 450 subjects will be randomised.
The duration of the trial from screening (Visit 1) to follow-up (Visit 34) will be 29 weeks with 
treatment duration of 26 weeks. The trial will include a screening visit (Visit 1) at which the 
eligibility of the subjects is determined followed by randomisation (Visit 2). The follow-up (Visit 
34) will be conducted 1 week after end of treatment. 
The trial design is summarised schematically below:
Figure 5–1
Trial design 
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Trial ID: NN9068-4166
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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. 
The current trial is designed to demonstrate superiority in HbA1c of IDegLira as compared to IDeg 
in subjects with T2DM. To enable an evaluation of the contribution of the liraglutide component of
IDegLira to glycaemic control and secondary endpoints, the maximum dose of the IDeg in the IDeg 
arm is set to 50 units (U), i.e. equivalent to the maximum dose of the IDeg component with 
IDegLira. 
A double-blind design is feasible due to the similar titration and will limit the occurrence of 
conscious and unconscious bias in the conduct and the interpretation of this trial arising from the 
influence which the knowledge of treatment may have on the subjects case, the attitudes of subjects 
to the treatment, the assessment of endpoints, the handling of withdrawals, the exclusion of data 
from the analysis etc.
To obtain improved HbA1c results to allow for a valid comparison of safety endpoints the TTT
approach has been chosen in order to ensure optimal treatment with frequent visits and titration of 
IDegLira and IDeg based on pre-breakfast self-measured plasma glucose (SMPG) values. 
5.3
Treatment of subjects
Subjects with T2DM treated with basal insulin and metformin with or without one additional OAD 
(AGI, SU, glinides orTZD) in accordance with the inclusion criterionare eligible for the trial. At 
randomisation basal insulin andOADs except for metformin will be discontinued. Subjects will 
receive IDegLira or IDeg subcutaneous once daily in combination withmetforminfor the treatment 
duration of 26 weeks. 
Because of blinding during conduct of the trial a common terminology for both trial products have 
been chosen to be dose steps, thus one dose step corresponds to either 1 unit of IDeg or 1 dose step 
of IDegLira (1 unitinsulindegludec/0.036 mg liraglutide). IDegLira and IDeg added to current 
metformin therapywill be given subcutaneously once daily. The starting dose of IDegLira is 16 
dose steps (16 units insulin degludec /0.6 mg liraglutide)and starting dose of IDeg is 16 units. 
The dose of IDegLira and IDeg willthereafterbe titrated twice weekly according to the Titration 
guideline(Appendix A).
The treatment with metformin will be continued withpre-trial dose. 
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Trial ID: NN9068-4166
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5.4
Treatment in follow-up period
After 26 weeks of trial product exposure, a 1 week interval between the end of treatment (Visit 33) 
and the follow-up (Visit 34) is necessary to allow for trial product wash out. Subjects should in this 
period be transferred to any other anti-diabetic treatment at the discretion of the investigator. 
However, treatment with IDeg, insulin detemir (Levemir ®) or any GLP-1 receptor agonist is not
permitted in the periods from the end of trial (Visit 33) to the follow up (Visit 34) due to the 
inference with the antibody measurements performed at Visit 34. If the subject refuses to come in 
for the follow up (Visit 34), the subject will be switched to a suitable marketed product as 
recommended by the investigator.
5.5
Treatment after end of trial
When completing the trial the subject should be switched to a suitable marketed product at the 
discretion of the investigator.
5.6
Rationale for treatment
Subjects will be treated with IDegLira or IDeg in order to demonstrate the efficacy and safety of 
IDegLira.
IDeg has been included as comparator in order to demonstrate a clinical benefit in terms of HbA1c
reduction of the fixed combination product as compared to this individual component. Given a TTT 
approach, the objective can only be achieved by capping the IDeg dose at 50U, leading to insulin 
dose equivalence in the two treatment arms, allowing a differentiation between the treatment arms 
based on the additional effects of the liraglutide component of IDegLira.
Start dose is 16 dose steps of IDeglira (16 units insulin degludec and 0,6 mg liraglutide) and IDeg 
(16 units insulin degludec) respectively. Due to the liraglutide component in IDegLira, the highest 
tolerable initiation dose of GLP-1 receptor agonist in GLP-1 naïve subjects is 16 dose steps (0.6 mg 
liraglutide, corresponding to maximum initial dose of liraglutide). 
In order to obtain differentiation between the two treatment arms as reflected in the liraglutide 
component of the combination, the highest dose at end of trial is pursued. Therefore, T2DM
subjects already treated – and inadequately controlled - with basal insulin are included to increase 
the chance of high dose at end of trial (i.e. approaching 50U or 50 dose steps). Pre-trial basal insulin 
therapy (treatment for at least 90 days and a total daily dose within the range of 20-50U, individual 
fluctuations of ∀5U within the 60 days prior to screening but not on the day of screening) will be 
discontinued at randomisation.
The current treatment cascade by the Chinese Diabetes Society and ADA/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 oral 
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Protocol
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anti-diabetic drugs (OADs), glucagon-like peptide 1 (GLP-1) receptor agonists or insulin as the 
disease progresses 5 6. Accordingly, the subjects will be on a background treatment including 
metformin in the present trial. The daily dose for metformin (# 1500 mg or maximum tolerated 
dose) is close to the maximum recommended dose for the treatment of T2DM according to local 
label. 
Subjects treated with AGI, SU, glinides or TZD will have this therapy discontinued at 
randomisation.
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6
Trial population
6.1
Number of subjects 
Country planned to participate: China
Number of subjects planned to be screened: 750
Number of subjects planned to be randomised: 450 (40% screening failure rate)
Number of subjects expected to complete the trial: 382 (withdrawal rate of 15%)
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 inform consent
3. Type 2 diabetes mellitus (clinically diagnosed)
4. HbA1c ≥ 7.5% by central laboratory analysis, with the aim of a median of 8.5%. When 
approximately 50% of the randomised subjects have an HbA1c above 8.5%, the remaining 
subjects must have an HbA1c of below or equal to 8.5% or when approximately 50% of the 
randomised subjects have an HbA1c below or equal to 8.5%, the remaining subjects 
randomised must have a HbA1c above 8.5%
5. Current treatment for at least 90 calendar days prior to screening with basal insulin + 
metformin ± AGI, SU, glinides and TZD. Subjects should be on a stable dose for at least 60 
calendar days prior to screening of: 
Basal insulin 20-50 U /day (both inclusive)* on the day of screening in combination with:
i. Metformin (≥1500 mg or max tolerated dose) or
ii. Metformin (≥1500 mg or max tolerated dose) and SU (≥half of the max 
approved dose according to local label) or
iii. Metformin (≥1500 mg or max tolerated dose) and glinide (≥half of the max 
approved dose according to local label) or
iv. Metformin (≥1500 mg or max tolerated dose) and AGI (≥half of the max 
approved dose according to local label) or
v. Metformin (≥1500 mg or max tolerated dose) and TZD (≥half of the max 
approved dose according to local label)
*Individual fluctuations of ± 5U during the 60 day period prior to the day of screening are 
acceptable
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6. Body mass index (BMI) ≥24 kg/m2
7. Able and willing to adhere to the protocol including performing self-monitoring of plasma 
glucose profiles, keeping a trial diary and to 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 before Visit 1
5. Current use of any anti-diabetic drug (except for basal insulin, AGI, SU, glinides and 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 GLP-1 receptor agonists, or DPP-4 inhibitors or insulin (except for basal 
insulin) within 90 days prior to Visit 1
8. Impaired liver function defined as alanine aminotransferase (ALAT) ≥ 2.5 times upper 
normal range (UNR)
9. Impaired renal function defined as serum-creatinine ≥133μmol/L (1.5 mg/dL) for males and 
≥125 μmol/L (1.4 mg/dL) for females, or as defined according to local contraindications for 
metformin
10. Screening calcitonin ≥ 50 ng/L
11. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine 
neoplasia type 2 (MEN2)
12. 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 period to screening and/or planned coronary, carotid or peripheral artery 
revascularisation procedures
13. Severe uncontrolled treated or untreated hypertension (systolic blood pressure ≥180 mm Hg 
or diastolic blood pressure ≥100 mm Hg)
14. Proliferative retinopathy or maculopathy (macular oedema) requiring acute treatment
15. Subject with a clinically significant, active (during the past 12 months) disease of the 
gastrointestinal, pulmonary, endocrinological (except for T2DM), neurological, 
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genitourinary or haematological system (except for conditions associated with T2DM) that 
in the opinion of the investigator may confound compliance and the results of the trial or 
pose additional risk in administering trial drug
16. Mental incapacity, unwillingness or language barrier precluding adequate understanding of 
the trial procedure or cooperation with the trial site personnel
17. Known or suspected abuse of alcohol or narcotics
18. History of  pancreatitis (acute or chronic)
19. Suffer from a life threatening disease including malignant neoplasms and medical history of 
malignant neoplasms and medical history of 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 providing an 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.
The subject must be withdrawn if the following applies:
1. Included 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 cortecoidsteroids)
5. If all  pre-breakfast SMPG values taken on three consecutive days or if any fasting plasma 
glucose (FPG) samples analysed by the central laboratory exceed 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 visit 
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. Subject must be withdrawn if diagnosed with acute pancreatitis must as a 
minimum have 2 out of 3: 
1. characteristic findings on ultrasound/computed axial tomography (CT)/magnetic 
resonance imaging (MRI)
2. characteristic abdominal pain
3. amylase and/or lipase >3x UNR
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6.5
Subject replacement
Subjects who are withdrawn will not be replaced.
6.6
Rationale for trial population
Subjects with T2DM on previous basal insulin therapy in need of treatment intensification (HbA1c≥ 
7.5%) to achieve glycaemic control are the target population for inclusion in this trial. 
Subjects should be on a stable insulin dose with basal insulin 20-50U/day (both inclusive, 
individual fluctuations of ± 5Uare acceptablebut not on the day of screening) for at least 60 days 
prior to screening and should be overweight (BMI ≥24 kg/m2) to ensure inclusion of subjects in 
which a high dose at the end of the trial can be expected. The rationale for including subjects on 
metformin with orwithout AGI, SU, glinides and TZDis to mimic common practise of diabetes 
treatment in subjects with T2DM failing on 1-2 OAD´s. When glycaemic control is not achieved or 
sustained on this background, the addition ofIDegLira can be considered.
The HbA1crange has been 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 median 
baseline HbA1clevel of 8.5% has been chosen to ensure to ensure somepatients in the study will be 
treated with the dose between 40-50 dosesteps.
Only serious concomitant conditions (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 the trial. 
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7
Milestones
Planned duration of recruitment period (first subject first visit - last subject last visit):
approximately 54 weeks. End of trial is defined as last subject last visit.
Recruitment will be performed according to an arrangement 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, agreed distribution of subjects between sites may be changed. 
The screening and randomisation rate will be followed closely via the IV/WRS in order to estimate 
when to stop screening. 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 Editors8, the Food and Drug Administration 
Amendment Act 9, European Commission Regulation for EudraCT 10 and 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 describe in more details. 
The investigator must keep a subject screening log, a subject identification code list and a subject 
enrolment log. The subject screening log and subject enrolment log may be combined in one list. 
8.1.1
Fasting requirements for blood sampling
As outlined in the flow chart subject must attend most of the visits fasting, i.e. at least eight hours 
without food and drink intake, except for water and any other prescribed medication. Trial products 
and metformin should be withheld on the day of the visit until blood sampling and body weight (if 
applicable) has been performed. Any other prescribed medication should be taken as usual. If the 
subject attend the site in a non-fasting state the blood sampling should be re-scheduled, see section 
8.1.7 for instructions. 
See section 8.1.6 for special requirements in relation to fasting prior to the follow up (Visit 34). 
8.1.2
Screening (Visit 1)
Must take place within 14 calendar days prior randomisation. 
Before screening, the Investigator must provide the subject 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 the subjects will be assigned a unique number which will remain the same throughout 
the trial. This number will be registered in the IV/WRS which will be used for screening,
randomisation and allocation of trial product to each subject throughout the trial (see section 9.5 and 
section 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 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 visit or destroy the card after the last visit. 
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 
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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, see section 8.1.3 how to 
screen fail the subject.
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 that will be reviewed by the 
investigator at all site visits/telephone contacts. See section 8.6 for source data to be captured in the 
diaries. 
Subjects will be provided with a BG meter for use throughout the trial. 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 to the electronic case 
report form (eCRF). Only serious adverse events (SAEs) from screening failures must be 
transcribed by the investigator into the eCRF. Follow-up of SAEs must be carried out according to 
section 12.3. 
Screening failures experiencing an adverse event (AE) that would otherwise qualify 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 the current insulin and OAD treatment andremain 
only on metformin. Subjects will then be randomised to receive IDegLira orIDeg in combination 
with metformin. See the Titration Guideline (Appendix A) for start doses and titration of 
randomised treatment. The dose of metformin should remain unchanged throughout the trial.
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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 subjects should demonstrate to the investigator, that they can use the pens correctly prior to 
leaving the site. Sites should, as necessary, repeat the directions for use to the subject at subsequent 
visits.
8.1.5
Treatment period (Visit 2 -Visit 33)
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.
A telephone contact may be changed into a site visit if needed. It is the responsibility of the 
investigator to ensure that the contact regardless of the format takes place.
At the end of treatment (Visit 33) subjects will be switched from trial product to an appropriate anti-
diabetic treatment at the discretion of the investigator. However, IDeg, insulin detemir (Levemir®) 
and any GLP-1 receptor agonists are not allowed, since they may interfere with antibodies 
measured at follow-up (Visit 34). 
8.1.6
Follow-up visit (Visit 34)
Due to the long half-life of IDeg, the procedures of the follow-up visit should be undertaken no 
earlier than 7 calendar days after Visit 33. 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 Visit 34 the subjects may be switched to any other suitable marketed product at the investigator’s 
discretion.
8.1.7
Unscheduled visit(s)
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)
For all of the above an unscheduled visit form must be completed in the eCRF, indicating the reason 
for the visit. 
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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, 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 for Visit 33 and 34 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 CRF.
8.2
Subject related information 
8.2.1
Demography
Demography 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 other) 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.
8.2.3
Adverse events
AE´s will be recorded throughout the trial in accordance with the procedure described in section 12.
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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 habits must be recorded at Visit 1 and Visit 33. 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 33.
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 to 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 recorded in the eCRF. 
If a change in concomitant medication 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 the nearest cm.
Body weight
Body weight should be measured without shoes and only wearing light clothing in kilograms (kg) 
with one decimal. The measurements are to be performed in a fasting state, except for the screening 
(Visit 1). Body weight should be assessed on the same equipment throughout the trial, if possible. 
Body Mass Index (BMI)
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Body mass index will be automatically calculated in the eCRF once height and weight are entered. 
At the Visit 1 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 circumference located midway 
between the lower rib margin and the iliac crest. 
Three consecutive measurements of waist circumference should be taken and recorded in the eCRF. 
The waist circumference will be measured to the nearest 0.5 cm using a non-stretchable measuring 
tape (will be provided to the site by Novo Nordisk). 
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 skin but not compress soft tissue and 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)
The measurement of systolic, diastolic blood pressure and pulse (beats per minute) should be 
assessed while the subject is in a sitting position and after 5 minutes of rest. 
Blood pressure must be measured three times and all three values must be entered to the eCRF. The 
mean value will be calculated by the eCRF and must be in accordance with the relevant exclusion 
criteria (see section 6.3).
If the investigator suspects white coat hypertension at Visit 1 and/or Visit 2, one re-assessment of 
the systolic and diastolic blood pressure (as described above) is allowed. 
8.2.9
Physical Examination
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
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The investigator must interpret if the results are “normal” or “abnormal”, and if “abnormal” 
whether the abnormality is “not clinically significant” or “clinically significant”.
8.2.10
Eye examination 
Eye examination (a fundoscopy or fundusphotography) must be performed by the investigator, a 
local ophthalmologist or an optometrist according to local practise. Dilation is not a requirement.
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 last 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 33 the procedure 
does not need to be repeated, if the results are available for evaluation at Visit 33 and no worsening 
of visual function since the last examination has occurred.
For all eye examinations the investigator must interpret if the results are “normal” or “abnormal”, 
and if “abnormal” whether the abnormality is “not clinically significant” or “clinically significant”. 
The investigator must sign and date the eye examination results to verify the review. 
8.2.11
ECG 
A 12-lead ECG must be performed as part of screening procedures so that results are available at 
Visit 2 prior to randomisation.
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 within14 calendar days prior to Visit 33 is acceptable, if the results are 
available for evaluation at Visit 33.
The investigator must interpret if the results are “normal” or “abnormal”, and if “abnormal” 
whether the abnormality is “not clinically significant” or “clinically significant”. The investigator 
must sign and date the ECG to verify the review.
8.2.12
Self-measured plasma glucose (SMPG)
At the screening visit, subjects will be provided with a blood glucose (BG) meter which must be 
used for all measurements during the trial. The subject should be supplied with oral and written 
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directions for use of the device including the performance of regular calibrations according to the 
manufacturer’s instructions. Sites should, as necessary, repeat the directions for use to the subject at 
subsequent visits. 
The BG meters use test strips calibrated to plasma glucose value. 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 self-measured plasma 
glucose (SMPG)values. 
Subjects should beinstructed how to record the values in the provided diaries and should only 
record the SMPG values based on measurements obtained with the provided BG meter. The 
recording of each measurement should include dateand value. 
Once daily SMPG valuesshould be obtainedfasting before breakfast. Diabetes medication should 
be withheld until after the measurement.
For telephone contacts the investigator or delegated site staff must transcribe the data used for the 
titration into the eCRF during/after the telephone contact. See Appendix A.  
8.2.13
Self measured 9-point blood glucose profile
Subjects will be instructed to perform measurements and record the SMPG values for a 9-point 
SMPG profile within one week prior to the site Visit 2, 19 and 33 on days where the subject does 
not anticipate unusual strenuous exercise. Anti-diabetic medication should be withheld until after 
the SMPG values have been obtained from the pre-breakfast measurement. 
The SMPG values should recorded in the diary (including actual clock time and date for the 
measurement) at the following time points, always starting with the measurement just 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
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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 34. 
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 and time and dose of last trial product administration (or other anti-diabetic treatment) 
prior to episode 
!
Type of last administered product (trial product or other anti-diabetic treatment) prior to the 
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" if oral 
carbohydrates, glucagon or IV glucose had to be administered to the subject by another person. 
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 11.
If the question "Was subject able to treat him/herself?" is answered "No", the following information 
should be recorded:
!
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)
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!
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 insulin 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 and storage of samples and 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
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 is retained at the investigator’s 
site as source documentation. Laboratory results will be sent by the central laboratory to the 
investigator on an ongoing basis. 
The central laboratory equipment may provide analysis not requested in the protocol but produced 
automatically in connection with the requested analyses. Such data will not be transferred to the 
trial database but may be reported to the investigator according to specifications in the laboratory 
standard operating procedures and requirements. The investigator must review all laboratory results 
for concomitant illnesses and AEs and report these according to this protocol.
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Blood sampling will be performed on subjects throughout the trial to determine levels of the 
following efficacy and safety parameters: 
Efficacy parameters
Glucose metabolism: HbA1c, FPG, Fasting insulin, Fasting glucagon, Fasting C-peptide and
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 dip stick
*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 hCG test should be sent to the central laboratory. 
Blood samples analysed at the central laboratory will be analysed and destroyed on an ongoing 
basis.
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 (CMC) of thyroid experts. The CMC will provide guidance to the investigator with 
regards to treatment and further investigations. If a subject is screen failed for other reasons than 
calcitonin exclusion criterion # 10 (calcitonin ≥ 50 ng/L), but has a value of calcitonin ≥10 ng/L, it 
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is recommended that they are referred to a thyroid expert for further evaluation.For details see 
Appendix D.
8.3.3
Antibodies sampling
Blood samples will be drawn as per flow chart (section 2) 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 34 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 sampling assessment should be performed prior to administering trial 
product. 
Antibody results will not be provided to the investigator as these results will not be used for any 
clinical evaluation during the trial. Instead they will be included in an analytical report after end of 
trial and retained at Novo Nordisk. For storage of blood samples used for the analysis of antibodies 
see section 24.2.
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 the subject 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 site as source data in accordance 
with section 14.1. From hand out 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. 
!
Date and dose of first trial product
!
Date and dose of last trial product
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!
Daily pre-breakfast SMPG values. See section 8.2.12
!
Last dose of last trial product taken prior to titration
!
New dose to be taken after titration
!
9-point SMPG profile, see section 8.2.13
!
Any AEs, hypoglycaemic episodes and changes in concomitant medication since last site
visit/telephone contact.
Based on the SMPG values the investigator/subject will assess whether the trial product dose needs 
adjustment according the Titration Guideline (see AppendixA).
The completed diary must be reviewed by the investigator to ensure that AEs, including any overall 
changes in health, and concomitant medication is reported. The review of the diary must be 
documented either on the front page of the diary and/or in the subjects medical records.
The investigator must transcribe data from the diary into the eCRF after each site visit or telephone
contactaccording 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records. 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. 
If a subject is found to be non-compliant, the investigator will remind the subject of the importance 
of following the instructions given including taking the trial products as prescribed. Substantial
failure to comply with the prescribed trial product 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 (TMM). 
Trial products 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 product
The following trial products are 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 in pre-
filled pen
subcutaneous
injection
Insulin degludec
100 units/mL
The insulin degludec/liraglutide and insulin degludec solutions are visually identical.
9.2
Non-Investigational Medicinal Product
Metformin is Non-Investigational Medicinal Product and is not considered trial product. Metformin 
will not be provided by Novo Nordisk. 
9.3
Labelling
IMPs will be packaged and labelled by Novo Nordisk A/S, and provided in non-subject specific 
boxes. Labelling of the trial products will be in accordance with Annex 1313, local regulations and 
trial requirements.
Each investigator site will be supplied with sufficient trial products for the trial on an on-going basis 
controlled by the IV/WRS. Dispensing units will be distributed to the sites according to enrolment 
and randomisation. Please refer to the IV/WRS user guidelines provided for detailed instructions of 
the IV/WRS. 
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Subjects will be provided with directions for use for the pre-filled pens by the investigator at each 
dispensing visit according the flow chart in section 2. The investigator must document that direction 
for use is given to the subject orally and/or in writing at each dispensing visit.
9.4
Storage 
The trial products must be stored according the storage conditions described below.
Table 9–2
Storage conditions for IMPs
Trial product
Storage 
conditions
(not-in-use)
In-use conditions
In-use time*
Insulin degludec/liraglutide 
Store in 
refrigerator (2°C 
to 8°C)
Do not freeze
Protect from light
Do not 
refrigerate.
Store below 30∃C
Protect from light
Use within 3 
weeks
Insulin degludec
* In-use time starts when first dose is taken
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.
9.5
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 (DUNs) 
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 must ensure: 
!
The correct DUN(s) are dispensed to the subject
!
The dispense date for any dispensed DUN should be confirmed in the IV/WRS drug 
accountability module after each dispensing
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!
Drug accountability is performed using the IV/WRS drug accountability module. Only 
dispensed DUNs returned by the subject (used/ partly used or returned unused) is accounted 
for
!
Subjects are instructed to return all used, partly used and unused trial products including 
empty packaging material at each dispensing visit. Returned trial product (used/partly used 
or unused including empty packaging material) trial product can be stored at room
temperature and must be stored separately from non-allocated trial product
Destruction will be done according to local procedures after accountability is finalised and verified 
by the monitor. Destruction of products must be documented.
9.6
Auxiliary supplies
The following auxiliary supplies will be provided by Novo Nordisk: 
!
Directions for use
!
Needles for pre-filled 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 which 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 a 
sufficient amount of trial product 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
!
Withdrawal
!
Completion
!
Code break
!
Drug accountability
!
Data change
IV/WRS user manuals will be provided to each trial site.
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11 Randomisation procedure and breaking of blinded codes
Randomisation will be done using the IV/WRS at Visit 2. The trial is a double-blinded trial. 
Randomisation will be carried out in a 2:1 manner and the subject will be assigned to one of the two 
treatment arms:
!
IDegLira
!
IDeg
Subjects will be stratified with respect to their previous anti-diabetic treatment (basal insulin and
metformin or basal insulin, metformin ± oneother OAD). 
When randomising subjects the IV/WRS is also used to ensure a trial population with a median 
HbA1clevelof 8.5%. When the number of subjects with an HbA1cbelow or equal to 8.5% reach 
50% of the required numberof subjects to be randomised, it will only be possible to randomise 
subjects with an HbA1cabove 8.5%and vice versa. The distribution of subjects having an HbA1c
above or below 8.5%will be followedclosely and investigators will be notified in due time before 
randomisation is closed. 
All investigators will be notified immediately when the recruitment period ends, after which no 
further subjects may be screened and the IV/WRS will be closed for further screening. All subjects 
included in the screening period and eligible for randomisation will be randomised.
11.1
Breaking of blinded codes
The IV/WRS will notify Novo Nordisk (monitor and the Global Safety department) immediately 
after the code is broken.
The code for a particular subject may be broken in a medical emergency if knowing the actual 
treatment would influence the treatment of the subject. Whenever a code is broken the person 
breaking the code must print the Code Break Confirmation Notification generated by the IV/WRS, 
record the reason, and sign and date the document.
When the code is broken, the treatment allocation will be accessible to the investigator and the 
Novo Nordisk Global Safety department.If IV/WRS is not accessible at the time of code break the 
IV/WRS vendor helpdesk should be contacted. Contact details are listed in Attachment I.
If the code has been broken the subject must be withdrawn and a withdrawal session must be 
completed in IV/WRS.
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12 Adverse events, technical complaints, and pregnancies
12.1
Definitions
Adverse event 
An adverse event (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 an AE:
!
Severity assessment
–
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.
!
Causality assessment
The following terms are used when assessing the relationship 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.
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–
Unlikely - The event is most likely related to aetiology other than the trial product.
!
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
A serious adverse event (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 threatening 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.
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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
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, see section 8.4.
6. Neoplasm
7. Thyroid disease, see section 8.5
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 lower or
higher than 20 % of the intended dose; however the administered dose must deviate from
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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.
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 
the end of the first 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. from 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 
and Figure 12–1.
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, either 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 or any updates thereto
IDeg: NN1250 CCDS or any updates thereto
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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.  
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
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 GCP.1 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 European Medicines Agency (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 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, 3 mL pre-filled pen.
!
Insulin degludec 100 units/mL, 3 mL pre-filled pen
!
Novo Nordisk needles for pre-filled pen 
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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 code or lot number or more than one DUN, 
a technical complaint form for each code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 or copy of the technical complaint form must be 
sent with the sample.
The investigator must ensure that the technical complaint sample contains thecode 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 9.4).
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12.5
Pregnancies
12.5.1
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 pregnancies:
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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.
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 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. 
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For further information see the IDegLira IB or any updates thereto.
For IDeg see the IB or the SmPC or any updates thereto.
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, insulin degludec and liraglutide. The 
IDegLira/NN9068 safety committee may recommend unblinding of any data for further analysis, 
and in this case an independent ad hoc group will be established in order to maintain the blinding of 
the trial personnel.
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
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AEs for adjudication must be reported according to 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.
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 instructions.
The following will be provided as paper CRFs only:
!
Pregnancy forms
In addition paper AE forms, safety information forms and technical complaints 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.
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 
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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 the site visit/telephone contact. The SMPG values and corresponding insulin 
doses for titration purpose must preferably be entered within 24 hours on week days after the site 
visit/telephone contact 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 as soon as possible after FPFV and 
no later than 6 weeks after the FPFV. The monitoring visit intervals will depend on the outcome of 
the remote monitoring of the CRFs, the trial site's recruitment rate and the compliance of the trial 
site to the protocol and GCP1, but will not exceed 8 weeks. A follow up letter (paper or electronic)
will be sent to the investigator following each monitoring visit addressing any action to be taken. 
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).
All data must be verifiable in source documentation other than the CRF. For all data recorded the 
source document 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.
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 must be questioned about these. 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. The monitor will ensure that the 
CRFs are completed and that any paper CRFs are collected.
For SMPG values it is accepted that the earliest practically retainable record should be considered 
as the source data. Therefore, the data recorded by the BG meter and transcribed into the diary by 
the subject will be considered as the 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
The monitor will collect CRF pages and other trial related forms containing data from screening 
failures. Source data requirements for screening failures are described in section 8.1.3. 
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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.
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 from the laboratory performing the 
analyses. In cases where data is transferred via non-secure electronic networks, data will be 
encrypted during transfer.
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.
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. 
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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.
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 anti-diabetic treatment (basal 
insulin and metformin or basal insulin, metformin and other OAD(s)) as fixed factors and the 
corresponding baseline value as a 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.
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 
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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 superiority of IDegLira vs. IDeg in controlling 
glycaemia in Chinese subjects with type 2 diabetes after 26 weeks of treatment. 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. IDeg.
Superiority in the primary endpoint for IDegLira versus  IDeg will be considered confirmed if the 
upper bound of the two-sided 95% confidence interval for the estimated mean treatment difference 
in change from baseline in HbA1c (for IDegLira - IDeg) is strictly below 0% or equivalently if the 
p-value for the two-sided test of
H0 D=0 against HA D≠0, 
is less than 5% and D<0, where D is the estimated  treatment difference. 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%.
The sample size is determined using a t-statistic under the assumption of a two-sided test of size 
5%, a mean difference in treatment of - 0.4%, and a standard deviation of SD=1.2%. It is also
assumed that 15% of the randomised subjects will be excluded from the PP analysis set. Superiority 
will be investigated for both the FAS and the PP analysis set in line with the Committee for 
Proprietary Medicinal Products (CPMP) Points to Consider 15. The above assumptions are based on 
experience from the phase 3a development programmes for IDegLira and IDeg. From these 
assumptions and based on a 2:1 randomisation the sample size is set to 300 subjects in the IDegLira 
arm and 150 subjects in the IDeg arm; in total 450 subjects will be randomised. This will ensure a 
power of 91.4% for confirming the primary objective in the full analysis set. Reducing the mean 
difference to -0.35% yields a power of 83%. 
17.2
Definition of analysis sets
The following analysis sets are defined in accordance with the ICH-E9 guidance 16.
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
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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”.
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, previous anti-diabetic treatment (basal insulin and metformin or 
basal insulin, metformin and other OAD(s)) as fixed effects and baseline HbA1c as covariate. 
Missing values after 26 weeks of treatment will be imputed LOCF using HbA1c values at and after 
baseline. 
Superiority of IDegLira vs. IDeg 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. Analysis based on the PP analysis set will be regarded as sensitivity analysis. 
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17.3.1
Sensitivity analysis
The primary efficacy 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 anti-diabetic treatment as fixed factors 
and baseline HbA1c as a 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 
clinical trial report.
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 superiority of IDegLira vs. IDeg with regards to the primary endpoint is 
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.
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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 (basal insulin and metformin or basal 
insulin, metformin and other OAD(s)) as fixed effect and baseline weight as covariate. 
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 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
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
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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 
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)
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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, low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein 
cholesterol (HDL cholesterol), very low density lipoprotein 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 (SMPG) 9-point profile
Three endpoints from the 9 point SMPG 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 PG 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 
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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-treatment emergent AE’s 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.
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-treatment emergent adverse events with onset date before the first day of exposure 
to randomised treatment will be presented. A listing will also be presented for non-treatment 
emergent adverse events 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 
hypoglycaemia17 (see Figure 17–1) and the ADA7 classification of hypoglycaemia (see Figure 17–
2).
Novo Nordisk classification of hypoglycaemia
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In normal physiology, symptoms of hypoglycaemia occur below a plasma glucose level of 3.1 
mmol/L (56 mg/dL) 17. Therefore, Novo Nordisk has included hypoglycaemia with plasma glucose 
levels below this cut-off point in the definition of blood glucose (BG) confirmed hypoglycaemia.
Novo Nordisk use the following classification (see Figure 17–1) in addition to the ADA 
classification: 
!
Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to 
the ADA classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) 
with symptoms consistent with hypoglycaemia. 
!
Severe or BG confirmed hypoglycaemia: An episode that is severe according to the ADA 
classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) 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 (70 
mg/dL).
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!
Documented symptomatic hypoglycaemia: An episode during which typical symptoms of 
hypoglycaemia are accompanied by a measured plasma glucose concentration ≤ 3.9 mmol/L 
(70 mg/dL).
!
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 (70 mg/dL) 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 (70 mg/dL).
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.  
The number of hypoglycaemic episodes during 26 weeks of treatment will be analysed separately 
for each endpoint 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 factor. 
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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, fundoscopy or fundus photography and ECG)
Eye examination (fundoscopy/fundus photography) 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 will apply in the evaluation of the result:
!
If the amylase or lipase baseline (at screening) value is > 3xUNR the information were
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.
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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 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)
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!
Subjects with at least one post baseline measurement outside reference range will be listed
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.
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18 Ethics
All subjects included in the trial will be treated with IDeglira or IDeg 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 
Helsinki 2.
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 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 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 (for Ideg and IDeglira)
!
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, if applicable
!
Signed and dated Investigator Agreement
!
Financial disclosure form from investigator and sub-investigator(s)
Novo Nordisk will analyse and report data from all trial sites together.
By signing the protocol, each investigator agrees to comply fully with ICH GCP 1 1, applicable 
regulatory requirements and the Declaration of Helsinki 22. 
By signing the protocol, each investigator also agrees to allow Novo Nordisk making investigator's 
name and information about trial 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.
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.
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 trial site personnel must have sufficient English skills according to their 
assigned task(s).
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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 International Committee of Medical Journal 
Editors 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 
International Committee of Medical Journal Editors (sometimes referred to as the Vancouver 
Criteria)18.
The investigator(s) offered authorship will be asked to comment and approve the publication. No 
permission to publish will be granted to any vendor involved in the trial described in this protocol. 
23.1.2
Site-specific publication(s) by investigator(s)
For a multi-centre clinical trial, analyses based on single-trial 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 trial 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 their own research subjects' data, and can be provided with the 
randomisation code after results are available if requested. 
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24 Retention of clinical trial documentation and human biospecimens
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 biospecimens
Antibody sample will be analysed and stored at a special laboratory outside of China until final 
feedback from the regulatory authorities in China 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 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.
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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 trial sites 
or investigators conducting the trial, or by persons for whom the said trial 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 World Medical Association. Declaration of Helsinki. Ethical principles for medical research 
involving human subjects. J Indian Med Assoc 2009; 107(6):403-405.
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. N 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 Jan 
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.
12 McAulay V, Deary IJ, Frier BM. Symptoms of hypoglycaemia in people with diabetes. Diabet 
Med 2001; 18(9):690-705.
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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. Food and Drug Administration, Code of Federal Regulations, 
Guidance for Industry, Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for 
Treatment and Prevention. Draft Guidance.  Feb 2008. 
15 EMEA-Committee for Proprietary Medicinal Products. CPMP/EWP/482/99 - Points to 
consider on switching between superiority and non-inferiority.  27 Jul 2000. 
16 International Conference on Harmonisation. ICH Harmonised Tripartite Guideline. Statistical 
principles for clinical trials E9. International Conference on Harmonisation E9 Expert 
Working Group.  5 Feb 1998. 
17 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.
18 De Angelius C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R et al. Clinical trial 
registration: a statement from the International Committee of Medical Journal Editors. New 
Engl J Med 2004; 351(12):1250-1251.
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Appendix A: Titration Guideline
NN9068-4166
DUAL! II China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD
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.


Trial ID: NN9068-4166
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Date:
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Protocol - Appendix A
Version:
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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
Basal insulin adjustment ................................................................................................................5
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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 adjusted 1 2 3 4 5 6 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 
subject’s welfare.
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2
Treatment regimens
At randomisation all subjects will be randomised 2:1 into two parallel treatment groups:
∀
Insulin degludec/liraglutide once daily + metformin
∀
Insulin degludec once daily+ metformin
First dosing should take place on day of randomisation or on the day following randomisation.
Maximum dose for insulin degludec/liraglutide and insulin degludec is 50 dose steps (50 units of 
insulin degludec and 1.8 mg of liraglutide/50 units of insulin degludec). 
There is no minimum dose for IDegLira or IDeg. 
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. 
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3
Initiation and titration
3.1
Initiation
At randomisation (Visit 2), all subjects will start on 16 dose steps of IDegLira (16 U of degludec 
and 0.6 mg of liraglutide) or 16 U IDeg once daily.
3.2
Titration
Dose will be adjusted twice weekly by the subject on two days 3-4 days apart. The investigator will 
support titration at all contacts. 
Titration should be performed based on the mean of three pre-breakfast 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
Basal insulin adjustment
Mean of three pre-breakfast SMPGs 
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, the subject must wait for the next titration day.
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.
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4
Data collection
The following data should be entered into the eCRF within 24 hours (on weekdays) after a site 
visit/telephone contact:
∀
Per protocol pre-breakfast SMPG values measured since last visit/telephone contact as 
described in sections 3.2
∀
Last dose of trial product taken prior to the titration
∀
New dose of trial product  to be taken after titration
∀
Reasons for deviation from the titration algorithms, if applicable
∀
Hypoglycaemic episodes
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5
Review procedure
Surveillance of titration data 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 
weekdays). 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 an inquiry, a response should be received at Novo Nordisk within 24 
hours (on weekdays). 
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 in a blinded manner.
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Trial ID: NN9068-4166
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Date:
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6
References
1 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.
2 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.
3 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.
4 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.
5 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.
6 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.
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
Novo Nordisk
Trial ID: NN9068-4166
Version:
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UTN: U1111-1154-6732 
Status:
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Appendix B: Medical events of special interest and events requiring 
adjudication
Trial ID: NN9068-4166
DUAL! II - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD
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: U1111-1154-6732 
Date:
07 October 2014
Status:
Final
Novo Nordisk
Trial ID: NN9068-4166
     
Version:
2.0
Page:
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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: U1111-1154-6732 
Date:
07 October 2014
Status:
Final
Novo Nordisk
Trial ID: NN9068-4166
     
Version:
2.0
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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: U1111-1154-6732 
Date:
07 October 2014
Status:
Final
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Trial ID: NN9068-4166
     
Version:
2.0
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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
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Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732 
Status:
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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 Karen A.Hicks HMJHKWM, Roxana Mehran, Steven E.Nissen, Norman L.Stockbridge, Shaari 
L.Targum, Robert Temple -on behalf of the Standardized Data Collection for Cardiovascular
Trials Initiative. Standardized Definitions for Cardiovascular and Stroke End Point Events in
Clinical Trials. https://www.cardiac-safety.org/think-tanks/ecrf-forms-for-
posting/Draft%20Definitions%20for%20Testing%20November%209-
%202012%20with%20MI%20Preamble%20CLEAN.pdf. 9 Nov 2012.
CONFIDENTIAL


Protocol - Appendix C
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4166
Version:
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UTN: U1111-1154-6732 
Status:
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Page:
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Appendix C: New York Heart Association criteria for functional capacity in 
heart failure
Trial ID: NN9068-4166
DUAL! II - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD
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: NN9068-4166
Version:
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UTN: U1111-1154-6732 
Status:
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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: NN9068-4166
Version:
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UTN: U1111-1154-6732 
Status:
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Appendix D: Monitoring of calcitonin levels 
Trial ID: NN9068-4166
DUAL! II - China
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD
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: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732 
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 ..........................................................4
2.1
CT ≥ 100 ng/L................................................................................................................................4
2.2
CT ≥ 50 and < 100 ng/L.................................................................................................................4
2.3
CT ≥ 20 and <50 ng/L....................................................................................................................5
2.4
CT ≥ 10 and < 20 ng/L...................................................................................................................5
3 References ......................................................................................................................................................6
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
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Trial ID: NN9068-4166
Version:
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UTN: U1111-1154-6732 
Status:
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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.
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732 
Status:
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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 section:
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, 
the subject should be assumed to have significant C-cell disease and a high likelihood of having 
medullary carcinoma of the thyroid. Diagnostic evaluation should consist of thyroid ultrasound, fine 
needle aspiration of any nodules >1 cm and potentially surgery with neck 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 
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732 
Status:
Final
     
Page:
5 of 6
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 # 10 (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. 1/216 had a subsequent basal (unstimulated) calcitonin of 33 ng/L, and had C-cell 
hyperplasia at surgery, a lesion of unknown clinical significance. Two other studies used a cutoff of 
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.
CONFIDENTIAL


Protocol - Appendix D
CONFIDENTIAL
Date:
07 October 2014
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732 
Status:
Final
Page:
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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:
Novo Nordisk
Version:
Status:
IDegLira
Trial ID: NN9068-4166
Clinical Trial Report
Appendix 16.1.1
04 December 2019
1.0
Final
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
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Protocol Amendment
no 1
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately
controlled with basal insulin therapy and metformin ± one other OAD
Trial phase: 3a
Applicable to China and Hong Kong
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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disclosed without prior written approval from Novo Nordisk. Access to this document must be restricted to relevant 
parties.


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
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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
Data on effect of time point for dosing........................................................................6
2.1.13
Trial product details.....................................................................................................7
2.1.14
IWRS ...........................................................................................................................7
2.1.15
Monitoring procedures more clearly specified ............................................................7
2.1.16
Statistical considerations..............................................................................................7
2.1.17
Ethics ...........................................................................................................................7
2.1.18
Reports and publications..............................................................................................7
2.1.19
Retention of human biosamples...................................................................................8
2.1.20
Flow Chart updates......................................................................................................8
2.1.21
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 re-imbursement 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 35, 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
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
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1
Introduction including rationale for the protocol amendment
The CFDA approved the NN9068-4166 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
CONFIDENTIAL
Date:
04 November 2016
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Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
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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.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
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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 SOP 110079 ed. 7.0. 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 SOP 110079 edition 9.0. 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 SOP 110079 ed. 7.0. 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 II 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
CONFIDENTIAL
Date:
04 November 2016
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Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
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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 8.3.4 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
Data on effect of time point for dosing
Rationale: To be able to provide data on the effect of time point for dosing being the same 
whatever medication is taken morning or evening which if we are asked to make analysis of this 
post hoc (we were asked from FDA about this).
Impact: Section 8.6 updated with additional bullet point for what to collect in diary.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
7 of 9
2.1.13
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.
2.1.14
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.
2.1.15
Monitoring procedures more clearly specified
Rationale: In order to comply with current edition of SOP 110079 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.
2.1.16
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.
2.1.17
Ethics
Rationale: In order to comply with current edition of SOP 110079 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.
2.1.18
Reports and publications
Rationale: In order to comply with current edition of SOP 110079 the protocol has been updated to 
reflect resent disclosure requirements.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
8 of 9
Impact: Section 23 updated.
2.1.19
Retention of human biosamples
Rationale: In order to comply with current edition of SOP 110079 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.
2.1.20
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.
2.1.21
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 ALT 
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 1.7 named Information about antibody sampling and exportation 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 re-imbursement fee
Impact: Section 4.3 updated.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
04 November 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
3.0
UTN: U1111-1154-6732
Status:
Final
Page:
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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 2.2.16 has been replaced by updated text in section 2.1.13.
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 35, 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: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
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Protocol Amendment
no 2
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately
controlled with basal insulin therapy and metformin ± one other OAD
Trial phase: 3a
Applicable to China and Hong Kong
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: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
2 of 3
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 NN9068-4166 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
CONFIDENTIAL
Date:
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Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
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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: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
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Protocol Amendment
no 3
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately
controlled with basal insulin therapy and metformin ± one other OAD
Trial phase: 3a
Applicable to China and Hong Kong
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: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
2 of 3
1
Changes to protocol
Section 8.4 subject diaries
Rationale: In the diary we collect the date, dose, injection site and exact clock time for injection 
from the previous 3 days of dosing. This was not included in the original protocol, but was added 
with amendment 1 for the purpose of being able to provide data on the effect of time point for 
dosing being the same whatever medication is taken morning or evening. The protocol text 
describing this procedure was copied from the NN9068-4148 protocol. However, in trial NN9068-
4148 the purpose of this text is to register data prior to PK sampling. When copying the text from 
NN9068-4148 to NN9068-4166 too much of the text was included (“Date, dose, injection site and 
exact clock time for injection from the previous three days of dosing and on the day of the visit”). 
The text which describes collecting the information “and on the day of the visit” does not apply to 
NN9068-4166 where the purpose is to document the dosing time and not register data prior to PK 
sampling. There is no PK sampling in NN9068-4166. Therefore the text in the protocol should be 
updated as follows: 
Current text: Date, dose, injection site and exact clock time for injection from the previous three 
days of dosing and on the day of the visit.
Updated text: Date, dose, injection site and exact clock time for injection from the previous three 
days of dosing.
Impact: Updated section 8.4.
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
31 August 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
3 of 3
2
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:
2.1.1
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:
07 October 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
1 of 5
Protocol Amendment
no 4
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately
controlled with basal insulin therapy and metformin ± one other OAD
Trial phase: 3a
Applicable to China and Hong Kong
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:
07 October 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
2 of 5
Introduction including rationale for the protocol amendment
After finalisation of NN9068-4166 protocol version 3.0 dated 31-Aug-2016 the following changes 
have been identified why an amendment is needed:
1.1
Section 18.1.1.1 Important identified risks
Rationale: 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.
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
Figure 5.1
Rationale: In protocol version 3.0 the below table is included:
Basal insulin and 
metformin ± one 
other OAD (AGI, 
SU, glinides or TZD)
-2
Insulin degludec/liraglutide OD ± metformin
Insulin degludec OD ± metformin
0
33
34
Screening
FU1
FU2
Week
Visit
Randomisation
Treatment period
26
2
1
35
27
30
End of
treatment
Figure 5.1 from protocol version 3.0 – to be replaced with figure below
This table mistakenly lists +/- metformin, which is not correct as all patients on both arms are to 
receive metformin +/- one other OAD. The figure has therefore been updated to include the 30-day 
FU2 visit based on the figure included in protocol version 2.0 as shown below:
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
07 October 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
3 of 5
Figure 5.1 from protocol version 3.3 – to be inserted instead of figure above
1.3
Section 7 Milestones
Rationale: Topographical correction to be compliant with Protocol SOP 110079 version 9.0 
template:
“Planned duration of recruitment period (First Subject First Visit – Last Subject FirstLast Visit): 54 
weeks. End of trial is defined as Last Subject Last Visit.”
1.4
Section 8.2.13
Rationale: A 9-point SMPG is to be performed between visit1 to visit2 according to flow chart, so 
the BG-meter should be handed out to the subject at visit1 and not visit 2:
“At visit 12, subjects will be provided with a BG-meter which must be used for all measurements 
during the trial. The subject 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. Sites 
should, as necessary, repeat the directions for use to the subject at subsequent visits.
1.5
Section 17 Statistical considerations
Rationale: 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.
From 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. 
Endpoints that are analysed untransformed and endpoints that are not formally analysed are 
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
07 October 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732
Status:
Final
Page:
4 of 5
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
“Superiority in the primary endpoint for IDegLira versus  IDeg will be considered confirmed if the 
upper bound of the two-sided 95% confidence interval for the estimated mean treatment difference 
in change from baseline in HbA1c (for IDegLira - IDeg) is strictly below 0% or equivalently if the 
p-value for the two-sided test of
H0 D=0 against HA D≠0,
is less than 5% and D<0, where D is the estimated  treatment difference. 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 superiority of IDegLira vs. IDeg with regards to the primary endpoint is 
confirmed.
In order to control the overall type I error on a two-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. 
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
07 October 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
2.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
5 of 5
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.
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.
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.
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 17.4.2.2 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:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
1 of 7
Protocol Amendment
no 5
to Protocol, final version 2.0
dated 07 October 2014
Trial ID: NN9068-4166
DUAL™ II China
A trial comparing the efficacy and safety of insulin degludec/liraglutide and insulin degludec in
combination with metformin in Chinese subjects with type 2 diabetes mellitus inadequately
controlled with basal insulin therapy and metformin ± one other OAD
Trial phase: 3a
Applicable to China and Hong Kong
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:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
2 of 7
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 section 18.1.1.1: Starting dose of liraglutide component................................................5
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...................7
3.1
Affected section 1.7: Baseline antibody samples shipped from 
to Novo Nordisk 
Måløv, Denmark............................................................................................................................7
3.2
Affected section 3.3: Storage time for antibody samples ..............................................................7
3.3
Affected section 2.1: What are the possible risks if you participate in this trial............................7
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
3 of 7
1
Introduction including rationale for the protocol amendment
After finalisation of NN9068-4166 protocol version 4.0 dated 28-Sep-2016 and the Subject 
information/informed consent form version 4.0 dated 08-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 the starting dose of the liraglutide component
!
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:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
4 of 7
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:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
5 of 7
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, so it has been decided that Fasting insulin 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 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 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 and fasting insulin). Because all results 
are summarised in the CTR the affected section is updated for consistency.
Updated text section 8.3.4 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.
2.4
Affected section 18.1.1.1: Starting dose of liraglutide component
Rationale: The starting dose of the liraglutide component is correctly listed as 0.6 mg in section 5.5 
Rationale for treatment but in section 18.1.1.1 Gastrointestinal adverse events it’s mistakenly listed 
as 0.36 mg. This means that the starting dose of liraglutide is the same and not less than the starting 
dose of liraglutide when administered as the mono-component.
Updated text section 18.1.1.1 Gastrointestinal adverse events
CONFIDENTIAL


Protocol Amendment
CONFIDENTIAL
Date:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
6 of 7
Gastrointestinal adverse events are considered class effects for GLP-1 RAs and are among the most 
frequently reported events in patients treated with IDegLira. The titration of IDegLira is slow and 
has previously shown to result in a lower frequency of gastrointestinal adverse effects. The dose of 
the liraglutide component in the start dose of IDegLira in the present trial is 0.36 0.6 mg, which is 
the same as less than the starting dose of liraglutide when administered as the mono-component 
(Victoza®).
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.
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:
06 December 2016
Novo Nordisk
Trial ID: NN9068-4166
Version:
1.0
UTN: U1111-1154-6732
Status:
Final
     
Page:
7 of 7
3
Changes to Subject information/informed consent form version 
4.0 dated 08-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. 
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 and fasting 
insulin samples including yours, will be shipped to a special laboratoriesy outside of China and 
Hong Kong. The antibody samples will be shipped to
 located in
 and to Novo 
Nordisk, located in Denmark, for analysis. and fFasting insulin samples will be shipped to
 
located in
 By involving only two one special laboratoriesy, 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 or Hong Kong.
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
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_000.pdf: 
Cover Page for Statistical Analysis Plan 
 
Sponsor name: 
Novo Nordisk A/S 
NCT number 
NCT03175120 
Sponsor trial ID: 
NN9068-4166 
Official title of study: 
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and 
metformin ± one other OAD. DUAL™ II China 
Document date: 
23 January 2020 
 
Redacted VWDWLVWLFDODQDO\VLVSODQ 
Includes redaction of personal identifiable information only. 
. 


Link
Link
List of contents
Statistical analysis plan......................................................................................................................
Statistical Gocumentation..................................................................................................................
CONFIDENTIAL
Date:
Novo Nordisk
Version:
Status:
IDegLira
Trial ID: NN9068-4166
Clinical Trial Report
Appendix 16.1.9
-DQXDU\
1.0
Final
16.1.9 Documentation of statistical methods
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
1 of 19
Statistical Analysis Plan
Trial ID: NN9068-4166
A trial comparing the efficacy and safety of insulin 
degludec/liraglutide and insulin degludec in combination with 
metformin in Chinese subjects with type 2 diabetes mellitus 
inadequately controlled with basal insulin therapy and metformin 
± one other OAD
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.
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.


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
2 of 19
Table of contents   
Page
Table of contents.........................................................................................................................................2
List of abbreviations ...................................................................................................................................3
1
Introduction .........................................................................................................................................4
1.1
Trial information.......................................................................................................................4
1.2
Scope of the statistical analysis plan..........................................................................................4
2
Statistical considerations .....................................................................................................................4
2.1
Sample size calculation .............................................................................................................5
2.2
Definition of analysis sets..........................................................................................................6
2.3
Primary endpoint.......................................................................................................................7
2.3.1
Sensitivity analysis ..................................................................................................7
2.4
Secondary endpoints .................................................................................................................8
2.4.1
Confirmatory secondary endpoints...........................................................................8
2.4.2
Supportive secondary endpoints.............................................................................10
2.4.2.1
Efficacy endpoints............................................................................10
2.4.2.2
Safety endpoints...............................................................................12
3
Changes to the statistical analyses planned in the protocol..............................................................18
4
References ..........................................................................................................................................19
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
3 of 19
List of abbreviations
ADA
American Diabetes Association
AE
adverse event
ANCOVA
analysis of covariance 
BG
blood glucose
BMI              body mass index
CAS
completer analysis set
CTR
clinical trial report
ECG
electrocardiogram
EOT              End of treatment
ET
End of treatment
FAS
full analysis set
FDA
U.S. Food and Drug Administration
FPG
fasting plasma glucose
HbA1c
glycosylated haemoglobin
HDL
high density lipoprotein
HOMA-β
homeostatic model assessment
IDegLira
insulin degludec/liraglutide
IDeg
insulin degludec
ITT
intention-to-treat 
LDL
low density lipoprotein
LLOQ
lower limit of quantification
LOCF
Last Observation Carried Forward 
SAE
serious adverse event
SAP
statistical analysis plan
SAS
safety analysis set
SD 
standard deviation 
SMPG
self-measured plasma glucose 
T2DM
type 2 diabetes mellitus
TEAEs
treatment emergent adverse events 
UNR             upper normal range
UTN
Universal Trial Number
VLDL
very low density lipoprotein
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
4 of 19
1
Introduction
1.1
Trial information
This is a 26 week, randomised, parallel two-arm, double-blind, multi-centre, treat-to-target (TTT) 
trial in Chinese subjects with T2DM inadequately controlled with basal insulin therapy and 
metformin ± one other OAD: α-glucosidase inhibitors (AGI), sulphonylureas (SU), glinides or 
thiazolidinediones (TZD). The trial is comparing efficacy and safety of insulin degludec/liraglutide 
(IDegLira) versus insulin degludec (IDeg) both 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 (06-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
performed 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).
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
5 of 19
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 antidiabetic treatment (basal 
insulin and metformin or basal insulin, metformin and other OAD(s)) as fixed factors and the 
corresponding baseline value as a 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 superiority of IDegLira vs. IDeg in controlling 
glycaemia in Chinese subjects with T2DM after 26 weeks of treatment. This is done by comparing 
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
6 of 19
the difference in change from baseline in HbA1cafter 26 weeks of treatment to a superiority margin 
of 0.0% for IDegLira vs. IDeg.
Superiority in the primary endpoint for IDegLira versus  IDeg will be considered confirmed if the 
upper bound of the two-sided 95% confidence interval for the estimated meantreatment difference 
in change from baseline in HbA1c(for IDegLira -IDeg) is strictly below 0% or equivalently if the 
p-value for the two-sided test of
H0D=0 against HAD≠0,
is less than 5% and D<0, where D is the estimated treatmentdifference. 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% (1-sided).
The sample size is determined using a t-statistic under the assumption of a two-sided test of size 
5%, a mean difference in treatment of -0.4%, and a standard deviation of SD=1.2%. It is also 
assumed that 15% of the randomised subjects will be excluded from the PP analysis set. Superiority 
will be investigated for both the FAS and the PP analysis set in line with the Committee for 
Proprietary Medicinal Products (CPMP) Points to Consider2. The above assumptions are based on 
experience from the phase 3a development programmes for IDegLira and IDeg. From these 
assumptions and based on a 2:1 randomisation the sample size is set to 300 subjects in the IDegLira 
arm and 150 subjects in the IDeg arm; in total 450 subjects will be randomised. This will ensure a 
power of 91.4% for confirming the primary objective in the full analysis set. Reducing the mean 
difference to -0.35%yields a power of 83%. 
2.2
Definition of analysis sets
The following analysis sets are defined in accordance with the ICH-E9 guidance3.
!
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:
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”.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
7 of 19
!
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, previous antidiabetic treatment (basal insulin and metformin or 
basal insulin, metformin and other OAD(s)) as fixed effects and baseline HbA1c as covariate. 
Missing values after 26 weeks of treatment will be imputed LOCF using HbA1c values at and after 
baseline.
Superiority of IDegLira vs. IDeg 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. Analysis based on the PP analysis set will be regarded as sensitivity analysis.
2.3.1
Sensitivity analysis
The primary efficacy 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 antidiabetic treatment as fixed factors 
and baseline HbA1c as a covariate. Interactions between visit and all factors and the covariate are 
also included in the model.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
8 of 19
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.
Further, a pattern mixture model approach, mimicking an intention-to-treat scenario will be applied. 
The imputation in the IDegLira arm will be based on IDeg values. It will be done as follows:
!
In the first step intermittent missing values are imputed using a Markov Chain Monte Carlo
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 anti-diabetic treatment as fixed factors, and baseline HbA1c as covariates is fitted to
the change in HbA1c from baseline to 4 weeks (V10) for the IDeg group only. The estimated
parameters, and their variances, from this model are used to impute missing values at 4 weeks
for subjects in IDeg and IDegLira treatment groups, based on previous anti-diabetic treatment
and HbA1c at baseline.
!
In the third step, for each of the 1000 copies of the dataset, missing HbA1c values at 8 weeks
(V15) 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 IDeg 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 (V33).
!
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 anti-diabetic treatment as fixed factors
and baseline HbA1c value as a covariate.
The estimates and standard deviations for data sets are pooled to one estimate and associated 
standard deviation using Rubin’s rule4. From these pooled estimates the confidence interval for the 
treatment differences and the associated p-value are calculated.
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
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
9 of 19
The tests for superiority of the confirmatory secondary endpoints will be based on the FAS and will 
only be carried out if superiority of IDegLira vs. IDeg with regards to the primary endpoint is 
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.
The change from baseline in body weight after 26 weeks of treatment will be analysed using an 
ANCOVA model with treatment and previous antidiabetictreatment (basal insulin and metformin 
or basal insulin, metformin and other OAD(s)) as fixed effect and baseline weight as covariate.
The similar sensitivity analyses as specified for the primary endpoint (ANCOVA on the PP analysis 
set and CAS, MMRM and thepattern mixture model) 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.
The 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.
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]) will be imputed using a multiple imputation technique5, and 
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
10 of 19
assuming that all subjects have an event rate in the period before and after withdrawal
corresponding to the event rate in the comparator group (IDeg). This 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.
!
In the second step, based on the estimated parameters for comparator (IDeg) 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 comparator
(IDeg). Multiple copies (1000 copies) of a complete data set are generated by sampling from the
estimated distribution.
!
In the third step, 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.
!
In the fourth step, the estimates and standard deviations for the 1000 data sets are pooled to one
estimate and associated standard deviation using Rubin’s rule4. From these pooled estimates the
confidence interval for the treatment ratio and the associated p-value are calculated.
2.4.2
Supportive secondary endpoints
2.4.2.1
Efficacy endpoints
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 insulin dose at screening 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 antidiabetic treatment as fixed factors and baseline HbA1c value as a 
covariate.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
11 of 19
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 antidiabetic 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 antidiabetic 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 antidiabetic 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.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
12 of 19
Fasting lipid profile
Cholesterol, low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein 
cholesterol (HDL cholesterol), very low density lipoprotein 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 (SMPG) 9-point profile
Three endpoints from the 9 point SMPG 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 PG 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 linear mixed effect model will be fitted to the 9-point SMPG profile data. The model will include 
treatment, previous antidiabetic treatment, time, the interaction between treatment and time and the 
interaction between previous antidiabetic 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 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.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
13 of 19
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, 
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-treatment emergent adverse events with onset date before the first day of exposure 
to randomised treatment will be presented. A listing will also be presented for non-treatment 
emergent adverse events 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 1) and the ADA classification of hypoglycaemia (see )LJXUH).
Novo Nordisk classificationof hypoglycaemia
In normal physiology, symptoms of hypoglycaemia occur below a plasma glucose level of 3.1
mmol/L.6Therefore, Novo Nordisk has included hypoglycaemia with plasma glucose levels below 
this cut-off point in the definition of BG confirmed hypoglycaemia.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
14 of 19
Novo Nordisk uses the following classification (see Figure 1) in addition to the ADA classification 
(see )LJXUH)
!
Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to
the ADA classification7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
classification7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 1
Novo Nordisk classification of hypoglycaemia
ADA classification of hypoglycaemia7
!
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.
CONFIDENTIAL


Statistical Analysis Plan
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Date:
12 July 2019
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Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
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EudraCT No.:
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!
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
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.
The number of hypoglycaemic episodes during 26 weeks of treatment will be analysed separately 
for each endpoint 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 factor.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
16 of 19
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, fundoscopy or fundus photography 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 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 will apply in the evaluation of the result:
!
If the amylase or lipase baseline (at screening) value is > 3xUNR the information were 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.
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
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UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
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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.
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
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
18 of 19
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.
Antibody measurements will be listed by subject and visit together with associated age, sex, BMI, 
HbA1c and dose
3
Changes to the statistical analyses planned in the protocol
!
Additional sensitivity analysis added to use pattern mixture model to evaluate the sensitivity of
using LOCF for primary endpoint HbA1c
!
Sensitivity analyses for confirmatory secondary endpoints have been added.
!
One minor change regarding the analysis model to the supportive secondary endpoint of 9-point
self-measured plasma glucose has been made
CONFIDENTIAL


Statistical Analysis Plan
CONFIDENTIAL
Date:
12 July 2019
Novo Nordisk
Trial ID:NN9068-4166
Version:
2.0
UTN:U1111-1154-6732
Status:
Final
EudraCT No.:
Page:
19 of 19
4
References
1 U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for 
Industry. Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and 
Prevention, Draft Guidance. 2008.
2 European Medicines Agency. Comitee for Proprietary Medical Products (CPMP): Points to 
consider on switching between superiority and non-inferiority (CPMP/EWP/482/99). EMEA 2000. 
2000.
3 International Conference on Harmonisation. ICH Harmonised Tripartite Guideline E9. Statistical 
Principles for Clinical Trials. 5 Feb 1998.
4 Little RJA, Rubin D.B. Statistical analysis with missing data. New York: John Wiley & Sons, 
1987.
5 Keene ONea. Missing data sensitivity analysis for recurrent event data using controlled 
imputation. Pharm Stat 2014; 13:258-264.
6 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.
7 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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NN9068
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Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
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1 of 334
Table of contents
Page
1: Actual daily total insulin dose after 26 weeks of treatment – supportive statistical analysis – full 
analysis set - appendix ...........................................................................................................................4
2: HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix ...........................................................................................................................7
3: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP 
analysis set - appendix .........................................................................................................................17
4: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix .........................................................................................................27
5: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM 
– full analysis set - appendix ................................................................................................................37
6: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix...............................................................57
7: Responder for HbA1c treatment target – supportive statistical analysis – full analysis set........................67
8: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed 
hypoglycaemic episodes – supportive statistical analysis – full analysis set ..........................................71
9: Responder for HbA1c treatment target without weight gain – supportive statistical analysis – full 
analysis set...........................................................................................................................................75
10: Responder for HbA1c treatment target without treatment emergent severe or BG confirmed
hypoglycaemic episodes and weight gain – supportive statistical analysis – full analysis set .................81
11: Body weight after 26 weeks of treatment – change from baseline – confirmatory statistical analysis 
– full analysis set - appendix ................................................................................................................87
12: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix ....................................................................................................................97
13: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix .......................................................................................................107
14: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix.................................................................................................117
15: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix.............................................................137
16: Waist circumference after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix.................................................................................................147
17: Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix.................................................................................................152
18: 9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical 
analysis – full analysis set ..................................................................................................................162
19: Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from 
baseline – supportive statistical analysis – full analysis set - appendix ................................................204
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Version:
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Status:
Final
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20: Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix............................214
21: Fasting insulin after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................254
22: Fasting C-peptide after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................257
23: Fasting glucagon after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................263
24: HOMA-B after 26 weeks of treatment – supportive statistical analysis – full analysis set - appendix....266
25: HDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................269
26: LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................275
27: VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................281
28: Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................287
29: Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................293
30: Free fatty acid after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix ............................................................................................................................................299
31: Hypoglycaemic episodes – treatment emergent – confirmatory statistical analysis – full analysis set ...305
32: Hypoglycaemic episodes – treatment emergent – statistical sensitivity analysis – multiple 
imputation – full analysis set..............................................................................................................307
33: Hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full analysis set .......310
34: Nocturnal hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full 
analysis set.........................................................................................................................................313
35: Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full 
analysis set - appendix .......................................................................................................................320
36: Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix.................................................................................................325
37: Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix.................................................................................................330
CONFIDENTIAL


NN9068
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Date:
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Version:
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Statistical document
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Statistical documentation
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NN9068
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Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
4 of 334
1: Actual daily total insulin dose after 26 weeks of treatment – supportive statistical analysis – full 
analysis set - appendix
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                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      7
Columns in Z                      0
Subjects                          1
Max Obs per Subject             450
          Number of Observations
Number of Observations Read             453
Number of Observations Used             450
Number of Observations Not Used           3
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       109.52
           Fit Statistics
-2 Res Log Likelihood          3384.2
AIC (Smaller is Better)        3386.2
AICC (Smaller is Better)       3386.2
BIC (Smaller is Better)        3390.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          7.9327    4.2569   445     1.86
trtpn                                                 1           -3.3593    1.0472   445    -3.21
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -1.0335    0.9944   445    -1.04
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
INSSCR                                                             0.4191   0.08246   445     5.08
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NN9068
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Date:
22 January 2020
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NN9068-4166
Version:
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Status:
Final
Statistical document
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Actual daily total insulin dose after 26 weeks of treatment – supportive statistical analysis –
full analysis set - appendix
Parameter Code=TOTDDAC
The Mixed Procedure
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
HBA1CBL                                                            2.1936    0.4169   445     5.26
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0631      0.05
trtpn                                                 1            0.0014      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2992      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
INSSCR                                                             <.0001      0.05
HBA1CBL                                                            <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -0.4334     16.2989
trtpn                                                 1           -5.4174     -1.3013
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -2.9879      0.9209
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
INSSCR                                                             0.2571      0.5812
HBA1CBL                                                            1.3742      3.0130
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445      10.29    0.0014
PREAD           1     445       1.08    0.2992
INSSCR          1     445      25.83    <.0001
HBA1CBL         1     445      27.68    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    34.2145     0.6057     445     56.49     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    37.5739     0.8529     445     44.05     <.0001     0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Status:
Final
Statistical document
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Actual daily total insulin dose after 26 weeks of treatment – supportive statistical analysis –
full analysis set - appendix
Parameter Code=TOTDDAC
The Mixed Procedure
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    33.0242    35.4049        7.231E14        2.199E14        2.378E15
trtpn    LSMeans, IDeg        35.8976    39.2501         2.08E16        3.892E15        1.112E17
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -3.3593     1.0472     445     -3.21
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0014    0.05   -5.4174   -1.3013        0.03476
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.004439           0.2722
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NN9068
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2: HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full 
analysis set - appendix
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         2   1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.7569
           Fit Statistics
-2 Res Log Likelihood          1171.1
AIC (Smaller is Better)        1173.1
AICC (Smaller is Better)       1173.1
BIC (Smaller is Better)        1177.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.8895    0.3187   449    15.34
TRTPN                                                 1           -0.9186   0.08674   449   -10.59
TRTPN                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2401   0.08191   449    -2.93
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3580   0.03449   449    10.38
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
TRTPN                                                 1            <.0001      0.05
TRTPN                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0036      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect    Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.2631      5.5159
TRTPN                                                 1           -1.0891     -0.7481
TRTPN                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4010    -0.07910
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2902      0.4258
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           1     449     112.15    <.0001
PREAD           1     449       8.59    0.0036
BASE            1     449     107.71    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
TRTPN    LSMeans, IDegLira   WORK.ADATA2     7.0585    0.05007     449    140.98     <.0001     0.05
TRTPN    LSMeans, IDeg       WORK.ADATA2     7.9771    0.07082     449    112.65     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
TRTPN    LSMeans, IDegLira     6.9601     7.1569         1162.68         1053.72         1282.90
TRTPN    LSMeans, IDeg         7.8379     8.1162         2913.40         2534.89         3348.43
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.9186    0.08674     449    -10.59
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Version:
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Final
Statistical document
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.0891   -0.7481         0.3991
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - IDeg         0.3365           0.4733
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      90.4255
           Fit Statistics
-2 Res Log Likelihood          3323.4
AIC (Smaller is Better)        3325.4
AICC (Smaller is Better)       3325.4
BIC (Smaller is Better)        3329.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.3549    2.7080   449    14.16
TRTPN                                                 1          -10.0402    0.9481   449   -10.59
TRTPN                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.6239    0.8952   449    -2.93
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3580   0.03449   449    10.38
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
11 of 334
HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
TRTPN                                                 1            <.0001      0.05
TRTPN                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0036      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0330     43.6767
TRTPN                                                 1          -11.9034     -8.1770
TRTPN                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.3832     -0.8645
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2902      0.4258
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           1     449     112.15    <.0001
PREAD           1     449       8.59    0.0036
BASE            1     449     107.71    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
TRTPN    LSMeans, IDegLira   WORK.ADATA2    53.6492     0.5473     449     98.03     <.0001     0.05
TRTPN    LSMeans, IDeg       WORK.ADATA2    63.6894     0.7740     449     82.29     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
TRTPN    LSMeans, IDegLira    52.5737    54.7247        1.993E23        6.799E22        5.843E23
TRTPN    LSMeans, IDeg        62.1683    65.2106        4.571E27        9.985E26        2.092E28
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
TRTPN   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -10.0402     0.9481     449    -10.59
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
TRTPN   Treatment contrast, IDegLira - IDeg    <.0001    0.05  -11.9034   -8.1770       0.000044
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
TRTPN   Treatment contrast, IDegLira - IDeg       6.767E-6         0.000281
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.7569
           Fit Statistics
-2 Res Log Likelihood          1171.1
AIC (Smaller is Better)        1173.1
AICC (Smaller is Better)       1173.1
BIC (Smaller is Better)        1177.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.8895    0.3187   449    15.34
TRTPN                                                 1           -0.9186   0.08674   449   -10.59
TRTPN                                                 2                 0                        
PREAD      BASAL INSULIN + METFORMIN                              -0.2401   0.08191   449    -2.93
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6420   0.03449   449   -18.61
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
TRTPN                                                 1            <.0001      0.05
TRTPN                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0036      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.2631      5.5159
TRTPN                                                 1           -1.0891     -0.7481
TRTPN                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4010    -0.07910
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.7098     -0.5742
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           1     449     112.15    <.0001
PREAD           1     449       8.59    0.0036
BASE            1     449     346.39    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
TRTPN   Change from baseline, IDegLira  WORK.ADATA2   -1.8843   0.05007    449   -37.64    <.0001
TRTPN   Change from baseline, IDeg      WORK.ADATA2   -0.9658   0.07082    449  -13.64    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
TRTPN   Change from baseline, IDegLira    0.05     -1.9827     -1.7859
TRTPN   Change from baseline, IDeg        0.05     -1.1049     -0.8266
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      90.4255
           Fit Statistics
-2 Res Log Likelihood          3323.4
AIC (Smaller is Better)        3325.4
AICC (Smaller is Better)       3325.4
BIC (Smaller is Better)        3329.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.3549    2.7080   449    14.16
TRTPN                                                 1          -10.0402    0.9481   449   -10.59
TRTPN                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.6239    0.8952   449    -2.93
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6420   0.03449   449   -18.61
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HbA1c after 26 weeks of treatment – change from baseline – confirmatory statistical analysis – full
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
TRTPN                                                 1            <.0001      0.05
TRTPN                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0036      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0330     43.6767
TRTPN                                                 1          -11.9034     -8.1770
TRTPN                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.3832     -0.8645
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.7098     -0.5742
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
TRTPN           1     449     112.15    <.0001
PREAD           1     449       8.59    0.0036
BASE            1     449     346.39    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
TRTPN   Change from baseline, IDegLira  WORK.ADATA2  -20.5959    0.5473    449   -37.64    <.0001
TRTPN   Change from baseline, IDeg      WORK.ADATA2  -10.5556    0.7740    449   -13.64    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
TRTPN   Change from baseline, IDegLira    0.05    -21.6714    -19.5204
TRTPN   Change from baseline, IDeg        0.05    -12.0768     -9.0345
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3: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP 
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.7326
           Fit Statistics
-2 Res Log Likelihood          1100.6
AIC (Smaller is Better)        1102.6
AICC (Smaller is Better)       1102.6
BIC (Smaller is Better)        1106.6
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.9698    0.3237   427    15.35
trtan                                                 1           -0.9065   0.08773   427   -10.33
trtan                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2699   0.08260   427    -3.27
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3456   0.03506   427     9.86
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HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtan                                                 1            <.0001      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0012      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.3335      5.6061
trtan                                                 1           -1.0790     -0.7341
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4322     -0.1075
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2767      0.4145
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427     106.78    <.0001
PREAD           1     427      10.67    0.0012
BASE            1     427      97.16    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2     7.0308    0.05035     427    139.64     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2     7.9373    0.07183     427    110.50     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira     6.9318     7.1298         1130.93         1024.37         1248.58
trtan    LSMeans, IDeg         7.7961     8.0785         2799.86         2431.19         3224.45
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.9065    0.08773     427    -10.33
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HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.0790   -0.7341         0.4039
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg         0.3399           0.4799
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HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      87.5168
           Fit Statistics
-2 Res Log Likelihood          3147.7
AIC (Smaller is Better)        3149.7
AICC (Smaller is Better)       3149.7
BIC (Smaller is Better)        3153.8
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.9418    2.7492   427    14.16
trtan                                                 1           -9.9084    0.9589   427   -10.33
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.9498    0.9029   427    -3.27
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3456   0.03506   427     9.86
CONFIDENTIAL


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HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtan                                                 1            <.0001      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0012      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.5380     44.3455
trtan                                                 1          -11.7931     -8.0237
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.7244     -1.1752
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2767      0.4145
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427     106.78    <.0001
PREAD           1     427      10.67    0.0012
BASE            1     427      97.16    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan   LSMeans, IDegLira   WORK.ADATA2    53.3466     0.5503     427     96.94     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2    63.2550     0.7851     427     80.57     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira    52.2649    54.4283        1.473E23        4.993E22        4.344E23
trtan    LSMeans, IDeg        61.7118    64.7982         2.96E27        6.325E26        1.385E28
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -9.9084     0.9589     427    -10.33
CONFIDENTIAL


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Statistical document
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HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    <.0001    0.05  -11.7931   -8.0237       0.000050
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg       7.557E-6         0.000328
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 – PP
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.7326
           Fit Statistics
-2 Res Log Likelihood          1100.6
AIC (Smaller is Better)        1102.6
AICC (Smaller is Better)       1102.6
BIC (Smaller is Better)        1106.6
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.9698    0.3237   427    15.35
trtan                                                 1           -0.9065   0.08773   427   -10.33
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2699   0.08260   427    -3.27
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6544   0.03506   427   -18.66
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 – PP
analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtan                                                 1            <.0001      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0012      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.3335      5.6061
trtan                                                 1           -1.0790     -0.7341
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4322     -0.1075
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.7233     -0.5855
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427     106.78    <.0001
PREAD           1     427      10.67    0.0012
BASE            1     427     348.31    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2   -1.9251   0.05035    427   -38.23    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2   -1.0186   0.07183    427   -14.18    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -2.0241     -1.8262
trtan   Change from baseline, IDeg        0.05     -1.1598     -0.8774
CONFIDENTIAL


NN9068
CONFIDENTIAL
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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 – PP
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      87.5168
           Fit Statistics
-2 Res Log Likelihood          3147.7
AIC (Smaller is Better)        3149.7
AICC (Smaller is Better)       3149.7
BIC (Smaller is Better)        3153.8
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.9418    2.7492   427    14.16
trtan                                                 1           -9.9084    0.9589   427   -10.33
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.9498    0.9029   427    -3.27
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6544   0.03506   427   -18.66
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
26 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – PP
analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtan                                                 1            <.0001      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0012      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.5380     44.3455
trtan                                                 1          -11.7931     -8.0237
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.7244     -1.1752
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.7233     -0.5855
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427     106.78    <.0001
PREAD           1     427      10.67    0.0012
BASE            1     427     348.31    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2  -21.0416    0.5503    427   -38.23    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2  -11.1332    0.7851    427   -14.18    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05    -22.1233    -19.9599
trtan   Change from baseline, IDeg        0.05    -12.6764     -9.5900
CONFIDENTIAL


NN9068
CONFIDENTIAL
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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4: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.7214
           Fit Statistics
-2 Res Log Likelihood          1089.0
AIC (Smaller is Better)        1091.0
AICC (Smaller is Better)       1091.0
BIC (Smaller is Better)        1095.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.9165    0.3212   425    15.31
trtpn                                                 1           -0.8833   0.08766   425   -10.08
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2517   0.08217   425    -3.06
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3478   0.03473   425    10.01
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
28 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0023      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.2851      5.5479
trtpn                                                 1           -1.0556     -0.7110
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4132    -0.09016
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2795      0.4160
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425     101.54    <.0001
PREAD           1     425       9.38    0.0023
BASE            1     425     100.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     7.0285    0.04988     425    140.90     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     7.9118    0.07206     425    109.79     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     6.9304     7.1265         1128.32         1022.95         1244.55
trtpn    LSMeans, IDeg         7.7701     8.0534         2729.27         2368.82         3144.55
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.8833    0.08766     425    -10.08
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
29 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.0556   -0.7110         0.4134
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.3480           0.4912
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
30 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      86.1783
           Fit Statistics
-2 Res Log Likelihood          3126.5
AIC (Smaller is Better)        3128.5
AICC (Smaller is Better)       3128.5
BIC (Smaller is Better)        3132.6
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.4099    2.7306   425    14.07
trtpn                                                 1           -9.6545    0.9581   425   -10.08
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.7507    0.8981   425    -3.06
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.3478   0.03473   425    10.01
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
31 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0023      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0428     43.7771
trtpn                                                 1          -11.5377     -7.7713
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.5160     -0.9855
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.2795      0.4160
        Type 3 Tests of Fixed Effects
              Num     Den
Effect        DF      DF    F Value    Pr > F
trtpn           1     425     101.54    <.0001
PREAD           1     425       9.38    0.0023
BASE            1     425     100.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    53.3214     0.5452     425     97.80     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    62.9758     0.7876     425     79.96     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    52.2497    54.3930        1.436E23        4.918E22        4.194E23
trtpn    LSMeans, IDeg        61.4277    64.5240        2.239E27        4.761E26        1.053E28
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -9.6545     0.9581     425    -10.08
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
32 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05  -11.5377   -7.7713       0.000064
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       9.756E-6         0.000422
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
33 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.7214
           Fit Statistics
-2 Res Log Likelihood          1089.0
AIC (Smaller is Better)        1091.0
AICC (Smaller is Better)       1091.0
BIC (Smaller is Better)        1095.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          4.9165    0.3212   425    15.31
trtpn                                                 1           -0.8833   0.08766   425   -10.08
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2517   0.08217   425    -3.06
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6522   0.03473   425   -18.78
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
34 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=C64849B
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0023      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          4.2851      5.5479
trtpn                                                 1           -1.0556     -0.7110
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4132    -0.09016
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.7205     -0.5840
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425     101.54    <.0001
PREAD           1     425       9.38    0.0023
BASE            1     425     352.70    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -1.9282   0.04988    425   -38.65    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -1.0449   0.07206    425   -14.50    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -2.0262     -1.8301
trtpn   Change from baseline, IDeg        0.05     -1.1865     -0.9032
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
35 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      86.1783
           Fit Statistics
-2 Res Log Likelihood          3126.5
AIC (Smaller is Better)        3128.5
AICC (Smaller is Better)       3128.5
BIC (Smaller is Better)        3132.6
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         38.4099    2.7306   425    14.07
trtpn                                                 1           -9.6545    0.9581   425   -10.08
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.7507    0.8981   425    -3.06
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.6522   0.03473   425   -18.78
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
36 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=HBA1CONV
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0023      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0428     43.7771
trtpn                                                 1          -11.5377     -7.7713
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.5160     -0.9855
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.7205     -0.5840
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425     101.54    <.0001
PREAD           1     425       9.38    0.0023
BASE            1     425     352.70    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -21.0747    0.5452    425   -38.65    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -11.4203    0.7876    425   -14.50    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -22.1464    -20.0031
trtpn   Change from baseline, IDeg        0.05    -12.9684     -9.8722
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
37 of 334
5: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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         2    1 2                           
AVISITN         6   100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
38 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
39 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2595
Number of Observations Not Used         123
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
40 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1      6180.47425772                
        1              2      2415.05948115      0.00247120
        2              1      2411.88149460      0.00009868
        3              1      2411.76403647      0.00000020
        4              1      2411.76380269      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       0.3328
UN(2,1)     SUBJID       0.3392
UN(2,2)     SUBJID       0.5343
UN(3,1)     SUBJID       0.2998
UN(3,2)     SUBJID       0.5436
UN(3,3)     SUBJID       0.6809
UN(4,1)     SUBJID       0.2578
UN(4,2)     SUBJID       0.4980
UN(4,3)     SUBJID       0.6498
UN(4,4)     SUBJID       0.7191
UN(5,1)     SUBJID       0.2311
UN(5,2)     SUBJID       0.4455
UN(5,3)     SUBJID       0.5985
UN(5,4)     SUBJID       0.6761
UN(5,5)     SUBJID       0.7336
UN(6,1)     SUBJID       0.2068
UN(6,2)     SUBJID       0.4124
UN(6,3)     SUBJID       0.5440
UN(6,4)     SUBJID       0.6102
UN(6,5)     SUBJID       0.6641
UN(6,6)     SUBJID       0.7317
           Fit Statistics
-2 Res Log Likelihood          2411.8
AIC (Smaller is Better)        2453.8
AICC (Smaller is Better)       2454.1
BIC (Smaller is Better)        2540.2
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       3768.71          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)       6     435      35.96    <.0001
PREAD(AVISITN)         6    432       2.36    0.0293
BASE(AVISITN)          6     433     213.91    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
41 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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    7.0309   0.05012  427.4   140.29    <.0001
TRT01PN(AVISITN)  LSMeans, IDeg      WORK.ANA_DATA    7.9479   0.07142  437.4   111.28    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(AVISITN)  LSMeans, IDegLira    0.05      6.9324      7.1294
TRT01PN(AVISITN)  LSMeans, IDeg        0.05      7.8075      8.0883
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
42 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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         2    1 2                           
AVISITN         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
43 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
44 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2595
Number of Observations Not Used         123
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
45 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     18506.32350920                
        1              2     14740.90873263      0.00056998
        2              1     14737.73074608      0.00002280
        3              1     14737.61328795      0.00000005
        4              1     14737.61305417      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      39.7612
UN(2,1)     SUBJID      40.5209
UN(2,2)     SUBJID      63.8318
UN(3,1)     SUBJID      35.8164
UN(3,2)     SUBJID      64.9397
UN(3,3)     SUBJID      81.3416
UN(4,1)     SUBJID      30.8032
UN(4,2)     SUBJID      59.4989
UN(4,3)     SUBJID      77.6293
UN(4,4)     SUBJID      85.9110
UN(5,1)     SUBJID      27.6057
UN(5,2)     SUBJID      53.2163
UN(5,3)     SUBJID      71.5019
UN(5,4)     SUBJID      80.7653
UN(5,5)     SUBJID      87.6338
UN(6,1)     SUBJID      24.7005
UN(6,2)     SUBJID      49.2619
UN(6,3)     SUBJID      64.9837
UN(6,4)     SUBJID      72.8959
UN(6,5)     SUBJID      79.3406
UN(6,6)     SUBJID      87.4072
           Fit Statistics
-2 Res Log Likelihood         14737.6
AIC (Smaller is Better)       14779.6
AICC (Smaller is Better)      14780.0
BIC (Smaller is Better)       14866.0
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       3768.71          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)       6     435      35.96    <.0001
PREAD(AVISITN)         6     432       2.36    0.0293
BASE(AVISITN)          6     433     213.91    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
46 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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   53.3477    0.5478  427.4    97.39    <.0001
TRT01PN(AVISITN)  LSMeans, IDeg      WORK.ANA_DATA   63.3707    0.7806  437.4    81.18    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(AVISITN)  LSMeans, IDegLira    0.05     52.2710     54.4243
TRT01PN(AVISITN)  LSMeans, IDeg        0.05     61.8365     64.9050
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
47 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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         2    1 2                           
AVISITN         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
48 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
49 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2595
Number of Observations Not Used         123
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
50 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=C64849B Long label=HbA1c (%)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1      6180.47425772                
        1              2      2415.05948115      0.00247120
        2              1      2411.88149460      0.00009868
        3              1      2411.76403647      0.00000020
        4              1      2411.76380269      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       0.3328
UN(2,1)     SUBJID       0.3392
UN(2,2)     SUBJID       0.5343
UN(3,1)     SUBJID       0.2998
UN(3,2)     SUBJID       0.5436
UN(3,3)     SUBJID       0.6809
UN(4,1)     SUBJID       0.2578
UN(4,2)     SUBJID       0.4980
UN(4,3)     SUBJID       0.6498
UN(4,4)     SUBJID       0.7191
UN(5,1)     SUBJID       0.2311
UN(5,2)     SUBJID       0.4455
UN(5,3)     SUBJID       0.5985
UN(5,4)     SUBJID       0.6761
UN(5,5)     SUBJID       0.7336
UN(6,1)     SUBJID       0.2068
UN(6,2)     SUBJID       0.4124
UN(6,3)     SUBJID       0.5440
UN(6,4)     SUBJID       0.6102
UN(6,5)     SUBJID       0.6641
UN(6,6)     SUBJID       0.7317
           Fit Statistics
-2 Res Log Likelihood          2411.8
AIC (Smaller is Better)        2453.8
AICC (Smaller is Better)       2454.1
BIC (Smaller is Better)        2540.2
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       3768.71          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)       6     435      35.96    <.0001
PREAD(AVISITN)         6    432       2.36    0.0293
BASE(AVISITN)          6     433      65.36    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
51 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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   -1.9341   0.05012  427.4   -38.59
TRT01PN(AVISITN)  Change from baseline, IDeg      WORK.ANA_DATA   -1.0171   0.07142  437.4   -14.24
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(AVISITN)  Change from baseline, IDegLira    <.0001      0.05     -2.0326     -1.8356
TRT01PN(AVISITN)  Change from baseline, IDeg        <.0001      0.05     -1.1574     -0.8767
                                   Least Squares Means Estimate
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -0.9170    0.08726   434.1
                                    Least Squares Means Estimate
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg   -10.51    <.0001    0.05   -1.0885   -0.7455
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
52 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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         2    1 2                           
AVISITN         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
53 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
54 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2595
Number of Observations Not Used         123
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
55 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
Short Topic Code=HBA1CONV Long label=HbA1c (mmol/mol)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     18506.32350920                
        1              2     14740.90873263      0.00056998
        2              1     14737.73074608      0.00002280
        3              1     14737.61328795      0.00000005
        4              1     14737.61305417      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID      39.7612
UN(2,1)     SUBJID      40.5209
UN(2,2)     SUBJID      63.8318
UN(3,1)     SUBJID      35.8164
UN(3,2)     SUBJID      64.9397
UN(3,3)     SUBJID      81.3416
UN(4,1)     SUBJID      30.8032
UN(4,2)     SUBJID      59.4989
UN(4,3)     SUBJID      77.6293
UN(4,4)     SUBJID      85.9110
UN(5,1)     SUBJID      27.6057
UN(5,2)     SUBJID      53.2163
UN(5,3)     SUBJID      71.5019
UN(5,4)     SUBJID      80.7653
UN(5,5)     SUBJID      87.6338
UN(6,1)     SUBJID      24.7005
UN(6,2)     SUBJID      49.2619
UN(6,3)     SUBJID      64.9837
UN(6,4)     SUBJID      72.8959
UN(6,5)     SUBJID      79.3406
UN(6,6)     SUBJID      87.4072
           Fit Statistics
-2 Res Log Likelihood         14737.6
AIC (Smaller is Better)       14779.6
AICC (Smaller is Better)      14780.0
BIC (Smaller is Better)       14866.0
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       3768.71          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(AVISITN)       6     435      35.96    <.0001
PREAD(AVISITN)         6     432       2.36    0.0293
BASE(AVISITN)          6     433      65.36    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
56 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis – MMRM
– full analysis set - appendix
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  -21.1395    0.5478  427.4   -38.59
TRT01PN(AVISITN)  Change from baseline, IDeg      WORK.ANA_DATA  -11.1164    0.7806  437.4   -14.24
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(AVISITN)  Change from baseline, IDegLira    <.0001      0.05    -22.2161    -20.0628
TRT01PN(AVISITN)  Change from baseline, IDeg        <.0001      0.05    -12.6506     -9.5822
                                   Least Squares Means Estimate
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA   -10.0231     0.9538   434.1
                                    Least Squares Means Estimate
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(AVISITN)  Treatment contrast, IDegLira - IDeg   -10.51    <.0001    0.05  -11.8977   -8.1485
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
57 of 334
6: HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=1 Parameter Code=C64849B Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000311       0.004942       0.005254   283778
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.063075       0.059339       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.934431       0.072481   7.792370   8.076492   283778       7.884262       7.988346
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             109.47     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
58 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=1 Parameter Code=C64849B Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000110       0.002470       0.002580   550770
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.044484       0.042592       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        7.051117       0.050797   6.951557   7.150676   550770       7.011871       7.088745
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             138.81     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
59 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=2 Parameter Code=HBA1CONV Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.037201       0.590373       0.627611   283778
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.063075      0.059339       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       63.223331       0.792219   61.67060   64.77606   283778      62.674980      63.812625
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              79.81     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
60 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=2 Parameter Code=HBA1CONV Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.013115       0.295126       0.308254   550770
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.044484       0.042592       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       53.568705       0.555206   52.48052   54.65689   550770      53.139750      53.979986
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              96.48     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
61 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=1 Parameter Code=C64849B Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000311       0.004942       0.005254   283778
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.063075       0.059339       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.008395       0.072481   -1.15046   -0.86633   283778      -1.058564      -0.954479
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -13.91     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
62 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=1 Parameter Code=C64849B Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000110       0.002470       0.002580   550770
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate        0.044484       0.042592       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.891709       0.050797   -1.99127   -1.79215   550770      -1.930955      -1.854080
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -37.24     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
63 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=1 Parameter Code=C64849B Label=Treatment contrast, IDegLira - IDeg Statement Number=2
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.000386       0.007414       0.007801   406826
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.052138       0.049559       0.999950
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -0.883314       0.088322   -1.05642   -0.71021   406826      -0.940071      -0.823341
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -10.00     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
64 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=2 Parameter Code=HBA1CONV Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.037201       0.590373       0.627611   283778
        Variance Information (1000 Imputations)
                Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.063075       0.059339       0.999941
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -11.021753       0.792219   -12.5745   -9.46903   283778     -11.570104     -10.432458
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -13.91     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
65 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=2 Parameter Code=HBA1CONV Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
           Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.013115       0.295126       0.308254   550770
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.044484       0.042592       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      -20.676379       0.555206   -21.7646   -19.5882   550770     -21.105334     -20.265098
        Parameter Estimates (1000 Imputations)
                                 t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -37.24     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
66 of 334
HbA1c after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
PARAMSORT=2 Parameter Code=HBA1CONV Label=Treatment contrast, IDegLira - IDeg Statement Number=2
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.046134       0.885743       0.931923   406826
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.052138       0.049559       0.999950
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF       Minimum        Maximum
Estimate       -9.654626       0.965362   -11.5467   -7.76255   406826     -10.274981      -8.999121
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             -10.00     <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
67 of 334
7: 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         453
Number of Observations Used         453
Number of Events                    106
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              106
       2    N              347
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter       Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -218.6220                
Full Log Likelihood                    -218.6220                
AIC (smaller is better)                 445.2439                
AICC (smaller is better)                445.3332                
BIC (smaller is better)                 461.7075                
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                    Standard       Wald 95%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    0.5081    1.0333   -1.5171    2.5332
TRTPN      1                                           1   1.9218    0.3530    1.2299    2.6138
TRTPN      2                                           0    0.0000    0.0000    0.0000    0.0000
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
68 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
PREAD      BASAL INSULIN + METFORMIN                   1    0.3170    0.2359   -0.1454    0.7795
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.3789    0.1138   -0.6019   -0.1559
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.24        0.6229
TRTPN      1                                               29.63        <.0001
TRTPN      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        1.81        0.1791
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    11.09        0.0009
Scale                                                                         
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   -0.7999      0.1284      -6.23      <.0001      0.05
TRTPN   LSMeans frequency, IDeg       -2.7218      0.3318      -8.20      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
TRTPN   LSMeans frequency, IDegLira   -1.0517   -0.5482         0.4494         0.3494         0.5780
TRTPN   LSMeans frequency, IDeg       -3.3721   -2.0715        0.06576        0.03432         0.1260
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
TRTPN    Treatment odds ratio, IDegLira / IDeg     1.9218     0.3530      5.44     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
TRTPN    Treatment odds ratio, IDegLira / IDeg     1.2299      2.6138           6.8335
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
TRTPN    Treatment odds ratio, IDegLira / IDeg          3.4209          13.6505
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
69 of 334
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         453
Number of Observations Used         453
Number of Events                    177
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              177
       2    N              276
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter      Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -260.6635                
Full Log Likelihood                    -260.6635                
AIC (smaller is better)                 529.3269                
AICC (smaller is better)                529.4162                
BIC (smaller is better)                 545.7905                
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                    Standard       Wald 95%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    2.0446    0.8816    0.3168    3.7724
TRTPN      1                                           1    1.8428    0.2613    1.3307    2.3550
TRTPN      2                                           0    0.0000    0.0000    0.0000    0.0000
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
70 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
PREAD      BASAL INSULIN + METFORMIN                   1    0.3773    0.2128   -0.0397    0.7944
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.4514    0.0989   -0.6452   -0.2576
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   5.38        0.0204
TRTPN      1                                               49.74        <.0001
TRTPN      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        3.14        0.0762
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    20.83        <.0001
Scale                                                                         
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   0.03918      0.1197       0.33      0.7433      0.05
TRTPN   LSMeans frequency, IDeg       -1.8037      0.2329      -7.75      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
TRTPN   LSMeans frequency, IDegLira   -0.1954    0.2737         1.0400         0.8225         1.3149
TRTPN   LSMeans frequency, IDeg       -2.2601   -1.3473         0.1647         0.1043         0.2600
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
TRTPN    Treatment odds ratio, IDegLira / IDeg     1.8428     0.2613      7.05     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
TRTPN    Treatment odds ratio, IDegLira / IDeg     1.3307      2.3550           6.3145
                         Least Squares Means Estimate
                                                Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
TRTPN    Treatment odds ratio, IDegLira / IDeg          3.7837          10.5380
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
71 of 334
8: 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         453
Number of Observations Used         453
Number of Events                    102
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              102
       2    N              351
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter      Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -213.6936                
Full Log Likelihood                    -213.6936                
AIC (smaller is better)                 435.3871                
AICC (smaller is better)                435.4764                
BIC (smaller is better)                 451.8507                
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                    Standard       Wald 95%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    0.2883    1.0497   -1.7691    2.3457
trtpn      1                                           1    1.9903    0.3689    1.2673    2.7132
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
72 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.3750    0.2392   -0.0939    0.8439
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.3703    0.1152   -0.5960   -0.1446
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.08        0.7836
trtpn      1                                               29.11        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        2.46        0.1170
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    10.34        0.0013
Scale                                                                         
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   -0.8458      0.1296      -6.53      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -2.8361      0.3483      -8.14      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.0998   -0.5918         0.4292         0.3329         0.5533
trtpn   LSMeans frequency, IDeg       -3.5188   -2.1534        0.05866        0.02964         0.1161
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.9903     0.3689      5.40     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2673      2.7132           7.3176
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          3.5513          15.0781
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
73 of 334
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         453
Number of Observations Used         453
Number of Events                    170
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                        
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              170
       2    N              283
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter       Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -260.9980                
Full Log Likelihood                    -260.9980                
AIC (smaller is better)                 529.9960                
AICC (smaller is better)                530.0853                
BIC (smaller is better)                 546.4596                
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                    Standard       Wald 95%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    1.5955    0.8770   -0.1235    3.3144
trtpn      1                                           1    1.8007    0.2638    1.2836    2.3179
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
74 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.3871    0.2125   -0.0293    0.8035
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.4061    0.0979   -0.5980   -0.2142
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   3.31        0.0689
trtpn      1                                               46.58        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        3.32        0.0685
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    17.21        <.0001
Scale                                                                         
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  -0.04197      0.1190      -0.35      0.7243      0.05
trtpn   LSMeans frequency, IDeg       -1.8427      0.2361      -7.80      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -0.2752    0.1913         0.9589         0.7594         1.2108
trtpn   LSMeans frequency, IDeg       -2.3055   -1.3799         0.1584        0.09971         0.2516
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     1.8007     0.2638      6.82     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2836      2.3179           6.0541
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          3.6096          10.1540
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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9: 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         453
Number of Observations Used         453
Number of Events                     62
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y               62
       2    N              391
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter      Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
Prm7            WGTBL                                                          
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -159.3887                
Full Log Likelihood                    -159.3887                
AIC (smaller is better)                 328.7775                
AICC (smaller is better)                328.9117                
BIC (smaller is better)                 349.3569                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
76 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1   -1.3809    1.5664   -4.4511    1.6892
trtpn      1                                           1    2.4694    0.6029    1.2877    3.6512
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.0531    0.2874   -0.5103   0.6165
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.3826    0.1438   -0.6645   -0.1007
WGTBL                                                 1    0.0107    0.0108   -0.0104    0.0318
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.78        0.3780
trtpn      1                                               16.77        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        0.03        0.8535
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                     7.08        0.0078
WGTBL                                                       0.99        0.3188
Scale                                                                         
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   -1.4921      0.1553      -9.61      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -3.9615      0.5867      -6.75      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.7965   -1.1877         0.2249         0.1659         0.3049
trtpn   LSMeans frequency, IDeg       -5.1113   -2.8117        0.01903       0.006028        0.06010
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     2.4694     0.6029      4.10     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2877      3.6512          11.8157
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
77 of 334
Responder for HbA1c treatment target without weight gain – supportive statistical analysis – full
analysis set
Parameter Code=HB65WOWG
The GENMOD Procedure
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          3.6243          38.5206
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
78 of 334
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         453
Number of Observations Used         453
Number of Events                    105
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              105
       2    N              348
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter       Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
Prm7            WGTBL                                                          
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -211.2368                
Full Log Likelihood                    -211.2368                
AIC (smaller is better)                 432.4737                
AICC (smaller is better)                432.6079                
BIC (smaller is better)                 453.0531                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
79 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    0.5368    1.2695   -1.9514    3.0251
trtpn      1                                           1    2.3385    0.4097    1.5354    3.1416
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.2414    0.2407   -0.2304    0.7132
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.4075    0.1165   -0.6359   -0.1791
WGTBL                                                  1   -0.0017    0.0094   -0.0200    0.0167
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.18        0.6724
trtpn      1                                               32.57        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        1.01        0.3160
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    12.23        0.0005
WGTBL                                                       0.03        0.8596
Scale                                                                         
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   -0.7744      0.1286      -6.02      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -3.1129      0.3918      -7.95      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.0264   -0.5224         0.4610         0.3583         0.5931
trtpn   LSMeans frequency, IDeg       -3.8807   -2.3450        0.04447        0.02064        0.09584
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     2.3385     0.4097      5.71     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.5354      3.1416          10.3655
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
80 of 334
Responder for HbA1c treatment target without weight gain – supportive statistical analysis – full
analysis set
Parameter Code=HBA7WOWG
The GENMOD Procedure
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          4.6432          23.1402
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
81 of 334
10: 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         453
Number of Observations Used         453
Number of Events                     61
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y               61
       2    N              392
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter       Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
Prm7            WGTBL                                                          
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -157.5765                
Full Log Likelihood                    -157.5765                
AIC (smaller is better)                 325.1529                
AICC (smaller is better)                325.2871                
BIC (smaller is better)                 345.7324                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
82 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1   -1.2594    1.5841   -4.3643    1.8454
trtpn      1                                           1    2.4496    0.6033    1.2671    3.6321
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.0944    0.2894   -0.4728    0.6615
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.4041    0.1466   -0.6915   -0.1167
WGTBL                                                  1    0.0113    0.0108   -0.0099    0.0325
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.63        0.4266
trtpn      1                                               16.48        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        0.11        0.7443
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                     7.59        0.0059
WGTBL                                                       1.09        0.2975
Scale                                                                         
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   -1.5204      0.1574      -9.66      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -3.9700      0.5871      -6.76      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.8288   -1.2120         0.2186         0.1606         0.2976
trtpn   LSMeans frequency, IDeg       -5.1208   -2.8192        0.01887       0.005972        0.05965
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     2.4496     0.6033      4.06     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.2671      3.6321          11.5836
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
83 of 334
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
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          3.5504          37.7934
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
84 of 334
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         453
Number of Observations Used         453
Number of Events                    101
Number of Trials                    453
                        Class Level Information
Class      Levels    Values
trtpn           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
       Response Profile
Ordered                 Total
   Value    AVALC    Frequency
       1    Y              101
       2    N              352
PROC GENMOD is modeling the probability that AVALC='Y'.
                             Parameter Information
Parameter       Effect       trtpn    PREAD
Prm1            Intercept                                                      
Prm2            trtpn        1                                                 
Prm3            trtpn        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
Prm6            HBA1CBL                                                        
Prm7            WGTBL                                                          
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Log Likelihood                         -209.2402                
Full Log Likelihood                    -209.2402                
AIC (smaller is better)                 428.4804                
AICC (smaller is better)                428.6146                
BIC (smaller is better)                 449.0598                
Algorithm converged.                                                       
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
85 of 334
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%
Parameter                                             DF  Estimate     Error   Confidence Limits
Intercept                                              1    0.1064    1.2722   -2.3869    2.5998
trtpn      1                                           1    2.2639    0.4097    1.4609    3.0669
trtpn      2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD      BASAL INSULIN + METFORMIN                   1    0.2414    0.2424   -0.2338    0.7166
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
HBA1CBL                                                1   -0.3788    0.1165   -0.6072   -0.1505
WGTBL                                                  1    0.0008    0.0094   -0.0176    0.0193
Scale                                                  0    1.0000    0.0000    1.0000    1.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                            Wald
Parameter                                             Chi-Square    Pr > ChiSq
Intercept                                                   0.01        0.9333
trtpn      1                                               30.53        <.0001
trtpn      2                                                                  
PREAD      BASAL INSULIN + METFORMIN                        0.99        0.3194
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
HBA1CBL                                                    10.57        0.0011
WGTBL                                                       0.01        0.9292
Scale                                                                         
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   -0.8334      0.1295      -6.44      <.0001      0.05
trtpn   LSMeans frequency, IDeg       -3.0973      0.3912      -7.92      <.0001      0.05
                                   Least Squares Means Estimates
                                                                        Exponentiated  Exponentiated
Effect  Label                           Lower     Upper  Exponentiated          Lower          Upper
trtpn   LSMeans frequency, IDegLira   -1.0873   -0.5796         0.4346         0.3371         0.5601
trtpn   LSMeans frequency, IDeg       -3.8640   -2.3306        0.04517        0.02098        0.09724
                                   Least Squares Means Estimate
                                                            Standard
Effect   Label                                   Estimate      Error   z Value   Pr > |z|    Alpha
trtpn    Treatment odds ratio, IDegLira / IDeg     2.2639     0.4097      5.53     <.0001     0.05
                             Least Squares Means Estimate
Effect   Label                                      Lower       Upper    Exponentiated
trtpn    Treatment odds ratio, IDegLira / IDeg     1.4609      3.0669           9.6205
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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
                         Least Squares Means Estimate
                                                 Exponentiated    Exponentiated
Effect   Label                                           Lower            Upper
trtpn    Treatment odds ratio, IDegLira / IDeg          4.3097          21.4759
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Statistical document
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11: Body weight after 26 weeks of treatment – change from baseline – confirmatory statistical analysis 
– full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
         Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       8.0164
           Fit Statistics
-2 Res Log Likelihood          2235.4
AIC (Smaller is Better)        2237.4
AICC (Smaller is Better)       2237.4
BIC (Smaller is Better)        2241.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.4889    0.8516   449    -1.75
trtpn                                                 1           -1.0762    0.2835   449    -3.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3488    0.2675   449     1.30
PREAD     BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0227   0.01074   449    95.25
CONFIDENTIAL


NN9068
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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 - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0811      0.05
trtpn                                                 1            0.0002      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1930      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.1625      0.1847
trtpn                                                 1           -1.6334     -0.5189
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1770      0.8746
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0016      1.0438
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      14.40    0.0002
PREAD           1     449       1.70    0.1930
BASE            1     449    9072.25    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    75.3159     0.1632     449    461.54     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    76.3920     0.2311     449    330.49     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect  Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    74.9952    75.6366         5.12E32        3.715E32        7.056E32
trtpn    LSMeans, IDeg        75.9378    76.8463        1.502E33        9.536E32        2.366E33
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.0762     0.2835     449     -3.80
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – confirmatory statistical analysis
– full analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0002    0.05   -1.6334   -0.5189         0.3409
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.1953           0.5952
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – confirmatory statistical analysis
– full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      38.9624
           Fit Statistics
-2 Res Log Likelihood          2946.9
AIC (Smaller is Better)        2948.9
AICC (Smaller is Better)       2948.9
BIC (Smaller is Better)        2953.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF t Value
Intercept                                                         -3.2825    1.8774   449    -1.75
trtpn                                                 1           -2.3725    0.6251   449    -3.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.7689    0.5898   449     1.30
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0227   0.01074   449    95.25
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 – confirmatory statistical analysis
– full analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0811      0.05
trtpn                                                 1            0.0002      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1930      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -6.9722      0.4072
trtpn                                                 1           -3.6010     -1.1440
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3902      1.9281
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0016      1.0438
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      14.40    0.0002
PREAD           1     449       1.70    0.1930
BASE            1     449    9072.25    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     166.04     0.3598     449    461.54     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     168.42     0.5096     449    330.49     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     165.34     166.75        1.293E72        6.376E71        2.622E72
trtpn    LSMeans, IDeg         167.41     169.42        1.387E73        5.094E72        3.775E73
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.3725     0.6251     449     -3.80
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 – confirmatory statistical analysis
– full analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0002    0.05   -3.6010   -1.1440        0.09325
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        0.02730           0.3185
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NN9068
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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 – confirmatory statistical analysis
– full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       8.0164
           Fit Statistics
-2 Res Log Likelihood          2235.4
AIC (Smaller is Better)        2237.4
AICC (Smaller is Better)       2237.4
BIC (Smaller is Better)        2241.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.4889    0.8516   449    -1.75
trtpn                                                 1           -1.0762    0.2835   449    -3.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3488    0.2675   449     1.30
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02267   0.01074   449     2.11
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
Status:
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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 - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0811      0.05
trtpn                                                 1            0.0002      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1930      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0353      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.1625      0.1847
trtpn                                                 1           -1.6334     -0.5189
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1770      0.8746
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.001572     0.04377
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      14.40    0.0002
PREAD           1     449       1.70    0.1930
BASE            1     449       4.46    0.0353
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.6766    0.1632    449    -4.15    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.3996    0.2311    449     1.73    0.0846
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.9973     -0.3559
trtpn   Change from baseline, IDeg        0.05    -0.05471      0.8538
CONFIDENTIAL


NN9068
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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 – confirmatory statistical analysis
– full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      38.9624
           Fit Statistics
-2 Res Log Likelihood          2946.9
AIC (Smaller is Better)        2948.9
AICC (Smaller is Better)       2948.9
BIC (Smaller is Better)        2953.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -3.2825    1.8774   449    -1.75
trtpn                                                 1           -2.3725    0.6251   449    -3.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.7689    0.5898   449     1.30
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02267   0.01074   449     2.11
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 - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0811      0.05
trtpn                                                 1            0.0002      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1930      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0353      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -6.9722      0.4072
trtpn                                                 1           -3.6010     -1.1440
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3902      1.9281
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.001572     0.04377
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      14.40    0.0002
PREAD           1     449       1.70    0.1930
BASE            1     449       4.46    0.0353
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -1.4916    0.3598    449    -4.15    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.8809    0.5096    449     1.73    0.0846
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -2.1987     -0.7846
trtpn   Change from baseline, IDeg        0.05     -0.1206      1.8823
CONFIDENTIAL


NN9068
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Statistical document
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12: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      8.3053
           Fit Statistics
-2 Res Log Likelihood          2142.1
AIC (Smaller is Better)        2144.1
AICC (Smaller is Better)       2144.1
BIC (Smaller is Better)        2148.1
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.5403    0.8925   427    -1.73
trtan                                                 1           -1.0802    0.2968   427    -3.64
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3398    0.2793   427     1.22
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0236   0.01127   427    90.86
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Clinical Trial Report
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Final
Statistical document
Page:
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0851      0.05
trtan                                                 1            0.0003      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2244      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.2945      0.2140
trtan                                                 1           -1.6637     -0.4967
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2092      0.8887
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0014      1.0457
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427      13.24    0.0003
PREAD           1     427       1.48    0.2244
BASE            1     427    8254.99    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2    75.2965     0.1698     427    443.42     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2    76.3767     0.2427     427    314.74     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira    74.9628    75.6303        5.022E32        3.597E32        7.012E32
trtan    LSMeans, IDeg        75.8998    76.8537        1.479E33         9.18E32        2.383E33
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.0802     0.2968     427     -3.64
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
99 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    0.0003    0.05   -1.6637   -0.4967         0.3395
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg         0.1894           0.6085
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      40.3667
           Fit Statistics
-2 Res Log Likelihood          2818.8
AIC (Smaller is Better)        2820.8
AICC (Smaller is Better)       2820.8
BIC (Smaller is Better)        2824.8
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -3.3957    1.9676   427    -1.73
trtan                                                 1           -2.3814    0.6544   427    -3.64
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.7491    0.6157   427     1.22
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0236   0.01127   427    90.86
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0851      0.05
trtan                                                 1            0.0003      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2244      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -7.2631      0.4717
trtan                                                 1           -3.6677     -1.0951
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4611      1.9593
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0014      1.0457
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427      13.24    0.0003
PREAD           1     427       1.48    0.2244
BASE            1     427    8254.99    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtan    LSMeans, IDegLira   WORK.ADATA2     166.00     0.3744     427    443.42     <.0001     0.05
trtan    LSMeans, IDeg       WORK.ADATA2     168.38     0.5350     427    314.74     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtan    LSMeans, IDegLira     165.26     166.74        1.239E72        5.936E71        2.586E72
trtan    LSMeans, IDeg         167.33     169.43        1.341E73        4.684E72        3.837E73
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtan   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.3814     0.6544     427     -3.64
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtan   Treatment contrast, IDegLira - IDeg    0.0003    0.05   -3.6677   -1.0951        0.09242
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtan   Treatment contrast, IDegLira - IDeg        0.02553           0.3345
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       8.3053
           Fit Statistics
-2 Res Log Likelihood          2142.1
AIC (Smaller is Better)        2144.1
AICC (Smaller is Better)       2144.1
BIC (Smaller is Better)        2148.1
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.5403    0.8925   427    -1.73
trtan                                                 1           -1.0802    0.2968   427    -3.64
trtan                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3398    0.2793   427     1.22
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02356   0.01127   427     2.09
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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 –
PP analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0851      0.05
trtan                                                 1            0.0003      0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2244      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0371      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.2945      0.2140
trtan                                                 1           -1.6637     -0.4967
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2092      0.8887
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.001415     0.04570
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427      13.24    0.0003
PREAD           1     427       1.48    0.2244
BASE            1     427       4.37    0.0371
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2   -0.6700    0.1698    427    -3.95    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2    0.4102    0.2427    427     1.69    0.0917
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -1.0038     -0.3363
trtan   Change from baseline, IDeg        0.05    -0.06682      0.8871
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NN9068
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
PP analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             431
          Number of Observations
Number of Observations Read             431
Number of Observations Used             431
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      40.3667
           Fit Statistics
-2 Res Log Likelihood          2818.8
AIC (Smaller is Better)        2820.8
AICC (Smaller is Better)       2820.8
BIC (Smaller is Better)        2824.8
                                    Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -3.3957    1.9676   427    -1.73
trtan                                                 1           -2.3814    0.6544   427    -3.64
trtan                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.7491    0.6157   427     1.22
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02356   0.01127   427     2.09
CONFIDENTIAL


NN9068
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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 – statistical sensitivity analysis –
PP analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                     Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0851      0.05
trtan                                                 1            0.0003     0.05
trtan                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2244      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                              
BASE                                                               0.0371      0.05
                             Solution for Fixed Effects
                                                      Actual
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -7.2631      0.4717
trtan                                                 1           -3.6677     -1.0951
trtan                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4611      1.9593
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.001415     0.04570
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtan           1     427      13.24    0.0003
PREAD           1     427       1.48    0.2244
BASE            1     427       4.37    0.0371
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtan   Change from baseline, IDegLira  WORK.ADATA2   -1.4772    0.3744    427    -3.95    <.0001
trtan   Change from baseline, IDeg      WORK.ADATA2    0.9042    0.5350    427     1.69    0.0917
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtan   Change from baseline, IDegLira    0.05     -2.2130     -0.7414
trtan   Change from baseline, IDeg        0.05     -0.1473      1.9558
CONFIDENTIAL


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Statistical document
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13: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       8.3003
           Fit Statistics
-2 Res Log Likelihood          2131.9
AIC (Smaller is Better)        2133.9
AICC (Smaller is Better)       2133.9
BIC (Smaller is Better)        2137.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.3952    0.8950   425    -1.56
trtpn                                                 1           -1.1604    0.2986   425    -3.89
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3621    0.2799   425     1.29
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0225   0.01126   425    90.79
CONFIDENTIAL


NN9068
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Date:
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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 – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.1198      0.05
trtpn                                                 1            0.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1964      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.1543      0.3639
trtpn                                                 1           -1.7473     -0.5735
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1880      0.9123
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0003      1.0446
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425      15.10    0.0001
PREAD           1     425       1.67    0.1964
BASE            1     425    8243.01    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    75.3056     0.1694     425    444.45     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    76.4660     0.2451     425    311.93     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    74.9726    75.6386        5.068E32        3.632E32         7.07E32
trtpn    LSMeans, IDeg        75.9842    76.9478        1.617E33        9.989E32        2.618E33
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.1604     0.2986     425     -3.89
CONFIDENTIAL


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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=C25208X
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0001    0.05   -1.7473   -0.5735         0.3134
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.1742           0.5635
CONFIDENTIAL


NN9068
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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 –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      40.3426
           Fit Statistics
-2 Res Log Likelihood          2805.4
AIC (Smaller is Better)        2807.4
AICC (Smaller is Better)       2807.5
BIC (Smaller is Better)        2811.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -3.0759    1.9731   425    -1.56
trtpn                                                 1           -2.5583    0.6583   425    -3.89
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.7984    0.6171   425     1.29
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               1.0225   0.01126   425    90.79
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
111 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.1198      0.05
trtpn                                                 1            0.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1964      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -6.9541      0.8023
trtpn                                                 1           -3.8522     -1.2644
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4145      2.0113
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               1.0003      1.0446
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425      15.10    0.0001
PREAD           1     425       1.67    0.1964
BASE            1     425    8243.01    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     166.02     0.3735     425    444.45     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     168.58     0.5404     425    311.93     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     165.29     166.75        1.264E72        6.066E71        2.634E72
trtpn    LSMeans, IDeg         167.52     169.64        1.632E73        5.642E72        4.722E73
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -2.5583     0.6583     425     -3.89
CONFIDENTIAL


NN9068
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Date:
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Clinical Trial Report
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Final
Statistical document
Page:
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0001    0.05   -3.8522   -1.2644        0.07744
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        0.02123           0.2824
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
113 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       8.3003
           Fit Statistics
-2 Res Log Likelihood          2131.9
AIC (Smaller is Better)        2133.9
AICC (Smaller is Better)       2133.9
BIC (Smaller is Better)        2137.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.3952    0.8950   425    -1.56
trtpn                                                 1           -1.1604    0.2986   425    -3.89
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3621    0.2799   425     1.29
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02247   0.01126   425     2.00
CONFIDENTIAL


NN9068
CONFIDENTIAL
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 - appendix
Parameter Code=C25208X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.1198      0.05
trtpn                                                 1            0.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1964      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0466      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -3.1543      0.3639
trtpn                                                 1           -1.7473     -0.5735
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1880      0.9123
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.000336     0.04461
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425      15.10    0.0001
PREAD           1     425       1.67    0.1964
BASE            1     425       3.98    0.0466
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.6760    0.1694    425    -3.99    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.4844    0.2451    425     1.98    0.0488
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -1.0090     -0.3429
trtpn   Change from baseline, IDeg        0.05    0.002600      0.9663
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
115 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             429
          Number of Observations
Number of Observations Read             429
Number of Observations Used             429
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      40.3426
           Fit Statistics
-2 Res Log Likelihood          2805.4
AIC (Smaller is Better)        2807.4
AICC (Smaller is Better)       2807.5
BIC (Smaller is Better)        2811.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -3.0759    1.9731   425    -1.56
trtpn                                                 1           -2.5583    0.6583   425    -3.89
trtpn                                                 2                 0                        
PREAD      BASAL INSULIN + METFORMIN                               0.7984    0.6171   425     1.29
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              0.02247   0.01126   425     2.00
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
116 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
completer analysis set - appendix
Parameter Code=WEIGHTU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.1198      0.05
trtpn                                                 1            0.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1964      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0466      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -6.9541      0.8023
trtpn                                                 1           -3.8522     -1.2644
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4145      2.0113
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                             0.000336     0.04461
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     425      15.10    0.0001
PREAD           1     425       1.67    0.1964
BASE            1     425       3.98    0.0466
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -1.4903    0.3735    425    -3.99    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.0680    0.5404    425     1.98    0.0488
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -2.2245     -0.7561
trtpn   Change from baseline, IDeg        0.05    0.005731      2.1302
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
117 of 334
14: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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         2    1 2                           
avisitn         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
118 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
119 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2597
Number of Observations Not Used         121
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
120 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     11799.74282062                
       1              2      8867.20333115      0.00000625
        2              1      8867.19027918      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       2.0140
UN(2,1)     SUBJID       1.9791
UN(2,2)     SUBJID       3.9752
UN(3,1)     SUBJID       2.1981
UN(3,2)     SUBJID       3.6319
UN(3,3)     SUBJID       5.2127
UN(4,1)     SUBJID       2.1194
UN(4,2)     SUBJID       3.6227
UN(4,3)     SUBJID       4.9685
UN(4,4)     SUBJID       6.0757
UN(5,1)     SUBJID       2.1682
UN(5,2)     SUBJID       3.7181
UN(5,3)     SUBJID       5.0852
UN(5,4)     SUBJID       5.7532
UN(5,5)     SUBJID       6.9717
UN(6,1)     SUBJID       2.3366
UN(6,2)     SUBJID       3.7858
UN(6,3)     SUBJID       5.2013
UN(6,4)     SUBJID       5.7740
UN(6,5)     SUBJID       6.5474
UN(6,6)     SUBJID       8.3028
           Fit Statistics
-2 Res Log Likelihood          8867.2
AIC (Smaller is Better)        8909.2
AICC (Smaller is Better)       8909.6
BIC (Smaller is Better)        8995.6
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       2932.55          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)       6     436       2.83    0.0103
PREAD(avisitn)         6     433       1.45    0.1950
BASE(avisitn)          6     433    5778.27    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
121 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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   75.2925    0.1691  431.5   445.17    <.0001
TRT01PN(avisitn)  LSMeans, IDeg      WORK.ANA_DATA   76.4274    0.2411  440.4   316.99    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(avisitn)  LSMeans, IDegLira    0.05     74.9601     75.6249
TRT01PN(avisitn)  LSMeans, IDeg        0.05     75.9536     76.9013
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
122 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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         2    1 2                           
avisitn         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
123 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID       453   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
124 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2597
Number of Observations Not Used         121
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
125 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     15877.43246205                
        1              2     12944.89297256      0.00000315
        2              1     12944.87992061      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       9.7886
UN(2,1)     SUBJID       9.6190
UN(2,2)     SUBJID      19.3211
UN(3,1)     SUBJID      10.6836
UN(3,2)     SUBJID      17.6521
UN(3,3)     SUBJID      25.3355
UN(4,1)     SUBJID      10.3012
UN(4,2)     SUBJID      17.6076
UN(4,3)     SUBJID      24.1485
UN(4,4)     SUBJID      29.5302
UN(5,1)     SUBJID      10.5383
UN(5,2)     SUBJID      18.0715
UN(5,3)     SUBJID      24.7161
UN(5,4)     SUBJID      27.9627
UN(5,5)     SUBJID      33.8849
UN(6,1)     SUBJID      11.3569
UN(6,2)     SUBJID      18.4005
UN(6,3)     SUBJID      25.2801
UN(6,4)     SUBJID      28.0636
UN(6,5)     SUBJID      31.8228
UN(6,6)     SUBJID      40.3546
           Fit Statistics
-2 Res Log Likelihood         12944.9
AIC (Smaller is Better)       12986.9
AICC (Smaller is Better)      12987.2
BIC (Smaller is Better)       13073.3
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       2932.55          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)       6     436       2.83    0.0103
PREAD(avisitn)         6     433       1.45    0.1950
BASE(avisitn)          6     433    5778.27    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
126 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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    165.99    0.3729  431.5   445.17    <.0001
TRT01PN(avisitn)  LSMeans, IDeg      WORK.ANA_DATA    168.49    0.5315  440.4   316.99    <.0001
                   Least Squares Means Estimates
Effect            Label               Alpha       Lower       Upper
TRT01PN(avisitn)  LSMeans, IDegLira    0.05      165.26      166.72
TRT01PN(avisitn)  LSMeans, IDeg        0.05      167.45      169.54
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
127 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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         2    1 2                           
avisitn         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
128 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
                    
  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
129 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2597
Number of Observations Not Used         121
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
130 of 334
Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=C25208X Long label=Body weight (kg)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations   -2 Res Log Like       Criterion
        0              1     11799.74282062                
        1              2      8867.20333114      0.00000625
        2              1      8867.19027918      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       2.0140
UN(2,1)     SUBJID       1.9791
UN(2,2)     SUBJID       3.9752
UN(3,1)     SUBJID      2.1981
UN(3,2)     SUBJID       3.6319
UN(3,3)     SUBJID       5.2127
UN(4,1)     SUBJID       2.1194
UN(4,2)     SUBJID       3.6227
UN(4,3)     SUBJID       4.9685
UN(4,4)     SUBJID       6.0757
UN(5,1)     SUBJID       2.1682
UN(5,2)     SUBJID      3.7181
UN(5,3)     SUBJID       5.0852
UN(5,4)     SUBJID       5.7532
UN(5,5)     SUBJID       6.9717
UN(6,1)     SUBJID       2.3366
UN(6,2)     SUBJID       3.7858
UN(6,3)     SUBJID       5.2013
UN(6,4)     SUBJID       5.7740
UN(6,5)     SUBJID      6.5474
UN(6,6)     SUBJID       8.3028
           Fit Statistics
-2 Res Log Likelihood          8867.2
AIC (Smaller is Better)        8909.2
AICC (Smaller is Better)       8909.6
BIC (Smaller is Better)        8995.6
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       2932.55          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)       6     436       2.83    0.0103
PREAD(avisitn)         6     433       1.45    0.1950
BASE(avisitn)          6     433       2.12    0.0498
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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   -0.6806    0.1691  431.5    -4.02
TRT01PN(avisitn)  Change from baseline, IDeg      WORK.ANA_DATA    0.4543    0.2411  440.4     1.88
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(avisitn)  Change from baseline, IDegLira    <.0001      0.05     -1.0131     -0.3482
TRT01PN(avisitn)  Change from baseline, IDeg        0.0602      0.05    -0.01953      0.9282
                                   Least Squares Means Estimate
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -1.1350     0.2951   437.4
                                    Least Squares Means Estimate
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg    -3.85    0.0001    0.05   -1.7150   -0.5549
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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         2    1 2                           
avisitn         6    100 150 190 230 270 330       
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
              Class Level Information
Class      Levels    Values
SUBJID        453   
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
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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 – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
                    
 
            Dimensions
Covariance Parameters            21
Columns in X                     31
Columns in Z                      0
Subjects                        453
Max Obs per Subject               6
          Number of Observations
Number of Observations Read            2718
Number of Observations Used            2597
Number of Observations Not Used         121
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Statistical document
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
MMRM – full analysis set - appendix
Short Topic Code=WEIGHTU Long label=Body weight (lb)
The Mixed Procedure
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     15877.43246205                
        1              2     12944.89297256      0.00000315
        2              1     12944.87992060      0.00000000
                   Convergence criteria met.                    
Covariance Parameter Estimates
Cov Parm    Subject    Estimate
UN(1,1)     SUBJID       9.7886
UN(2,1)     SUBJID       9.6190
UN(2,2)     SUBJID      19.3211
UN(3,1)     SUBJID      10.6836
UN(3,2)     SUBJID      17.6521
UN(3,3)     SUBJID      25.3355
UN(4,1)     SUBJID      10.3012
UN(4,2)     SUBJID      17.6076
UN(4,3)     SUBJID      24.1485
UN(4,4)     SUBJID      29.5302
UN(5,1)     SUBJID      10.5383
UN(5,2)     SUBJID      18.0715
UN(5,3)     SUBJID      24.7161
UN(5,4)     SUBJID      27.9627
UN(5,5)     SUBJID      33.8849
UN(6,1)     SUBJID      11.3569
UN(6,2)     SUBJID      18.4005
UN(6,3)     SUBJID      25.2801
UN(6,4)     SUBJID      28.0636
UN(6,5)     SUBJID      31.8228
UN(6,6)     SUBJID      40.3546
           Fit Statistics
-2 Res Log Likelihood         12944.9
AIC (Smaller is Better)       12986.9
AICC (Smaller is Better)      12987.2
BIC (Smaller is Better)       13073.3
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
    20       2932.55          <.0001
            Type 3 Tests of Fixed Effects
                     Num     Den
Effect                DF      DF    F Value    Pr > F
TRT01PN(avisitn)       6     436       2.83    0.0103
PREAD(avisitn)         6     433       1.45    0.1950
BASE(avisitn)          6     433       2.12    0.0498
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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 – statistical sensitivity analysis –
MMRM – full analysis set - appendix
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   -1.5006    0.3729  431.5    -4.02
TRT01PN(avisitn)  Change from baseline, IDeg      WORK.ANA_DATA    1.0016    0.5315  440.4     1.88
                               Least Squares Means Estimates
Effect            Label                           Pr > |t|     Alpha       Lower       Upper
TRT01PN(avisitn)  Change from baseline, IDegLira    <.0001      0.05     -2.2334     -0.7677
TRT01PN(avisitn)  Change from baseline, IDeg        0.0602      0.05    -0.04305      2.0463
                                   Least Squares Means Estimate
                                                                                  Standard
Effect            Label                                Margins         Estimate      Error      DF
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg  WORK.ANA_DATA    -2.5022     0.6506   437.4
                                    Least Squares Means Estimate
Effect            Label                                t Value  Pr > |t|   Alpha     Lower     Upper
TRT01PN(avisitn)  Treatment contrast, IDegLira - IDeg    -3.85    0.0001    0.05   -3.7810   -1.2234
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15: Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
paramsort=1 Parameter Code=C25208X Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.003073       0.055557       0.058633   362883
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.055374       0.052474       0.999948
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       76.457794       0.242143   75.98320   76.93239   362883      76.282848      76.635672
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             315.75     <.0001
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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 - appendix
paramsort=1 Parameter Code=C25208X Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.001029       0.027690       0.028721   776179
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.037211       0.035878       0.999964
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       75.358828       0.169471   75.02667   75.69099   776179      75.271846      75.482403
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             444.67     <.0001
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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 – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
paramsort=2 Parameter Code=WEIGHTU Label=LSMeans, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.014938       0.270027       0.284980   362883
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.055374       0.052474       0.999948
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      168.560582       0.533835   167.5143   169.6069   362883     168.174892     168.952737
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             315.75     <.0001
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NN9068
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Version:
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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 - appendix
paramsort=2 Parameter Code=WEIGHTU Label=LSMeans, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_ABS_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005003       0.134584       0.139592   776179
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.037211       0.035878       0.999964
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate      166.137776       0.373621   165.4055   166.8701   776179     165.946014     166.410213
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0             444.67     <.0001
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NN9068
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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 - appendix
paramsort=1 Parameter Code=C25208X Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.003073       0.055557       0.058633   362883
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate        0.055374       0.052474       0.999948
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        0.465300       0.242143   -0.00929   0.939894   362883       0.290354       0.643178
        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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Version:
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Statistical document
Page:
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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
paramsort=1 Parameter Code=C25208X Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.001029       0.027690       0.028721   776179
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.037211       0.035878       0.999964
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -0.633667       0.169471   -0.96583   -0.30151   776179      -0.720649      -0.510092
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -3.74     0.0002
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NN9068
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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 - appendix
paramsort=1 Parameter Code=C25208X Label=Treatment contrast, IDegLira - IDeg Statement Number=2
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.003720       0.083600       0.087324   549385
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.044542       0.042646       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.098966       0.295507   -1.67815   -0.51978   549385      -1.284088      -0.904160
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -3.72     0.0002
CONFIDENTIAL


NN9068
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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 - appendix
paramsort=2 Parameter Code=WEIGHTU Label=Change from baseline, IDeg Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.014938       0.270027       0.284980   362883
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.055374       0.052474       0.999948
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        1.025810       0.533835   -0.02049   2.072111   362883       0.640120       1.417965
        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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Body weight after 26 weeks of treatment – change from baseline – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
paramsort=2 Parameter Code=WEIGHTU Label=Change from baseline, IDegLira Statement Number=1
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005003       0.134584       0.139592   776179
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.037211       0.035878       0.999964
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter      Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -1.396996       0.373621   -2.12928   -0.66471   776179      -1.588758      -1.124560
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -3.74     0.0002
CONFIDENTIAL


NN9068
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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 – statistical sensitivity analysis –
conditional multiple imputation – full analysis set - appendix
paramsort=2 Parameter Code=WEIGHTU Label=Treatment contrast, IDegLira - IDeg Statement Number=2
The MIANALYZE Procedure
            Model Information
Data Set                  WORK.LSME_CHG_MI
Number of Imputations     1000            
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.018081       0.406328       0.424427   549385
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.044542       0.042646       0.999957
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -2.422806       0.651481   -3.69969   -1.14592   549385      -2.830930      -1.993332
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -3.72     0.0002
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Statistical document
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16: Waist circumference after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      15.5557
           Fit Statistics
-2 Res Log Likelihood          2532.4
AIC (Smaller is Better)        2534.4
AICC (Smaller is Better)       2534.4
BIC (Smaller is Better)        2538.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          6.1773    2.0732   449     2.98
trtpn                                                 1           -0.8684    0.3938   449    -2.21
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3609    0.3724   449     0.97
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.9397   0.02113   449    44.48
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Waist circumference after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=MEANWAIC
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0030      0.05
trtpn                                                 1            0.0279      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3330      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.1029     10.2517
trtpn                                                 1           -1.6422    -0.09459
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3710      1.0928
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.8982      0.9812
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       4.86    0.0279
PREAD           1     449       0.94    0.3330
BASE            1     449    1978.54    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    96.2124     0.2271     449    423.69     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    97.0808     0.3213     449    302.13     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    95.7661    96.6586        6.088E41        3.897E41        9.513E41
trtpn    LSMeans, IDeg        96.4493    97.7123        1.451E42        7.716E41        2.728E42
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.8684     0.3938     449     -2.21
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Version:
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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 - appendix
Parameter Code=MEANWAIC
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0279    0.05   -1.6422  -0.09459         0.4196
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.1935           0.9097
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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 - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      15.5557
           Fit Statistics
-2 Res Log Likelihood          2532.4
AIC (Smaller is Better)        2534.4
AICC (Smaller is Better)       2534.4
BIC (Smaller is Better)        2538.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          6.1773    2.0732   449     2.98
trtpn                                                 1           -0.8684    0.3938   449    -2.21
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.3609    0.3724   449     0.97
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                             -0.06029   0.02113   449    -2.85
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NN9068
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Date:
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
151 of 334
Waist circumference after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=MEANWAIC
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0030      0.05
trtpn                                                 1            0.0279      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3330      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0045      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.1029     10.2517
trtpn                                                 1           -1.6422    -0.09459
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3710      1.0928
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.1018    -0.01877
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       4.86    0.0279
PREAD           1     449       0.94    0.3330
BASE            1     449       8.15    0.0045
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.3413    0.2271    449    -1.50    0.1335
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.5271    0.3213    449     1.64    0.1016
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.7876      0.1049
trtpn   Change from baseline, IDeg        0.05     -0.1044      1.1585
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
Page:
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17: Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.9791
           Fit Statistics
-2 Res Log Likelihood          1788.0
AIC (Smaller is Better)        1790.0
AICC (Smaller is Better)       1790.0
BIC (Smaller is Better)        1794.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          5.8339    0.3212   449    18.16
trtpn                                                 1           -0.4165    0.1722   449    -2.42
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.1213    0.1624   449    -0.75
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1052   0.02893   449     3.64
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
153 of 334
Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=C105585P
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4557      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0003      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          5.2026      6.4651
trtpn                                                 1           -0.7550    -0.07803
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4405      0.1980
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.04833      0.1621
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       5.85    0.0160
PREAD           1     449       0.56    0.4557
BASE            1     449      13.22    0.0003
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     6.3857    0.09936     449     64.27     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     6.8022     0.1406     449     48.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     6.1904     6.5809          593.28          488.05          721.21
trtpn    LSMeans, IDeg         6.5259     7.0784          899.79          682.61         1186.08
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.4165     0.1722     449     -2.42
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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Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=C105585P
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0160    0.05   -0.7550  -0.07803         0.6594
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4700           0.9249
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       967.38
           Fit Statistics
-2 Res Log Likelihood          4390.3
AIC (Smaller is Better)        4392.3
AICC (Smaller is Better)       4392.3
BIC (Smaller is Better)        4396.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          105.13    5.7880   449    18.16
trtpn                                                 1           -7.5052    3.1034   449    -2.42
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.1852    2.9272   449    -0.75
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1052   0.02893   449     3.64
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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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 - appendix
Parameter Code=FPGU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4557      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               0.0003      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         93.7515      116.50
trtpn                                                 1          -13.6042     -1.4062
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -7.9378      3.5675
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.04833      0.1621
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       5.85    0.0160
PREAD           1     449       0.56    0.4557
BASE            1     449      13.22    0.0003
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     115.07     1.7904     449     64.27     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     122.58     2.5330     449     48.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     111.55     118.59        9.423E49        2.793E48        3.179E51
trtpn    LSMeans, IDeg         117.60     127.55        1.713E53         1.18E51        2.486E55
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -7.5052     3.1034     449     -2.42
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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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 - appendix
Parameter Code=FPGU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0160    0.05  -13.6042   -1.4062       0.000550
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       1.235E-6           0.2451
CONFIDENTIAL


NN9068
CONFIDENTIAL
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Clinical Trial Report
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Statistical document
Page:
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Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.9791
           Fit Statistics
-2 Res Log Likelihood          1788.0
AIC (Smaller is Better)        1790.0
AICC (Smaller is Better)       1790.0
BIC (Smaller is Better)        1794.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          5.8339    0.3212   449    18.16
trtpn                                                 1           -0.4165    0.1722   449    -2.42
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.1213    0.1624   449    -0.75
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8948   0.02893   449   -30.93
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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Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=C105585P
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4557      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          5.2026      6.4651
trtpn                                                 1           -0.7550    -0.07803
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4405      0.1980
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.9517     -0.8379
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       5.85    0.0160
PREAD           1     449       0.56    0.4557
BASE            1     449     956.44    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.3662   0.09936    449   -33.88    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -2.9497    0.1406    449  -20.98    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -3.5615     -3.1709
trtpn   Change from baseline, IDeg        0.05     -3.2260     -2.6735
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
160 of 334
Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       967.38
           Fit Statistics
-2 Res Log Likelihood          4390.3
AIC (Smaller is Better)        4392.3
AICC (Smaller is Better)       4392.3
BIC (Smaller is Better)        4396.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          105.13    5.7880   449    18.16
trtpn                                                 1           -7.5052    3.1034   449    -2.42
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -2.1852    2.9272   449    -0.75
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8948   0.02893   449   -30.93
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
161 of 334
Fasting plasma glucose after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=FPGU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4557      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         93.7515      116.50
trtpn                                                 1          -13.6042     -1.4062
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -7.9378      3.5675
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.9517     -0.8379
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       5.85    0.0160
PREAD           1     449       0.56    0.4557
BASE            1     449     956.44    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -60.6590    1.7904    449   -33.88    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -53.1538    2.5330    449   -20.98    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -64.1776    -57.1403
trtpn   Change from baseline, IDeg        0.05    -58.1318    -48.1758
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Final
Statistical document
Page:
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18: 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:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
163 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
              Class Level Information
Class      Levels    Values
USUBJID       453   
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
164 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
165 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
166 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
167 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
168 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
                   
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
169 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
TRTPN           2    1 2                           
ATPTN           9    1 2 3 4 5 6 7 8 9             
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
            Dimensions
Covariance Parameters             2
Columns in X                     39
Columns in Z                      0
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
170 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=C105585Y
The Mixed Procedure
            Dimensions
Subjects                        453
Max Obs per Subject               9
          Number of Observations
Number of Observations Read            4077
Number of Observations Used            3987
Number of Observations Not Used          90
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     17980.86879431                
        1              2     16986.47007207      0.00000000
                   Convergence criteria met.                    
                                   Covariance Parameter Estimates
                                    Standard         Z
Cov Parm     Subject    Estimate       Error     Value        Pr Z     Alpha       Lower       Upper
CS           USUBJID      1.9446      0.1557     12.49      <.0001      0.05      1.6394      2.2499
Residual                  3.3601     0.08020     41.90      <.0001      0.05      3.2083      3.5230
Asymptotic Covariance Matrix of Estimates
Row    Cov Parm        CovP1       CovP2
   1    CS            0.02425    -0.00074
   2    Residual     -0.00074    0.006432
           Fit Statistics
-2 Res Log Likelihood         16986.5
AIC (Smaller is Better)       16990.5
AICC (Smaller is Better)      16990.5
BIC (Smaller is Better)       16998.7
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
     1        994.40          <.0001
                                   Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint            Standard
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Estimate     Error
Intercept                                                                        5.9802    0.2158
TRTPN                                                    1                      -0.3993    0.2304
TRTPN                                                    2                            0          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
171 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint            Standard
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Estimate     Error
TRTPN(ATPTN)                                             1          1           0.03903    0.1878
TRTPN(ATPTN)                                             2          1            0.1496    0.2428
TRTPN(ATPTN)                                             1          2            3.9868    0.1890
TRTPN(ATPTN)                                             2          2            4.8504    0.2441
TRTPN(ATPTN)                                             1          3            1.2229    0.1887
TRTPN(ATPTN)                                             2          3            2.1036    0.2445
TRTPN(ATPTN)                                             1          4            4.0424    0.1883
TRTPN(ATPTN)                                             2          4            5.1013    0.2434
TRTPN(ATPTN)                                             1          5            1.8419    0.1886
TRTPN(ATPTN)                                            2          5            2.1763    0.2442
TRTPN(ATPTN)                                             1          6            4.4428    0.1885
TRTPN(ATPTN)                                             2          6            5.0832    0.2451
TRTPN(ATPTN)                                             1          7            3.0157    0.1906
TRTPN(ATPTN)                                             2          7            3.6866    0.2462
TRTPN(ATPTN)                                             1          8            0.4344    0.1905
TRTPN(ATPTN)                                             2          8            0.7451    0.2450
TRTPN(ATPTN)                                             1          9                 0          
TRTPN(ATPTN)                                             2          9                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1           -0.1512    0.2168
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2          -0.03748    0.2188
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3            0.3374    0.2187
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4            0.2126    0.2180
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5           -0.1693    0.2183
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6          -0.09171    0.2191
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7           0.05532    0.2205
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8          -0.05872    0.2204
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9          -0.02011    0.2172
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                 0          
                                 Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)          DF   t Value
Intercept                                                                      1934     27.71
TRTPN                                                    1                     1940     -1.73
TRTPN                                                    2                                   
TRTPN(ATPTN)                                             1          1          3512      0.21
TRTPN(ATPTN)                                             2          1          3513      0.62
TRTPN(ATPTN)                                             1          2          3516     21.09
TRTPN(ATPTN)                                             2          2          3514     19.87
TRTPN(ATPTN)                                             1          3          3515      6.48
TRTPN(ATPTN)                                             2          3          3516      8.60
TRTPN(ATPTN)                                             1          4          3514     21.47
TRTPN(ATPTN)                                             2          4          3513     20.96
TRTPN(ATPTN)                                             1          5          3515      9.77
TRTPN(ATPTN)                                             2          5          3515      8.91
TRTPN(ATPTN)                                             1          6          3515     23.57
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
172 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)          DF   t Value
TRTPN(ATPTN)                                             2          6          3516     20.74
TRTPN(ATPTN)                                             1          7          3518     15.82
TRTPN(ATPTN)                                             2          7          3517     14.98
TRTPN(ATPTN)                                             1          8          3518      2.28
TRTPN(ATPTN)                                             2          8          3516      3.04
TRTPN(ATPTN)                                             1          9                        
TRTPN(ATPTN)                                             2          9                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1          1927     -0.70
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2          1970     -0.17
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3          1965      1.54
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4          1949      0.98
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5          1956     -0.78
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6          1975     -0.42
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7          2009      0.25
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8          2006     -0.27
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9          1934     -0.09
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                        
                              Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Pr > |t|
Intercept                                                                        <.0001
TRTPN                                                    1                       0.0833
TRTPN                                                    2                             
TRTPN(ATPTN)                                             1          1            0.8354
TRTPN(ATPTN)                                             2          1            0.5380
TRTPN(ATPTN)                                             1          2            <.0001
TRTPN(ATPTN)                                             2          2            <.0001
TRTPN(ATPTN)                                             1          3            <.0001
TRTPN(ATPTN)                                             2          3            <.0001
TRTPN(ATPTN)                                             1          4            <.0001
TRTPN(ATPTN)                                             2          4            <.0001
TRTPN(ATPTN)                                             1          5            <.0001
TRTPN(ATPTN)                                             2          5            <.0001
TRTPN(ATPTN)                                             1          6           <.0001
TRTPN(ATPTN)                                             2          6            <.0001
TRTPN(ATPTN)                                             1          7            <.0001
TRTPN(ATPTN)                                             2          7            <.0001
TRTPN(ATPTN)                                             1          8            0.0227
TRTPN(ATPTN)                                             2          8            0.0024
TRTPN(ATPTN)                                             1          9                  
TRTPN(ATPTN)                                             2          9                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1            0.4855
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2            0.8640
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
173 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Pr > |t|
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3            0.1230
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4            0.3295
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5            0.4381
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6            0.6755
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7            0.8020
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8            0.7900
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9            0.9262
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                  
          Type 3 Tests of Fixed Effects
                 Num     Den
Effect            DF      DF    F Value    Pr > F
TRTPN              1     451      38.01    <.0001
TRTPN(ATPTN)       8    3517       3.99    0.0001
PREAD(ATPTN)       9    3357       0.83    0.5889
                                     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    5.5482    0.1325  1927    41.86    <.0001
TRTPN(ATPTN)  2          1          WORK.ANA_DATA    6.0580    0.1875  1927    32.32    <.0001
TRTPN(ATPTN)  1          2          WORK.ANA_DATA    9.5499    0.1332  1950    71.70    <.0001
TRTPN(ATPTN)  2          2          WORK.ANA_DATA   10.8128    0.1909  2006    56.65    <.0001
TRTPN(ATPTN)  1          3          WORK.ANA_DATA    6.9640    0.1330  1943    52.34    <.0001
TRTPN(ATPTN)  2          3          WORK.ANA_DATA    8.2440    0.1909  2006    43.20    <.0001
TRTPN(ATPTN)  1          4         WORK.ANA_DATA    9.7242    0.1331  1944    73.08    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  1          1            0.05      5.2882      5.8081
TRTPN(ATPTN)  2          1            0.05      5.6903      6.4256
TRTPN(ATPTN)  1          2            0.05      9.2887      9.8111
TRTPN(ATPTN)  2          2            0.05     10.4385     11.1871
TRTPN(ATPTN)  1          3            0.05      6.7030      7.2249
TRTPN(ATPTN)  2          3            0.05      7.8697      8.6182
TRTPN(ATPTN)  1          4            0.05      9.4632      9.9851
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
174 of 334
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)  2          4          WORK.ANA_DATA   11.1823    0.1890  1957    59.18    <.0001
TRTPN(ATPTN)  1          5          WORK.ANA_DATA    7.3424    0.1330  1943    55.19    <.0001
TRTPN(ATPTN)  2          5          WORK.ANA_DATA    8.0761    0.1899  1981    42.52    <.0001
TRTPN(ATPTN)  1          6          WORK.ANA_DATA    9.9802    0.1332  1950    74.92    <.0001
TRTPN(ATPTN)  2          6          WORK.ANA_DATA   11.0199    0.1913  2018    57.60    <.0001
TRTPN(ATPTN)  1          7          WORK.ANA_DATA    8.6229    0.1343  1992    64.20    <.0001
TRTPN(ATPTN)  2          7          WORK.ANA_DATA    9.6930    0.1923  2044    50.41    <.0001
TRTPN(ATPTN)  1          8          WORK.ANA_DATA    5.9875    0.1345  1998    44.52    <.0001
TRTPN(ATPTN)  2          8          WORK.ANA_DATA    6.6974    0.1914  2018    35.00    <.0001
TRTPN(ATPTN)  1          9          WORK.ANA_DATA    5.5714    0.1325  1927    42.03    <.0001
TRTPN(ATPTN)  2          9          WORK.ANA_DATA    5.9706    0.1884  1947    31.69    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  2          4            0.05     10.8118     11.5529
TRTPN(ATPTN)  1          5            0.05      7.0815      7.6034
TRTPN(ATPTN)  2          5            0.05      7.7036      8.4486
TRTPN(ATPTN)  1          6            0.05      9.7190     10.2415
TRTPN(ATPTN)  2          6            0.05     10.6446     11.3951
TRTPN(ATPTN)  1          7            0.05      8.3594      8.8863
TRTPN(ATPTN)  2          7            0.05      9.3159     10.0701
TRTPN(ATPTN)  1          8            0.05      5.7237      6.2512
TRTPN(ATPTN)  2          8            0.05      6.3221      7.0727
TRTPN(ATPTN)  1          9            0.05      5.3114      5.8313
TRTPN(ATPTN)  2          9            0.05      5.6011      6.3402
                               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   -0.5098    0.2296  1927
TRTPN(ATPTN)  1          1          1          2          WORK.ANA_DATA  -4.0018    0.1498  3513
TRTPN(ATPTN)  1          1          2          2          WORK.ANA_DATA   -5.2646    0.2324  1979
TRTPN(ATPTN)  1          1          1          3          WORK.ANA_DATA   -1.4158    0.1496  3514
TRTPN(ATPTN)  1          1         2          3          WORK.ANA_DATA   -2.6958    0.2324  1979
TRTPN(ATPTN)  1          1          1          4          WORK.ANA_DATA   -4.1760    0.1496  3514
TRTPN(ATPTN)  1          1          2          4          WORK.ANA_DATA   -5.6342    0.2308  1947
TRTPN(ATPTN)  1          1          1          5          WORK.ANA_DATA   -1.7943    0.1496  3514
TRTPN(ATPTN)  1          1          2          5          WORK.ANA_DATA   -2.5279    0.2316  1963
TRTPN(ATPTN)  1          1          1          6         WORK.ANA_DATA   -4.4321    0.1498  3514
TRTPN(ATPTN)  1          1          2          6          WORK.ANA_DATA   -5.4717    0.2328  1988
TRTPN(ATPTN)  1          1          1          7          WORK.ANA_DATA   -3.0747    0.1508  3516
TRTPN(ATPTN)  1          1          2          7          WORK.ANA_DATA   -4.1448    0.2336  2005
TRTPN(ATPTN)  1          1          1          8          WORK.ANA_DATA   -0.4393    0.1509  3516
TRTPN(ATPTN)  1          1          2          8          WORK.ANA_DATA   -1.1492    0.2328  1988
TRTPN(ATPTN)  1          1          1          9          WORK.ANA_DATA  -0.02320    0.1492  3511
TRTPN(ATPTN)  1          1          2          9          WORK.ANA_DATA   -0.4225    0.2304  1940
TRTPN(ATPTN)  2          1          1          2          WORK.ANA_DATA   -3.4920    0.2300  1934
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
175 of 334
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          1          2          2          WORK.ANA_DATA   -4.7548    0.2140  3526
TRTPN(ATPTN)  2          1          1          3          WORK.ANA_DATA   -0.9060    0.2299  1932
TRTPN(ATPTN)  2          1          2          3          WORK.ANA_DATA   -2.1860    0.2140  3526
TRTPN(ATPTN)  2          1          1          4          WORK.ANA_DATA   -3.6662    0.2299  1932
TRTPN(ATPTN)  2          1          2          4          WORK.ANA_DATA   -5.1244    0.2123  3522
TRTPN(ATPTN)  2          1          1          5          WORK.ANA_DATA   -1.2845    0.2299  1932
TRTPN(ATPTN)  2          1          2          5          WORK.ANA_DATA   -2.0181    0.2132  3525
TRTPN(ATPTN)  2          1          1          6          WORK.ANA_DATA   -3.9223    0.2300  1934
TRTPN(ATPTN)  2          1          2          6          WORK.ANA_DATA   -4.9619    0.2144  3527
TRTPN(ATPTN)  2          1          1          7          WORK.ANA_DATA   -2.5649    0.2306  1948
TRTPN(ATPTN)  2          1          2          7          WORK.ANA_DATA   -3.6350    0.2153  3528
TRTPN(ATPTN)  2          1          1          8          WORK.ANA_DATA   0.07050    0.2307  1950
TRTPN(ATPTN)  2          1          2          8          WORK.ANA_DATA   -0.6394    0.2145  3527
TRTPN(ATPTN)  2          1          1          9          WORK.ANA_DATA    0.4866    0.2296  1926
TRTPN(ATPTN)  2          1          2          9          WORK.ANA_DATA   0.08734    0.2119  3517
TRTPN(ATPTN)  1          2          2          2          WORK.ANA_DATA   -1.2629    0.2327  1987
TRTPN(ATPTN)  1          2          1          3          WORK.ANA_DATA   2.5860    0.1501  3513
TRTPN(ATPTN)  1          2          2          3          WORK.ANA_DATA    1.3060    0.2327  1987
TRTPN(ATPTN)  1          2          1          4          WORK.ANA_DATA   -0.1742    0.1501  3513
TRTPN(ATPTN)  1          2          2          4          WORK.ANA_DATA   -1.6324    0.2312  1954
TRTPN(ATPTN)  1          2          1          5          WORK.ANA_DATA    2.2075    0.1501  3513
TRTPN(ATPTN)  1          2          2          5          WORK.ANA_DATA    1.4738    0.2320  1970
TRTPN(ATPTN)  1          2          1          6          WORK.ANA_DATA   -0.4303    0.1503  3513
TRTPN(ATPTN)  1          2          2          6          WORK.ANA_DATA   -1.4699    0.2331  1995
TRTPN(ATPTN)  1          2          1          7          WORK.ANA_DATA    0.9271    0.1513  3515
TRTPN(ATPTN)  1          2          2          7          WORK.ANA_DATA   -0.1431    0.2339  2013
TRTPN(ATPTN)  1          2          1          8          WORK.ANA_DATA    3.5625    0.1514  3515
TRTPN(ATPTN)  1          2          2          8          WORK.ANA_DATA    2.8525    0.2331  1995
TRTPN(ATPTN)  1          2          1          9          WORK.ANA_DATA    3.9786    0.1498  3513
TRTPN(ATPTN)  1          2          2          9          WORK.ANA_DATA    3.5793    0.2308  1947
TRTPN(ATPTN)  2          2          1          3          WORK.ANA_DATA    3.8488    0.2327  1985
TRTPN(ATPTN)  2          2          2          3          WORK.ANA_DATA    2.5689    0.2163  3516
TRTPN(ATPTN)  2          2          1          4          WORK.ANA_DATA    1.0886    0.2327  1985
TRTPN(ATPTN)  2          2          2          4          WORK.ANA_DATA   -0.3695    0.2148  3515
TRTPN(ATPTN)  2          2          1          5          WORK.ANA_DATA    3.4704    0.2327  1985
TRTPN(ATPTN)  2          2          2          5          WORK.ANA_DATA    2.7367    0.2156  3516
TRTPN(ATPTN)  2          2          1          6          WORK.ANA_DATA    0.8326    0.2328  1987
TRTPN(ATPTN)  2          2          2          6          WORK.ANA_DATA   -0.2071    0.2166  3514
TRTPN(ATPTN)  2          2          1          7          WORK.ANA_DATA    2.1900    0.2334  2001
TRTPN(ATPTN)  2          2          2          7          WORK.ANA_DATA    1.1198    0.2175  3515
TRTPN(ATPTN)  2          2          1          8          WORK.ANA_DATA    4.8253    0.2335  2003
TRTPN(ATPTN)  2          2          2          8          WORK.ANA_DATA    4.1154    0.2167  3516
TRTPN(ATPTN)  2          2          1          9          WORK.ANA_DATA    5.2414    0.2324  1979
TRTPN(ATPTN)  2          2          2          9          WORK.ANA_DATA    4.8422    0.2146  3520
TRTPN(ATPTN)  1          3          2          3          WORK.ANA_DATA   -1.2800    0.2327  1985
TRTPN(ATPTN)  1          3          1          4          WORK.ANA_DATA   -2.7602    0.1500  3511
TRTPN(ATPTN)  1          3          2          4          WORK.ANA_DATA   -4.2184    0.2311  1952
TRTPN(ATPTN)  1          3          1          5          WORK.ANA_DATA   -0.3785    0.1500  3511
TRTPN(ATPTN)  1          3          2          5          WORK.ANA_DATA   -1.1121    0.2319  1968
TRTPN(ATPTN)  1          3          1          6          WORK.ANA_DATA   -3.0163    0.1501  3512
TRTPN(ATPTN)  1          3          2          6          WORK.ANA_DATA   -4.0559    0.2330  1993
TRTPN(ATPTN)  1          3          1          7          WORK.ANA_DATA   -1.6589    0.1511  3513
TRTPN(ATPTN)  1          3          2          7          WORK.ANA_DATA   -2.7290    0.2338  2011
TRTPN(ATPTN)  1          3          1          8          WORK.ANA_DATA    0.9765    0.1512  3514
TRTPN(ATPTN)  1          3          2          8          WORK.ANA_DATA    0.2666    0.2331  1993
TRTPN(ATPTN)  1          3          1          9          WORK.ANA_DATA    1.3926    0.1496 3514
TRTPN(ATPTN)  1          3          2          9          WORK.ANA_DATA    0.9933    0.2307  1945
TRTPN(ATPTN)  2          3          1          4          WORK.ANA_DATA   -1.4802    0.2327  1985
TRTPN(ATPTN)  2          3          2          4          WORK.ANA_DATA   -2.9384    0.2149  3518
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
176 of 334
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          3          1          5          WORK.ANA_DATA    0.9015    0.2327  1985
TRTPN(ATPTN)  2          3          2          5          WORK.ANA_DATA    0.1679    0.2154  3512
TRTPN(ATPTN)  2          3          1          6          WORK.ANA_DATA   -1.7363    0.2328  1987
TRTPN(ATPTN)  2          3          2          6          WORK.ANA_DATA   -2.7759    0.2167  3516
TRTPN(ATPTN)  2          3          1          7          WORK.ANA_DATA   -0.3789    0.2334  2001
TRTPN(ATPTN)  2          3          2          7          WORK.ANA_DATA   -1.4490    0.2176  3518
TRTPN(ATPTN)  2          3          1          8          WORK.ANA_DATA    2.2565    0.2335  2003
TRTPN(ATPTN)  2          3          2          8          WORK.ANA_DATA    1.5466    0.2166  3513
TRTPN(ATPTN)  2          3          1          9          WORK.ANA_DATA    2.6726    0.2324  1979
TRTPN(ATPTN)  2          3          2          9          WORK.ANA_DATA    2.2733    0.2146  3520
TRTPN(ATPTN)  1          4          2          4          WORK.ANA_DATA   -1.4582    0.2311  1952
TRTPN(ATPTN)  1          4          1          5          WORK.ANA_DATA    2.3817    0.1500  3511
TRTPN(ATPTN)  1          4          2          5          WORK.ANA_DATA    1.6481    0.2319  1968
TRTPN(ATPTN)  1          4          1          6          WORK.ANA_DATA   -0.2561    0.1501  3511
TRTPN(ATPTN)  1          4          2          6          WORK.ANA_DATA   -1.2957    0.2331  1993
TRTPN(ATPTN)  1          4          1          7          WORK.ANA_DATA    1.1013    0.1511  3514
TRTPN(ATPTN)  1          4          2          7          WORK.ANA_DATA   0.03118    0.2338  2011
TRTPN(ATPTN)  1          4          1          8          WORK.ANA_DATA    3.7367    0.1512  3514
TRTPN(ATPTN)  1          4          2          8          WORK.ANA_DATA    3.0268    0.2331 1993
TRTPN(ATPTN)  1          4          1          9          WORK.ANA_DATA    4.1528    0.1496  3514
TRTPN(ATPTN)  1          4          2          9          WORK.ANA_DATA    3.7535    0.2307  1945
TRTPN(ATPTN)  2          4          1          5          WORK.ANA_DATA    3.8399    0.2311  1952
TRTPN(ATPTN)  2          4          2          5          WORK.ANA_DATA    3.1062    0.2141  3517
TRTPN(ATPTN)  2          4          1          6          WORK.ANA_DATA    1.2021    0.2312  1954
TRTPN(ATPTN)  2          4          2          6          WORK.ANA_DATA    0.1625    0.2152  3516
TRTPN(ATPTN)  2          4          1          7          WORK.ANA_DATA    2.5595    0.2318  1968
TRTPN(ATPTN)  2          4          2          7          WORK.ANA_DATA    1.4894    0.2160  3517
TRTPN(ATPTN)  2          4          1          8          WORK.ANA_DATA    5.1949    0.2319  1970
TRTPN(ATPTN)  2          4          2          8          WORK.ANA_DATA    4.4850    0.2152  3516
TRTPN(ATPTN)  2          4          1          9          WORK.ANA_DATA    5.6110    0.2308  1947
TRTPN(ATPTN)  2          4          2          9          WORK.ANA_DATA    5.2117    0.2129  3516
TRTPN(ATPTN)  1          5          2          5          WORK.ANA_DATA   -0.7336    0.2319  1968
TRTPN(ATPTN)  1          5          1          6          WORK.ANA_DATA   -2.6378    0.1501  3512
TRTPN(ATPTN)  1          5          2          6          WORK.ANA_DATA   -3.6774    0.2330  1993
TRTPN(ATPTN)  1          5          1          7          WORK.ANA_DATA   -1.2804    0.1511  3513
TRTPN(ATPTN)  1          5          2          7          WORK.ANA_DATA   -2.3505    0.2338  2011
TRTPN(ATPTN)  1          5          1          8          WORK.ANA_DATA    1.3550    0.1512  3513
TRTPN(ATPTN)  1          5          2          8          WORK.ANA_DATA    0.6451    0.2331  1993
TRTPN(ATPTN)  1          5          1          9          WORK.ANA_DATA    1.7711    0.1496  3514
TRTPN(ATPTN)  1          5          2          9          WORK.ANA_DATA    1.3718    0.2307  1945
TRTPN(ATPTN)  2          5          1          6          WORK.ANA_DATA   -1.9041    0.2320  1970
TRTPN(ATPTN)  2          5          2          6          WORK.ANA_DATA   -2.9438    0.2159  3515
TRTPN(ATPTN)  2          5          1          7          WORK.ANA_DATA   -0.5468    0.2326  1984
TRTPN(ATPTN)  2          5          2          7          WORK.ANA_DATA   -1.6169    0.2168  3516
TRTPN(ATPTN)  2          5          1          8          WORK.ANA_DATA    2.0886    0.2327  1986
TRTPN(ATPTN)  2          5          2          8          WORK.ANA_DATA    1.3787    0.2158  3513
TRTPN(ATPTN)  2          5          1          9          WORK.ANA_DATA    2.5047    0.2316  1963
TRTPN(ATPTN)  2          5          2          9          WORK.ANA_DATA    2.1055    0.2138  3519
TRTPN(ATPTN)  1          6          2          6          WORK.ANA_DATA   -1.0396    0.2331  1995
TRTPN(ATPTN)  1          6          1          7          WORK.ANA_DATA    1.3574    0.1512  3514
TRTPN(ATPTN)  1          6          2          7          WORK.ANA_DATA    0.2872    0.2339  2013
TRTPN(ATPTN)  1          6          1          8          WORK.ANA_DATA    3.9928    0.1514  3514
TRTPN(ATPTN)  1          6          2          8          WORK.ANA_DATA    3.2828    0.2332  1995
TRTPN(ATPTN)  1          6          1          9          WORK.ANA_DATA    4.4089    0.1498  3514
TRTPN(ATPTN)  1          6          2          9          WORK.ANA_DATA    4.0096    0.2308  1947
TRTPN(ATPTN)  2          6          1          7          WORK.ANA_DATA    2.3970    0.2338  2009
TRTPN(ATPTN)  2          6          2          7          WORK.ANA_DATA    1.3269    0.2180  3518
TRTPN(ATPTN)  2          6          1          8          WORK.ANA_DATA    5.0324    0.2339  2011
TRTPN(ATPTN)  2          6          2          8          WORK.ANA_DATA    4.3225    0.2170  3515
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
177 of 334
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    5.4485    0.2328  1988
TRTPN(ATPTN)  2          6          2          9          WORK.ANA_DATA    5.0492    0.2150  3521
TRTPN(ATPTN)  1          7          2          7          WORK.ANA_DATA   -1.0701    0.2346  2026
TRTPN(ATPTN)  1          7          1          8          WORK.ANA_DATA    2.6354    0.1523  3514
TRTPN(ATPTN)  1          7          2          8          WORK.ANA_DATA    1.9255    0.2338  2009
TRTPN(ATPTN)  1          7          1          9          WORK.ANA_DATA    3.0515    0.1508  3516
TRTPN(ATPTN)  1          7          2          9          WORK.ANA_DATA    2.6522    0.2314  1961
TRTPN(ATPTN)  2          7          1          8          WORK.ANA_DATA    3.7055    0.2347  2029
TRTPN(ATPTN)  2          7          2          8          WORK.ANA_DATA    2.9956    0.2179  3516
TRTPN(ATPTN)  2          7          1          9          WORK.ANA_DATA    4.1216    0.2336  2005
TRTPN(ATPTN)  2          7          2          9          WORK.ANA_DATA    3.7224    0.2159  3522
TRTPN(ATPTN)  1          8          2          8          WORK.ANA_DATA   -0.7099    0.2339  2011
TRTPN(ATPTN)  1          8          1          9          WORK.ANA_DATA    0.4161    0.1509  3516
TRTPN(ATPTN)  1          8          2          9          WORK.ANA_DATA   0.01684    0.2315  1964
TRTPN(ATPTN)  2          8          1          9          WORK.ANA_DATA    1.1260    0.2328  1988
TRTPN(ATPTN)  2          8          2          9          WORK.ANA_DATA    0.7268    0.2151  3522
TRTPN(ATPTN)  1          9          2          9          WORK.ANA_DATA   -0.3993    0.2304  1940
                          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            -2.22      0.0265      0.05
TRTPN(ATPTN)  1          1          1          2           -26.72      <.0001      0.05
TRTPN(ATPTN)  1          1          2          2           -22.66      <.0001      0.05
TRTPN(ATPTN)  1          1          1          3            -9.46      <.0001      0.05
TRTPN(ATPTN)  1          1          2          3           -11.60      <.0001      0.05
TRTPN(ATPTN)  1          1          1          4           -27.91      <.0001      0.05
TRTPN(ATPTN)  1          1          2          4           -24.41      <.0001      0.05
TRTPN(ATPTN)  1          1          1          5           -11.99      <.0001      0.05
TRTPN(ATPTN)  1          1          2          5           -10.91      <.0001      0.05
TRTPN(ATPTN)  1          1          1          6           -29.59      <.0001      0.05
TRTPN(ATPTN)  1          1          2          6           -23.51      <.0001      0.05
TRTPN(ATPTN)  1          1          1          7           -20.39      <.0001      0.05
TRTPN(ATPTN)  1          1          2          7           -17.75      <.0001      0.05
TRTPN(ATPTN)  1          1          1          8            -2.91      0.0036      0.05
TRTPN(ATPTN)  1          1          2          8            -4.94      <.0001      0.05
TRTPN(ATPTN)  1          1          1          9            -0.16      0.8764      0.05
TRTPN(ATPTN)  1          1          2          9            -1.83      0.0669      0.05
TRTPN(ATPTN)  2          1          1          2           -15.18      <.0001      0.05
TRTPN(ATPTN)  2          1          2          2           -22.22      <.0001      0.05
TRTPN(ATPTN)  2          1          1          3            -3.94      <.0001      0.05
TRTPN(ATPTN)  2          1          2          3           -10.21      <.0001      0.05
TRTPN(ATPTN)  2          1          1          4           -15.95      <.0001      0.05
TRTPN(ATPTN)  2          1          2          4           -24.13      <.0001      0.05
TRTPN(ATPTN)  2          1          1          5            -5.59      <.0001      0.05
TRTPN(ATPTN)  2          1          2          5            -9.47      <.0001      0.05
TRTPN(ATPTN)  2          1          1          6           -17.05      <.0001      0.05
TRTPN(ATPTN)  2          1          2          6           -23.14      <.0001      0.05
TRTPN(ATPTN)  2          1          1          7           -11.12      <.0001      0.05
TRTPN(ATPTN)  2          1          2          7           -16.88      <.0001      0.05
TRTPN(ATPTN)  2          1          1          8             0.31      0.7600      0.05
TRTPN(ATPTN)  2          1          2          8            -2.98      0.0029      0.05
TRTPN(ATPTN)  2          1          1          9             2.12      0.0342      0.05
TRTPN(ATPTN)  2          1          2          9             0.41      0.6802      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
178 of 334
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          2          2          2            -5.43      <.0001      0.05
TRTPN(ATPTN)  1          2          1          3            17.22      <.0001      0.05
TRTPN(ATPTN)  1          2          2          3             5.61      <.0001      0.05
TRTPN(ATPTN)  1          2          1          4            -1.16      0.2459      0.05
TRTPN(ATPTN)  1          2          2          4            -7.06      <.0001      0.05
TRTPN(ATPTN)  1          2         1          5            14.70      <.0001      0.05
TRTPN(ATPTN)  1          2          2          5             6.35      <.0001      0.05
TRTPN(ATPTN)  1          2          1          6            -2.86      0.0042      0.05
TRTPN(ATPTN)  1          2          2          6            -6.31      <.0001      0.05
TRTPN(ATPTN)  1          2          1          7             6.13      <.0001      0.05
TRTPN(ATPTN)  1          2          2          7            -0.61      0.5409      0.05
TRTPN(ATPTN)  1          2          1          8            23.53      <.0001      0.05
TRTPN(ATPTN)  1          2          2          8            12.24      <.0001      0.05
TRTPN(ATPTN)  1          2          1          9            26.57      <.0001      0.05
TRTPN(ATPTN)  1          2          2          9            15.51      <.0001      0.05
TRTPN(ATPTN)  2          2          1          3            16.54      <.0001      0.05
TRTPN(ATPTN)  2          2          2          3            11.87      <.0001      0.05
TRTPN(ATPTN)  2          2          1          4             4.68      <.0001      0.05
TRTPN(ATPTN)  2          2          2          4            -1.72      0.0854      0.05
TRTPN(ATPTN)  2          2          1          5            14.92      <.0001      0.05
TRTPN(ATPTN)  2          2          2          5            12.69      <.0001      0.05
TRTPN(ATPTN)  2          2          1          6             3.58      0.0004      0.05
TRTPN(ATPTN)  2          2          2          6            -0.96      0.3392      0.05
TRTPN(ATPTN)  2          2          1          7             9.38      <.0001      0.05
TRTPN(ATPTN)  2          2          2          7             5.15      <.0001      0.05
TRTPN(ATPTN)  2          2          1          8            20.67      <.0001      0.05
TRTPN(ATPTN)  2          2          2          8            18.99      <.0001      0.05
TRTPN(ATPTN)  2          2          1          9            22.56      <.0001      0.05
TRTPN(ATPTN)  2          2          2          9            22.56      <.0001      0.05
TRTPN(ATPTN)  1          3          2          3            -5.50      <.0001      0.05
TRTPN(ATPTN)  1          3          1          4           -18.41      <.0001      0.05
TRTPN(ATPTN)  1          3          2          4           -18.25      <.0001      0.05
TRTPN(ATPTN)  1          3          1          5            -2.52      0.0117      0.05
TRTPN(ATPTN)  1          3          2          5            -4.80      <.0001      0.05
TRTPN(ATPTN)  1          3          1          6           -20.09      <.0001      0.05
TRTPN(ATPTN)  1          3          2          6           -17.40      <.0001      0.05
TRTPN(ATPTN)  1          3          1          7           -10.98      <.0001      0.05
TRTPN(ATPTN)  1          3          2          7           -11.67      <.0001      0.05
TRTPN(ATPTN)  1          3          1          8             6.46      <.0001      0.05
TRTPN(ATPTN)  1          3          2          8             1.14      0.2528      0.05
TRTPN(ATPTN)  1          3          1          9             9.31      <.0001      0.05
TRTPN(ATPTN)  1          3          2          9             4.31      <.0001      0.05
TRTPN(ATPTN)  2          3          1          4            -6.36      <.0001      0.05
TRTPN(ATPTN)  2          3          2          4           -13.67      <.0001      0.05
TRTPN(ATPTN)  2          3          1          5             3.87      0.0001      0.05
TRTPN(ATPTN)  2          3          2          5             0.78      0.4358      0.05
TRTPN(ATPTN)  2          3          1          6            -7.46      <.0001      0.05
TRTPN(ATPTN)  2          3          2          6           -12.81      <.0001      0.05
TRTPN(ATPTN)  2          3          1          7            -1.62      0.1046      0.05
TRTPN(ATPTN)  2          3          2          7            -6.66      <.0001      0.05
TRTPN(ATPTN)  2          3          1          8             9.66      <.0001      0.05
TRTPN(ATPTN)  2          3          2          8             7.14      <.0001      0.05
TRTPN(ATPTN)  2          3          1          9            11.50      <.0001      0.05
TRTPN(ATPTN)  2          3          2          9            10.59      <.0001      0.05
TRTPN(ATPTN)  1          4          2          4            -6.31      <.0001      0.05
TRTPN(ATPTN)  1          4          1          5            15.88      <.0001      0.05
TRTPN(ATPTN)  1          4          2          5             7.11      <.0001      0.05
TRTPN(ATPTN)  1          4          1          6            -1.71      0.0881      0.05
TRTPN(ATPTN)  1          4          2          6            -5.56      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
179 of 334
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          4          1          7             7.29      <.0001      0.05
TRTPN(ATPTN)  1          4          2          7             0.13      0.8939      0.05
TRTPN(ATPTN)  1          4          1          8            24.71      <.0001      0.05
TRTPN(ATPTN)  1          4          2          8            12.99      <.0001      0.05
TRTPN(ATPTN) 1          4          1          9            27.75      <.0001      0.05
TRTPN(ATPTN)  1          4          2          9            16.27      <.0001      0.05
TRTPN(ATPTN)  2          4          1          5            16.62      <.0001      0.05
TRTPN(ATPTN)  2          4          2          5            14.51      <.0001      0.05
TRTPN(ATPTN)  2          4          1          6             5.20      <.0001      0.05
TRTPN(ATPTN)  2          4          2          6             0.75      0.4503      0.05
TRTPN(ATPTN)  2          4          1          7            11.04      <.0001      0.05
TRTPN(ATPTN)  2          4          2          7             6.89      <.0001      0.05
TRTPN(ATPTN)  2          4          1          8            22.40      <.0001      0.05
TRTPN(ATPTN)  2          4          2          8            20.84      <.0001      0.05
TRTPN(ATPTN)  2          4          1          9            24.31      <.0001      0.05
TRTPN(ATPTN)  2          4          2          9            24.48      <.0001      0.05
TRTPN(ATPTN)  1          5          2          5            -3.16      0.0016      0.05
TRTPN(ATPTN)  1          5          1          6           -17.57      <.0001      0.05
TRTPN(ATPTN)  1          5          2          6           -15.78      <.0001      0.05
TRTPN(ATPTN)  1          5          1          7            -8.48      <.0001      0.05
TRTPN(ATPTN)  1          5          2          7           -10.05      <.0001      0.05
TRTPN(ATPTN)  1          5          1          8             8.96      <.0001      0.05
TRTPN(ATPTN)  1          5          2          8             2.77      0.0057      0.05
TRTPN(ATPTN)  1          5          1          9            11.84      <.0001      0.05
TRTPN(ATPTN)  1          5          2          9             5.95      <.0001      0.05
TRTPN(ATPTN)  2          5          1          6            -8.21      <.0001      0.05
TRTPN(ATPTN)  2          5          2          6           -13.63      <.0001      0.05
TRTPN(ATPTN)  2          5          1          7            -2.35      0.0189      0.05
TRTPN(ATPTN)  2          5          2          7            -7.46      <.0001      0.05
TRTPN(ATPTN)  2          5          1          8             8.97      <.0001      0.05
TRTPN(ATPTN)  2          5          2          8             6.39      <.0001      0.05
TRTPN(ATPTN)  2          5          1          9            10.81      <.0001      0.05
TRTPN(ATPTN)  2          5          2          9             9.85      <.0001      0.05
TRTPN(ATPTN)  1          6          2          6            -4.46      <.0001      0.05
TRTPN(ATPTN)  1          6          1          7             8.98      <.0001      0.05
TRTPN(ATPTN)  1          6          2          7             1.23      0.2196      0.05
TRTPN(ATPTN) 1          6          1          8            26.38      <.0001      0.05
TRTPN(ATPTN)  1          6          2          8            14.08      <.0001      0.05
TRTPN(ATPTN)  1          6          1          9            29.44      <.0001      0.05
TRTPN(ATPTN)  1          6          2          9            17.38      <.0001      0.05
TRTPN(ATPTN)  2          6          1          7            10.25      <.0001      0.05
TRTPN(ATPTN)  2          6          2          7             6.09      <.0001      0.05
TRTPN(ATPTN)  2          6          1          8            21.52      <.0001      0.05
TRTPN(ATPTN)  2          6          2          8            19.91      <.0001      0.05
TRTPN(ATPTN)  2          6          1          9            23.41      <.0001      0.05
TRTPN(ATPTN)  2          6          2          9            23.48      <.0001      0.05
TRTPN(ATPTN)  1          7          2          7            -4.56      <.0001      0.05
TRTPN(ATPTN)  1          7          1          8            17.31      <.0001      0.05
TRTPN(ATPTN)  1          7          2          8             8.24      <.0001      0.05
TRTPN(ATPTN)  1          7          1          9            20.24      <.0001      0.05
TRTPN(ATPTN)  1          7          2          9            11.46      <.0001      0.05
TRTPN(ATPTN)  2          7          1          8            15.79      <.0001      0.05
TRTPN(ATPTN)  2          7          2          8            13.75      <.0001      0.05
TRTPN(ATPTN)  2          7          1          9            17.65      <.0001      0.05
TRTPN(ATPTN)  2          7          2          9            17.24      <.0001      0.05
TRTPN(ATPTN)  1          8          2          8            -3.04      0.0024      0.05
TRTPN(ATPTN)  1          8          1          9             2.76      0.0059      0.05
TRTPN(ATPTN)  1          8          2          9             0.07      0.9420      0.05
TRTPN(ATPTN)  2          8          1          9             4.84      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
180 of 334
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          8          2          9             3.38      0.0007      0.05
TRTPN(ATPTN)  1          9          2          9            -1.73      0.0833      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           -0.9601    -0.05948
TRTPN(ATPTN)  1          1          1          2           -4.2954     -3.7081
TRTPN(ATPTN)  1          1          2          2           -5.7204     -4.8089
TRTPN(ATPTN)  1          1          1          3           -1.7092     -1.1224
TRTPN(ATPTN)  1          1          2          3           -3.1515     -2.2401
TRTPN(ATPTN)  1          1          1          4           -4.4694     -3.8826
TRTPN(ATPTN)  1          1          2          4           -6.0869     -5.1815
TRTPN(ATPTN)  1          1          1          5           -2.0876     -1.5009
TRTPN(ATPTN)  1          1          2          5           -2.9821     -2.0737
TRTPN(ATPTN)  1          1          1          6           -4.7257     -4.1384
TRTPN(ATPTN)  1          1          2          6           -5.9282     -5.0152
TRTPN(ATPTN)  1          1          1          7           -3.3703     -2.7791
TRTPN(ATPTN)  1          1          2          7           -4.6028     -3.6868
TRTPN(ATPTN)  1          1          1          8           -0.7352     -0.1434
TRTPN(ATPTN)  1          1          2          8           -1.6057     -0.6927
TRTPN(ATPTN)  1          1          1          9           -0.3157      0.2693
TRTPN(ATPTN)  1          1          2          9           -0.8743     0.02937
TRTPN(ATPTN)  2          1          1          2           -3.9430     -3.0410
TRTPN(ATPTN)  2          1          2          2           -5.1744     -4.3352
TRTPN(ATPTN)  2          1          1          3           -1.3569     -0.4552
TRTPN(ATPTN)  2          1          2          3           -2.6056     -1.7664
TRTPN(ATPTN)  2          1          1          4           -4.1171     -3.2153
TRTPN(ATPTN)  2          1          2          4           -5.5407     -4.7081
TRTPN(ATPTN)  2          1          1          5           -1.7353     -0.8336
TRTPN(ATPTN)  2          1          2          5           -2.4361     -1.6002
TRTPN(ATPTN)  2          1          1          6           -4.3733     -3.4712
TRTPN(ATPTN)  2          1          2          6           -5.3823     -4.5415
TRTPN(ATPTN)  2          1          1          7           -3.0172     -2.1126
TRTPN(ATPTN)  2          1          2          7           -4.0571     -3.2129
TRTPN(ATPTN)  2          1          1          8           -0.3820      0.5230
TRTPN(ATPTN)  2          1          2          8           -1.0599     -0.2189
TRTPN(ATPTN)  2          1          1          9           0.03632      0.9369
TRTPN(ATPTN)  2          1          2          9           -0.3280      0.5027
TRTPN(ATPTN)  1          2          2          2           -1.7193     -0.8065
TRTPN(ATPTN)  1          2          1          3            2.2916      2.8803
TRTPN(ATPTN)  1          2          2          3            0.8495      1.7624
TRTPN(ATPTN)  1          2          1          4           -0.4686      0.1201
TRTPN(ATPTN)  1          2          2          4           -2.0858     -1.1790
TRTPN(ATPTN)  1          2         1          5            1.9131      2.5018
TRTPN(ATPTN)  1          2          2          5            1.0189      1.9288
TRTPN(ATPTN)  1          2          1          6           -0.7250     -0.1357
TRTPN(ATPTN)  1          2          2          6           -1.9271     -1.0127
TRTPN(ATPTN)  1          2          1          7            0.6305      1.2237
TRTPN(ATPTN)  1          2          2          7           -0.6018      0.3157
TRTPN(ATPTN)  1          2          1          8            3.2656      3.8593
TRTPN(ATPTN)  1          2          2          8            2.3953      3.3098
TRTPN(ATPTN)  1          2          1          9            3.6849      4.2722
TRTPN(ATPTN)  1          2          2          9            3.1268      4.0318
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
181 of 334
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)  2          2          1          3            3.3925      4.3051
TRTPN(ATPTN)  2          2          2          3            2.1447      2.9930
TRTPN(ATPTN)  2          2          1          4            0.6323      1.5449
TRTPN(ATPTN)  2          2          2          4           -0.7906     0.05156
TRTPN(ATPTN)  2          2          1          5            3.0141      3.9266
TRTPN(ATPTN)  2          2          2          5            2.3140      3.1594
TRTPN(ATPTN)  2          2          1          6            0.3761      1.2890
TRTPN(ATPTN)  2          2          2          6           -0.6318      0.2177
TRTPN(ATPTN)  2          2          1          7            1.7322      2.6477
TRTPN(ATPTN)  2          2          2          7            0.6934      1.5462
TRTPN(ATPTN)  2          2          1          8            4.3674      5.2832
TRTPN(ATPTN)  2          2          2          8            3.6905      4.5404
TRTPN(ATPTN)  2          2          1          9            4.7857      5.6972
TRTPN(ATPTN)  2          2          2          9            4.4214      5.2630
TRTPN(ATPTN)  1          3          2          3           -1.7362     -0.8237
TRTPN(ATPTN)  1          3          1          4           -3.0542     -2.4662
TRTPN(ATPTN)  1          3          2          4           -4.6716     -3.7651
TRTPN(ATPTN)  1          3          1          5           -0.6725    -0.08446
TRTPN(ATPTN)  1          3          2          5           -1.5669     -0.6573
TRTPN(ATPTN)  1          3          1          6           -3.3106     -2.7220
TRTPN(ATPTN)  1          3          2          6           -4.5129     -3.5989
TRTPN(ATPTN)  1          3          1          7           -1.9551     -1.3627
TRTPN(ATPTN)  1          3          2          7           -3.1876     -2.2704
TRTPN(ATPTN)  1          3          1          8            0.6800      1.2730
TRTPN(ATPTN)  1          3          2          8           -0.1905      0.7237
TRTPN(ATPTN)  1          3          1          9            1.0992      1.6860
TRTPN(ATPTN)  1          3          2          9            0.5410      1.4457
TRTPN(ATPTN)  2          3          1          4           -1.9365     -1.0239
TRTPN(ATPTN)  2          3          2          4           -3.3597     -2.5170
TRTPN(ATPTN)  2          3          1          5            0.4452      1.3578
TRTPN(ATPTN)  2          3          2          5           -0.2544      0.5901
TRTPN(ATPTN)  2          3          1          6           -2.1927     -1.2798
TRTPN(ATPTN)  2          3          2          6           -3.2009     -2.3510
TRTPN(ATPTN)  2          3          1          7           -0.8366     0.07881
TRTPN(ATPTN)  2          3          2          7           -1.8756     -1.0224
TRTPN(ATPTN)  2          3          1          8            1.7986      2.7144
TRTPN(ATPTN)  2          3          2          8            1.1220      1.9712
TRTPN(ATPTN)  2          3          1          9            2.2169      3.1283
TRTPN(ATPTN)  2          3          2          9            1.8525      2.6941
TRTPN(ATPTN)  1          4          2          4           -1.9114     -1.0049
TRTPN(ATPTN)  1          4          1          5            2.0877      2.6757
TRTPN(ATPTN)  1          4          2          5            1.1933      2.1029
TRTPN(ATPTN)  1          4          1          6           -0.5503     0.03819
TRTPN(ATPTN)  1          4          2          6           -1.7527     -0.8386
TRTPN(ATPTN)  1          4          1          7            0.8051      1.3976
TRTPN(ATPTN)  1          4          2          7           -0.4274      0.4898
TRTPN(ATPTN)  1          4          1          8            3.4402      4.0332
TRTPN(ATPTN)  1          4          2          8            2.5697      3.4839
TRTPN(ATPTN)  1          4          1          9            3.8594      4.4462
TRTPN(ATPTN)  1          4          2          9            3.3011      4.2059
TRTPN(ATPTN)  2          4          1          5            3.3866      4.2931
TRTPN(ATPTN)  2          4         2          5            2.6865      3.5260
TRTPN(ATPTN)  2          4          1          6            0.7487      1.6555
TRTPN(ATPTN)  2          4          2          6           -0.2594      0.5844
TRTPN(ATPTN)  2          4          1          7            2.1048      3.0142
TRTPN(ATPTN)  2          4          2          7            1.0658      1.9129
TRTPN(ATPTN)  2          4          1          8            4.7400      5.6497
TRTPN(ATPTN)  2          4          2          8            4.0630      4.9069
TRTPN(ATPTN)  2          4          1          9            5.1583      6.0637
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
182 of 334
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)  2          4          2          9            4.7942      5.6292
TRTPN(ATPTN)  1          5          2          5           -1.1884     -0.2789
TRTPN(ATPTN)  1          5          1          6           -2.9321     -2.3435
TRTPN(ATPTN)  1          5          2          6           -4.1345     -3.2204
TRTPN(ATPTN)  1          5          1          7           -1.5766     -0.9842
TRTPN(ATPTN)  1          5          2          7           -2.8091     -1.8920
TRTPN(ATPTN)  1          5          1          8            1.0585      1.6514
TRTPN(ATPTN)  1          5          2          8            0.1880      1.1021
TRTPN(ATPTN)  1          5          1          9            1.4777      2.0645
TRTPN(ATPTN)  1          5          2          9            0.9194      1.8242
TRTPN(ATPTN)  2          5          1          6           -2.3591     -1.4492
TRTPN(ATPTN)  2          5          2          6           -3.3671     -2.5205
TRTPN(ATPTN)  2          5          1          7           -1.0030    -0.09055
TRTPN(ATPTN)  2          5          2          7           -2.0419     -1.1919
TRTPN(ATPTN)  2          5          1          8            1.6322      2.5450
TRTPN(ATPTN)  2          5          2          8            0.9556      1.8018
TRTPN(ATPTN)  2          5          1          9            2.0505      2.9589
TRTPN(ATPTN)  2          5          2          9            1.6863      2.5246
TRTPN(ATPTN)  1          6          2          6           -1.4969     -0.5824
TRTPN(ATPTN)  1          6          1          7            1.0609      1.6539
TRTPN(ATPTN)  1          6          2          7           -0.1715      0.7460
TRTPN(ATPTN)  1          6          1          8            3.6960      4.2896
TRTPN(ATPTN)  1          6          2          8            2.8256      3.7401
TRTPN(ATPTN)  1          6          1          9            4.1152      4.7025
TRTPN(ATPTN)  1          6          2          9            3.5570      4.4622
TRTPN(ATPTN)  2          6          1          7            1.9385      2.8555
TRTPN(ATPTN)  2          6          2          7            0.8995      1.7543
TRTPN(ATPTN)  2          6          1          8            4.5737      5.4911
TRTPN(ATPTN)  2          6          2          8            3.8969      4.7480
TRTPN(ATPTN)  2          6          1          9            4.9920      5.9050
TRTPN(ATPTN)  2          6          2          9            4.6276      5.4709
TRTPN(ATPTN)  1          7          2          7           -1.5301     -0.6101
TRTPN(ATPTN)  1          7          1          8            2.3368      2.9339
TRTPN(ATPTN)  1          7          2          8            1.4670      2.3840
TRTPN(ATPTN)  1          7          1          9            2.7559      3.3471
TRTPN(ATPTN)  1          7          2          9            2.1984      3.1061
TRTPN(ATPTN)  2          7          1          8            3.2453      4.1657
TRTPN(ATPTN)  2          7          2          8            2.5684      3.4228
TRTPN(ATPTN)  2          7          1          9            3.6636      4.5796
TRTPN(ATPTN)  2          7          2          9            3.2991      4.1457
TRTPN(ATPTN)  1          8          2          8           -1.1686     -0.2512
TRTPN(ATPTN)  1          8          1          9            0.1202      0.7120
TRTPN(ATPTN)  1          8          2          9           -0.4372      0.4709
TRTPN(ATPTN)  2          8          1          9            0.6695      1.5825
TRTPN(ATPTN)  2          8          2          9            0.3051      1.1484
TRTPN(ATPTN)  1          9          2          9           -0.8511     0.05258
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
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=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:
22 January 2020
Novo Nordisk
NN9068-4166
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=SMPGCOL
The Mixed Procedure
              Class Level Information
Class      Levels    Values
USUBJID       453  
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
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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The Mixed Procedure
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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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
Parameter Code=SMPGCOL
The Mixed Procedure
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
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=SMPGCOL
The Mixed Procedure
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
                    
           
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
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=SMPGCOL
The Mixed Procedure
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
                   
         
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
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=SMPGCOL
The Mixed Procedure
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
                   
          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
190 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
                    
          
                    
          
                    
          
                    
          
                   
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
                    
          
TRTPN           2    1 2                           
ATPTN           9    1 2 3 4 5 6 7 8 9             
PREAD           2    BASAL INSULIN + METFORMIN     
                     BASAL INSULIN + METFORMIN +   
                     ONE OTHER OAD                 
            Dimensions
Covariance Parameters             2
Columns in X                     39
Columns in Z                      0
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
191 of 334
9-point self-measured plasma glucose profile after 26 weeks of treatment – supportive statistical
analysis – full analysis set
Parameter Code=SMPGCOL
The Mixed Procedure
            Dimensions
Subjects                        453
Max Obs per Subject               9
          Number of Observations
Number of Observations Read            4077
Number of Observations Used            3987
Number of Observations Not Used          90
                     Iteration History
Iteration    Evaluations    -2 Res Log Like       Criterion
        0              1     40881.40823158                
        1              2     39887.00950934      0.00000000
                   Convergence criteria met.                    
                                   Covariance Parameter Estimates
                                    Standard         Z
Cov Parm     Subject    Estimate       Error     Value        Pr Z     Alpha       Lower       Upper
CS           USUBJID      631.46     50.5711     12.49      <.0001      0.05      532.34      730.57
Residual                 1091.10     26.0426     41.90      <.0001      0.05     1041.80     1143.99
Asymptotic Covariance Matrix of Estimates
Row    Cov Parm        CovP1       CovP2
   1    CS            2557.44    -77.8457
   2    Residual     -77.8457      678.22
           Fit Statistics
-2 Res Log Likelihood         39887.0
AIC (Smaller is Better)       39891.0
AICC (Smaller is Better)      39891.0
BIC (Smaller is Better)       39899.2
  Null Model Likelihood Ratio Test
    DF    Chi-Square      Pr > ChiSq
     1        994.40          <.0001
                                   Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint            Standard
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Estimate     Error
Intercept                                                                        107.76    3.8891
TRTPN                                                    1                      -7.1946    4.1516
TRTPN                                                    2                            0          
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
192 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint            Standard
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Estimate     Error
TRTPN(ATPTN)                                             1          1            0.7033    3.3840
TRTPN(ATPTN)                                             2          1            2.6952    4.3757
TRTPN(ATPTN)                                             1          2           71.8421    3.4058
TRTPN(ATPTN)                                             2          2           87.4046    4.3979
TRTPN(ATPTN)                                             1          3           22.0372    3.4006
TRTPN(ATPTN)                                             2          3           37.9077    4.4057
TRTPN(ATPTN)                                             1          4           72.8432    3.3924
TRTPN(ATPTN)                                             2          4           91.9248    4.3856
TRTPN(ATPTN)                                             1          5           33.1905    3.3989
TRTPN(ATPTN)                                             2          5           39.2162    4.3997
TRTPN(ATPTN)                                             1          6           80.0601    3.3967
TRTPN(ATPTN)                                             2          6           91.5997   4.4173
TRTPN(ATPTN)                                             1          7           54.3426    3.4347
TRTPN(ATPTN)                                             2          7           66.4318    4.4361
TRTPN(ATPTN)                                             1          8            7.8283    3.4334
TRTPN(ATPTN)                                             2          8           13.4264    4.4143
TRTPN(ATPTN)                                             1          9                 0          
TRTPN(ATPTN)                                             2          9                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1           -2.7250    3.9060
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2           -0.6754    3.9435
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3            6.0799    3.9403
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4            3.8311    3.9276
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5           -3.0503    3.9334
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6           -1.6527    3.9476
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7            0.9968    3.9739
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8           -1.0581    3.9719
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                 0          
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9           -0.3624    3.9131
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                 0          
                                 Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)          DF   t Value
Intercept                                                                      1934     27.71
TRTPN                                                    1                     1940     -1.73
TRTPN                                                    2                                   
TRTPN(ATPTN)                                             1          1          3512      0.21
TRTPN(ATPTN)                                             2          1          3513      0.62
TRTPN(ATPTN)                                             1          2          3516     21.09
TRTPN(ATPTN)                                             2          2          3514     19.87
TRTPN(ATPTN)                                             1          3          3515      6.48
TRTPN(ATPTN)                                             2          3          3516      8.60
TRTPN(ATPTN)                                             1          4          3514     21.47
TRTPN(ATPTN)                                             2          4          3513     20.96
TRTPN(ATPTN)                                             1          5          3515      9.77
TRTPN(ATPTN)                                             2          5          3515      8.91
TRTPN(ATPTN)                                             1          6          3515     23.57
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
193 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)          DF   t Value
TRTPN(ATPTN)                                             2          6          3516     20.74
TRTPN(ATPTN)                                             1          7          3518     15.82
TRTPN(ATPTN)                                             2          7          3517     14.98
TRTPN(ATPTN)                                             1          8          3518      2.28
TRTPN(ATPTN)                                             2          8          3516      3.04
TRTPN(ATPTN)                                             1          9                        
TRTPN(ATPTN)                                             2          9                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1          1927     -0.70
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2          1970     -0.17
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3          1965      1.54
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4          1949      0.98
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5          1956     -0.78
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6          1975     -0.42
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7          2009      0.25
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8          2006     -0.27
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                        
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9          1934     -0.09
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                        
                              Solution for Fixed Effects
                                                         Planned
                                                         Treatment
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Pr > |t|
Intercept                                                                        <.0001
TRTPN                                                    1                       0.0833
TRTPN                                                    2                             
TRTPN(ATPTN)                                             1          1            0.8354
TRTPN(ATPTN)                                             2          1            0.5380
TRTPN(ATPTN)                                             1          2            <.0001
TRTPN(ATPTN)                                             2          2            <.0001
TRTPN(ATPTN)                                             1          3            <.0001
TRTPN(ATPTN)                                             2          3            <.0001
TRTPN(ATPTN)                                             1          4            <.0001
TRTPN(ATPTN)                                             2          4            <.0001
TRTPN(ATPTN)                                             1          5            <.0001
TRTPN(ATPTN)                                             2          5            <.0001
TRTPN(ATPTN)                                             1          6            <.0001
TRTPN(ATPTN)                                             2          6            <.0001
TRTPN(ATPTN)                                             1          7            <.0001
TRTPN(ATPTN)                                             2          7            <.0001
TRTPN(ATPTN)                                             1          8            0.0227
TRTPN(ATPTN)                                             2          8            0.0024
TRTPN(ATPTN)                                             1          9                  
TRTPN(ATPTN)                                             2          9                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             1            0.4855
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             1                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             2            0.8640
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             2                  
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
194 of 334
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
                                                         for        Analysis
                                                         Period     Timepoint
Effect        Pre Trial anti-Diabetic treatment          01 (N)     (N)        Pr > |t|
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             3            0.1230
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             3                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             4            0.3295
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             4                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             5            0.4381
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             5                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             6            0.6755
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             6                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             7            0.8020
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             7                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             8            0.7900
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             8                  
PREAD(ATPTN)  BASAL INSULIN + METFORMIN                             9            0.9262
PREAD(ATPTN)  BASAL INSULIN + METFORMIN + ONE OTHER OAD             9                  
          Type 3 Tests of Fixed Effects
                 Num     Den
Effect            DF      DF    F Value    Pr > F
TRTPN              1     451      38.01    <.0001
TRTPN(ATPTN)       8    3517       3.99    0.0001
PREAD(ATPTN)       9    3357       0.83    0.5889
                                     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   99.9780    2.3885  1927    41.86    <.0001
TRTPN(ATPTN)  2          1          WORK.ANA_DATA    109.16    3.3781  1927    32.32    <.0001
TRTPN(ATPTN)  1          2          WORK.ANA_DATA    172.09    2.4000  1950    71.70    <.0001
TRTPN(ATPTN)  2          2          WORK.ANA_DATA    194.85    3.4392  2006    56.65    <.0001
TRTPN(ATPTN)  1          3          WORK.ANA_DATA    125.49    2.3975  1943    52.34    <.0001
TRTPN(ATPTN)  2          3          WORK.ANA_DATA    148.56    3.4392  2006    43.20    <.0001
TRTPN(ATPTN)  1          4          WORK.ANA_DATA    175.23    2.3976  1944    73.08    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  1          1            0.05     95.2938      104.66
TRTPN(ATPTN)  2          1            0.05      102.54      115.79
TRTPN(ATPTN)  1          2            0.05      167.38      176.80
TRTPN(ATPTN)  2          2            0.05      188.10      201.59
TRTPN(ATPTN)  1          3            0.05      120.79      130.19
TRTPN(ATPTN)  2          3            0.05      141.81      155.30
TRTPN(ATPTN)  1          4            0.05      170.53      179.93
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
195 of 334
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)  2          4          WORK.ANA_DATA    201.51    3.4051  1957    59.18    <.0001
TRTPN(ATPTN)  1          5          WORK.ANA_DATA    132.31    2.3975  1943    55.19    <.0001
TRTPN(ATPTN)  2          5          WORK.ANA_DATA    145.53    3.4223  1981    42.52    <.0001
TRTPN(ATPTN)  1          6          WORK.ANA_DATA    179.84    2.4005  1950    74.92    <.0001
TRTPN(ATPTN)  2          6          WORK.ANA_DATA    198.58    3.4477  2018    57.60    <.0001
TRTPN(ATPTN)  1          7          WORK.ANA_DATA    155.38    2.4205  1992    64.20    <.0001
TRTPN(ATPTN)  2          7          WORK.ANA_DATA    174.67    3.4650  2044    50.41    <.0001
TRTPN(ATPTN)  1          8          WORK.ANA_DATA    107.89    2.4234  1998    44.52    <.0001
TRTPN(ATPTN)  2          8          WORK.ANA_DATA    120.69    3.4481  2018    35.00    <.0001
TRTPN(ATPTN)  1          9          WORK.ANA_DATA    100.40    2.3885  1927    42.03    <.0001
TRTPN(ATPTN)  2          9          WORK.ANA_DATA    107.59    3.3954  1947    31.69    <.0001
                       Least Squares Means
              Planned
              Treatment
              for        Analysis
              Period     Timepoint
Effect        01 (N)     (N)         Alpha       Lower       Upper
TRTPN(ATPTN)  2          4            0.05      194.83      208.18
TRTPN(ATPTN)  1          5            0.05      127.61      137.01
TRTPN(ATPTN)  2          5            0.05      138.82      152.24
TRTPN(ATPTN)  1          6            0.05      175.14      184.55
TRTPN(ATPTN)  2          6            0.05      191.82      205.34
TRTPN(ATPTN)  1          7            0.05      150.64      160.13
TRTPN(ATPTN)  2          7            0.05      167.87      181.46
TRTPN(ATPTN)  1          8            0.05      103.14      112.65
TRTPN(ATPTN)  2          8            0.05      113.92      127.45
TRTPN(ATPTN)  1          9            0.05     95.7118      105.08
TRTPN(ATPTN)  2          9            0.05      100.93      114.25
                               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   -9.1865    4.1376  1927
TRTPN(ATPTN)  1          1          1          2          WORK.ANA_DATA  -72.1116    2.6986  3513
TRTPN(ATPTN)  1          1          2          2          WORK.ANA_DATA  -94.8687    4.1874  1979
TRTPN(ATPTN)  1          1          1          3          WORK.ANA_DATA  -25.5128    2.6963  3514
TRTPN(ATPTN)  1          1          2          3          WORK.ANA_DATA  -48.5780    4.1874  1979
TRTPN(ATPTN)  1          1          1          4          WORK.ANA_DATA  -75.2515    2.6964  3514
TRTPN(ATPTN)  1          1          2          4          WORK.ANA_DATA   -101.53    4.1594  1947
TRTPN(ATPTN)  1          1          1          5          WORK.ANA_DATA  -32.3329    2.6964  3514
TRTPN(ATPTN)  1          1          2          5          WORK.ANA_DATA  -45.5531    4.1735  1963
TRTPN(ATPTN)  1          1          1          6          WORK.ANA_DATA  -79.8657    2.6990  3514
TRTPN(ATPTN)  1          1          2          6          WORK.ANA_DATA  -98.6000    4.1944  1988
TRTPN(ATPTN)  1          1          1          7          WORK.ANA_DATA  -55.4058    2.7168  3516
TRTPN(ATPTN)  1          1          2          7          WORK.ANA_DATA  -74.6896    4.2086  2005
TRTPN(ATPTN)  1          1          1          8          WORK.ANA_DATA   -7.9162    2.7194  3516
TRTPN(ATPTN)  1          1          2          8          WORK.ANA_DATA  -20.7089    4.1947  1988
TRTPN(ATPTN)  1          1          1          9          WORK.ANA_DATA   -0.4180    2.6883  3511
TRTPN(ATPTN)  1          1          2          9          WORK.ANA_DATA   -7.6126    4.1515  1940
TRTPN(ATPTN)  2          1          1          2          WORK.ANA_DATA  -62.9251    4.1440  1934
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
196 of 334
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          1          2          2          WORK.ANA_DATA  -85.6821    3.8566  3526
TRTPN(ATPTN)  2          1          1          3          WORK.ANA_DATA  -16.3263    4.1425  1932
TRTPN(ATPTN)  2          1          2          3          WORK.ANA_DATA  -39.3915    3.8565  3526
TRTPN(ATPTN)  2          1          1          4          WORK.ANA_DATA  -66.0650    4.1426  1932
TRTPN(ATPTN)  2          1          2          4          WORK.ANA_DATA  -92.3412    3.8262  3522
TRTPN(ATPTN)  2          1          1          5          WORK.ANA_DATA  -23.1463    4.1426  1932
TRTPN(ATPTN)  2          1          2          5          WORK.ANA_DATA  -36.3666    3.8415  3525
TRTPN(ATPTN)  2          1          1          6          WORK.ANA_DATA  -70.6792    4.1443  1934
TRTPN(ATPTN)  2          1          2          6          WORK.ANA_DATA  -89.4134    3.8642  3527
TRTPN(ATPTN)  2          1          1          7          WORK.ANA_DATA  -46.2192    4.1559  1948
TRTPN(ATPTN)  2          1          2          7          WORK.ANA_DATA  -65.5031    3.8796  3528
TRTPN(ATPTN)  2          1          1          8          WORK.ANA_DATA    1.2704    4.1576  1950
TRTPN(ATPTN)  2          1          2          8          WORK.ANA_DATA  -11.5224    3.8645  3527
TRTPN(ATPTN)  2          1          1          9          WORK.ANA_DATA    8.7685    4.1373  1926
TRTPN(ATPTN)  2          1          2          9          WORK.ANA_DATA    1.5739    3.8176  3517
TRTPN(ATPTN)  1          2          2          2          WORK.ANA_DATA  -22.7570    4.1938  1987
TRTPN(ATPTN)  1          2          1          3          WORK.ANA_DATA   46.5988    2.7054  3513
TRTPN(ATPTN)  1          2          2          3          WORK.ANA_DATA   23.5336    4.1939  1987
TRTPN(ATPTN)  1          2          1          4          WORK.ANA_DATA   -3.1399    2.7055  3513
TRTPN(ATPTN)  1          2          2          4          WORK.ANA_DATA  -29.4161    4.1660  1954
TRTPN(ATPTN)  1          2          1          5          WORK.ANA_DATA   39.7788    2.7054  3513
TRTPN(ATPTN)  1          2          2          5          WORK.ANA_DATA   26.5585    4.1801  1970
TRTPN(ATPTN)  1          2          1          6          WORK.ANA_DATA   -7.7541    2.7081  3513
TRTPN(ATPTN)  1          2          2          6          WORK.ANA_DATA  -26.4884    4.2009  1995
TRTPN(ATPTN)  1          2          1          7          WORK.ANA_DATA   16.7059    2.7258  3515
TRTPN(ATPTN)  1          2          2          7          WORK.ANA_DATA   -2.5780    4.2151  2013
TRTPN(ATPTN)  1          2          1          8          WORK.ANA_DATA   64.1955    2.7279  3515
TRTPN(ATPTN)  1          2          2          8          WORK.ANA_DATA   51.4027    4.2012  1995
TRTPN(ATPTN)  1          2          1          9          WORK.ANA_DATA   71.6936    2.6986  3513
TRTPN(ATPTN)  1          2          2          9          WORK.ANA_DATA   64.4990    4.1581  1947
TRTPN(ATPTN)  2          2          1          3          WORK.ANA_DATA   69.3559    4.1925  1985
TRTPN(ATPTN)  2          2          2          3          WORK.ANA_DATA   46.2907    3.8985  3516
TRTPN(ATPTN)  2          2          1          4          WORK.ANA_DATA   19.6172    4.1926  1985
TRTPN(ATPTN)  2          2          2          4          WORK.ANA_DATA   -6.6591    3.8703  3515
TRTPN(ATPTN)  2          2          1          5          WORK.ANA_DATA   62.5358    4.1925  1985
TRTPN(ATPTN)  2          2          2          5          WORK.ANA_DATA   49.3156    3.8851  3516
TRTPN(ATPTN)  2          2          1          6          WORK.ANA_DATA   15.0029    4.1943  1987
TRTPN(ATPTN)  2          2          2          6          WORK.ANA_DATA   -3.7313    3.9037  3514
TRTPN(ATPTN)  2          2          1          7          WORK.ANA_DATA   39.4629    4.2057  2001
TRTPN(ATPTN)  2          2          2          7          WORK.ANA_DATA   20.1791    3.9190  3515
TRTPN(ATPTN)  2          2          1          8          WORK.ANA_DATA   86.9525    4.2074  2003
TRTPN(ATPTN)  2          2          2          8          WORK.ANA_DATA   74.1598    3.9057  3516
TRTPN(ATPTN)  2          2          1          9          WORK.ANA_DATA   94.4506    4.1874  1979
TRTPN(ATPTN)  2          2          2          9          WORK.ANA_DATA   87.2560    3.8675  3520
TRTPN(ATPTN)  1          3          2          3          WORK.ANA_DATA  -23.0652    4.1924  1985
TRTPN(ATPTN)  1          3          1          4          WORK.ANA_DATA  -49.7387    2.7023  3511
TRTPN(ATPTN)  1          3          2          4          WORK.ANA_DATA  -76.0149    4.1646  1952
TRTPN(ATPTN)  1          3          1          5          WORK.ANA_DATA   -6.8201    2.7022  3511
TRTPN(ATPTN)  1          3          2          5          WORK.ANA_DATA  -20.0403    4.1787  1968
TRTPN(ATPTN)  1          3          1          6          WORK.ANA_DATA  -54.3530    2.7049  3512
TRTPN(ATPTN)  1          3          2          6          WORK.ANA_DATA  -73.0872    4.1995  1993
TRTPN(ATPTN)  1          3          1          7          WORK.ANA_DATA  -29.8930    2.7221  3513
TRTPN(ATPTN)  1          3          2          7          WORK.ANA_DATA  -49.1768    4.2137  2011
TRTPN(ATPTN)  1          3          1          8          WORK.ANA_DATA   17.5966    2.7253  3514
TRTPN(ATPTN)  1          3          2          8          WORK.ANA_DATA    4.8039    4.1998  1993
TRTPN(ATPTN)  1          3          1          9          WORK.ANA_DATA   25.0948    2.6963  3514
TRTPN(ATPTN)  1          3          2          9          WORK.ANA_DATA   17.9001    4.1567  1945
TRTPN(ATPTN)  2          3          1          4          WORK.ANA_DATA  -26.6735    4.1926  1985
TRTPN(ATPTN)  2          3          2          4          WORK.ANA_DATA  -52.9497    3.8725  3518
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
197 of 334
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          3          1          5          WORK.ANA_DATA   16.2451    4.1925  1985
TRTPN(ATPTN)  2          3          2          5          WORK.ANA_DATA    3.0249    3.8810  3512
TRTPN(ATPTN)  2          3          1          6          WORK.ANA_DATA  -31.2878    4.1942  1987
TRTPN(ATPTN)  2          3          2          6          WORK.ANA_DATA  -50.0220    3.9056  3516
TRTPN(ATPTN)  2          3          1          7          WORK.ANA_DATA   -6.8278    4.2056  2001
TRTPN(ATPTN)  2          3          2          7          WORK.ANA_DATA  -26.1116    3.9209  3518
TRTPN(ATPTN)  2          3          1          8          WORK.ANA_DATA   40.6618    4.2074  2003
TRTPN(ATPTN)  2          3          2          8          WORK.ANA_DATA   27.8691    3.9024  3513
TRTPN(ATPTN)  2          3          1          9          WORK.ANA_DATA   48.1600    4.1873  1979
TRTPN(ATPTN)  2          3          2          9          WORK.ANA_DATA   40.9653    3.8674  3520
TRTPN(ATPTN)  1          4          2          4          WORK.ANA_DATA  -26.2762    4.1647  1952
TRTPN(ATPTN)  1          4          1          5          WORK.ANA_DATA   42.9186    2.7023  3511
TRTPN(ATPTN)  1          4          2          5          WORK.ANA_DATA   29.6984    4.1788  1968
TRTPN(ATPTN)  1          4          1          6          WORK.ANA_DATA   -4.6142    2.7045  3511
TRTPN(ATPTN)  1          4          2          6          WORK.ANA_DATA  -23.3485    4.1996  1993
TRTPN(ATPTN)  1          4          1          7          WORK.ANA_DATA   19.8457    2.7227  3514
TRTPN(ATPTN)  1          4          2          7          WORK.ANA_DATA    0.5619    4.2138  2011
TRTPN(ATPTN)  1          4          1          8          WORK.ANA_DATA   67.3353    2.7254  3514
TRTPN(ATPTN)  1          4          2          8          WORK.ANA_DATA   54.5426    4.1999  1993
TRTPN(ATPTN)  1          4          1          9          WORK.ANA_DATA   74.8335    2.6964  3514
TRTPN(ATPTN)  1          4          2          9          WORK.ANA_DATA   67.6388    4.1568  1945
TRTPN(ATPTN)  2          4          1          5          WORK.ANA_DATA   69.1949    4.1646  1952
TRTPN(ATPTN)  2          4          2          5          WORK.ANA_DATA   55.9746    3.8575  3517
TRTPN(ATPTN)  2          4          1          6          WORK.ANA_DATA   21.6620    4.1663  1954
TRTPN(ATPTN)  2          4          2          6          WORK.ANA_DATA    2.9278    3.8778  3516
TRTPN(ATPTN)  2          4          1          7          WORK.ANA_DATA   46.1220    4.1778  1968
TRTPN(ATPTN)  2          4          2          7          WORK.ANA_DATA   26.8381    3.8932  3517
TRTPN(ATPTN)  2          4          1          8          WORK.ANA_DATA   93.6116    4.1796  1970
TRTPN(ATPTN)  2          4          2          8          WORK.ANA_DATA   80.8188    3.8782  3516
TRTPN(ATPTN)  2          4          1          9          WORK.ANA_DATA    101.11    4.1594  1947
TRTPN(ATPTN)  2          4          2          9          WORK.ANA_DATA   93.9151    3.8371  3516
TRTPN(ATPTN)  1          5          2          5          WORK.ANA_DATA  -13.2203    4.1788  1968
TRTPN(ATPTN)  1          5          1          6          WORK.ANA_DATA  -47.5329    2.7049  3512
TRTPN(ATPTN)  1          5          2          6          WORK.ANA_DATA  -66.2671    4.1995  1993
TRTPN(ATPTN)  1          5          1          7          WORK.ANA_DATA  -23.0729    2.7221  3513
TRTPN(ATPTN)  1          5          2          7          WORK.ANA_DATA  -42.3568    4.2137  2011
TRTPN(ATPTN)  1          5          1          8          WORK.ANA_DATA   24.4167    2.7247  3513
TRTPN(ATPTN)  1          5          2          8          WORK.ANA_DATA   11.6240    4.1998  1993
TRTPN(ATPTN)  1          5          1          9          WORK.ANA_DATA   31.9148    2.6964  3514
TRTPN(ATPTN)  1          5          2          9          WORK.ANA_DATA   24.7202    4.1567  1945
TRTPN(ATPTN)  2          5          1          6          WORK.ANA_DATA  -34.3126    4.1804  1970
TRTPN(ATPTN)  2          5          2          6          WORK.ANA_DATA  -53.0469    3.8907  3515
TRTPN(ATPTN)  2          5          1          7          WORK.ANA_DATA   -9.8526    4.1919  1984
TRTPN(ATPTN)  2          5          2          7          WORK.ANA_DATA  -29.1365    3.9060  3516
TRTPN(ATPTN)  2          5          1          8          WORK.ANA_DATA   37.6369    4.1936  1986
TRTPN(ATPTN)  2          5          2          8          WORK.ANA_DATA   24.8442    3.8890  3513
TRTPN(ATPTN)  2          5          1          9          WORK.ANA_DATA   45.1351    4.1735  1963
TRTPN(ATPTN)  2          5          2          9          WORK.ANA_DATA   37.9405    3.8524  3519
TRTPN(ATPTN)  1          6          2          6          WORK.ANA_DATA -18.7342    4.2012  1995
TRTPN(ATPTN)  1          6          1          7          WORK.ANA_DATA   24.4600    2.7253  3514
TRTPN(ATPTN)  1          6          2          7          WORK.ANA_DATA    5.1761    4.2154  2013
TRTPN(ATPTN)  1          6          1          8          WORK.ANA_DATA   71.9496    2.7279  3514
TRTPN(ATPTN)  1          6          2          8          WORK.ANA_DATA   59.1568    4.2015  1995
TRTPN(ATPTN)  1          6          1          9          WORK.ANA_DATA   79.4477    2.6990  3514
TRTPN(ATPTN)  1          6          2          9          WORK.ANA_DATA   72.2531    4.1584  1947
TRTPN(ATPTN)  2          6          1          7          WORK.ANA_DATA   43.1942    4.2127  2009
TRTPN(ATPTN)  2          6          2          7          WORK.ANA_DATA   23.9104    3.9282  3518
TRTPN(ATPTN)  2          6          1          8          WORK.ANA_DATA   90.6838    4.2144  2011
TRTPN(ATPTN)  2          6          2          8          WORK.ANA_DATA   77.8911    3.9112  3515
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
198 of 334
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   98.1819    4.1944  1988
TRTPN(ATPTN)  2          6          2          9          WORK.ANA_DATA   90.9873    3.8750  3521
TRTPN(ATPTN)  1          7          2          7          WORK.ANA_DATA  -19.2838    4.2268  2026
TRTPN(ATPTN)  1          7          1          8          WORK.ANA_DATA   47.4896    2.7440  3514
TRTPN(ATPTN)  1          7          2          8          WORK.ANA_DATA   34.6969    4.2130  2009
TRTPN(ATPTN)  1          7          1          9          WORK.ANA_DATA   54.9877    2.7168  3516
TRTPN(ATPTN)  1          7          2          9          WORK.ANA_DATA   47.7931    4.1700  1961
TRTPN(ATPTN)  2          7          1          8          WORK.ANA_DATA   66.7734    4.2285  2029
TRTPN(ATPTN)  2          7          2          8          WORK.ANA_DATA   53.9807    3.9265  3516
TRTPN(ATPTN)  2          7          1          9          WORK.ANA_DATA   74.2716    4.2086  2005
TRTPN(ATPTN)  2          7          2          9          WORK.ANA_DATA   67.0770    3.8904  3522
TRTPN(ATPTN)  1          8          2          8          WORK.ANA_DATA  -12.7927    4.2147  2011
TRTPN(ATPTN)  1          8          1          9          WORK.ANA_DATA    7.4981    2.7194  3516
TRTPN(ATPTN)  1          8          2          9          WORK.ANA_DATA    0.3035    4.1717  1964
TRTPN(ATPTN)  2          8          1          9          WORK.ANA_DATA   20.2909    4.1947  1988
TRTPN(ATPTN)  2          8          2          9          WORK.ANA_DATA   13.0962    3.8754  3522
TRTPN(ATPTN)  1          9          2          9          WORK.ANA_DATA   -7.1946    4.1516  1940
                          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            -2.22      0.0265      0.05
TRTPN(ATPTN)  1          1          1          2           -26.72      <.0001      0.05
TRTPN(ATPTN)  1          1          2          2           -22.66      <.0001      0.05
TRTPN(ATPTN)  1          1          1          3            -9.46      <.0001      0.05
TRTPN(ATPTN)  1          1          2          3           -11.60      <.0001      0.05
TRTPN(ATPTN)  1          1          1          4           -27.91      <.0001      0.05
TRTPN(ATPTN)  1          1          2          4           -24.41      <.0001      0.05
TRTPN(ATPTN)  1          1          1          5           -11.99      <.0001      0.05
TRTPN(ATPTN)  1          1          2          5           -10.91      <.0001      0.05
TRTPN(ATPTN)  1          1          1          6           -29.59      <.0001      0.05
TRTPN(ATPTN)  1          1          2          6           -23.51      <.0001      0.05
TRTPN(ATPTN)  1          1          1          7           -20.39      <.0001      0.05
TRTPN(ATPTN)  1          1          2          7           -17.75      <.0001      0.05
TRTPN(ATPTN)  1          1          1          8            -2.91      0.0036      0.05
TRTPN(ATPTN)  1          1          2          8            -4.94      <.0001      0.05
TRTPN(ATPTN)  1          1          1          9            -0.16      0.8764      0.05
TRTPN(ATPTN)  1          1          2          9            -1.83      0.0669      0.05
TRTPN(ATPTN)  2          1          1          2           -15.18      <.0001      0.05
TRTPN(ATPTN)  2          1          2          2           -22.22      <.0001      0.05
TRTPN(ATPTN)  2          1          1          3            -3.94      <.0001      0.05
TRTPN(ATPTN)  2          1          2          3           -10.21      <.0001      0.05
TRTPN(ATPTN)  2          1          1          4           -15.95      <.0001      0.05
TRTPN(ATPTN)  2          1          2          4           -24.13      <.0001      0.05
TRTPN(ATPTN)  2          1          1          5            -5.59      <.0001      0.05
TRTPN(ATPTN)  2          1          2          5            -9.47      <.0001      0.05
TRTPN(ATPTN)  2          1          1          6           -17.05      <.0001      0.05
TRTPN(ATPTN)  2          1          2          6           -23.14      <.0001      0.05
TRTPN(ATPTN)  2          1          1          7           -11.12      <.0001      0.05
TRTPN(ATPTN)  2          1          2          7           -16.88      <.0001      0.05
TRTPN(ATPTN)  2          1          1          8             0.31      0.7600      0.05
TRTPN(ATPTN)  2          1          2          8            -2.98      0.0029      0.05
TRTPN(ATPTN)  2          1          1          9             2.12      0.0342      0.05
TRTPN(ATPTN)  2          1          2          9             0.41      0.6802      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
199 of 334
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          2          2          2            -5.43      <.0001      0.05
TRTPN(ATPTN)  1          2          1          3            17.22      <.0001      0.05
TRTPN(ATPTN)  1          2          2          3             5.61      <.0001      0.05
TRTPN(ATPTN)  1          2          1          4            -1.16      0.2459      0.05
TRTPN(ATPTN)  1          2          2          4            -7.06      <.0001      0.05
TRTPN(ATPTN)  1          2          1          5            14.70      <.0001      0.05
TRTPN(ATPTN)  1          2          2          5             6.35      <.0001      0.05
TRTPN(ATPTN)  1          2          1          6            -2.86      0.0042      0.05
TRTPN(ATPTN)  1          2          2          6            -6.31      <.0001      0.05
TRTPN(ATPTN)  1          2          1          7             6.13      <.0001      0.05
TRTPN(ATPTN)  1          2          2          7            -0.61      0.5409      0.05
TRTPN(ATPTN)  1          2          1          8            23.53      <.0001      0.05
TRTPN(ATPTN)  1          2          2          8            12.24      <.0001      0.05
TRTPN(ATPTN)  1          2          1          9            26.57      <.0001      0.05
TRTPN(ATPTN)  1          2          2          9            15.51      <.0001      0.05
TRTPN(ATPTN)  2          2          1          3            16.54      <.0001      0.05
TRTPN(ATPTN)  2          2          2          3            11.87      <.0001      0.05
TRTPN(ATPTN)  2          2          1          4             4.68      <.0001      0.05
TRTPN(ATPTN)  2          2          2          4            -1.72      0.0854      0.05
TRTPN(ATPTN)  2          2          1          5            14.92      <.0001      0.05
TRTPN(ATPTN)  2          2          2          5            12.69      <.0001      0.05
TRTPN(ATPTN)  2          2          1          6             3.58      0.0004      0.05
TRTPN(ATPTN)  2          2          2          6            -0.96      0.3392      0.05
TRTPN(ATPTN)  2          2          1          7             9.38      <.0001      0.05
TRTPN(ATPTN)  2         2          2          7             5.15      <.0001      0.05
TRTPN(ATPTN)  2          2          1          8            20.67      <.0001      0.05
TRTPN(ATPTN)  2          2          2          8            18.99      <.0001      0.05
TRTPN(ATPTN)  2          2          1          9            22.56      <.0001      0.05
TRTPN(ATPTN)  2          2          2          9            22.56      <.0001      0.05
TRTPN(ATPTN)  1          3          2          3            -5.50      <.0001      0.05
TRTPN(ATPTN)  1          3          1          4           -18.41      <.0001      0.05
TRTPN(ATPTN)  1          3          2          4           -18.25      <.0001      0.05
TRTPN(ATPTN)  1          3          1          5            -2.52      0.0117      0.05
TRTPN(ATPTN)  1          3          2          5            -4.80      <.0001      0.05
TRTPN(ATPTN)  1          3          1          6           -20.09      <.0001      0.05
TRTPN(ATPTN)  1          3          2          6           -17.40      <.0001      0.05
TRTPN(ATPTN)  1          3          1          7           -10.98      <.0001      0.05
TRTPN(ATPTN)  1          3          2          7           -11.67      <.0001      0.05
TRTPN(ATPTN)  1          3          1          8             6.46      <.0001      0.05
TRTPN(ATPTN)  1          3          2          8             1.14      0.2528      0.05
TRTPN(ATPTN)  1          3          1          9             9.31      <.0001      0.05
TRTPN(ATPTN)  1          3          2          9             4.31      <.0001      0.05
TRTPN(ATPTN)  2          3          1          4            -6.36      <.0001      0.05
TRTPN(ATPTN)  2          3          2          4           -13.67      <.0001      0.05
TRTPN(ATPTN)  2          3          1          5             3.87      0.0001      0.05
TRTPN(ATPTN)  2          3          2          5             0.78      0.4358      0.05
TRTPN(ATPTN)  2          3          1          6            -7.46      <.0001      0.05
TRTPN(ATPTN)  2          3          2          6           -12.81      <.0001      0.05
TRTPN(ATPTN)  2          3          1          7            -1.62      0.1046      0.05
TRTPN(ATPTN)  2          3          2          7            -6.66      <.0001      0.05
TRTPN(ATPTN)  2          3          1          8             9.66      <.0001      0.05
TRTPN(ATPTN)  2          3          2          8             7.14      <.0001      0.05
TRTPN(ATPTN)  2          3          1          9            11.50      <.0001      0.05
TRTPN(ATPTN)  2          3          2          9            10.59      <.0001      0.05
TRTPN(ATPTN)  1          4          2          4            -6.31      <.0001      0.05
TRTPN(ATPTN)  1          4          1          5            15.88      <.0001      0.05
TRTPN(ATPTN)  1          4          2          5             7.11      <.0001      0.05
TRTPN(ATPTN)  1          4          1          6            -1.71      0.0881      0.05
TRTPN(ATPTN)  1          4          2          6            -5.56      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
200 of 334
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          4          1          7             7.29      <.0001      0.05
TRTPN(ATPTN)  1          4         2          7             0.13      0.8939      0.05
TRTPN(ATPTN)  1          4          1          8            24.71      <.0001      0.05
TRTPN(ATPTN)  1          4          2          8            12.99      <.0001      0.05
TRTPN(ATPTN)  1          4          1          9            27.75      <.0001      0.05
TRTPN(ATPTN)  1          4          2          9            16.27      <.0001      0.05
TRTPN(ATPTN)  2          4          1          5            16.62      <.0001      0.05
TRTPN(ATPTN)  2          4          2          5            14.51      <.0001      0.05
TRTPN(ATPTN)  2          4          1          6             5.20      <.0001      0.05
TRTPN(ATPTN)  2          4          2          6             0.75      0.4503      0.05
TRTPN(ATPTN)  2          4          1          7            11.04      <.0001      0.05
TRTPN(ATPTN)  2          4          2          7             6.89      <.0001      0.05
TRTPN(ATPTN)  2          4          1          8            22.40      <.0001      0.05
TRTPN(ATPTN)  2          4          2          8            20.84      <.0001      0.05
TRTPN(ATPTN)  2          4          1          9            24.31      <.0001      0.05
TRTPN(ATPTN)  2          4          2          9            24.48      <.0001      0.05
TRTPN(ATPTN)  1          5          2          5            -3.16      0.0016      0.05
TRTPN(ATPTN)  1          5          1          6           -17.57      <.0001      0.05
TRTPN(ATPTN)  1          5          2          6           -15.78      <.0001      0.05
TRTPN(ATPTN)  1          5          1          7            -8.48      <.0001      0.05
TRTPN(ATPTN)  1          5          2          7           -10.05      <.0001      0.05
TRTPN(ATPTN)  1          5          1          8             8.96      <.0001      0.05
TRTPN(ATPTN)  1          5          2          8             2.77      0.0057      0.05
TRTPN(ATPTN)  1          5          1          9            11.84      <.0001      0.05
TRTPN(ATPTN)  1          5          2          9             5.95      <.0001      0.05
TRTPN(ATPTN)  2          5          1          6            -8.21      <.0001      0.05
TRTPN(ATPTN)  2          5          2          6           -13.63      <.0001      0.05
TRTPN(ATPTN)  2          5          1          7            -2.35      0.0189      0.05
TRTPN(ATPTN)  2          5          2          7            -7.46      <.0001      0.05
TRTPN(ATPTN)  2          5          1          8             8.97      <.0001      0.05
TRTPN(ATPTN)  2          5          2          8             6.39      <.0001      0.05
TRTPN(ATPTN)  2          5          1          9            10.81      <.0001      0.05
TRTPN(ATPTN)  2          5          2          9             9.85      <.0001      0.05
TRTPN(ATPTN)  1          6         2          6            -4.46      <.0001      0.05
TRTPN(ATPTN)  1          6          1          7             8.98      <.0001      0.05
TRTPN(ATPTN)  1          6          2          7             1.23      0.2196      0.05
TRTPN(ATPTN)  1          6          1          8            26.38      <.0001      0.05
TRTPN(ATPTN)  1          6          2          8            14.08      <.0001      0.05
TRTPN(ATPTN)  1          6          1          9            29.44      <.0001      0.05
TRTPN(ATPTN)  1          6          2          9            17.38      <.0001      0.05
TRTPN(ATPTN)  2          6          1          7            10.25      <.0001      0.05
TRTPN(ATPTN)  2          6          2          7             6.09      <.0001      0.05
TRTPN(ATPTN)  2          6          1          8            21.52      <.0001      0.05
TRTPN(ATPTN)  2          6          2          8            19.91      <.0001      0.05
TRTPN(ATPTN)  2          6          1          9            23.41      <.0001      0.05
TRTPN(ATPTN)  2          6          2          9            23.48      <.0001      0.05
TRTPN(ATPTN)  1          7          2          7            -4.56      <.0001      0.05
TRTPN(ATPTN)  1          7          1          8            17.31      <.0001      0.05
TRTPN(ATPTN)  1          7          2          8             8.24      <.0001      0.05
TRTPN(ATPTN)  1          7          1          9            20.24      <.0001      0.05
TRTPN(ATPTN)  1          7          2          9            11.46      <.0001      0.05
TRTPN(ATPTN)  2          7          1          8            15.79      <.0001      0.05
TRTPN(ATPTN)  2          7          2          8            13.75      <.0001      0.05
TRTPN(ATPTN)  2          7          1          9            17.65      <.0001      0.05
TRTPN(ATPTN)  2          7          2          9            17.24      <.0001      0.05
TRTPN(ATPTN)  1          8          2          8            -3.04      0.0024      0.05
TRTPN(ATPTN)  1          8          1          9             2.76      0.0059      0.05
TRTPN(ATPTN)  1          8          2          9             0.07      0.9420      0.05
TRTPN(ATPTN)  2          8          1          9             4.84      <.0001      0.05
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
201 of 334
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          8          2          9             3.38      0.0007      0.05
TRTPN(ATPTN)  1          9          2          9            -1.73      0.0833      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          -17.3012     -1.0719
TRTPN(ATPTN)  1          1          1          2          -77.4025    -66.8207
TRTPN(ATPTN)  1          1          2          2           -103.08    -86.6565
TRTPN(ATPTN)  1          1          1          3          -30.7993    -20.2263
TRTPN(ATPTN)  1          1          2          3          -56.7901    -40.3659
TRTPN(ATPTN)  1          1          1          4          -80.5382    -69.9648
TRTPN(ATPTN)  1          1          2          4           -109.69    -93.3704
TRTPN(ATPTN)  1          1          1          5          -37.6195    -27.0463
TRTPN(ATPTN)  1          1          2          5          -53.7382    -37.3681
TRTPN(ATPTN)  1          1          1          6          -85.1576    -74.5739
TRTPN(ATPTN)  1          1          2          6           -106.83    -90.3741
TRTPN(ATPTN)  1          1          1          7          -60.7324    -50.0791
TRTPN(ATPTN)  1          1          2          7          -82.9433    -66.4359
TRTPN(ATPTN)  1          1          1          8          -13.2480     -2.5843
TRTPN(ATPTN)  1          1          2          8          -28.9354    -12.4824
TRTPN(ATPTN)  1          1          1          9           -5.6888      4.8528
TRTPN(ATPTN)  1          1          2          9          -15.7546      0.5293
TRTPN(ATPTN)  2          1          1          2          -71.0522    -54.7980
TRTPN(ATPTN)  2          1          2          2          -93.2435    -78.1208
TRTPN(ATPTN)  2          1          1          3          -24.4506     -8.2020
TRTPN(ATPTN)  2          1          2          3          -46.9527    -31.8302
TRTPN(ATPTN)  2          1          1          4          -74.1894    -57.9405
TRTPN(ATPTN)  2          1          2          4          -99.8429    -84.8395
TRTPN(ATPTN)  2          1          1          5          -31.2707    -15.0220
TRTPN(ATPTN)  2          1          2          5          -43.8984    -28.8347
TRTPN(ATPTN)  2          1          1          6          -78.8069    -62.5515
TRTPN(ATPTN)  2          1          2          6          -96.9897    -81.8372
TRTPN(ATPTN)  2          1          1          7          -54.3697    -38.0688
TRTPN(ATPTN)  2          1          2          7          -73.1096    -57.8966
TRTPN(ATPTN)  2          1          1          8           -6.8835      9.4242
TRTPN(ATPTN)  2          1          2          8          -19.0993     -3.9454
TRTPN(ATPTN)  2          1          1          9            0.6544     16.8826
TRTPN(ATPTN)  2          1          2          9           -5.9110      9.0588
TRTPN(ATPTN)  1          2          2          2          -30.9818    -14.5323
TRTPN(ATPTN)  1          2          1          3           41.2945     51.9031
TRTPN(ATPTN)  1          2          2          3           15.3088     31.7585
TRTPN(ATPTN)  1          2          1          4           -8.4444      2.1646
TRTPN(ATPTN)  1          2          2          4          -37.5863    -21.2459
TRTPN(ATPTN)  1          2          1          5           34.4744     45.0831
TRTPN(ATPTN)  1          2          2          5           18.3606     34.7564
TRTPN(ATPTN)  1          2          1          6          -13.0637     -2.4445
TRTPN(ATPTN)  1          2          2          6          -34.7270    -18.2497
TRTPN(ATPTN)  1          2          1          7           11.3615     22.0503
TRTPN(ATPTN)  1          2          2          7          -10.8444      5.6884
TRTPN(ATPTN)  1          2          1          8           58.8470     69.5440
TRTPN(ATPTN)  1          2          2          8           43.1635     59.6420
TRTPN(ATPTN)  1          2          1          9           66.4027     76.9845
TRTPN(ATPTN)  1          2          2          9           56.3441     72.6538
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
202 of 334
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)  2          2          1          3           61.1337     77.5781
TRTPN(ATPTN)  2          2          2          3           38.6471     53.9343
TRTPN(ATPTN)  2          2          1          4           11.3948     27.8396
TRTPN(ATPTN)  2          2          2          4          -14.2472      0.9291
TRTPN(ATPTN)  2          2          1          5           54.3136     70.7581
TRTPN(ATPTN)  2          2          2          5           41.6983     56.9329
TRTPN(ATPTN)  2          2          1          6            6.7773     23.2285
TRTPN(ATPTN)  2          2          2          6          -11.3851      3.9225
TRTPN(ATPTN)  2          2          1          7           31.2149     47.7109
TRTPN(ATPTN)  2          2          2          7           12.4953     27.8629
TRTPN(ATPTN)  2          2          1          8           78.7012     95.2038
TRTPN(ATPTN)  2          2          2          8           66.5021     81.8174
TRTPN(ATPTN)  2          2          1          9           86.2385      102.66
TRTPN(ATPTN)  2          2          2          9           79.6733     94.8387
TRTPN(ATPTN)  1          3          2          3          -31.2872    -14.8432
TRTPN(ATPTN)  1          3          1          4          -55.0370    -44.4405
TRTPN(ATPTN)  1          3          2          4          -84.1824    -67.8475
TRTPN(ATPTN)  1          3          1          5          -12.1182     -1.5220
TRTPN(ATPTN)  1          3          2          5          -28.2354    -11.8452
TRTPN(ATPTN)  1          3          1          6          -59.6563    -49.0497
TRTPN(ATPTN)  1          3          2          6          -81.3230    -64.8513
TRTPN(ATPTN)  1          3          1          7          -35.2301    -24.5559
TRTPN(ATPTN)  1          3          2          7          -57.4405    -40.9131
TRTPN(ATPTN)  1          3          1          8           12.2533     22.9399
TRTPN(ATPTN)  1          3          2          8           -3.4326     13.0404
TRTPN(ATPTN)  1          3          1          9           19.8082     30.3813
TRTPN(ATPTN)  1          3          2          9            9.7481     26.0522
TRTPN(ATPTN)  2          3          1          4          -34.8958    -18.4512
TRTPN(ATPTN)  2          3          2          4          -60.5424    -45.3571
TRTPN(ATPTN)  2          3          1          5            8.0230     24.4673
TRTPN(ATPTN)  2          3          2          5           -4.5845     10.6342
TRTPN(ATPTN)  2          3          1          6          -39.5132    -23.0623
TRTPN(ATPTN)  2          3          2          6          -57.6795    -42.3645
TRTPN(ATPTN)  2          3          1          7          -15.0757      1.4201
TRTPN(ATPTN)  2          3          2          7          -33.7992    -18.4241
TRTPN(ATPTN)  2          3          1          8           32.4106     48.9131
TRTPN(ATPTN)  2          3          2          8           20.2179     35.5202
TRTPN(ATPTN)  2          3          1          9           39.9479     56.3720
TRTPN(ATPTN)  2          3          2          9           33.3828     48.5479
TRTPN(ATPTN)  1          4         2          4          -34.4440    -18.1084
TRTPN(ATPTN)  1          4          1          5           37.6203     48.2170
TRTPN(ATPTN)  1          4          2          5           21.5031     37.8936
TRTPN(ATPTN)  1          4          1          6           -9.9167      0.6882
TRTPN(ATPTN)  1          4          2          6          -31.5845    -15.1125
TRTPN(ATPTN)  1          4          1          7           14.5074     25.1841
TRTPN(ATPTN)  1          4          2          7           -7.7019      8.8257
TRTPN(ATPTN)  1          4          1          8           61.9919     72.6788
TRTPN(ATPTN)  1          4          2          8           46.3059     62.7793
TRTPN(ATPTN)  1          4          1          9           69.5467     80.1202
TRTPN(ATPTN) 1          4          2          9           59.4867     75.7910
TRTPN(ATPTN)  2          4          1          5           61.0274     77.3624
TRTPN(ATPTN)  2          4          2          5           48.4114     63.5379
TRTPN(ATPTN)  2          4          1          6           13.4911     29.8328
TRTPN(ATPTN)  2          4          2          6           -4.6753     10.5308
TRTPN(ATPTN)  2          4          1          7           37.9285     54.3154
TRTPN(ATPTN)  2          4          2          7           19.2050     34.4713
TRTPN(ATPTN)  2          4          1          8           85.4148      101.81
TRTPN(ATPTN)  2          4          2          8           73.2151     88.4226
TRTPN(ATPTN)  2          4          1          9           92.9524      109.27
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
203 of 334
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)  2          4          2          9           86.3920      101.44
TRTPN(ATPTN)  1          5          2          5          -21.4155     -5.0250
TRTPN(ATPTN)  1          5          1          6          -52.8363    -42.2295
TRTPN(ATPTN)  1          5          2          6          -74.5030    -58.0312
TRTPN(ATPTN)  1          5          1          7          -28.4099    -17.7359
TRTPN(ATPTN)  1          5          2          7          -50.6205    -34.0930
TRTPN(ATPTN)  1          5          1          8           19.0745     29.7589
TRTPN(ATPTN)  1          5          2          8            3.3874     19.8605
TRTPN(ATPTN)  1          5          1          9           26.6282     37.2014
TRTPN(ATPTN)  1          5          2          9           16.5681     32.8723
TRTPN(ATPTN)  2          5          1          6          -42.5111    -26.1142
TRTPN(ATPTN)  2          5          2          6          -60.6751    -45.4187
TRTPN(ATPTN)  2          5          1          7          -18.0737     -1.6316
TRTPN(ATPTN)  2          5          2          7          -36.7948    -21.4782
TRTPN(ATPTN)  2          5          1          8           29.4126     45.8613
TRTPN(ATPTN)  2          5          2          8           17.2193     32.4692
TRTPN(ATPTN)  2          5          1          9           36.9501     53.3201
TRTPN(ATPTN)  2          5          2          9           30.3873     45.4936
TRTPN(ATPTN)  1          6          2          6          -26.9735    -10.4950
TRTPN(ATPTN)  1          6          1          7           19.1166     29.8033
TRTPN(ATPTN)  1          6          2          7           -3.0909     13.4432
TRTPN(ATPTN)  1          6          1          8           66.6011     77.2981
TRTPN(ATPTN)  1          6          2          8           50.9170     67.3967
TRTPN(ATPTN)  1          6          1          9           74.1559     84.7395
TRTPN(ATPTN)  1          6          2          9           64.0976     80.4086
TRTPN(ATPTN)  2          6          1          7           34.9326     51.4559
TRTPN(ATPTN)  2          6          2          7           16.2086     31.6121
TRTPN(ATPTN)  2          6          1          8           82.4188     98.9488
TRTPN(ATPTN)  2          6          2          8           70.2227     85.5595
TRTPN(ATPTN)  2          6          1          9           89.9561      106.41
TRTPN(ATPTN)  2          6          2          9           83.3898     98.5849
TRTPN(ATPTN)  1          7          2          7          -27.5732    -10.9945
TRTPN(ATPTN)  1          7          1          8           42.1096     52.8696
TRTPN(ATPTN)  1          7          2          8           26.4346     42.9591
TRTPN(ATPTN)  1          7          1          9           49.6611     60.3144
TRTPN(ATPTN)  1          7          2          9           39.6150     55.9712
TRTPN(ATPTN)  2          7          1          8           58.4808     75.0661
TRTPN(ATPTN)  2          7          2          8           46.2823     61.6792
TRTPN(ATPTN)  2          7          1          9           66.0179     82.5252
TRTPN(ATPTN)  2          7          2          9           59.4492     74.7047
TRTPN(ATPTN)  1          8          2          8          -21.0583     -4.5272
TRTPN(ATPTN)  1          8          1          9            2.1663     12.8300
TRTPN(ATPTN)  1          8          2          9           -7.8779      8.4850
TRTPN(ATPTN)  2          8          1          9           12.0644     28.5173
TRTPN(ATPTN)  2          8          2          9            5.4980     20.6945
TRTPN(ATPTN)  1          9          2          9          -15.3368      0.9475
CONFIDENTIAL


NN9068
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Date:
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Version:
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Statistical document
Page:
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19: Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from 
baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.4827
           Fit Statistics
-2 Res Log Likelihood          1668.3
AIC (Smaller is Better)        1670.3
AICC (Smaller is Better)       1670.3
BIC (Smaller is Better)        1674.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          7.2884    0.3649   439    19.97
trtpn                                                 1           -0.9761    0.1585   439    -6.16
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.02534    0.1500   439    -0.17
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1399   0.03066   439     4.56
CONFIDENTIAL


NN9068
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Date:
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Version:
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Statistical document
Page:
205 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PSMPGM
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8659      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          6.5712      8.0055
trtpn                                                 1           -1.2877     -0.6645
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3201      0.2695
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.07968      0.2002
        Type 3 Tests of Fixed Effects
              Num     Den
Effect        DF      DF    F Value    Pr > F
trtpn           1     439      37.90    <.0001
PREAD           1     439       0.03    0.8659
BASE            1     439      20.83    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     7.8491    0.09191     439     85.40     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     8.8252     0.1291     439     68.34     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     7.6685     8.0298         2563.52         2139.86         3071.06
trtpn    LSMeans, IDeg         8.5714     9.0790         6803.49         5278.49         8769.08
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.9761     0.1585     439     -6.16
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Statistical document
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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 - appendix
Parameter Code=P9PSMPGM
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05   -1.2877   -0.6645         0.3768
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.2759           0.5146
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NN9068
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Statistical document
Page:
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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 - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       806.17
           Fit Statistics
-2 Res Log Likelihood          4212.8
AIC (Smaller is Better)        4214.8
AICC (Smaller is Better)       4214.8
BIC (Smaller is Better)        4218.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          131.34    6.5753   439    19.97
trtpn                                                 1          -17.5886    2.8570   439    -6.16
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.4567    2.7030   439    -0.17
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1399   0.03066   439     4.56
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:
208 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9SMPGMU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8659      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          118.41      144.26
trtpn                                                 1          -23.2036    -11.9735
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -5.7691      4.8557
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.07968      0.2002
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     439      37.90    <.0001
PREAD           1     439       0.03    0.8659
BASE            1     439      20.83    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     141.44     1.6563     439     85.40     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     159.03     2.3270     439     68.34     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     138.19     144.70        2.674E61        1.032E60        6.933E62
trtpn    LSMeans, IDeg         154.46     163.60        1.164E69        1.201E67        1.127E71
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -17.5886     2.8570     439     -6.16
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
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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 - appendix
Parameter Code=P9SMPGMU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05  -23.2036  -11.9735       2.298E-8
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       8.37E-11         6.309E-6
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
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Statistical document
Page:
210 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.4827
           Fit Statistics
-2 Res Log Likelihood          1668.3
AIC (Smaller is Better)        1670.3
AICC (Smaller is Better)       1670.3
BIC (Smaller is Better)        1674.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          7.2884    0.3649   439    19.97
trtpn                                                 1           -0.9761    0.1585   439    -6.16
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.02534    0.1500   439    -0.17
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8601   0.03066   439   -28.05
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
211 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PSMPGM
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8659      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          6.5712      8.0055
trtpn                                                 1           -1.2877     -0.6645
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.3201      0.2695
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.9203     -0.7998
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     439      37.90    <.0001
PREAD           1     439       0.03    0.8659
BASE            1     439     786.85    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.2198   0.09191    439   -35.03    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -2.2437    0.1291    439   -17.38    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -3.4004     -3.0391
trtpn   Change from baseline, IDeg        0.05     -2.4975     -1.9899
CONFIDENTIAL


NN9068
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Version:
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Statistical document
Page:
212 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       806.17
           Fit Statistics
-2 Res Log Likelihood          4212.8
AIC (Smaller is Better)        4214.8
AICC (Smaller is Better)       4214.8
BIC (Smaller is Better)        4218.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF t Value
Intercept                                                          131.34    6.5753   439    19.97
trtpn                                                 1          -17.5886    2.8570   439    -6.16
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.4567    2.7030   439    -0.17
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8601   0.03066   439   -28.05
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
213 of 334
Mean of 9-point self-measured plasma glucose profile after 26 weeks of treatment – change from
baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9SMPGMU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8659      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          118.41      144.26
trtpn                                                 1          -23.2036    -11.9735
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -5.7691      4.8557
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.9203     -0.7998
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     439      37.90    <.0001
PREAD           1     439       0.03    0.8659
BASE            1     439     786.84    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -58.0206    1.6563    439   -35.03    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2  -40.4320    2.3270    439  -17.38    <.0001
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -61.2758    -54.7654
trtpn   Change from baseline, IDeg        0.05    -45.0054    -35.8586
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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20: Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2154.91
           Fit Statistics
-2 Res Log Likelihood          4708.0
AIC (Smaller is Better)        4710.0
AICC (Smaller is Better)       4710.0
BIC (Smaller is Better)        4714.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         62.1279    5.6099   445    11.07
trtpn                                                 1          -13.8531    4.6458   445    -2.98
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               3.8477    4.3900   445     0.88
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2690   0.03980   445     6.76
CONFIDENTIAL


NN9068
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
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Parameter Code=P9PGIBU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0030      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3813      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect    Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         51.1026     73.1532
trtpn                                                 1          -22.9835     -4.7226
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.7801     12.4754
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.1908      0.3472
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       8.89    0.0030
PREAD           1     445       0.77    0.3813
BASE            1     445      45.67    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    73.0519     2.6908     445     27.15     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    86.9050     3.7824     445     22.98     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    67.7637    78.3402        5.322E31        2.688E29        1.054E34
trtpn    LSMeans, IDeg        79.4713    94.3386        5.525E37        3.266E34        9.348E40
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -13.8531     4.6458     445     -2.98
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIBU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0030    0.05  -22.9835   -4.7226       9.632E-7
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                       Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       1.04E-10         0.008892
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             446
          Number of Observations
Number of Observations Read             453
Number of Observations Used             446
Number of Observations Not Used           7
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      1879.19
           Fit Statistics
-2 Res Log Likelihood          4616.1
AIC (Smaller is Better)        4618.1
AICC (Smaller is Better)       4618.1
BIC (Smaller is Better)        4622.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         45.9181    4.3240   442    10.62
trtpn                                                 1           -4.3682    4.3513   442    -1.00
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.5936    4.1296   442    -0.14
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1500   0.03431   442     4.37
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIEU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.3160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8858      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         37.4199     54.4163
trtpn                                                 1          -12.9200      4.1836
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -8.7098      7.5226
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.08253      0.2174
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     442       1.01    0.3160
PREAD           1     442       0.02    0.8858
BASE            1     442      19.10    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    47.7303     2.5209     442     18.93     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    52.0985     3.5430     442     14.70     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn   LSMeans, IDegLira    42.7758    52.6848        5.358E20        3.778E18        7.598E22
trtpn    LSMeans, IDeg        45.1352    59.0618        4.228E22        3.999E19        4.469E25
                                  Least Squares Means Estimate
                                                                     Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -4.3682     4.3513     442     -1.00
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIEU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.3160    0.05  -12.9200    4.1836        0.01267
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       2.449E-6          65.6022
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2310.04
           Fit Statistics
-2 Res Log Likelihood          4739.1
AIC (Smaller is Better)        4741.1
AICC (Smaller is Better)       4741.1
BIC (Smaller is Better)        4745.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF t Value
Intercept                                                         44.9769    4.7616   445     9.45
trtpn                                                 1           -1.2247    4.8065   445    -0.25
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -4.4637    4.5624   445    -0.98
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2018   0.03834   445     5.26
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NN9068
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGILU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7990      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3284      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         35.6189     54.3350
trtpn                                                 1          -10.6710      8.2215
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -13.4301      4.5028
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.1264      0.2771
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       0.06    0.7990
PREAD           1     445       0.96    0.3284
BASE            1     445      27.70    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    50.1525     2.7853     445     18.01     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    51.3772     3.9142     445     13.13     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    44.6786    55.6264        6.039E21        2.533E19         1.44E24
trtpn    LSMeans, IDeg        43.6845    59.0699        2.055E22        9.374E18        4.505E25
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -1.2247     4.8065     445     -0.25
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGILU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.7990    0.05  -10.6710    8.2215         0.2938
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.000023          3720.21
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NN9068
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.9392
           Fit Statistics
-2 Res Log Likelihood          1777.4
AIC (Smaller is Better)        1779.4
AICC (Smaller is Better)       1779.4
BIC (Smaller is Better)        1783.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.7808    0.2026   448    13.73
trtpn                                                 1           -0.4039    0.1715   448    -2.36
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.09210    0.1624   448    -0.57
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2575   0.03900   448     6.60
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:
224 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINC
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0189      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5709      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.3826      3.1789
trtpn                                                 1           -0.7410    -0.06690
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4112      0.2271
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.1808      0.3341
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       5.55    0.0189
PREAD           1     448       0.32    0.5709
BASE            1     448      43.59    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.1460    0.09892     448     31.80     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.5500     0.1398     448     25.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.9516     3.3404         23.2435         19.1370         28.2313
trtpn    LSMeans, IDeg         3.2752     3.8247         34.8123         26.4488         45.8205
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.4039     0.1715     448     -2.36
CONFIDENTIAL


NN9068
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Statistical document
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINC
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0189    0.05   -0.7410  -0.06690         0.6677
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4766           0.9353
CONFIDENTIAL


NN9068
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.6362
           Fit Statistics
-2 Res Log Likelihood          2128.8
AIC (Smaller is Better)        2130.8
AICC (Smaller is Better)       2130.8
BIC (Smaller is Better)        2134.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          3.4477    0.3113   445    11.07
trtpn                                                 1           -0.7688    0.2578   445    -2.98
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                               0.2135    0.2436   445     0.88
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2690   0.03980   445     6.76
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
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Clinical Trial Report
Status:
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Statistical document
Page:
227 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCB
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001     0.05
trtpn                                                 1            0.0030      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3813      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.8359      4.0596
trtpn                                                 1           -1.2754     -0.2621
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2653      0.6923
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.1908      0.3472
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       8.89    0.0030
PREAD           1     445       0.77    0.3813
BASE            1     445      45.67    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     4.0539     0.1493     445     27.15     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     4.8227     0.2099     445     22.98     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.7605     4.3474         57.6238         42.9686         77.2775
trtpn    LSMeans, IDeg         4.4102     5.2352          124.30         82.2838          187.77
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.7688     0.2578     445     -2.98
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
228 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCB
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0030    0.05   -1.2754   -0.2621         0.4636
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.2793           0.7695
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
229 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             446
          Number of Observations
Number of Observations Read             453
Number of Observations Used             446
Number of Observations Not Used           7
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       5.7871
           Fit Statistics
-2 Res Log Likelihood          2054.2
AIC (Smaller is Better)        2056.2
AICC (Smaller is Better)       2056.3
BIC (Smaller is Better)        2060.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.5482    0.2400   442    10.62
trtpn                                                 1           -0.2424    0.2415   442    -1.00
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.03294    0.2292   442    -0.14
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.1500   0.03431   442     4.37
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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Version:
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Status:
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Statistical document
Page:
230 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCE
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.3160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8858      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.0766      3.0198
trtpn                                                 1           -0.7170      0.2322
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4833      0.4175
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              0.08253      0.2174
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     442       1.01    0.3160
PREAD           1     442       0.02    0.8858
BASE            1     442      19.10    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     2.6487     0.1399     442     18.93     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     2.8911     0.1966     442     14.70     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect  Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.3738     2.9237         14.1362         10.7381         18.6098
trtpn    LSMeans, IDeg         2.5047     3.2776         18.0140         12.2402         26.5113
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -0.2424     0.2415     442     -1.00
CONFIDENTIAL


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Version:
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCE
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.3160    0.05   -0.7170    0.2322         0.7847
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.4882           1.2613
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:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      7.1139
           Fit Statistics
-2 Res Log Likelihood          2159.9
AIC (Smaller is Better)        2161.9
AICC (Smaller is Better)       2161.9
BIC (Smaller is Better)        2166.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.4959    0.2642   445     9.45
trtpn                                                 1          -0.06796    0.2667   445    -0.25
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2477    0.2532   445    -0.98
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2018   0.03834   445     5.26
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCL
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7990      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3284      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.9766      3.0153
trtpn                                                 1           -0.5922      0.4562
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.7453      0.2499
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.1264      0.2771
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       0.06    0.7990
PREAD           1     445       0.96    0.3284
BASE            1     445      27.70    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     2.7832     0.1546     445     18.01     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     2.8511     0.2172     445     13.13     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     2.4794     3.0869         16.1700         11.9340         21.9096
trtpn    LSMeans, IDeg         2.4242     3.2780         17.3072         11.2935         26.5232
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2   -0.06796     0.2667     445     -0.25
CONFIDENTIAL


NN9068
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Date:
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCL
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.7990    0.05   -0.5922    0.4562         0.9343
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.5531           1.5781
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
235 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       954.43
           Fit Statistics
-2 Res Log Likelihood          4373.9
AIC (Smaller is Better)        4375.9
AICC (Smaller is Better)       4376.0
BIC (Smaller is Better)        4380.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         50.1099    3.6507   448    13.73
trtpn                                                 1           -7.2791    3.0904   448    -2.36
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                              -1.6597    2.9264   448    -0.57
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.2575   0.03900   448     6.60
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
236 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0189      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5709      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         42.9353     57.2845
trtpn                                                 1          -13.3526     -1.2055
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -7.4108      4.0914
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                               0.1808      0.3341
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       5.55    0.0189
PREAD           1     448       0.32    0.5709
BASE            1     448      43.59    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label              Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    56.6914     1.7825     448     31.80     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    63.9705     2.5193     448     25.39     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    53.1882    60.1946        4.176E24        1.257E23        1.387E26
trtpn    LSMeans, IDeg        59.0193    68.9216        6.054E27        4.283E25        8.556E29
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -7.2791     3.0904     448     -2.36
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
237 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIU
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0189   0.05  -13.3526   -1.2055       0.000690
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       1.589E-6           0.2995
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
238 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2154.91
           Fit Statistics
-2 Res Log Likelihood          4708.0
AIC (Smaller is Better)        4710.0
AICC (Smaller is Better)       4710.0
BIC (Smaller is Better)        4714.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         62.1279    5.6099   445    11.07
trtpn                                                 1          -13.8531    4.6458   445    -2.98
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               3.8477    4.3900   445     0.88
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7310   0.03980   445   -18.37
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
239 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIBU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0030      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3813      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         51.1026     73.1532
trtpn                                                 1          -22.9835     -4.7226
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -4.7801     12.4754
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.8092     -0.6528
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       8.89    0.0030
PREAD           1     445       0.77    0.3813
BASE            1     445     337.31    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -12.3083    2.6908    445    -4.57    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.5448    3.7824    445     0.41    0.6832
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -17.5966     -7.0200
trtpn   Change from baseline, IDeg        0.05     -5.8889      8.9784
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
240 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             446
          Number of Observations
Number of Observations Read             453
Number of Observations Used             446
Number of Observations Not Used           7
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      1879.19
           Fit Statistics
-2 Res Log Likelihood          4616.1
AIC (Smaller is Better)        4618.1
AICC (Smaller is Better)       4618.1
BIC (Smaller is Better)        4622.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         45.9181    4.3240   442    10.62
trtpn                                                 1           -4.3682    4.3513   442    -1.00
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.5936    4.1296   442    -0.14
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8500   0.03431   442   -24.78
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
241 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIEU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.3160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8858      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         37.4199     54.4163
trtpn                                                 1          -12.9200      4.1836
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -8.7098      7.5226
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.9175     -0.7826
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     442       1.01    0.3160
PREAD           1     442       0.02    0.8858
BASE            1     442     613.81    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    4.6278    2.5209    442     1.84    0.0671
trtpn   Change from baseline, IDeg      WORK.ADATA2    8.9960    3.5430    442     2.54    0.0115
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.3267      9.5823
trtpn   Change from baseline, IDeg        0.05      2.0327     15.9593
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
242 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      2310.04
           Fit Statistics
-2 Res Log Likelihood          4739.1
AIC (Smaller is Better)        4741.1
AICC (Smaller is Better)       4741.1
BIC (Smaller is Better)        4745.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         44.9769    4.7616   445     9.45
trtpn                                                 1           -1.2247    4.8065   445    -0.25
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -4.4637    4.5624   445    -0.98
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7982   0.03834   445   -20.82
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
243 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGILU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7990      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3284      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         35.6189     54.3350
trtpn                                                 1          -10.6710      8.2215
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -13.4301      4.5028
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.8736     -0.7229
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       0.06    0.7990
PREAD           1     445       0.96    0.3284
BASE            1     445     433.46    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    7.8878    2.7853    445     2.83    0.0048
trtpn   Change from baseline, IDeg      WORK.ADATA2    9.1125    3.9142    445     2.33    0.0204
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05      2.4138     13.3617
trtpn   Change from baseline, IDeg        0.05      1.4198     16.8052
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
244 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       2.9392
           Fit Statistics
-2 Res Log Likelihood          1777.4
AIC (Smaller is Better)        1779.4
AICC (Smaller is Better)       1779.4
BIC (Smaller is Better)        1783.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                     Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.7808    0.2026   448    13.73
trtpn                                                 1           -0.4039    0.1715   448    -2.36
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.09210    0.1624   448    -0.57
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7425   0.03900   448   -19.04
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
245 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINC
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0189      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5709      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.3826      3.1789
trtpn                                                 1           -0.7410    -0.06690
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4112      0.2271
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.8192     -0.6659
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       5.55    0.0189
PREAD           1     448       0.32    0.5709
BASE            1     448     362.57    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2  -0.01168   0.09892    448    -0.12    0.9061
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.3923    0.1398    448     2.81    0.0052
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.2061      0.1827
trtpn   Change from baseline, IDeg        0.05      0.1175      0.6670
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
246 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       6.6362
           Fit Statistics
-2 Res Log Likelihood          2128.8
AIC (Smaller is Better)        2130.8
AICC (Smaller is Better)       2130.8
BIC (Smaller is Better)        2134.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          3.4477    0.3113   445    11.07
trtpn                                                 1           -0.7688    0.2578   445    -2.98
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               0.2135    0.2436   445     0.88
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7310   0.03980   445   -18.37
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
247 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCB
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0030      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3813      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.8359      4.0596
trtpn                                                 1           -1.2754     -0.2621
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2653      0.6923
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
BASE                                                              -0.8092     -0.6528
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       8.89    0.0030
PREAD           1     445       0.77    0.3813
BASE            1     445     337.31    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.6830    0.1493    445    -4.57    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   0.08572    0.2099    445     0.41    0.6832
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.9765     -0.3896
trtpn   Change from baseline, IDeg        0.05     -0.3268      0.4982
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
248 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             446
          Number of Observations
Number of Observations Read             453
Number of Observations Used             446
Number of Observations Not Used           7
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       5.7871
           Fit Statistics
-2 Res Log Likelihood          2054.2
AIC (Smaller is Better)        2056.2
AICC (Smaller is Better)       2056.3
BIC (Smaller is Better)        2060.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.5482    0.2400   442    10.62
trtpn                                                 1           -0.2424    0.2415   442    -1.00
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.03294    0.2292   442    -0.14
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.8500   0.03431   442   -24.78
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
249 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCE
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.3160      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8858      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect    Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.0766      3.0198
trtpn                                                 1           -0.7170      0.2322
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.4833      0.4175
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.9175     -0.7826
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     442       1.01    0.3160
PREAD           1     442       0.02    0.8858
BASE            1     442     613.81    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.2568    0.1399    442     1.84    0.0671
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.4992    0.1966    442     2.54    0.0115
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05    -0.01813      0.5318
trtpn   Change from baseline, IDeg        0.05      0.1128      0.8856
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
250 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       7.1139
           Fit Statistics
-2 Res Log Likelihood          2159.9
AIC (Smaller is Better)        2161.9
AICC (Smaller is Better)       2161.9
BIC (Smaller is Better)        2166.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.4959    0.2642   445     9.45
trtpn                                                 1          -0.06796    0.2667   445    -0.25
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2477    0.2532   445    -0.98
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7982   0.03834   445   -20.82
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
251 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGINCL
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7990      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.3284      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.9766      3.0153
trtpn                                                 1           -0.5922      0.4562
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.7453      0.2499
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.8736     -0.7229
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445       0.06    0.7990
PREAD           1     445       0.96    0.3284
BASE            1     445     433.46    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.4377    0.1546    445     2.83    0.0048
trtpn   Change from baseline, IDeg      WORK.ADATA2    0.5057    0.2172    445     2.33    0.0204
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05      0.1340      0.7415
trtpn   Change from baseline, IDeg        0.05     0.07879      0.9326
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
252 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       954.43
           Fit Statistics
-2 Res Log Likelihood          4373.9
AIC (Smaller is Better)        4375.9
AICC (Smaller is Better)       4376.0
BIC (Smaller is Better)        4380.1
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         50.1099    3.6507   448    13.73
trtpn                                                 1           -7.2791    3.0904   448    -2.36
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -1.6597    2.9264   448    -0.57
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.7425   0.03900   448   -19.04
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
253 of 334
Prandial increment after 26 weeks of treatment – 9-point self-measured plasma glucose profile –
change from baseline – supportive statistical analysis – full analysis set - appendix
Parameter Code=P9PGIU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0189      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5709      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         42.9353     57.2845
trtpn                                                 1          -13.3526     -1.2055
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -7.4108      4.0914
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.8192     -0.6659
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       5.55    0.0189
PREAD           1     448       0.32    0.5709
BASE            1     448     362.56    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -0.2105    1.7825    448    -0.12    0.9061
trtpn   Change from baseline, IDeg      WORK.ADATA2    7.0686    2.5193    448     2.81    0.0052
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -3.7136      3.2927
trtpn   Change from baseline, IDeg        0.05      2.1174     12.0198
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
254 of 334
21: Fasting insulin after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5659
           Fit Statistics
-2 Res Log Likelihood          1037.6
AIC (Smaller is Better)        1039.6
AICC (Smaller is Better)       1039.6
BIC (Smaller is Better)        1043.7
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.4173    0.1666   448     8.50
trtpn                                                 1            0.2632   0.07509   448     3.50
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.01274   0.07095   448    -0.18
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.4230   0.04125   448    10.26
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Parameter Code=INS_TO_S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0005      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8576      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.0897      1.7448
trtpn                                                 1            0.1156      0.4107
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1522      0.1267
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.3419      0.5041
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448      12.28    0.0005
PREAD           1     448       0.03    0.8576
base_log        1     448     105.17    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.2281    0.04337     448     74.42     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     2.9649    0.06126     448     48.40     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.1428     3.3133         25.2310         23.1694         27.4761
trtpn    LSMeans, IDeg         2.8445     3.0853         19.3931         17.1935         21.8742
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.2632   0.07509    448     3.50    0.0005
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Statistical document
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appendix
Parameter Code=INS_TO_S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.1156      0.4107           1.3010
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.1225           1.5079
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22: Fasting C-peptide after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3774
           Fit Statistics
-2 Res Log Likelihood           849.9
AIC (Smaller is Better)         851.9
AICC (Smaller is Better)        851.9
BIC (Smaller is Better)         856.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -0.9362   0.06948   445   -13.47
trtpn                                                 1            0.2201   0.06149   445     3.58
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.04696   0.05821   445     0.81
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.7072   0.04482   445    15.78
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- appendix
Parameter Code=C74736S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0004      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4203      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -1.0728     -0.7997
trtpn                                                 1          0.09929      0.3410
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.06745      0.1614
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.6191      0.7953
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445      12.82    0.0004
PREAD           1     445       0.65    0.4203
base_log        1     445     249.02    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -1.3460    0.03553     445    -37.88     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -1.5661    0.05017     445    -31.21     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -1.4158    -1.2761          0.2603          0.2427          0.2791
trtpn    LSMeans, IDeg        -1.6647    -1.4675          0.2089          0.1892          0.2305
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.2201   0.06149    445     3.58    0.0004
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- appendix
Parameter Code=C74736S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     0.09929      0.3410           1.2463
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.1044           1.4064
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- appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             449
          Number of Observations
Number of Observations Read             453
Number of Observations Used             449
Number of Observations Not Used           4
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.3774
           Fit Statistics
-2 Res Log Likelihood           849.9
AIC (Smaller is Better)         851.9
AICC (Smaller is Better)        851.9
BIC (Smaller is Better)         856.0
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -0.6126   0.05878   445   -10.42
trtpn                                                 1            0.2201   0.06149   445     3.58
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.04696   0.05821   445     0.81
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.7072   0.04482   445    15.78
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Statistical document
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- appendix
Parameter Code=CPEPTI_U
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0004      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4203      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -0.7282     -0.4971
trtpn                                                 1           0.09929      0.3410
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.06745      0.1614
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.6191      0.7953
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     445      12.82    0.0004
PREAD           1     445       0.65    0.4203
base_log        1     445     249.02    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -0.2407    0.03553     445     -6.77     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -0.4608    0.05017     445     -9.18     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -0.3105    -0.1709          0.7861          0.7331          0.8429
trtpn    LSMeans, IDeg        -0.5595    -0.3622          0.6308          0.5715          0.6961
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.2201   0.06149    445     3.58    0.0004
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Statistical document
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- appendix
Parameter Code=CPEPTI_U
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     0.09929      0.3410           1.2463
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.1044           1.4064
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23: Fasting glucagon after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             451
          Number of Observations
Number of Observations Read             453
Number of Observations Used             451
Number of Observations Not Used           2
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2747
           Fit Statistics
-2 Res Log Likelihood           711.8
AIC (Smaller is Better)         713.8
AICC (Smaller is Better)        713.8
BIC (Smaller is Better)         717.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          2.5453    0.1201   447    21.19
trtpn                                                 1          -0.03858   0.05240   447    -0.74
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.06470   0.04944   447    -1.31
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.2213   0.03481   447     6.36
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NN9068
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- appendix
Parameter Code=C74859P
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.4619      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1913      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          2.3093      2.7814
trtpn                                                 1           -0.1416     0.06440
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1619     0.03246
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.1529      0.2898
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     447       0.54    0.4619
PREAD           1     447       1.71    0.1913
base_log        1     447      40.42    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.1743    0.03021     447    105.07     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.2128    0.04280     447     75.06     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.1149     3.2336         23.9091         22.5308         25.3717
trtpn    LSMeans, IDeg         3.1287     3.2970         24.8495         22.8447         27.0302
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.03858   0.05240    447    -0.74    0.4619
CONFIDENTIAL


NN9068
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Statistical document
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- appendix
Parameter Code=C74859P
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1416     0.06440           0.9622
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8680           1.0665
CONFIDENTIAL


NN9068
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24: HOMA-B after 26 weeks of treatment – supportive statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.5070
           Fit Statistics
-2 Res Log Likelihood           988.5
AIC (Smaller is Better)         990.5
AICC (Smaller is Better)        990.5
BIC (Smaller is Better)         994.6
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.8932    0.1322   448    14.32
trtpn                                                 1            0.3901   0.07103   448     5.49
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.01262   0.06714   448    -0.19
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.3927   0.03605   448    10.89
CONFIDENTIAL


NN9068
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Statistical document
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HOMA-B after 26 weeks of treatment – supportive statistical analysis – full analysis set - appendix
Parameter Code=HOMA_BCS
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.8510      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.6334      2.1530
trtpn                                                 1            0.2505      0.5297
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1446      0.1193
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.3218      0.4635
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448      30.15    <.0001
PREAD           1     448       0.04    0.8510
base_log        1     448     118.62    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.5154    0.04105     448     85.64     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.1254    0.05796     448     53.92     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.4348     3.5961         33.6300         31.0237         36.4553
trtpn    LSMeans, IDeg         3.0114     3.2393         22.7680         20.3168         25.5149
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2    0.3901   0.07103    448     5.49    <.0001
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Clinical Trial Report
Status:
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Statistical document
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HOMA-B after 26 weeks of treatment – supportive statistical analysis – full analysis set - appendix
Parameter Code=HOMA_BCS
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05      0.2505      0.5297           1.4771
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         1.2846           1.6984
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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25: HDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02369
           Fit Statistics
-2 Res Log Likelihood          -387.4
AIC (Smaller is Better)        -385.4
AICC (Smaller is Better)       -385.3
BIC (Smaller is Better)        -381.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         0.05515   0.01465   449     3.76
trtpn                                                 1          -0.02691   0.01535   449    -1.75
trtpn                                                 2                0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.01619   0.01449   449    -1.12
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.7660   0.02813   449    27.23
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Statistical document
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appendix
Parameter Code=C105587S
The Mixed Procedure
                           Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0002      0.05
trtpn                                                 1            0.0802      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2643      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         0.02635     0.08395
trtpn                                                 1          -0.05708    0.003252
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.04466     0.01228
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.7107      0.8213
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       3.07    0.0802
PREAD           1     449       1.25    0.2643
base_log        1     449     741.32    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    0.09836   0.008859     449     11.10     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     0.1253    0.01253     449     10.00     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    0.08095     0.1158          1.1034          1.0843          1.1227
trtpn    LSMeans, IDeg         0.1006     0.1499          1.1335          1.1059          1.1617
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.02691   0.01535    449    -1.75    0.0802
CONFIDENTIAL


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Date:
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Statistical document
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appendix
Parameter Code=C105587S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.05708    0.003252           0.9734
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9445           1.0033
CONFIDENTIAL


NN9068
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Date:
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Statistical document
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HDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.02369
           Fit Statistics
-2 Res Log Likelihood          -387.4
AIC (Smaller is Better)        -385.4
AICC (Smaller is Better)       -385.3
BIC (Smaller is Better)        -381.2
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          0.9101    0.1065   449     8.55
trtpn                                                 1          -0.02691   0.01535   449    -1.75
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.01619   0.01449   449    -1.12
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.7660   0.02813   449    27.23
CONFIDENTIAL


NN9068
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Date:
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Clinical Trial Report
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Statistical document
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HDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=HDL_SU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0802      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2643      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          0.7008      1.1194
trtpn                                                 1          -0.05708    0.003252
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.04466     0.01228
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.7107      0.8213
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       3.07    0.0802
PREAD           1     449       1.25    0.2643
base_log        1     449     741.32    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.7519   0.008859     449    423.51     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.7788    0.01253     449    301.57     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.7345     3.7693         42.6008         41.8655         43.3490
trtpn    LSMeans, IDeg         3.7542     3.8034         43.7629         42.6983         44.8539
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.02691   0.01535    449    -1.75    0.0802
CONFIDENTIAL


NN9068
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Date:
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Clinical Trial Report
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Statistical document
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HDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=HDL_SU
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.05708    0.003252           0.9734
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn  Treatment ratio, IDegLira - IDeg         0.9445           1.0033
CONFIDENTIAL


NN9068
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Date:
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Clinical Trial Report
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Statistical document
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26: LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.09192
           Fit Statistics
-2 Res Log Likelihood           217.4
AIC (Smaller is Better)         219.4
AICC (Smaller is Better)        219.4
BIC (Smaller is Better)         223.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF t Value
Intercept                                                          0.2451   0.04507   439     5.44
trtpn                                                 1          -0.05261   0.03067   439    -1.72
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.01684   0.02889   439     0.58
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6372   0.04110   439    15.50
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
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LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=C105588S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0869      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5603      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          0.1565      0.3337
trtpn                                                 1           -0.1129    0.007660
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.03995     0.07363
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
base_log                                                           0.5564      0.7179
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     439       2.94    0.0869
PREAD           1     439       0.34    0.5603
base_log        1     439     240.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     0.7561    0.01760     439     42.97     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     0.8087    0.02510     439     32.21     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     0.7215     0.7906          2.1299          2.0575          2.2048
trtpn    LSMeans, IDeg         0.7593     0.8580          2.2449          2.1369          2.3585
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.05261   0.03067    439    -1.72    0.0869
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
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Statistical document
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LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=C105588S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1129    0.007660           0.9487
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8933           1.0077
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             443
          Number of Observations
Number of Observations Read             453
Number of Observations Used             443
Number of Observations Not Used          10
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.09192
           Fit Statistics
-2 Res Log Likelihood           217.4
AIC (Smaller is Better)         219.4
AICC (Smaller is Better)        219.4
BIC (Smaller is Better)         223.4
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.5708    0.1870   439     8.40
trtpn                                                 1          -0.05261   0.03067   439    -1.72
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.01684   0.02889   439     0.58
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6372   0.04110   439    15.50
CONFIDENTIAL


NN9068
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22 January 2020
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Clinical Trial Report
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Statistical document
Page:
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LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=LDL_SU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0869      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.5603      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.2033      1.9382
trtpn                                                 1           -0.1129    0.007660
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.03995     0.07363
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.5564      0.7179
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     439       2.94    0.0869
PREAD           1     439       0.34    0.5603
base_log        1     439     240.29    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     4.4096    0.01760     439    250.59     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     4.4622    0.02510     439    177.75     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     4.3750     4.4442         82.2346         79.4392         85.1283
trtpn    LSMeans, IDeg         4.4129     4.5115         86.6770         82.5043         91.0608
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.05261   0.03067    439    -1.72    0.0869
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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LDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=LDL_SU
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1129    0.007660           0.9487
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8933           1.0077
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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27: VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.1867
           Fit Statistics
-2 Res Log Likelihood           541.2
AIC (Smaller is Better)         543.2
AICC (Smaller is Better)        543.2
BIC (Smaller is Better)         547.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -0.1883   0.04107   449    -4.58
trtpn                                                 1          -0.01158   0.04308   449    -0.27
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.07290   0.04067   449     1.79
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6095   0.03509   449    17.37
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
282 of 334
VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=C105589S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7881      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0737      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -0.2690     -0.1076
trtpn                                                 1          -0.09625     0.07308
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.00703      0.1528
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.5405      0.6784
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       0.07    0.7881
PREAD           1     449       3.21    0.0737
base_log        1     449     301.77    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -0.2924    0.02487     449    -11.76     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -0.2809    0.03517     449     -7.98     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -0.3413    -0.2436          0.7464          0.7108          0.7838
trtpn    LSMeans, IDeg        -0.3500    -0.2117          0.7551          0.7047          0.8092
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01158   0.04308    449    -0.27    0.7881
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
283 of 334
VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=C105589S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.09625     0.07308           0.9885
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9082           1.0758
CONFIDENTIAL


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Statistical document
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- appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.1867
           Fit Statistics
-2 Res Log Likelihood           541.2
AIC (Smaller is Better)         543.2
AICC (Smaller is Better)        543.2
BIC (Smaller is Better)         547.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.2385    0.1275   449     9.71
trtpn                                                 1          -0.01158   0.04308   449    -0.27
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.07290   0.04067   449     1.79
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6095   0.03509   449    17.37
CONFIDENTIAL


NN9068
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Date:
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Version:
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Statistical document
Page:
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VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=VLDL_SU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7881      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.0737      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          0.9879      1.4890
trtpn                                                 1          -0.09625     0.07308
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.00703      0.1528
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.5405      0.6784
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       0.07    0.7881
PREAD           1     449       3.21    0.0737
base_log        1     449     301.77    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     3.3611    0.02487     449    135.15     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     3.3727    0.03517     449     95.89     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     3.3122     3.4099         28.8201         27.4455         30.2637
trtpn    LSMeans, IDeg         3.3035     3.4418         29.1559         27.2086         31.2426
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01158   0.04308    449    -0.27    0.7881
CONFIDENTIAL


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Date:
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Clinical Trial Report
Status:
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Statistical document
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VLDL cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=VLDL_SU
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.09625     0.07308           0.9885
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9082           1.0758
CONFIDENTIAL


NN9068
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Statistical document
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28: Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.2371
           Fit Statistics
-2 Res Log Likelihood           648.7
AIC (Smaller is Better)         650.7
AICC (Smaller is Better)        650.7
BIC (Smaller is Better)         654.8
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          0.1298   0.05020   449     2.59
trtpn                                                 1          -0.01325   0.04855   449    -0.27
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.06990   0.04585   449     1.52
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6028   0.03500   449    17.22
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
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Statistical document
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Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=C64812S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          0.0100      0.05
trtpn                                                 1            0.7851      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1281      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         0.03115      0.2285
trtpn                                                 1           -0.1087     0.08216
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.02021      0.1600
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.5340      0.6716
        Type 3 Tests of Fixed Effects
              Num     Den
Effect        DF      DF    F Value    Pr > F
trtpn           1     449       0.07    0.7851
PREAD           1     449       2.32    0.1281
base_log        1     449     296.62    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     0.5207    0.02802     449     18.58     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     0.5340    0.03963     449     13.47     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     0.4657     0.5758          1.6833          1.5931          1.7786
trtpn    LSMeans, IDeg         0.4561     0.6119          1.7057          1.5779          1.8439
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01325   0.04855    449    -0.27    0.7851
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
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Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=C64812S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1087     0.08216           0.9868
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8970           1.0856
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
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Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2371
           Fit Statistics
-2 Res Log Likelihood           648.7
AIC (Smaller is Better)         650.7
AICC (Smaller is Better)        650.7
BIC (Smaller is Better)         654.8
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.9126    0.1840   449    10.40
trtpn                                                 1          -0.01325   0.04855   449    -0.27
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.06990   0.04585   449     1.52
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6028   0.03500   449    17.22
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=TRIG_SU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.7851      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1281      0.05
PREAD     BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.5511      2.2741
trtpn                                                 1           -0.1087     0.08216
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.02021      0.1600
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.5340      0.6716
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       0.07    0.7851
PREAD           1     449       2.32    0.1281
base_log        1     449     296.62    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     5.0094    0.02802     449    178.76     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     5.0226    0.03963     449    126.73     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     4.9543     5.0645          149.81          141.78          158.29
trtpn    LSMeans, IDeg         4.9447     5.1005          151.81          140.43          164.11
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01325   0.04855    449    -0.27    0.7851
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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Triglycerides after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
Parameter Code=TRIG_SU
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1087     0.08216           0.9868
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8970           1.0856
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Clinical Trial Report
Status:
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Statistical document
Page:
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29: Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.03056
           Fit Statistics
-2 Res Log Likelihood          -273.4
AIC (Smaller is Better)        -271.4
AICC (Smaller is Better)       -271.4
BIC (Smaller is Better)        -267.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          0.4374   0.05797   449     7.55
trtpn                                                 1          -0.03841   0.01743   449    -2.20
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.02172   0.01647   449     1.32
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6782   0.03724   449    18.21
CONFIDENTIAL


NN9068
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Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=C105586S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0281      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1879      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          0.3235      0.5513
trtpn                                                 1          -0.07267    -0.00415
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.01064     0.05409
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.6050      0.7513
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       4.86    0.0281
PREAD           1     449       1.74    0.1879
base_log        1     449     331.61    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     1.4326    0.01006     449    142.39     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     1.4710    0.01423     449    103.37     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     1.4128     1.4523          4.1895          4.1075          4.2731
trtpn    LSMeans, IDeg         1.4430     1.4990          4.3535          4.2335          4.4770
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.03841   0.01743    449    -2.20    0.0281
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
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Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=C105586S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.07267    -0.00415           0.9623
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9299           0.9959
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
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Clinical Trial Report
Status:
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Statistical document
Page:
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Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      0.03056
           Fit Statistics
-2 Res Log Likelihood          -273.4
AIC (Smaller is Better)        -271.4
AICC (Smaller is Better)       -271.4
BIC (Smaller is Better)        -267.3
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.6132    0.1924   449     8.39
trtpn                                                 1          -0.03841   0.01743   449    -2.20
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              0.02172   0.01647   449     1.32
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.6782   0.03724   449    18.21
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Total cholesterol after 26 weeks of treatment – supportive statistical analysis – full analysis set
- appendix
Parameter Code=T_CHOL_U
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0281      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1879      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.2352      1.9913
trtpn                                                 1          -0.07267    -0.00415
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                             -0.01064     0.05409
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.6050      0.7513
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       4.86    0.0281
PREAD           1     449       1.74    0.1879
base_log        1     449     331.61    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     5.0861    0.01006     449    505.54     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     5.1245    0.01423     449    360.12     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     5.0663     5.1059          161.76          158.59          164.99
trtpn    LSMeans, IDeg         5.0965     5.1525          168.09          163.45          172.86
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.03841   0.01743    449    -2.20    0.0281
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- appendix
Parameter Code=T_CHOL_U
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05    -0.07267    -0.00415           0.9623
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.9299           0.9959
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30: Free fatty acid after 26 weeks of treatment – supportive statistical analysis – full analysis set -
appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2601
           Fit Statistics
-2 Res Log Likelihood           688.4
AIC (Smaller is Better)         690.4
AICC (Smaller is Better)        690.4
BIC (Smaller is Better)         694.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         -1.1035   0.06468   448   -17.06
trtpn                                                 1          -0.01181   0.05099   448    -0.23
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.03834   0.04808   448    -0.80
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.2370   0.04606   448     5.15
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appendix
Parameter Code=C80200S
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.8170      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4256      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect    Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         -1.2306     -0.9764
trtpn                                                 1           -0.1120     0.08841
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1328     0.05615
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                
base_log                                                           0.1465      0.3275
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       0.05    0.8170
PREAD           1     448       0.64    0.4256
base_log        1     448      26.48    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label              Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    -1.3590    0.02936     448    -46.29     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    -1.3472    0.04167     448    -32.33     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    -1.4167    -1.3013          0.2569          0.2425          0.2722
trtpn    LSMeans, IDeg        -1.4291    -1.2653          0.2600          0.2395          0.2822
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01181   0.05099    448    -0.23    0.8170
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appendix
Parameter Code=C80200S
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1120     0.08841           0.9883
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8940           1.0924
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appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             452
          Number of Observations
Number of Observations Read             453
Number of Observations Used             452
Number of Observations Not Used           1
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       0.2601
           Fit Statistics
-2 Res Log Likelihood           688.4
AIC (Smaller is Better)         690.4
AICC (Smaller is Better)        690.4
BIC (Smaller is Better)         694.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                          1.4444    0.1203   448    12.01
trtpn                                                 1          -0.01181   0.05099   448    -0.23
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                             -0.03834   0.04808   448    -0.80
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
base_log                                                           0.2370   0.04606   448     5.15
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appendix
Parameter Code=FFAU
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.8170      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.4256      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
base_log                                                           <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                          1.2080      1.6809
trtpn                                                 1           -0.1120     0.08841
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.1328     0.05615
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
base_log                                                           0.1465      0.3275
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     448       0.05    0.8170
PREAD           1     448       0.64    0.4256
base_log        1     448      26.48    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     1.9803    0.02936     448     67.45     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     1.9921    0.04167     448     47.81     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     1.9226     2.0380          7.2452          6.8390          7.6755
trtpn    LSMeans, IDeg         1.9102     2.0740          7.3312          6.7548          7.9568
                                   Least Squares Means Estimate
                                                                 Standard
Effect  Label                             Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Treatment ratio, IDegLira - IDeg  WORK.ADATA2  -0.01181   0.05099    448    -0.23    0.8170
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appendix
Parameter Code=FFAU
The Mixed Procedure
                              Least Squares Means Estimate
Effect  Label                              Alpha       Lower       Upper    Exponentiated
trtpn   Treatment ratio, IDegLira - IDeg    0.05     -0.1120     0.08841           0.9883
                      Least Squares Means Estimate
                                          Exponentiated    Exponentiated
Effect  Label                                     Lower            Upper
trtpn   Treatment ratio, IDegLira - IDeg         0.8940           1.0924
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31: 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         453
Number of Observations Used         452
Missing Values                        1
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
                             Parameter Information
Parameter       Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -272.05183    4.8722249    -0.133255    0.0535432     0.9030346
   1        1    -210.31256    4.3017337     -0.38207    -0.019395     0.5621385
   2        1    -196.63064    4.0111682    -0.544379    0.0204517     0.7702072
   3     0.06    -192.79932    4.0350243    -0.558915    0.0141844     6.3310514
   4        0    -189.55465    3.6343238    -0.650209    0.3457195     3.2510687
   5        0    -189.37048     3.755194    -0.639949    0.2514424     3.1348703
   6        0     -189.3701    3.7514615    -0.640906    0.2552308      3.154036
   7        0     -189.3701    3.7514508    -0.640908    0.2552416     3.1540135
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     449        191.5532          0.4266
Scaled Deviance              449        191.5532          0.4266
Pearson Chi-Square           449        572.5233          1.2751
Scaled Pearson X2            449        572.5233          1.2751
Log Likelihood                         -189.3701                
Full Log Likelihood                    -208.8157                
AIC (smaller is better)                 425.6314                
AICC (smaller is better)                425.7209                
BIC (smaller is better)                 442.0862                
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Parameter Code=HYCNFSE
The GENMOD Procedure
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        -4.23E-11      1.307E-10      -5.34E-11       -1.11E-10
Prm1            47.012506      26.834407      24.205977       -0.177861
Prm2            26.834407      26.834407      13.519355       -0.138454
Prm4            24.205977      13.519355      24.205977       -0.132367
Dispersion      -0.177861      -0.138454      -0.132367       0.8529003
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                     Standard       Wald 95%
Parameter                                              DF  Estimate     Error   Confidence Limits
Intercept                                               1    3.7515    0.2710    3.2202    4.2827
TRTPN       1                                           1   -0.6409    0.2948   -1.2187   -0.0632
TRTPN       2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD       BASAL INSULIN + METFORMIN                   1    0.2552    0.2919   -0.3170    0.8274
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
Dispersion                                              1    3.1540    1.0834    1.6087    6.1837
              Analysis Of Maximum Likelihood Parameter Estimates
                                                             Wald
Parameter                                              Chi-Square    Pr > ChiSq
Intercept                                                  191.58        <.0001
TRTPN       1                                                4.73        0.0297
TRTPN       2                                                                  
PREAD       BASAL INSULIN + METFORMIN                        0.76        0.3820
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
Dispersion                                                                     
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             3.2382     0.1931     16.77     <.0001     0.05     2.8596     3.6167         25.4869
2             3.8791     0.2228     17.41     <.0001     0.05     3.4424     4.3157         48.3793
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                 17.4553          37.2140
2                 31.2620          74.8691
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2            -0.6409     0.2948     -2.17     0.0297     0.05    -1.2187   -0.06315
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Parameter Code=HYCNFSE
The GENMOD Procedure
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.5268           0.2956           0.9388
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg    -0.6409     0.2948     -2.17     0.0297     0.05    -1.2187   -0.06315
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.5268           0.2956           0.9388
32: Hypoglycaemic episodes – treatment emergent – statistical sensitivity analysis – multiple 
imputation – full analysis set
Parameter Code=HYCNFSE Planned Treatment (N)=1 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI 
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.003123       0.035506       0.038632   152521
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate        0.088058       0.080943       0.999919
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        3.271298       0.196551   2.886063   3.656534   152521       3.193123       3.464076
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              16.64     <.0001
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imputation – full analysis set
Parameter Code=HYCNFSE Planned Treatment (N)=2 Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSM_MI 
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.002588       0.048444       0.051034   387717
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate         0.053475       0.050765       0.999949
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate        3.880257       0.225908   3.437485   4.323030   387717       3.817666       4.255104
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              17.18     <.0001
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imputation – full analysis set
Parameter Code=HYCNFSE Label=IDegLira / IDeg Statement Number=1
The MIANALYZE Procedure
          Model Information
Data Set                  WORK.LSME_MI
Number of Imputations     1000        
            Variance Information (1000 Imputations)
             -----------------Variance-----------------
Parameter         Between         Within          Total       DF
Estimate         0.005649       0.083893       0.089548   250504
        Variance Information (1000 Imputations)
                 Relative       Fraction
                 Increase        Missing       Relative
Parameter     in Variance    Information     Efficiency
Estimate        0.067407       0.063158       0.999937
                               Parameter Estimates (1000 Imputations)
                                             95% Confidence
Parameter       Estimate      Std Error          Limits             DF        Minimum        Maximum
Estimate       -0.608959       0.299246   -1.19547   -0.02244   250504      -1.010738      -0.360220
        Parameter Estimates (1000 Imputations)
                                  t for H0:
Parameter         Theta0   Parameter=Theta0   Pr > |t|
Estimate               0              -2.03     0.0419
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33: 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         453
Number of Observations Used         452
Missing Values                        1
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
                             Parameter Information
Parameter       Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -248.88659    4.7823425    -0.097818    0.0546535     0.8596882
   1        1      -150.683    3.7018963    -0.473071    -0.076207     0.0626182
   2     0.06    -144.39901    3.2524477    -0.570648    0.3099962     0.1619065
   3        1    -143.90765    3.1384215    -0.614858    0.4166656     0.1781804
   4        1    -143.75331    3.0873625    -0.619769     0.482044     0.1989049
   5        1     -143.6442    3.0615369    -0.615829     0.514276     0.2241457
   6        1    -143.53327    3.0479009    -0.611319    0.5296764     0.2550337
   7        1    -143.40811     3.040686     -0.60782    0.5369217     0.2932181
   8        1    -143.26397    3.0369288    -0.605294    0.5401102     0.3408479
   9        1    -143.09875    3.0350577    -0.603396     0.541174      0.400609
  10     0.06    -141.69204    3.0387866    -0.593892    0.5282424     2.4021374
  11        0    -141.64987    3.0413466    -0.583393    0.5170532     2.0466411
  12        0    -141.64952    3.0412361    -0.583948    0.5177205     2.0124952
  13        0    -141.64952     3.041235    -0.583949    0.5177226     2.0121329
  14        0    -141.64952     3.041235    -0.583949    0.5177226     2.0121329
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     449        161.6466          0.3600
Scaled Deviance              449        161.6466          0.3600
Pearson Chi-Square           449        487.6689          1.0861
Scaled Pearson X2            449        487.6689          1.0861
Log Likelihood                         -141.6495                
Full Log Likelihood                    -146.6193                
AIC (smaller is better)                 301.2387                
AICC (smaller is better)                301.3281                
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
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Parameter Code=HYCNFSES
The GENMOD Procedure
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
BIC (smaller is better)                 317.6934                
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        -2.874E-9      -2.428E-9      -2.36E-10       2.4602E-8
Prm1            35.798234      19.712382      21.111393       -0.077305
Prm2            19.712382      19.712382      11.018598        -0.12625
Prm4            21.111393      11.018598      21.111393       0.0691198
Dispersion      -0.077305       -0.12625      0.0691198       0.5954467
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                     Standard       Wald 95%
Parameter                                              DF  Estimate     Error   Confidence Limits
Intercept                                               1    3.0412    0.3284    2.3975    3.6850
TRTPN       1                                           1   -0.5839    0.3370   -1.2444    0.0765
TRTPN       2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD       BASAL INSULIN + METFORMIN                   1    0.5177    0.3410   -0.1506    1.1861
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
Dispersion                                              1    2.0121    1.2985    0.5680    7.1278
              Analysis Of Maximum Likelihood Parameter Estimates
                                                             Wald
Parameter                                              Chi-Square    Pr > ChiSq
Intercept                                                   85.74        <.0001
TRTPN       1                                                3.00        0.0831
TRTPN       2                                                                  
PREAD       BASAL INSULIN + METFORMIN                        2.31        0.1290
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
Dispersion                                                                     
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             2.7161     0.2263     12.00     <.0001     0.05     2.2726     3.1597         15.1219
2             3.3001     0.2531     13.04     <.0001     0.05     2.8041     3.7961         27.1153
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  9.7044          23.5640
2                 16.5114          44.5290
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Statistical document
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Hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full analysis set
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           2            -0.5839     0.3370     -1.73     0.0831     0.05    -1.2444    0.07654
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.5577           0.2881           1.0795
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg    -0.5839     0.3370     -1.73     0.0831     0.05    -1.2444    0.07654
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.5577           0.2881           1.0795
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34: Nocturnal hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full 
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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         453
Number of Observations Used         452
Missing Values                        1
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
                             Parameter Information
Parameter       Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge   Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -215.96192    4.6893282    -0.053017    0.0516002     0.8341748
   1       16    -167.98527    4.4687164    -0.190605    -0.037648     0.8571859
   2        1    -90.768506    3.5294783    -0.439246    -0.082759      0.170072
   3     0.06    -72.013485    2.6019258    -0.475368    0.3715303     0.0162736
   4     0.06    -67.946168    1.9188902    -0.540226    0.9677594     0.0165235
   5     0.06    -67.192355    1.4811743    -0.565808    1.4152555     0.0170752
   6     0.06    -67.124605    1.3101504    -0.563508    1.5891586     0.0177306
   7     0.06    -67.122096    1.2752562    -0.559966    1.6240807     0.0184492
   8     0.06    -67.121743    1.2704551    -0.559052    1.6287998     0.0192286
   9     0.06    -67.121401    1.2698432    -0.558894    1.6293805     0.0200756
  10     0.06    -67.121031    1.2697606    -0.558857    1.6294463     0.0209996
  11     0.06    -67.120625    1.2697436    -0.558834    1.6294478     0.0220114
  12     0.06    -67.120181    1.2697341    -0.558812    1.6294408     0.0231238
  13     0.06    -67.119691    1.2697247    -0.558788    1.6294319     0.0243527
  14     0.06     -67.11915    1.2697144     -0.55876    1.6294219     0.0257169
  15     0.06    -67.118547     1.269703     -0.55873    1.6294107     0.0272398
  16     0.06    -67.117872    1.2696902    -0.558696    1.6293982     0.0289502
  17     0.06    -67.117112    1.2696757    -0.558658     1.629384     0.0308844
  18     0.06    -67.116251    1.2696593    -0.558615    1.6293679     0.0330885
  19     0.06    -67.115266    1.2696404    -0.558565    1.6293494     0.0356219
  20     0.06     -67.11413    1.2696185    -0.558507    1.6293279     0.0385624
  21     0.06    -67.112806    1.2695928    -0.558439    1.6293027     0.0420137
  22     0.06    -67.111246    1.2695624    -0.558358    1.6292729     0.0461171
  23     0.06    -67.109383    1.2695258    -0.558262     1.629237     0.0510694
  24     0.06    -67.107124     1.269481    -0.558143     1.629193     0.0571518
  25     0.06    -67.104336     1.269425    -0.557995     1.629138     0.0647792
  26     0.06    -67.100824    1.2693535    -0.557805    1.6290678     0.0745844
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Parameter Code=HYNOCSE
The GENMOD Procedure
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
  27     0.06    -67.096295    1.2692595    -0.557556    1.6289753     0.0875714
  28     0.06    -67.090299    1.2691315    -0.557218    1.6288495     0.1054017
  29     0.06     -67.08214    1.2689504    -0.556738    1.6286715     0.1309448
  30     0.06    -67.070793    1.2686826    -0.556029    1.6284083     0.1693051
  31     0.06    -67.055061    1.2682702    -0.554938    1.6280038     0.2293512
  32     0.06    -67.034869     1.267629    -0.553245    1.6273782     0.3234446
  33     0.06    -67.014505    1.2667097     -0.55083    1.6264928     0.4546296
  34        0    -67.000492    1.2637589      -0.5432    1.6237742     1.0469637
  35        0    -66.994046    1.2635923    -0.542893     1.623724     0.8558277
  36        0    -66.993831    1.2637759    -0.543338    1.6238771     0.8174085
  37        0     -66.99383    1.2637833    -0.543357    1.6238838     0.8156145
  38        0     -66.99383    1.2637833    -0.543357    1.6238838     0.8156145
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     449         91.8805          0.2046
Scaled Deviance              449         91.8805          0.2046
Pearson Chi-Square           449        471.5693          1.0503
Scaled Pearson X2            449        471.5693          1.0503
Log Likelihood                          -66.9938                
Full Log Likelihood                     -67.6870                
AIC (smaller is better)                 143.3740                
AICC (smaller is better)                143.4634                
BIC (smaller is better)                 159.8287                
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        7.2041E-8      -9.852E-8       8.936E-8       1.0772E-6
Prm1            16.193152      8.6776345      13.226628       0.0434796
Prm2            8.6776345      8.6776345      7.0138944       -0.053721
Prm4            13.226628      7.0138944      13.226628       0.0530582
Dispersion      0.0434796      -0.053721      0.0530582        0.272279
Algorithm converged.                                                       
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                     Standard       Wald 95%
Parameter                                              DF  Estimate     Error   Confidence Limits
Intercept                                               1    1.2638    0.6445    0.0005    2.5271
TRTPN       1                                           1   -0.5434    0.4998   -1.5229    0.4362
TRTPN       2                                           0    0.0000    0.0000    0.0000    0.0000
              Analysis Of Maximum Likelihood Parameter Estimates
                                                             Wald
Parameter                                              Chi-Square    Pr > ChiSq
Intercept                                                    3.84        0.0499
TRTPN       1                                                1.18        0.2769
TRTPN       2                                                                  
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Parameter Code=HYNOCSE
The GENMOD Procedure
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                     Standard       Wald 95%
Parameter                                              DF  Estimate     Error   Confidence Limits
PREAD       BASAL INSULIN + METFORMIN                   1    1.6239    0.6427    0.3642    2.8836
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
Dispersion                                              1    0.8156    1.9224    0.0080   82.7552
              Analysis Of Maximum Likelihood Parameter Estimates
                                                             Wald
Parameter                                              Chi-Square    Pr > ChiSq
PREAD       BASAL INSULIN + METFORMIN                        6.38        0.0115
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
Dispersion                                                                     
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             1.5324     0.3934      3.90     <.0001     0.05     0.7614     2.3033          4.6291
2             2.0757     0.4214      4.93     <.0001     0.05     1.2499     2.9016          7.9703
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  2.1413          10.0075
2                  3.4899          18.2029
                           Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment              Standard
(N)         (N)         Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
1           2            -0.5434     0.4998     -1.09     0.2769     0.05    -1.5229     0.4362
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.5808           0.2181           1.5468
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg    -0.5434     0.4998     -1.09     0.2769     0.05    -1.5229     0.4362
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Parameter Code=HYNOCSE
The GENMOD Procedure
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.5808           0.2181           1.5468
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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         453
Number of Observations Used         452
Missing Values                        1
                        Class Level Information
Class      Levels    Values
TRTPN           2    1 2                                               
PREAD           2    BASAL INSULIN + METFORMIN BASAL INSULIN +         
                     METFORMIN + ONE OTHER OAD                         
                             Parameter Information
Parameter       Effect       TRTPN    PREAD
Prm1            Intercept                                                      
Prm2            TRTPN        1                                                 
Prm3            TRTPN        2                                                 
Prm4            PREAD                 BASAL INSULIN + METFORMIN                
Prm5            PREAD                 BASAL INSULIN + METFORMIN + ONE OTHER OAD
                    Iteration History For Parameter Estimates
                        Log
Iter    Ridge    Likelihood         Prm1         Prm2         Prm4    Dispersion
   0        0    -212.11027    4.6898332    -0.053761     0.038275     0.8351092
   1       16    -162.95238    4.4666039       -0.193    -0.053776     0.8590154
   2        1    -81.103474    3.4686626    -0.455285    -0.129406      0.125644
   3     0.06    -63.352907    2.6085205    -0.526344     0.230995     0.0522172
   4     0.06    -59.275366    1.9430772    -0.623397    0.7585306     0.0580303
   5     0.06     -58.55622    1.5250015    -0.677486    1.1872585      0.073142
   6     0.06    -58.483218    1.3669014    -0.682462      1.35142     0.1028472
   7     0.06    -58.448149    1.3378943     -0.67888    1.3802064       0.17162
   8     0.06    -58.351696    1.3337319    -0.675113    1.3819333      0.421137
   9     0.06    -58.185224    1.3299425    -0.662876    1.3760787     1.7256941
  10        0    -58.184617    1.3257512    -0.649048    1.3695915     1.7974982
  11        0    -58.184617    1.3256893    -0.648998    1.3695947     1.7956447
  12        0    -58.184617    1.3256893    -0.648998    1.3695947     1.7956447
             Criteria For Assessing Goodness Of Fit
Criterion                     DF           Value        Value/DF
Deviance                     449         74.9894          0.1670
Scaled Deviance              449         74.9894          0.1670
Pearson Chi-Square           449        474.3927          1.0566
Scaled Pearson X2            449        474.3927          1.0566
Log Likelihood                          -58.1846                
Full Log Likelihood                     -58.8778                
AIC (smaller is better)                 125.7555                
AICC (smaller is better)                125.8450                
BIC (smaller is better)                 142.2103                
CONFIDENTIAL


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Nocturnal hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full
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Parameter Code=HYNOCSES
The GENMOD Procedure
      Last Evaluation Of The Negative Of The Gradient and Hessian
                     Prm1           Prm2           Prm4      Dispersion
Gradient        -9.349E-9      -3.309E-8      3.9818E-9       1.6756E-7
Prm1            12.891925      6.6108821      9.9666887       0.0342268
Prm2            6.6108821      6.6108821      5.0193772       -0.037243
Prm4            9.9666887      5.0193772      9.9666887       0.0460269
Dispersion      0.0342268      -0.037243      0.0460269       0.1113227
Algorithm converged.                                                      
                       Analysis Of Maximum Likelihood Parameter Estimates
                                                                     Standard       Wald 95%
Parameter                                              DF  Estimate     Error   Confidence Limits
Intercept                                               1    1.3257    0.6589    0.0343    2.6170
TRTPN       1                                           1   -0.6490    0.5598   -1.7462    0.4482
TRTPN       2                                           0    0.0000    0.0000    0.0000    0.0000
PREAD       BASAL INSULIN + METFORMIN                   1    1.3696    0.6658    0.0647    2.6745
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD   0    0.0000    0.0000    0.0000    0.0000
Dispersion                                              1    1.7956    3.0130    0.0670   48.1374
              Analysis Of Maximum Likelihood Parameter Estimates
                                                             Wald
Parameter                                              Chi-Square    Pr > ChiSq
Intercept                                                    4.05        0.0442
TRTPN       1                                                1.34        0.2463
TRTPN       2                                                                  
PREAD       BASAL INSULIN + METFORMIN                        4.23        0.0397
PREAD       BASAL INSULIN + METFORMIN + ONE OTHER OAD                          
Dispersion                                                                     
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             1.3615     0.4261      3.20     0.0014     0.05     0.5264     2.1966          3.9020
2             2.0105     0.4434      4.53     <.0001     0.05     1.1415     2.8795          7.4670
        TRTPN Least Squares Means
Planned
Treatment   Exponentiated    Exponentiated
(N)                 Lower            Upper
1                  1.6927           8.9946
2                  3.1314          17.8055
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Nocturnal hypoglycaemic episodes – treatment emergent – supportive statistical analysis – full
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Parameter Code=HYNOCSES
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           -0.6490     0.5598     -1.16     0.2463     0.05    -1.7462     0.4482
               Differences of TRTPN Least Squares Means
Planned     Planned
Treatment   Treatment                    Exponentiated    Exponentiated
(N)         (N)         Exponentiated            Lower            Upper
1           2                  0.5226           0.1744           1.5655
                                   Least Squares Means Estimate
                                      Standard
Effect   Label             Estimate      Error   z Value   Pr > |z|    Alpha      Lower      Upper
TRTPN    IDegLira / IDeg    -0.6490     0.5598     -1.16     0.2463     0.05    -1.7462     0.4482
                       Least Squares Means Estimate
                                            Exponentiated    Exponentiated
Effect   Label             Exponentiated            Lower            Upper
TRTPN    IDegLira / IDeg          0.5226           0.1744           1.5655
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35: Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full 
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      65.0379
           Fit Statistics
-2 Res Log Likelihood          3174.8
AIC (Smaller is Better)        3176.8
AICC (Smaller is Better)       3176.9
BIC (Smaller is Better)        3180.9
                                   Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         39.2829    3.1653   449    12.41
trtpn                                                 1            4.4149    0.8040   449     5.49
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2566    0.7591   449    -0.34
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.5115   0.03986   449    12.83
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Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set - appendix
Parameter Code=C49676X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.7355      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0623     45.5036
trtpn                                                 1            2.8348      5.9950
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -1.7485      1.2352
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.4332      0.5898
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      30.15    <.0001
PREAD           1     449       0.11    0.7355
BASE            1     449     164.70    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    83.1604     0.4641     449    179.18     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    78.7455     0.6564     449    119.97     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    82.2483    84.0725        1.306E36        5.248E35        3.252E36
trtpn    LSMeans, IDeg        77.4555    80.0355         1.58E34         4.35E33        5.741E34
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2     4.4149     0.8040     449      5.49
CONFIDENTIAL


NN9068
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Version:
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Statistical document
Page:
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Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set - appendix
Parameter Code=C49676X
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    <.0001    0.05    2.8348    5.9950        82.6739
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg        17.0278           401.40
CONFIDENTIAL


NN9068
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Statistical document
Page:
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Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      65.0379
           Fit Statistics
-2 Res Log Likelihood          3174.8
AIC (Smaller is Better)        3176.8
AICC (Smaller is Better)       3176.9
BIC (Smaller is Better)        3180.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         39.2829    3.1653   449    12.41
trtpn                                                 1            4.4149    0.8040   449     5.49
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                              -0.2566    0.7591   449    -0.34
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.4885   0.03986   449   -12.26
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
324 of 334
Pulse after 26 weeks of treatment – change from baseline – supportive statistical analysis – full
analysis set - appendix
Parameter Code=C49676X
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            <.0001      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.7355      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         33.0623     45.5036
trtpn                                                 1            2.8348      5.9950
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -1.7485      1.2352
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.5668     -0.4102
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449      30.15    <.0001
PREAD           1     449       0.11    0.7355
BASE            1     449     150.22    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    5.7719    0.4641    449    12.44    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2    1.3570    0.6564    449     2.07    0.0393
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05      4.8598      6.6839
trtpn   Change from baseline, IDeg        0.05     0.06695      2.6470
CONFIDENTIAL


NN9068
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Clinical Trial Report
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Statistical document
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36: Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       125.53
           Fit Statistics
-2 Res Log Likelihood          3470.8
AIC (Smaller is Better)        3472.8
AICC (Smaller is Better)       3472.9
BIC (Smaller is Better)        3476.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         64.3085    4.9405   449    13.02
trtpn                                                 1           -3.1299    1.1171   449    -2.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               1.2168    1.0553   449     1.15
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.4942   0.03775   449    13.09
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:
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Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=SYSBPMEA
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0053      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2495      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         54.5991     74.0178
trtpn                                                 1           -5.3252     -0.9345
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.8572      3.2909
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.4200      0.5684
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       7.85    0.0053
PREAD           1     449       1.33    0.2495
BASE            1     449     171.34    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2     125.38     0.6448     449    194.45     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2     128.51     0.9120     449    140.92     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect   Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira     124.11     126.65        2.834E54        7.981E53        1.006E55
trtpn    LSMeans, IDeg         126.72     130.30        6.482E55         1.08E55        3.891E56
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2    -3.1299     1.1171     449     -2.80
CONFIDENTIAL


NN9068
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Date:
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NN9068-4166
Version:
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Clinical Trial Report
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Statistical document
Page:
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Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=SYSBPMEA
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.0053    0.05   -5.3252   -0.9345        0.04372
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg       0.004867           0.3928
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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NN9068-4166
Version:
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Clinical Trial Report
Status:
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Statistical document
Page:
328 of 334
Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual       125.53
           Fit Statistics
-2 Res Log Likelihood          3470.8
AIC (Smaller is Better)        3472.8
AICC (Smaller is Better)       3472.9
BIC (Smaller is Better)        3476.9
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         64.3085    4.9405   449    13.02
trtpn                                                 1           -3.1299    1.1171   449    -2.80
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               1.2168    1.0553   449     1.15
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.5058   0.03775   449   -13.40
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
329 of 334
Systolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical
analysis – full analysis set - appendix
Parameter Code=SYSBPMEA
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.0053      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.2495      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         54.5991     74.0178
trtpn                                                 1           -5.3252     -0.9345
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.8572      3.2909
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.5800     -0.4316
        Type 3 Tests of Fixed Effects
             Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       7.85    0.0053
PREAD           1     449       1.33    0.2495
BASE            1     449     179.51    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2   -3.3685    0.6448    449    -5.22    <.0001
trtpn   Change from baseline, IDeg      WORK.ADATA2   -0.2387    0.9120    449    -0.26    0.7937
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -4.6357     -2.1014
trtpn   Change from baseline, IDeg        0.05     -2.0309      1.5536
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
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Version:
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Clinical Trial Report
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Statistical document
Page:
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37: Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive statistical 
analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      49.8665
           Fit Statistics
-2 Res Log Likelihood          3055.4
AIC (Smaller is Better)        3057.4
AICC (Smaller is Better)       3057.4
BIC (Smaller is Better)        3061.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         31.4557    3.1010   449    10.14
trtpn                                                 1            0.3195    0.7041   449     0.45
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               1.0538    0.6650   449     1.58
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                               0.5940   0.03829   449    15.51
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
331 of 334
Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive
statistical analysis – full analysis set - appendix
Parameter Code=DIABPMEA
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                     Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.6502      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1137      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         25.3613     37.5500
trtpn                                                 1           -1.0642      1.7031
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2530      2.3606
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                               0.5188      0.6693
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       0.21    0.6502
PREAD           1     449       2.51    0.1137
BASE            1     449     240.63    <.0001
                                   Least Squares Means Estimates
                                                      Standard
Effect   Label               Margins       Estimate      Error      DF   t Value   Pr > |t|    Alpha
trtpn    LSMeans, IDegLira   WORK.ADATA2    79.3361     0.4064     449    195.22     <.0001     0.05
trtpn    LSMeans, IDeg       WORK.ADATA2    79.0166     0.5748     449    137.47     <.0001     0.05
                                 Least Squares Means Estimates
                                                                   Exponentiated   Exponentiated
Effect  Label                  Lower      Upper   Exponentiated           Lower           Upper
trtpn    LSMeans, IDegLira    78.5374    80.1347        2.852E34        1.283E34         6.34E34
trtpn    LSMeans, IDeg        77.8870    80.1462        2.072E34        6.697E33        6.413E34
                                  Least Squares Means Estimate
                                                                      Standard
Effect  Label                                Margins       Estimate      Error      DF   t Value
trtpn   Treatment contrast, IDegLira - IDeg  WORK.ADATA2     0.3195     0.7041     449      0.45
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
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NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
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Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive
statistical analysis – full analysis set - appendix
Parameter Code=DIABPMEA
The Mixed Procedure
                                  Least Squares Means Estimate
Effect  Label                                Pr > |t|   Alpha     Lower     Upper  Exponentiated
trtpn   Treatment contrast, IDegLira - IDeg    0.6502    0.05   -1.0642    1.7031         1.3764
                       Least Squares Means Estimate
                                             Exponentiated    Exponentiated
Effect  Label                                        Lower            Upper
trtpn   Treatment contrast, IDegLira - IDeg         0.3450           5.4912
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
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Clinical Trial Report
Status:
Final
Statistical document
Page:
333 of 334
Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive
statistical analysis – full analysis set - appendix
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         2    1 2                           
PREAD         2    BASAL INSULIN + METFORMIN     
                   BASAL INSULIN + METFORMIN +   
                   ONE OTHER OAD                 
            Dimensions
Covariance Parameters             1
Columns in X                      6
Columns in Z                      0
Subjects                          1
Max Obs per Subject             453
          Number of Observations
Number of Observations Read             453
Number of Observations Used             453
Number of Observations Not Used           0
Covariance Parameter
      Estimates
Cov Parm     Estimate
Residual      49.8665
           Fit Statistics
-2 Res Log Likelihood          3055.4
AIC (Smaller is Better)        3057.4
AICC (Smaller is Better)       3057.4
BIC (Smaller is Better)        3061.5
                                    Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period               Standard
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Estimate     Error    DF  t Value
Intercept                                                         31.4557    3.1010   449    10.14
trtpn                                                 1            0.3195    0.7041   449     0.45
trtpn                                                 2                 0                         
PREAD      BASAL INSULIN + METFORMIN                               1.0538    0.6650   449     1.58
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                    0                         
BASE                                                              -0.4060   0.03829   449   -10.60
CONFIDENTIAL


NN9068
CONFIDENTIAL
Date:
22 January 2020
Novo Nordisk
NN9068-4166
Version:
1.0
Clinical Trial Report
Status:
Final
Statistical document
Page:
334 of 334
Diastolic blood pressure after 26 weeks of treatment – change from baseline – supportive
statistical analysis – full analysis set - appendix
Parameter Code=DIABPMEA
The Mixed Procedure
                            Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect     Pre Trial anti-Diabetic treatment          01 (N)     Pr > |t|     Alpha
Intercept                                                          <.0001      0.05
trtpn                                                 1            0.6502      0.05
trtpn                                                 2                            
PREAD      BASAL INSULIN + METFORMIN                               0.1137      0.05
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                               
BASE                                                               <.0001      0.05
                             Solution for Fixed Effects
                                                      Planned
                                                      Treatment
                                                      for
                                                      Period
Effect    Pre Trial anti-Diabetic treatment          01 (N)        Lower       Upper
Intercept                                                         25.3613     37.5500
trtpn                                                 1           -1.0642      1.7031
trtpn                                                 2                              
PREAD      BASAL INSULIN + METFORMIN                              -0.2530      2.3606
PREAD      BASAL INSULIN + METFORMIN + ONE OTHER OAD                                 
BASE                                                              -0.4812     -0.3307
        Type 3 Tests of Fixed Effects
              Num     Den
Effect         DF      DF    F Value    Pr > F
trtpn           1     449       0.21    0.6502
PREAD           1     449       2.51    0.1137
BASE            1     449     112.39    <.0001
                                  Least Squares Means Estimates
                                                               Standard
Effect  Label                           Margins      Estimate     Error     DF  t Value  Pr > |t|
trtpn   Change from baseline, IDegLira  WORK.ADATA2    0.1124    0.4064    449     0.28    0.7823
trtpn   Change from baseline, IDeg      WORK.ADATA2   -0.2071    0.5748    449    -0.36    0.7188
                    Least Squares Means Estimates
Effect  Label                            Alpha       Lower       Upper
trtpn   Change from baseline, IDegLira    0.05     -0.6863      0.9111
trtpn   Change from baseline, IDeg        0.05     -1.3367      0.9225
CONFIDENTIAL