A Phase 2, Randomized, Parallel, Open-Label Comparator-Controlled Trial to Evaluate the Safety and Efficacy of LY3209590 in Study Participants With Type 1 Diabetes Mellitus Previously Treated With Multiple Daily Injection Therapy
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Sponsor: Eli Lilly and Company

 
 
 
 
Protocol I8H-MC-BDCP(d) 
 
 
A Phase 2, Randomized, Parallel, Open-Label Comparator-Controlled 
Trial to Evaluate the Safety and Efficacy of LY3209590 in Study 
Participants with Type 1 Diabetes Mellitus Previously Treated with 
Multiple Daily Injection Therapy. 
 
 
NCT04450407    
 
 
Approval Date: 28-Oct-2020 

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
1
Title P a ge
C o nfi d e nti al I nf or m ati o n
T h e i nf or m ati o n c o nt ai n e d i n t hi s d o c u m e nt i s c o nfi d e nti al a n d i s i nt e n d e d f or t h e u s e of cli ni c al i n v e sti g at or s.  It i s t h e pr o p ert y of 
Eli Lill y a n d C o m p a n y or it s s u b si di ari e s a n d s h o ul d n ot b e c o pi e d b y or di stri b ut e d t o p er s o n s n ot i n v ol v e d i n t h e cli ni c al 
i n v e sti g ati o n of L Y 3 2 0 9 5 9 0 , u nl e s s s u c h p er s o n s ar e b o u n d b y a c o nfi d e nti alit y a gr e e m e nt wit h Eli Lill y a n d C o m p a n y or it s 
s u b si di ari e s .
N ot e t o R e g ul at or y A ut h oriti e s:   T hi s d o c u m e nt m a y c o nt ai n pr ot e ct e d p er s o n al d at a a n d/ or c o m m er ci all y c o nfi d e nti al 
i nfor m ati o n e x e m pt fr o m p u bli c di s cl o s ur e.  Eli Lill y a n d C o m p a n y r e q u e st s c o n s ult ati o n r e g ar di n g r el e a s e/r e d a cti o n pri or t o a n y 
p u bli c r el e a s e.  I n t h e U nit e d St at e s, t hi s d o c u m e nt i s s u bj e ct t o Fr e e d o m of I nf or m ati o n A ct ( F OI A) E x e m pti o n 4 a n d m a y n ot b e 
r epr o d u c e d or ot h er wi s e di s s e mi n at e d wit h o ut t h e writt e n a p pr o v al of Eli Lill y a n d C o m p a n y or it s s u b si di ari e s.
Pr ot oc ol Title:
A P hase 2, Ra n d o mize d, Parallel, O pe n -La bel  C o m parat or -C o nt r olle d Tri al t o 
E val uate t he Safet y a n d Efficac y of L Y 3 2 0 9 5 9 0 i n St u d y  P artici pa nts wit h T ype 
1 Dia betes Mellit us Pre vi o usl y Treate d wit h M ult i ple Dail y I njecti on T hera p y
Pr ot oc ol N u m ber:
I 8H- M C -B D C P
A me n d me nt N u m ber:
d
C o m p o u n d : L Y 3 2 0 9 5 9 0
St u d y P h ase: P hase 2
S h ort Title: A St u d y  of L Y 3 2 0 9 5 9 0 i n Partici pa nts w ith T y pe 1 Di a betes Mellit us
S p o ns or N a me:
El i Lill y a n d C o m pa n y
Le g al Re gistere d A d dress:
I n dia na p olis, I n dia na U S A 4 6 2 8 5
Re g ul at or y A ge nc y I de ntifier N u m ber(s)
I N D: 1 2 9 3 9 0
E u dra C T:  2 0 1 9- 0 0 3 5 8 9- 4 1
A p pr o v al D ate:
Pr ot oc ol A me n d me nt (d) El ectr o nicall y Si g ne d a n d A p pr o ve d b y Lill y o n date 
pr o vi de d bel o w.
Lill y Me dic al N a me a n d C o nt act I nf or m ati o n will be pr o vi de d se p ar atel y .
A p pr o v al D at e: 2 8- O ct- 2 0 2 0 G M T

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
2
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Original Protocol
11-Dec-2019
Amendment (a)
08-Apr-2020
Amendment (b)
12-Jun-2020
Amendment (c)
14-Aug-2020
Amendment [d] 
This amendment is considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
The amendment provides information to reflect termination of the investigational medical device 
study arm evaluating the individualized accruing data algorithm (Algorithm 2) investigational 
device in the Phase 2 Study 18H-MC-BDCP (BDCP).  Study BDCP will continue to evaluate
dosing regimens of investigational medicinal product LY3209590, a long-acting insulin receptor 
agonist that is being developed as a basal insulin administered once-weekly for treatment of type 
1 diabetes mellitus (T1DM).  Study BDCP is evaluating T1DM participants previously treated 
with multiple daily injections (MDI) therapy in paper algorithm (Algorithm 1).  Insulin degludec 
is an unblinded active comparator in this study. 
Lilly is terminating the Algorithm 2 study arm due to the extent of data entry errors generated by 
patients and the impact these errors have on dosing recommendations from the investigational 
device Algorithm 2. These errors (missing, unchecked, or uncorrected by site verification) 
provide less than complete data set inputs that are submitted by the investigator into the 
Algorithm 2 dosing calculation.  The limited data set inputs have revealed shortcomings in the 
dosing calculation confounding factors for the limited number of Algorithm 2 dosing 
recommendations observed from a limited number of sites and participants during the early 
enrollment phase.  In some cases, had the investigator not applied clinical judgement to override 
the recommended dose, a serious adverse consequence on patient health and/or safety associated 
with the device may have resulted. 
The extent of the investigator Algorithm 2 recommended dose overrides experienced to date 
have confounded evaluation of Algorithm 2’s effectiveness.  Lilly recognized that the planned 
expansion to include all sites participating in the United States would increase both the number 
of participants exposed to the investigational device Algorithm 2 and the number of investigators 
providing oversite of the Algorithm 2 dosing recommendations. This amendment reflects the 
preventive action to terminate the Algorithm 2 investigational device trial arm of Study BDCP 
due to challenges associated with the ability to evaluate the effectiveness of Algorithm 2, to 
prevent potential patient safety issues and avoid a delay in the study.

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I8H-MC-BDCP(d)
LY3209590
3
Section # and Name
Description of Change
Brief Rationale
Throughout the document
Removal of language related to 
Algorithm 2
Alignment of protocol for removal of 
Algorithm 2
Section 1.1. Synopsis
Section 6.1. Study 
Intervention(s) Administered
Section 9.2. Sample Size 
Determination 
Section 10.10. Appendix 10:
Changes to Study Procedures 
due to the COVID-19 
Pandemic or Natural Disasters
Change in number of 
participants, randomization 
ratio, and distribution by 
country
Based on the removal of Algorithm 2, the 
participant number was updated and 
randomization variation by country is no 
longer applicable.
Section 1.3. Schedule of 
Activities
Addition of language for 
footnote d
Clarification that a triplicate ECG for insulin 
degludec is only required one time.
Addition of language for
footnote e
Clarification of the collection of 2 PK 
samples is for LY3209590. 
Removal of CGM data 
download at Visit 16
Removed CGM data download at Study Visit 
16 as this is a phone visit and download is 
not possible. 
Section 6.1. Study 
Interventions(s) Administered
Addition of language for 
participants transitioning from 
Algorithm 2
Clarification for participants in Algorithm 2 
to proceed with study procedures for those 
treated with LY3209590. 
Section 8.4. Treatment of 
Overdose
Addition of procedural 
language 
Clarification added to contact the sponsor in 
case of an accidental overdose.
Section 9.3. Populations for 
Analysis
Section 9.4.1. General 
Considerations
Section 9.4.2.2. Patient 
Characteristics
Section 9.4.6.3. 
Hypoglycemia Episodes
Change in language related 
removal of Algorithm 2
Update of statistical analysis after removal of 
Algorithm 2
Section 10.3.3. Definition of 
an Unanticipated Adverse 
Device Effect (UADE)
Removal of section related to 
Algorithm 2
Clarification that UADE will not be 
applicable after removal of Algorithm 2
Section 10.8. Appendix 8:  
Dosing Guidance for 
LY3209590 and Insulin 
Degludec
Updated title of appendix
Clarification that dosing guidance is available 
for LY3209590 and Insulin Degludec
Section 10.10. Appendix 10: 
Change to Study Procedures 
due to the COVID-19 
Pandemic or Natural Disasters
Addition of language for 
Remote Visits
Clarification that sites must receive sponsor 
approval prior to implementing site mobile 
visits and visits by a sponsor organized home 
nursing service provider to replace on-site 
visits.
Throughout the document
Minor editorial and document 
formatting revisions
These are minor changes; therefore, they 
have not been summarized.

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I8H-MC-BDCP(d)
LY3209590
4
Table of Contents
1.
Protocol Summary......................................................................................................7
1.1.
Synopsis.......................................................................................................................7
1.2.
Schema.......................................................................................................................10
1.3.
Schedule of Activities (SoA) ......................................................................................11
2.
Introduction..............................................................................................................23
2.1.
Study Rationale ..........................................................................................................23
2.2.
Background ................................................................................................................23
2.3.
Benefit/Risk Assessment ............................................................................................24
2.3.1.
Protocol Risk Mitigation Features...............................................................................24
3.
Objectives and Endpoints.........................................................................................25
4.
Study Design .............................................................................................................27
4.1.
Overall Design............................................................................................................27
4.1.1.
Study Visits ................................................................................................................27
4.2.
Scientific Rationale for Study Design .........................................................................30
4.3.
Justification for Dose..................................................................................................30
4.4.
End of Study Definition..............................................................................................31
5.
Study Population ......................................................................................................32
5.1.
Inclusion Criteria........................................................................................................32
5.2.
Exclusion Criteria.......................................................................................................34
5.3.
Lifestyle Considerations .............................................................................................37
5.3.1.
Meals and Dietary Restrictions ...................................................................................37
5.4.
Screen Failures...........................................................................................................37
6.
Study Intervention....................................................................................................38
6.1.
Study Intervention(s) Administered ............................................................................38
6.1.1.
Selection and Timing of Doses ...................................................................................39
6.1.2.
Special Treatment Considerations...............................................................................39
6.1.3.
Medical Devices.........................................................................................................41
6.2.
Preparation/Handling/Storage/Accountability.............................................................41
6.3.
Measures to Minimize Bias:  Randomization and Blinding .........................................41
6.4.
Study Intervention Compliance...................................................................................42
6.5.
Concomitant Therapy .................................................................................................42
6.5.1.
Medications that Promote Weight Loss.......................................................................43
6.5.2.
Systemic Glucocorticoids ...........................................................................................43
6.5.3.
Antihypertensive Medications.....................................................................................43
6.5.4.
Dyslipidemia Medication............................................................................................43
6.6.
Dose Modification......................................................................................................44
6.7.
Intervention after the End of the Study........................................................................44
6.7.1.
Treatment after Study Completion ..............................................................................44
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................45
7.1.
Discontinuation of Study Intervention ........................................................................45
7.1.1.
Permanent Discontinuation from Study Treatment......................................................45

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I8H-MC-BDCP(d)
LY3209590
5
7.1.2.
Temporary Discontinuation ........................................................................................46
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................46
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................47
7.3.
Lost to Follow up .......................................................................................................47
8.
Study Assessments and Procedures .........................................................................49
8.1.
Efficacy Assessments .................................................................................................49
8.1.1.
Primary Efficacy Assessment......................................................................................49
8.1.2.
Secondary Efficacy Assessments ................................................................................49
8.2.
Safety Assessments ....................................................................................................49
8.2.1.
Physical Examinations................................................................................................49
8.2.2.
Vital Signs..................................................................................................................49
8.2.3.
Electrocardiograms.....................................................................................................50
8.2.4.
Self-monitoring of Blood Glucose (SMBG)................................................................50
8.2.5.
Clinical Safety Laboratory Assessments .....................................................................51
8.2.6.
Safety Monitoring.......................................................................................................51
8.2.7.
Body Weight ..............................................................................................................52
8.3.
Adverse Events and Serious Adverse Events ..............................................................52
8.3.1.
Time Period and Frequency for Collecting AE and SAE 
Information.................................................................................................................52
8.3.2.
Method of Detecting AEs and SAEs ...........................................................................53
8.3.3.
Follow-up of AEs and SAEs.......................................................................................53
8.3.4.
Regulatory Reporting Requirements for SAEs............................................................53
8.3.5.
Pregnancy...................................................................................................................54
8.3.6.
Cardiovascular Events ................................................................................................54
8.3.7.
Adverse Events of Special Interest..............................................................................54
8.3.8.
Product Complaints ....................................................................................................55
8.4.
Treatment of Overdose ...............................................................................................56
8.5.
Pharmacokinetics........................................................................................................56
8.6.
Pharmacodynamics.....................................................................................................57
8.7.
Genetics .....................................................................................................................57
8.8.
Biomarkers.................................................................................................................57
8.9.
Immunogenicity Assessments.....................................................................................57
8.10.
Health Economics.......................................................................................................58
9.
Statistical Considerations.........................................................................................59
9.1.
Statistical Hypotheses.................................................................................................59
9.2.
Sample Size Determination.........................................................................................59
9.3.
Populations for Analyses ............................................................................................60
9.4.
Statistical Analyses.....................................................................................................60
9.4.1.
General Considerations...............................................................................................61
9.4.2.
Treatment Group Comparability .................................................................................61
9.4.3.
Primary endpoint(s)....................................................................................................62
9.4.4.
Secondary endpoint(s) ................................................................................................62
9.4.5.
Tertiary/exploratory endpoint(s) .................................................................................62
9.4.6.
Safety Analyse(s)........................................................................................................62
9.4.7.
Pharmacokinetic/Pharmacodynamic Analyses ............................................................63
9.4.8.
Evaluation of Immunogenicity....................................................................................64

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I8H-MC-BDCP(d)
LY3209590
6
9.4.9.
Other Analyses ...........................................................................................................64
9.5.
Interim Analyses.........................................................................................................64
9.6.
Data Monitoring Committee (DMC)...........................................................................64
10.
Supporting Documentation and Operational Considerations ................................65
10.1.
Appendix 1:  Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................65
10.1.1.
Regulatory and Ethical Considerations........................................................................65
10.1.2.
Financial Disclosure ...................................................................................................66
10.1.3.
Informed Consent Process ..........................................................................................66
10.1.4.
Data Protection...........................................................................................................66
10.1.5.
Dissemination of Clinical Study Data .........................................................................66
10.1.6.
Data Quality Assurance ..............................................................................................67
10.1.7.
Source Documents......................................................................................................69
10.1.8.
Study and Site Start and Closure.................................................................................69
10.1.9.
Publication Policy.......................................................................................................70
10.1.10. Investigator Information .............................................................................................70
10.1.11. Long-Term Sample Retention.....................................................................................70
10.2.
Appendix 2:  Clinical Laboratory Tests.......................................................................71
10.3.
Appendix 3:  Adverse Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.......................................................74
10.3.1.
Definition of AE.........................................................................................................74
10.3.2.
Definition of SAE.......................................................................................................75
10.3.3.
Recording and Follow-Up of AE and/or SAE .............................................................76
10.3.4.
Reporting of SAEs......................................................................................................78
10.4.
Appendix 4:  Contraceptive Guidance and Collection of 
Pregnancy Information ...............................................................................................79
10.5.
Appendix 5:  Liver Safety:  Suggested Actions and Follow-up 
Assessments ...............................................................................................................81
10.6.
Appendix 6:  New York Heart Association Cardiac Disease 
Classification..............................................................................................................82
10.7.
Appendix 7:  Genetics ................................................................................................83
10.8.
Appendix 8:  Dosing Guidance for LY3209590 and Insulin 
Degludec ....................................................................................................................84
10.8.1.
LY3209590 Algorithm 1 (paper algorithm).................................................................84
10.8.2.
Insulin Degludec.........................................................................................................87
10.9.
Appendix 9:  Recommended Laboratory Testing for 
Hypersensitivity Events..............................................................................................89
10.10.
Appendix 10:  Changes to Study Procedures due to the COVID-
19 Pandemic or Natural Disasters ...............................................................................91
10.11.
Appendix 11:  Abbreviations ......................................................................................93
10.12.
Appendix 12: Protocol Amendment History ...............................................................97
11.
References...............................................................................................................102

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
7
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Phase 2, Randomized, Parallel, Open-Label Comparator-Controlled Trial to 
Evaluate the Safety and Efficacy of LY3209590 in Study Participants with Type 1 Diabetes 
Mellitus Previously Treated with Multiple Daily Injection Therapy
Short Title: A Study of LY3209590 in Participants with Type 1 Diabetes Mellitus
Rationale:
LY3209590 is a long-acting insulin receptor agonist being developed for the treatment of type 1
diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).  This Phase 2 study of 
LY3209590 will evaluate the effects of LY3209590 on glycemic control compared with insulin 
degludec in T1DM participants previously treated with multiple daily injections (MDI) therapy.

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
8
Objectives and Endpoints
Objectives
Endpoints
Primary

To investigate the efficacy of 
LY3209590 compared with insulin 
degludec in study participants with 
T1DM

HbA1c change from baseline to 
Week 26
Secondary
Efficacy

To investigate the efficacy of 
LY3209590 compared with insulin
degludec in study participants with 
T1DM

HbA1c change from baseline to 
Week 12

Fasting glucose change from baseline 
to Weeks 12 and 26

Insulin dose change for bolus insulin 
from baseline to Weeks 12 and 26
Safety

To investigate the safety of 
LY3209590 compared with insulin
degludec in study participants with 
T1DM

Incidence and rate of hypoglycemia 
events during the treatment period

Incidence of treatment-emergent 
serious AEs
Pharmacokinetics 

To characterize the PK of LY3209590 
in study participants with T1DM

LY3209590 population-based 
parameters, such as AUC within 
dosing interval at Weeks 12 and 26
Abbreviations:  AE = adverse event; AUC = area under the curve; HbA1c = hemoglobin A1c; 
PK = pharmacokinetics; T1DM = type 1 diabetes mellitus.

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
9
Overall Design
Study I8H-MC-BDCP is a multicenter, randomized, open-label, parallel, comparator-controlled 
Phase 2 study with 3 study periods.  The study is designed to evaluate the efficacy and safety of 
LY3209590 compared with insulin degludec in patients with T1DM treated with MDI without 
interruption for at least 3 months.  
Disclosure Statement: This is a parallel, unblinded, treatment study with 2 arms.
Number of Participants:
Approximately 238 participants will be randomly assigned to study intervention such that 
approximately 190 evaluable participants complete the study. 
Intervention Groups and Duration:
Participants will be randomized in a 1:1 ratio to receive the interventions listed below:

LY3209590 subcutaneously weekly, dosed per Algorithm 1

Insulin degludec subcutaneously daily, dosed per a modified Riddle algorithm
The maximum total duration of study participation for each participant is up to 33 weeks, across 
the following study periods: 

Study Period 1:  screening and lead-in period, approximately 2 weeks

Study Period 2:  treatment period, 26 weeks

Study Period 3:  safety follow-up period, 5 weeks
Data Monitoring Committee: No

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I8H-MC-BDCP(d)
LY3209590
10
1.2.
Schema

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I8H-MC-BDCP(d)
LY3209590
11
1.3.
Schedule of Activities (SoA)
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Informed 
consent
X
Inclusion 
and 
exclusion 
criteria
X
Randomiz
ation
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
12
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Clinical Assessments
Height
X
Body 
weight
X
X
X
X
X
X
X
X
X
X
X
X
See Section 
8.2.7.
Blood 
pressure 
and pulse 
rate
X
X
X
X
X
X
X
X
X
X
X
X
See Section 
8.2.2.
Demo-
graphy
X
Medical 
history 
(includes 
substance 
usage and 
family 
history of 
premature 
CV disease)
X
Substances: 
drugs, alcohol, 
tobacco, and 
caffeine
Pre-existing 
conditions  
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
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Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Concomi-
tant 
medication 
review
X
X
X
X
X
X
X
X
X
X
X
X
Full 
physical 
examination
X
X
X
X
X
X
12-lead 
ECG
X
Xd
X
d
X
d
Xd
Xd
X
X
X
X
X
AE/SAE/
PC review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
14
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Laboratory Assessments
Pharmaco-
kinetic 
samples 
(LY3209590)
Xe
X
X
X
X
X
X
X
X
X
X
X
X
Collected for 
participants 
randomized to 
LY3209590. 
See Section 8.5. 
Serum 
pregnancy 
test (WCBP 
only)
X
See Section 5.1.
Urine 
pregnancy 
test (WCBP 
only)
X
X
X
X
Additional 
pregnancy 
testing may be 
performed if 
required by 
local 
regulations.

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
15
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
FSH
X
Collect for 
women whose 
menopausal 
status needs to 
be determined.  
If menopausal 
status is known, 
this test does
not need to be 
collected.
Urinalysis
X
X
X
X
X
X
eGFR
X
X
X
X
Chemistry 
panel
X
X
X
X
X
X
X
X
X
X
X
X
Hepatitis B 
X
HbA1c
X
X
X
X
X
X
X
X
Hematology
X
X
X
X
X
X
X
X
X
X
HDL, LDL
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
16
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Free fatty 
acid
X
X
X
X
X
X
X
X
X
X
X
X
Immuno
genicity
X
X
X
X
X
X
X
X
X
See Section 8.9.
C-peptide
X
If the C-peptide 
was assessed in 
a non-fasting 
state at V1 and 
was >0.30 
nmol/L, the 
evaluation can 
be repeated at 
V2 in a fasting 
state
Pharmaco-
genetic 
sample
X
Nonpharma
cogenetic 
Stored 
Samples
(plasma/
serum)
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
17
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Ancillary Supplies/
Diaries/
Investigational Product
Study 
participant 
training/
education
X
Includes 
diabetes 
counseling, 
hypoglycemia
Section 
8.3.7.1), diary 
completion, and 
CGM sensor 
replacement 
Dispense 
supplies 
X
X
X
X
X
X
X
X
Participant 
diaries will be 
visit specific.  
All of the 
diaries will be 
electronic.
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
18
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Remind 
participants 
to document
6-point 
glucose
profiles in 
the week 
prior to next 
indicated 
visit
X
X
X
X
X
X
See next line 
for indicated 
visits.  See 
Section 4.1.1
for additional 
details.
Review 
6-point 
SMBG 
profiles
X
X
X
X
X
X
X
Review diary 
data and 
make dose 
individualiz-
ation 
assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Assessment 
performed per 
participant 
assigned group 
(Algorithm 1 or 
insulin degludec)
Dispense IP
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
19
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
Study 
personnel 
administer 
IP at site
X
X
X
X
X
X
X
X
X
Train 
participants
in IP 
administra-
tion
X
X
X
X
X
IP can be self-
administered by 
study 
participants 
Weeks 13-25. 
Information on 
self-injection 
can be 
reviewed as 
necessary 
throughout the 
study.
Study 
participant 
CGMf
training
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
20
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
CGM 
sensor 
insertion at 
site
X
Distribute 
CGM 
sensor if 
necessary
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patients will 
replace CGM 
sensor every 10
days at home 
and will be 
trained for this 
procedure at 
Visit 2.  At 
each visit 
patient will be 
supplied with 
the necessary 
sensors for the 
respective 
interval
CGM data 
download
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
21
Procedure
Study 
Period 
1
Screen
ing
and
Lead-in
Study Period 2
Treatment Period
Early 
Discontinua
tion
Study 
Period 
3
Follow
-up
ET
Notes
eCRF Visit 
Number
1
2
3a
4
5
6
7
8
9
10
11
12
13
14
15
16b
17
18
19
20 c
ED1
ED2c
801c
Weeks
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
14
16
20
24
26
ED1 
+5
31
Visit 
window, 
days
±
7
±
3
±
2
±
2
±
3
±
2
±
2
±
3
±
2
±
2
±
2
±
2
±
2
±3
±3
±3
±
3
±3
±3
±3
±3
±3
Fasting
X
X
X
X
X
X
X
X
X
X
X
X
Minimum 8 
hours
LY3209590 
and insulin 
degludec 
accounta-
bility 
(collect 
used and 
unused IP)
X
X
X
X

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
22
Abbreviations:  AE = adverse event; BG = blood glucose; CGM = Continuous Glucose Monitoring; CV = cardiovascular; ECG = electrocardiogram; eCRF = 
electronic case report form; eGFR = estimated glomerular filtration rate; ET = early termination; FSH = follicle-stimulating hormone; HbA1c = glycated 
hemoglobin; HDL = high density lipoprotein; HIV = human immunodeficiency virus; IP = investigational product; IWRS = interactive web response system; 
LDL = low density lipoprotein; LY = LY3209590; PC = product complaint; PK = pharmacokinetics; SAE = serious adverse event; SMBG = self-monitoring 
blood glucose; WCBP = women of childbearing potential.
a
All measures to be performed at Visit 3 should be done prior to injection of the participant’s assigned investigational product (IP) to ensure that appropriate 
baseline measurements are obtained.
b
Visit 16 is a Phone visit.
c
Visits 20 and ED1 are performed approximately 1 week after the last dose of LY and 1 day after the last dose of degludec.  Visit 801 is performed for 
participants who complete Visit 20.  ED1 and ED2 are performed for participants who discontinue study drug but remain in the study.  
d
A triplicate, central ECG will be performed in a fasting state at Visits 3, 6, 9, 15, and 17, prior to each PK sample. Patients randomized to insulin degludec 
treatment will undergo ECG in a fasting state without PK sampling.  Only one triplicate ECG is needed for insulin degludec treated patients.
e
Collect 2 PK samples of LY3209590:  1 predose and one approximately 2 hours postdose or as late as possible just prior to departure from the site. ECG will 
be performed in triplicate prior to the time of each PK sampling at this visit. Note:  PK samples are not intended to be collected for participants in the insulin 
degludec treatment group.
f
Patients will be fitted with Dexcom G6® for CGM monitoring.
Note:  Additional visits to ensure correct dosing, titration, and study drug administration can occur anytime during the study if deemed necessary by the 
investigator and are explicitly allowed and part of the protocol.

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
2 3
2.
I ntr o d ucti o n
2. 1.
St u d y R ati o n ale
L Y 3 2 0 9 5 9 0 is a lo n g- acti n g i ns uli n rece pt or a g o nist bei n g de vel o pe d f or t he treat me nt of t y pe 1
di a betes mellit us ( T1 D M ) a n d t ype 2 dia betes m ellit us (T 2 D M ).  T his P hase 2 st u d y of 
L Y 3 2 0 9 5 9 0 will e val uate t he effects of L Y 3 2 0 9 5 9 0 o n gl yce mic c o ntr ol c o m pare d wit h i ns uli n 
de gl u dec i n T 1 D M pat ient s pre vi o usl y treate d wit h m ult i ple dail y inject i on ( M DI) t hera p y .
2. 2.
B ac k gr o u n d
L Y 3 2 0 9 5 9 0 was desi g ne d as a n o vel, o nce -wee kl y, l o n g- act i n g i ns uli n rece pt or a g o nist t hat is 
i nte n de d f or t he treat me nt of h y per gl yce mia i n st u d y partici pa nts wit h T1 D M a n d T 2 D M.  I n real 
life, o nl y a b o ut 3 0 % of patie nts wit h T 1 D M i n t he U nite d Ki n g d o m ( U K ) reac h t he tar get 
H b A 1c o f < 7. 5 % ( 5 8 m m o l/ m ol) (N D A 2 0 1 7 ), a n d a o nce-wee kl y  ins uli n rece pt or a g o nist c o ul d 
hel p t o i ncrease t his n u m ber.   T he p ote ntial d o w nsi de of s uc h a l o n g -acti n g i ns uli n rece pt or 
a g o nist c o ul d t he oreticall y be a hi g her ris k f or h y p o gl yce mic e ve nts or a l o n ger d urati o n of  s uc h 
e ve nts.  I n c o ntrast t o t his t he oretical ris k t he l o n g-acti n g i ns uli n de gl u dec has s h o w n a re d uce d 
p ote nti al t o i n d uce h y p o gl yce mia as c o m pare d t o i ns uli n glar gi ne w hile its half-life is t wice as 
l on g as t hat of i ns uli n glar gi ne ( Heise et al. 2 0 1 2 ).  T he c urre nt P hase 2 st u d y will t h er efor e 
e val uate t he safet y a n d efficac y of  L Y 3 2 0 9 5 9 0 c o m pare d t o i ns uli n de gl u dec w hile ver y clos el y 
m o nit ori n g gl yce mic pr ofiles.
P hase 1 st u dies e val uat i n g t he p har mac o ki netics ( P K) a n d p har mac o d y na mic s ( P D) effect o f 
L Y 3 2 0 9 5 9 0 i n heal t hy v o l unt eers a n d pat ient s wit h T 2 D M ha ve bee n c om p lete d.  Data fr om 
, w hic h was t he si n gle-asce n di n g d ose ( S A D) st u d y, d e mo nstrate d cl ear e vi de nce of 
gl uc ose l o weri n g i n st u d y  p artici pa nts wit h T 2 D M f oll owi n g si n gle d oses of L Y 3 2 0 9 5 9 0 ra n gi n g 
fr om 
 mg.  T he P K of L Y 3 2 0 9 5 9 0 f o ll owi n g si n gle d oses de m o nstrate d pr ol o n ge d ti me -
actio n pr ofile t o s u p p ort o nce -wee kl y  a d mi nistrati o n.  L Y 3 2 0 9 5 9 0 reac he d ma xi m u m 
c o nce ntrati o n a p pr o xi matel y 4 da ys after d osi n g, f oll o we d b y a mea n eli mi nat i on 
 
 i n st u d y partici pa nts wit h T 2 D M.  Wit h a 
l on g eli mi nat i on half -life, f oll owi n g a wee kl y  fi xe d-d ose re gi me n, P K stea d y -state was pre dicte d 
t o be reac he d i n 
 wit h a p pr o xi matel y 
 hi g her c o nce ntrati o n 
d ue t o acc u m ulati o n t ha n after si n gle d ose.  T heref ore, base d o n P K m o deli n g a l oa di n g d ose 
strate g y  ti mes t he wee kl y d os e w o uld ac hie ve stea d y -state e x p os ure after 1 d ose.  Base d o n 
data i n st u d y  B D C B, the m ulti p le-asce n di n g d ose ( M A D) st u d y, P K f oll owi n g a si n gle l oa di n g 
d ose ( 
t he i nit ial wee kl y d ose) d uri n g t he first wee k was de m o nstrate d t o be c o m para ble t o 
c o nce ntrati o n pr ofile at Wee k 6 (at 
d ose deli vere d o nce wee kl y), s u p p orti n g t he l oa di n g d ose 
strate g y.  N o cli nicall y si g nifica nt persiste nce i n h y p o gl yce mia was o bser ve d i n t he st u d y.  
Besi des t he k n o w n ris k of h y p o gl yce mia, n o rele va nt safet y si g nals ha ve bee n o bser ve d i n t he 
P hase 1 st u dies.  
T he t o xi cit y pr ofile of L Y 3 2 0 9 5 9 0 has bee n c haracterize d i n 6-wee k a n d 6 -m o nt h re peat -d ose 
t o xic o l og y  st u dies i n rats a n d d o gs, a n d re pr o d ucti ve t o xic o l og y  st u dies i n rats a n d ra b bits.  
T hese st u dies de m o nstrate d a fa miliar s pectr u m of effects t y picall y  ass ociate d wit h c ha n ges 
sec o n dar y t o h yp o gl yce mia a n d/ or h yperi ns uli ne mia res ult i n g fr o m re peat d osi n g of e x o ge n o us 
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
24
insulin in normoglycemic test systems.  All findings were considered to be target-related with no 
evidence of off-target effects in any of the parameters assessed.  
Additional information about LY3209590 can be found in the Investigator’s Brochure (IB).
2.3.
Benefit/Risk Assessment
The data from the SAD study and the MAD study (studies BDCA and BDCB, respectively), as 
well as the ongoing Phase 2 BDCM study have shown that LY3209590 was well tolerated and 
the adverse drug reactions are in line with those reported for long-acting insulins.
Potential risks associated with LY3209590, derived from the known risks of long-acting insulins
are hypoglycemia, hypersensitivity reactions (localized allergy and/or systemic allergy),
undesirable effects at the injection site (injection-site reactions and lipodystrophy), and
peripheral edema. Besides the expected risk of hypoglycemia, serious presentations of the listed 
side effects have not been observed in study participants or healthy volunteers exposed to 
LY3209590 for up to 12 weeks.
Taking into account the measures taken to minimize risk to participants in this study, the 
potential risks identified in association with LY3209590 are justified by the anticipated benefits 
that may be offered to participants with T1DM.
More information about the known and expected benefits, risks, Serious Adverse Events (SAEs), 
and reasonably anticipated adverse events (AEs) of LY3209590 may be found in the IB.
The Algorithm 1 (paper) was developed to initiate and guide LY3209590 dose adjustment for 
this study to safely and efficiently achieve glycemic goals. 
2.3.1.
Protocol Risk Mitigation Features 
Methods to minimize potential risks are relevant for participants assigned to LY3209590 
Algorithm 1 and insulin degludec treatment groups.  These include:

Thorough training on the protocol design elements and inclusion/exclusion criteria; use 
of an electronic diary (eDiary), a web-interface, and reporting system along with 
availability of associated instruction manuals and reference documents.

Careful data validation:  After patient-reported data has been entered and synced 
remotely to the central web server, the investigator is able to view the data through the 
web portal and generate summary reports.  An important feature of the study requires 
careful review of the reported information with the patient and verification of its 
accuracy at each study visit. 

Email notification to investigator any time the patient reports a potential severe episode 
of hypoglycemia (requiring assistance due to neurological impairment) in the eDiary.

Specific criteria for fasting or persistent hyperglycemia are described protocol 
Section 6.1.2.3.

Use of CGM with appropriate low/high glucose alarms throughout the study.
Importantly, in both treatment groups, the final dosing decisions remain subject to clinical 
judgement of the investigator.  Decisions to override an algorithm recommended dose are 
documented in the electronic case report form (eCRF) for Algorithm 1 and insulin degludec.

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3.
Objectives and Endpoints
Objectives
Endpoints
Primary

To investigate the efficacy of 
LY3209590 compared with insulin 
degludec in study participants with 
T1DM

HbA1c change from baseline to 
Week 26
Secondary
Efficacy

To investigate the efficacy of 
LY3209590 compared with insulin
degludec in study participants with 
T1DM

HbA1c change from baseline to 
Week 12

Fasting glucose change from baseline 
to Weeks 12 and 26

Insulin dose change for bolus insulin 
from baseline to Weeks 12 and 26
Safety

To investigate the safety of 
LY3209590 compared with insulin
degludec in study participants with 
T1DM

Incidence and rate of hypoglycemia 
events during the treatment period

Incidence of treatment-emergent 
serious AEs
Pharmacokinetics 

To characterize the PK of LY3209590 
in study participants with T1DM

LY3209590 population-based 
parameters, such as AUC within 
dosing interval at Weeks 12 and 26
Tertiary/Exploratory

To establish the equivalent dose of 
LY3209590 relative to insulin 
degludec

Insulin dose at baseline and Week 26

To investigate the safety and 
tolerability of LY3209590 compared 
with insulin degludec in study 
participants with T1DM

Treatment-emergent AEs

Incidence and rate of hypoglycemia 
events during the post-treatment 
follow-up period

Discontinuation of IP due to AEs

Clinical laboratory results

Systematic assessment of injection site 
reactions

Insulin dose for prandial as well as 
basal insulin during treatment period 
and follow-up period

Incidence and rate of hypoglycemia 
during treatment and follow-up period

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Objectives
Endpoints

Incidence and rate of daytime 
hypoglycemia

Liver aminotransferase change from 
baseline to Weeks 12 and 26

Triglyceride and FFA change from 
baseline to Weeks 12 and 26

Body weight change from baseline to
Weeks 12 and 26

To explore quality of glycemic control 
compared with insulin degludec using 
CGM

Glucose time in target range, time in 
hyperglycemia, time in hypoglycemia

Duration of hypoglycemic events

To establish the relationships between 
dose/exposure and key safety and 
efficacy measures for LY3209590 

LY3209590 exposure-response 
relationships for key efficacy and 
safety measures (e.g., glycemic 
control, hypoglycemia and safety 
labs).

To characterize the effects of 
LY3209590 on exploratory PD 
biomarkers

To explore the development of 
LY3209590 ADAs

To explore the compliance with the 
dosing regimen

Lipids (cholesterol, LDL, HDL, 
triglycerides)

6-point SMBG glucose profiles

Biomarkers of lipolysis (FFA)

The frequency of antibody formation 
to LY3209590 and relationship to 
safety and efficacy markers will be 
determined

Incidence and percentage of missed 
doses of LY3209590 and insulin 
degludec.
Abbreviations:  ADA = antidrug antibodies; AE = adverse events; AUC = area under the curve; CGM = continued 
glucose monitoring; FFA = free fatty acids; HbA1c = glycated hemoglobin; HDL = high density lipoprotein; 
IP = investigational product; LDL = low density lipoprotein; PD = pharmacodynamics; SMBG = self-monitoring
blood glucose; T1DM = type 1 diabetes mellitus.

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4.
Study Design
4.1.
Overall Design
Study I8H-MC-BDCP (BDCP) is a multicenter, randomized, open-label, parallel, comparator-
controlled Phase 2 study with 3 study periods.  The study is designed to evaluate the efficacy and 
safety of LY3209590 compared with insulin degludec in patients with T1DM treated with MDI 
for at least 3 months prior to screening.
The study will consist of 3 periods:  

Study Period 1:  screening and lead-in period, approximately 2 weeks

Study Period 2:  treatment period, 26 weeks

Study Period 3:  safety follow-up period, 5 weeks
The study schema is presented in Section 1.2.
Study governance considerations are described in detail in Section 10.1.
4.1.1.
Study Visits
Study Period 1:  Screening and Lead-in
The purpose of procedures at screening is to establish eligibility for inclusion in the study (see 
Sections 5.1 and 5.2.  During this period (upon signing the informed consent form [ICF]), study 
participants will be trained on disease monitoring and disease management procedures, study 
diaries, and study procedures.  
Electronic participant diaries and participant paper note sheets will be dispensed at Visit 2 and as 
specified in the Schedule of Activities (Section 1.3) for future visits. Collection of baseline self-
monitoring blood glucose (SMBG) profiles via continuous glucose monitoring (CGM) will start 
at Visit 2.  Participants will continue on their same regimen of basal and short acting insulin 
during the lead-in period up to randomization.  
A participant will be considered ineligible and will be discontinued from a trial before 
randomization if they: 

initiate agents that are prohibited (Section 6.5), or

initiate insulin pump treatment (Section 5.2)
For all study participants meeting study entry criteria, the Dexcom G6® CGM device will be 
inserted and activated at (Visit 2).  The CGM sensor, transmitter and receiver will be distributed 
to the participant as needed per the Schedule of Activities (Section 1.3).  
SMBG:
Participants will record two 6-point glucose profiles (using the CGM device) at non-consecutive 
days between Visit 2 and Visit 3.  The profile should include readings before and 2 hours after 
each major meal of the day (breakfast, lunch, and dinner).  
Continuous Glucose Monitoring (CGM)
A standard system, Dexcom G6, will be used according to manufacturer’s directions for CGM in 
an unblinded mode.  The study participants will wear this device beginning at Visit 2, as shown 

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in the Schedule of Activities (Section 1.3).  In addition, all study participants will be allowed to 
use their personal blood glucose (BG) meters for additional BG testing, or for taking SMBG 
measurements during the outpatient period. Therapeutic decisions will be based on the CGM 
readings. Blood glucose meters must not be used to calibrate the CGM device.  CGM calibration 
must be done using the code provided with each sensor. Participants must use the study-specific 
CGM receiver and are not allowed to connect the transmitter of the CGM system to a personal 
smartphone to ensure data availability for download from the receiver at the respective visits as 
described in the Schedule of Activities (Section 1.3).
At Visit 2, study participants who fulfill eligibility criteria will be trained on the use of the CGM 
device, CGM sensor replacement, interpretation of CGM-based BG values and alarms, and the 
requirements for CGM.  For the first CGM session, study participants meeting all study-entry 
criteria will have the CGM sensor inserted as part of the Visit 2 activities.
Study Period 2:  Treatment Period
Randomization
Participants who continue to be eligible for the study will be randomized to 1 of the 2 treatment 
groups.  All measures, including a urine pregnancy test, to be performed at Visit 3 (see Schedule 
of Activities, Section 1.3) should be done prior to injection of the participant’s assigned 
investigational product (IP) to ensure that appropriate baseline measurements are obtained.  The 
participant will begin IP if the urine pregnancy test is negative.  If the result of the serum 
pregnancy test is positive, the participant will be discontinued from the study (see Section 7.2)
Study personnel will inject the first dose of IP at the study site.  The PK sample and 
electrocardiograms (ECGs) at randomization must be collected as described in the Schedule of 
Activities (Section 1.3).
Treatment
Following randomization at Visit 3, participants will participate in a 26-week treatment period. 
For patients randomized to the LY3209590 arm the following guidance for IP administration is 
applicable:

During Weeks 0 to 8, site personnel will administer IP at the site.  Participants will 
receive education and training on how to self-administer IP (for details, see the Schedule 
of Activities).  The training should include information on reconstitution of IP, 
appropriate injection site locations, injection technique, and the signs and symptoms of 
local adverse reactions, should those occur.  

During Weeks 9 to 12, IP will be reconstituted and administered at the site by the 
participant, under supervision of trained site personnel to assure that the participant is 
capable of self-administration. 

During Weeks 13 to 25, outside of titration visits IP can be self-administered by the 
participant at home unless local regulations require administration at the site, or 
optionally can be administered once weekly by site personnel.  

Information on self-injection can be reviewed as necessary throughout the study. 
Additional visits to ensure correct dosing, titration, and study drug administration can 
occur anytime during the study if deemed necessary by the investigator.

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LY3209590 will be administered as follows:  

Algorithm 1 (paper algorithm): dose adjustment guidance provided; study participant
will receive an individualized LY3209590 loading dose on Day 1 with weekly 
adjustments based on fasting glucose (FG) and hypoglycemia data for the first 
12 weeks, then every 4 weeks.
For patients randomized to LY3209590 Algorithm 1, documented guidance for dose adjustment 
is provided (Section 10.8). 
For patients randomized to the insulin degludec arm the following guidance for administration is 
applicable.
Insulin degludec will be self-administered daily by participants after a training and first 
administration under site personnel supervision on Day 1 according to a modified Riddle 
algorithm (Section 10.8).
General considerations
Study procedures will be performed as listed in the Schedule of Activities (Section 1.3).  
To allow timely sampling for PK assessments, visits for collection of the samples will be 
scheduled within the required time windows provided in the Schedule of Activities (Section 1.3).
Participants will continue to use concomitant short-acting insulin throughout the treatment 
period.  Discontinuation or changes to regimen are not permitted, except in situations where dose 
adjustment is required for medical reasons or when allowed per study protocol (see Section 6.5).  
Study participants will be instructed to document fasting glucose (FG) each day in their 
electronic diary (eDiary) by using the values displayed on their CGM device after wakening.  In 
addition, two 6-point SMBG profiles (prior to and 2 hours after the morning, midday, and 
evening meals) should be done on nonconsecutive days in the week prior to the required visits 
noted in the Schedule of Activities (Section 1.3). 
Participants who develop severe, persistent hyperglycemia based on prespecified thresholds (see 
Section 6.1.2.3) will receive an unscheduled intensification of their insulin treatment based on 
clinical judgment of the investigator with a parallel information of Lilly Medical by email.  
Participants who need unscheduled intensification of their insulin treatment will continue on IP 
in the trial until they complete all study visits.  
Study Period 3: End-of-Treatment and Safety Follow-up, Visits 20, 801, Early 
Discontinuation 1 and 2 (ED1 and ED2)
All randomized participants should have a comprehensive efficacy and safety evaluation 
approximately 1 week after the last dose of LY3209590 and 1 day after the last dose of insulin 
degludec, and a safety follow-up visit approximately 6 weeks after the last dose of LY3209590 
and 5 weeks after the last dose of insulin degludec.  During the safety follow-up study period, 
participants will continue CGM and will be switched back to their previously used basal insulin 
therapy if appropriate (see Section 6.7.1).  Participants will also be required to return any 
remaining used or unused IP at Visit 20 and the eDiary at Visit 801 to the investigative site.
Participants who complete the treatment period will have a comprehensive End-of-Treatment 
efficacy and safety assessment (Week 26; Visit 20) approximately 1 week after the last dose of 

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
3 0
L Y 3 2 0 9 5 9 0 a n d 1 da y  aft er last d ose of i ns uli n d e gl u dec a n d a safet y fol l ow- u p assess me nt 
( Visit 8 0 1) a p pr o xi matel y 6 wee ks after t he last d ose of L Y 3 2 0 9 5 9 0 a n d 5 wee ks after t he last 
d ose of i ns uli n de gl u dec .  
P arti cipa nts w h o disc o nti n ue I P pri or t o c o m pleti o n of  t he treat me nt perio d f or a n y reas o n 
s h o uld f oll ow t he visit sc he d ule off st u d y  dr u g a n d als o ha ve a c o m pre he nsi ve E n d-of -Treat me nt 
efficac y a nd safet y  assess me nt (E D 1 ) a p pr o xi matel y 1 wee k after t he last d ose of L Y 3 2 0 9 5 9 0
a n d 1 da y aft er t he last d ose of  i ns uli n de gl u dec or as s o o n as reas o na bl y p ossi ble t hereafter, a n d 
s h o uld ha ve a safet y f oll ow- u p assess me nt ( E D 2 ) a p pr o xi matel y 6 wee ks after t he last d ose of 
L Y 3 2 0 9 5 9 0 a n d 5 wee ks after t he last d ose of i ns uli n de gl u dec .  St u d y acti vities at Visits E D 1 
a n d E D 2 are ide nt ical t o Wee k 2 6 ( Visit 2 0) a n d Visit 8 0 1, res pecti vel y. T his cl ose f o ll ow- u p i s 
necessar y  si nce L Y 3 2 0 9 5 9 0 has a 
 a n d t he s witc h t o a n 
alter nati ve, c o m merciall y a vaila ble i ns uli n m ust be cl osel y m o nit ore d t o pre ve nt h yp o gl yce mia 
d ue t o a n acc u m ulat i on of i ns uli n acti o n.  
P arti cipa nts w h o di sc o nti n ue I P prior t o t he c o mpl eti o n of  t he treat me nt perio d will be 
e nc o ura ge d t o re mai n i n t he st u d y a n d t o c o mplete a n y sc he d ule d st u d y  pr oce d ures t hat occ ur 
u n til Visi t 2 0.  Parti ci pa nts re mai ni n g i n t he st u d y will recei ve a n a p pr o priate gl uc ose-l oweri n g 
re gi me n.  
P arti cipa nts w h o disc o nti n ue I P f or a ny re as o n a n d are u n w illi n g t o ret ur n f or a s afety f oll o w- u p
visit, will be as ke d t o perf or m a n earl y  ter mi nati on ( E T) visit as t heir fi nal st u d y visit.  At t his 
visit, partici pa nts will p erf or m  pr oce d ures liste d i n t he Sc he d ule of Act i vities (Secti o n 1. 3 ).
4. 2.
Scie ntific R ati o n ale f or St u d y Desi g n
T his st u d y  will e val uate L Y 3 2 0 9 5 9 0 in pat ient s wit h T 1 D M, c o m pare d wit h a n acti ve c o ntr ol.  
T he st u d y  will last 2 6 wee ks t o ha ve a n a de q uate d urati o n of  e x p os ure necessar y t o assess 
efficac y a nd safet y of L Y 3 2 0 9 5 9 0 .
I ns uli n de gl u dec is a n u n bli n de d acti ve c o m parat or i n t his st u d y a n d will be use d t o c o mpare t he 
effects of L Y 3 2 0 9 5 9 0 o n gl yce mic c o ntr ol, h y p o gl yce mia, a n d wei g ht gai n wit h a dail y basal 
i ns uli n.
4. 3.
J u stific ati o n f or D ose
 
 
a si n gle l oa di n g d ose , foll o w e d b y wee kl y d ose a dj ust me nt s is 
rec o m me n de d f or L Y 3 2 0 9 5 9 0 d osi n g re gi me n.  T he l oa di n g d ose is deter mi ne d base d o n t he 
pati e nt 's pre vi o usl y use d basal i ns uli n d ose, baseli ne fasti n g gl uc ose, a n d a vaila ble L Y 3 2 0 9 5 9 0 
data t o i nf or m t he
l oa di n g d ose strate g y.  D ose a dj ust me nts are base d o n pri or fasti n g gl uc ose 
a n d h y p o gl yce mia e ve nts.  Alterati o ns t o t he d oses rec o m me n de d b y t hese d ose a dj ust me nt 
alg ori t h ms are als o u n der discreti o n of t he i n vesti gat or a n d will ta ke h y p o gl yce mia a n d ot her 
st u d y partici pa nt safet y  c o ncer ns i nt o acc o u nt. I n case of a de viati o n fr om t he alg ori t h m-
rec o m me n de d d ose, a me dical ratio nale f or t hi s de viati on m u st be d oc u me nte d b y t he pri nci p al 
i n vesti gat or.
C CI
C CI
C CI

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The starting dose for insulin degludec is the same dose as the basal insulin that the study 
participant used prior to entering the study.  The study participant will start a titration phase 
based on FG and the presence of hypoglycemia or other safety concerns.  Dose adjustments will 
be performed according to a modified Riddle algorithm, which is widely used in clinical trials 
and clinical practice (Section 10.8).  
As it may be desirable to achieve therapeutic goal of LY3209590 in less than 12 weeks with low 
risk of hyperglycemia, an initiation dose strategy may be appropriate where the first dose 
sufficient to achieve an efficacious exposure is given initially, followed by individually 
optimized weekly dose adjustments to achieve target response. Table for Algorithm 1 shows the 
loading doses, as well as those to be used when adjusting the dose during the dose-
individualization visits.  See Section 10.8 for description of the dose adjustment algorithms. 
Guidance is provided for dosing suggestions for investigators based on FG and hypoglycemia of 
the study participant (Section 10.8).
Safety of study participants will be closely monitored during the early stages of dose titration to 
determine whether adjustments to the conversion and dose adjustment algorithm is needed.  As 
additional data emerges, guidance from the sponsor on these dosing algorithms may be modified 
(Section 10.8). 
4.4.
End of Study Definition
End of the trial is the date of the last visit or last scheduled procedure shown in the Schedule of 
Activities (Section 1.3) for the last patient.

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5.
Study Population
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
5.1.
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Type of Study Participant and Disease Characteristics
[1]
Have a diagnosis of T1DM for at least 1 year.  A diagnosis of T1DM is based 
on medical history with a fasting C-peptide ≤0.30 nmol/L at screening or 
before randomization.
[2]
Have been using MDIs without interruption for at least 3 months prior to 
screening.
Study Participant Characteristics
[3a] No male contraception required except in compliance with specific local 
government study requirements.
[3b] Female participants:
1) Women of child-bearing potential who are abstinent (if this is complete 
abstinence, as their preferred and usual lifestyle) or in a same sex 
relationship (as part of their preferred and usual lifestyle) must agree to 
either remain abstinent or stay in a same sex relationship without sexual 
relationships with males. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, post-ovulation methods), declaration of abstinence just for 
the duration of a trial, and withdrawal are not acceptable methods of 
contraception.
2) Otherwise, women of child-bearing potential participating must agree to 
use 1 highly effective method (less than 1% failure rate) of contraception, 
or a combination of 2 effective methods of contraception for the entirety of 
the study.
a) Women of child-bearing potential participating must test negative for 
pregnancy prior to initiation of treatment as indicated by a negative
serum pregnancy test at the screening visit followed by a negative urine 
pregnancy test within 24 hours prior to exposure.

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b) Either 1 highly effective method of contraception (such as combination 
oral contraceptives, implanted contraceptives or intrauterine device) or 
a combination of 2 effective methods of contraception (such as male or 
female condoms with spermicide, diaphragms with spermicide or 
cervical sponges) will be used. The participant may choose to use a 
double barrier method of contraception.  Barrier protection methods 
without concomitant use of a spermicide are not a reliable or acceptable 
method. Thus, each barrier method must include use of a spermicide. 
It should be noted that the use of male and female condoms as a double 
barrier method is not considered acceptable due to the high failure rate 
when these methods are combined.
3) Women not of childbearing potential may participate and include those 
who are:
a) infertile due to surgical sterilization (hysterectomy, bilateral 
oophorectomy, or tubal ligation), congenital anomaly such as mullerian 
agenesis; or
b) post-menopausal – defined as either
i)
A woman at least 40 years of age with an intact uterus, not on 
hormone therapy, who has cessation of menses for at least 1 year 
without an alternative medical cause, AND a follicle-stimulating 
hormone (FSH) >40 mIU/mL; or
ii) A woman 55 or older not on hormone therapy, who has had at least 
12 months of spontaneous amenorrhea; or
iii) A woman at least 55 years of age with a diagnosis of menopause 
prior to starting hormone replacement therapy.
[4]
Are at least 18 years of age, at the time of signing the informed consent.
[5]
Have HbA1c values of 5.6% to 9.5% inclusive, as determined by the central 
laboratory at screening.
[6]
Have been treated with a stable regimen of once- or twice-daily insulin 
glargine (U-100 or U-300), insulin detemir, or insulin degludec (U-100 or 
U-200) for 3 months prior to screening.
[7]
Are currently treated with the same SC rapid-acting analog insulin (insulin 
lispro U-100 or U-200, insulin aspart, FiAsp, or insulin glulisine) in MDI for 
at least the last 30 days prior to screening.
[8]
Have a body mass index (BMI) ≤35 kg/m2, with no significant weight gain or 
loss in the past 3 months (≥5%).
[9]
In the investigator’s opinion, are well-motivated, capable, and willing to:

learn how to self-inject treatment;

maintain study diaries, as required for this protocol; 

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
wear study-provided CGM (Dexcom G6) during the complete study 
duration without interruption and use this device for therapeutic decision-
making;

must have a normal wake/sleep pattern such that midnight to 0600 hours 
will reliably reflect a usual sleeping period.
[10] In the investigator’s opinion, are proficient in: 

counting carbohydrates 

adjusting meal- and correction boluses based on glucose readings with a 
stable insulin/carbohydrate ratio as well as correction factors

adjusting insulin and dietary therapy during special situations (e.g.,
exercise, stress, intermittent diseases)
[11] Are willing and able to follow the visit schedule during the complete duration
of the trial.
Informed Consent
[12] Capable of giving signed informed consent as described in Section 10.1, 
which includes compliance with the requirements and restrictions listed in the 
ICF and in this protocol.
5.2.
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
[13] Have had more than 1 emergency room visit or hospitalization due to poor 
glucose control (hyperglycemia or diabetic ketoacidosis [DKA]) within 
6 months prior to screening.
[14] Have had any episodes of severe hypoglycemia (defined as requiring 
assistance due to neurologically disabling hypoglycemia) and/or
hypoglycemia unawareness within the 6 months prior to screening.
[15] Have significant lipohypertrophy, lipoatrophy, scars, or h/o abscess in areas of 
injection.
[16] Have vision or hearing loss that impairs recognition of CGM screens, alerts 
and alarms.
[17] Cardiovascular (CV):  have had any of the follow CV conditions: acute 
myocardial infarction, New York Heart Association Class III or IV heart 
failure (Section 10.6), or cerebrovascular accident (stroke)
[18] Gastrointestinal:  have gastroparesis or have undergone gastric bypass 
(bariatric) surgery or restrictive bariatric surgery (e.g., Lap-Band®) prior to 
screening

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[19] Hepatic:  have acute or chronic hepatitis, or obvious clinical signs or 
symptoms of any other liver disease except non-alcoholic fatty liver disease 
(NAFLD) (i.e., patients with NAFLD are eligible for participation), and/or 
have elevated liver enzyme measurements, as determined by the central 
laboratory at screening and as indicated below:

Total bilirubin level (TBL) >2x the upper limit of normal (ULN), or

Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase 
(SGPT) >2.5x ULN, or

Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase 
(SGOT) >2.5x ULN
[20] Renal:  

Have history of renal transplantation

Are currently receiving renal dialysis

Have serum creatinine >2.0 mg/dL (177 µmol/L) at screening, or

Have an estimated glomerular filtration rate (eGFR) of 
<30 mL/min/1.73 m2
[21] Have experienced significant weight loss or gain (>5%) in body weight in the 
3 months prior to screening.
[22] Have active or untreated malignancy, or have been in remission from
clinically significant malignancy (other than basal cell or squamous cell skin 
cancer) for less than 5 years or are at increased risk for developing cancer or a 
recurrence of cancer in the opinion of the investigator.
[23] Have known hypersensitivity or allergy to any of the study medications or 
their excipients.
[24] Have any other serious disease or condition (e.g., known drug or alcohol 
abuse/regular consumption or psychiatric disorder) that, in the opinion of the 
investigator, would pose a significant risk to the patient, preclude the patient 
from following and completing the protocol, or interfere with the 
interpretation of safety, efficacy, or PD data.
Alcohol abuse/regular consumption is defined as an average daily intake of >3
units for males or >2 units for females within 6 months prior to the study.  
One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass 
(125 mL) of wine or 1 (25 mL) measure of spirits.
[25] Have had a blood transfusion or severe blood loss within 3 months prior to 
screening or have any hematologic condition that may interfere with HbA1c 
measurement (e.g., hemoglobinopathy, hemolytic anemia, sickle-cell disease).
[26] Have fasting triglycerides >400 mg/dL or non-fasting triglycerides 
>600 mg/dL.

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[27] Women of childbearing potential who
i)
are pregnant or intend to become pregnant
ii) are lactating/breastfeeding (including the use of a breast pump)
iii) are unwilling to remain abstinent or use birth control as described in
Appendix 4
iv) test positive for pregnancy at the time of screening (Visit 1). Note: a 
urine pregnancy test is conducted at Visit 3.
Prior/Concomitant Therapy
[28] Are taking drugs that may significantly affect glycemic control (e.g., niacin 
[allowed if <1.0 g/day], bile acid sequestrants).
[29] Are receiving chronic (lasting longer than 14 consecutive days) systemic 
glucocorticoid therapy (including intravenous, intramuscular, SC, and oral) or 
intra-articular (but excluding topical, intraocular, intranasal, and inhaled 
preparations), or have received such therapy within 4 weeks immediately prior 
to screening with the exception of replacement therapy for adrenal 
insufficiency.
[30] Are currently taking or have taken within the 3 months preceding screening, 
prescription or over-the-counter medications to promote weight loss.  Patients 
who participate must agree not to initiate a diet and/or exercise program 
during the study with the intent of reducing body weight other than the 
lifestyle and dietary measures for diabetes treatment.
[31] Are taking total daily dose of insulin >100 Units at the time of screening.
[32] Are receiving any oral or injectable medication intended for the treatment of 
diabetes mellitus other than rapid-acting and basal analog insulin in MDI in 
the 90 days prior to screening.
[33] Are using or have used blood pressure-lowering medication at a dose that has 
not been stable for 1 month prior to screening.
Prior/Concurrent Clinical Trial Experience
[34] Are currently enrolled in any other clinical study involving an IP or any other 
type of medical research judged not to be scientifically or medically 
compatible with this study.
[35] Have participated, within the last 30 days in a clinical trial involving an IP. If 
the previous IP has a long half-life, 3 months or 5 half-lives (whichever is 
longer) should have passed.
[36] Have previously completed or withdrawn from this study or any other study 
investigating LY3209590.  

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Other Exclusions
[37] Are investigator site personnel directly affiliated with this study and/or their 
immediate families.  Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted.
[38] Are Lilly employees.
5.3.
Lifestyle Considerations
Per the Schedule of Activities (Section 1.3), qualified medical staff will provide diabetes
management counseling, which will include instructions on diet and exercise and education 
about the signs, symptoms, and treatment of hypoglycemia, should it occur. 
Prescription or over the counter (OTC) medications that promote weight loss are exclusionary if 
used within 3 months prior to screening (study entry), or between screening and randomization.  
These medications are also not allowed at any time during the treatment period.  If started after 
randomization, these medications should be immediately withdrawn.  
Study participants should be instructed not to donate blood or blood products during the study or 
for 4 weeks following the study.
5.3.1.
Meals and Dietary Restrictions
Patients should continue their usual exercise habits and generally follow a healthy meal plan 
(with consistent meal size and time of day) throughout the course of the study. Dietary 
counseling may be reviewed throughout the study, as needed.
In addition, patients should not receive an intensive diet/exercise program with the intent of 
reducing body weight at any time during the study, other than the lifestyle and dietary measures 
for diabetes treatment.
5.4.
Screen Failures
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study intervention.  A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any SAE.
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once. The interval between screening and rescreening should be at least 4 weeks. A
new ICF must be signed at the time of rescreening and the study participant will be assigned a 
new identification number. A single repeat testing of suspected erroneous/spurious central 
laboratory results is allowed without rescreening the study participant.

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
3 8
6.
St u d y I nter ve nti o n
St u d y  i nter ve nt i on is defi ne d as a ny i n vesti gati onal i nter ve nt i on (s), mar kete d pr o d uct(s), 
pl ace b o , or m e dical de vice(s) i nte n de d t o be a d mi nistere d t o a st u d y partici pa nt acc or di n g t o t he 
st u d y pr ot oc ol .
6. 1.
St u d y I nter ve nti o n(s) A d mi nister e d
L Y 3 2 0 9 5 9 0 will be pr o vi de d i n a 2 0 m g vial of l y o p hilize d p o w der.  U p o n rec o nstit uti o n per t he 
p har mac y i nstr ucti o ns pr o vi de d b y  t he s p o ns or, L Y 3 2 0 9 5 9 0 will be a d mi nistere d o nce wee kl y as 
S C i nject i ons.  Eac h patie nt will recei ve 1 i nject i on eac h wee k, as descri be d i n t he “ Treat me nt  
Re gi me ns” ta ble bel o w.  S C i nject i ons of L Y 3 2 0 9 5 9 0 will be a d mi nistere d r otati n g bet wee n left 
a n d rig ht a b d o mi nal  r e gio n s, a n d u p per a n d l o wer q ua dra nts.  Refer t o St u d y Peri o d 2 i n 
Secti o n 4. 1. 1 f or details o n h o w I P will be a d mi nistere d.
P ati e nts will recei ve treat me nt wit h L Y 3 2 0 9 5 9 0 b y a n alg ori t h m descri be d i n Secti o n 1 0. 8 .
T he L Y 3 2 0 9 5 9 0 Al g ori t h m 1 is a pa per-base d al g orit h m t hat uses si milar pri nci pals t o t he 
esta blis he d Ri d dle al g orit h m.
I ns uli n de gl ud ec will use t he esta blis he d Ri d dle al g orit h m a n d is a pa per- base d al g ori t h m.
A p pr o xi matel y  o ne-half of  t he s u bjects will be ra n d o mize d i n eac h of  t he 2 re mai ni n g treat me nt 
ar ms.
I ns uli n d e gl u dec will be pr o vi de d as 1 0 0 u nits/ m L i n a prefille d pe n .  It will be a d mi nistere d 
o nce dail y  at a p pr o xi matel y t he sa me ti me of da y, r otati n g bet wee n left a n d ri g ht a b d omi nal 
r e gio ns, a n d u p per a n d l o wer q ua dra nts.
See Secti o n 6. 7. 1 f or tra nsiti oni n g t o treat me nt after st u d y  c o mplet i on.
Tre at me nt Re gi me ns
Re gi me n
D ose
R a n d o miz ati o n t hr o u g h Wee k 2 6
L Y D ose Al g orit h m 1 
(pa per )
L Y i njecti o n
I ns uli n de gl u dec
i ns uli n de gl u dec i njecti o n ( o pe n -la bel)
A b bre viati o ns:  L Y = L Y 3 2 0 9 5 9 0 .
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The investigator or his/her designee is responsible for the following:

explaining the correct use and reconstitution of the investigational agent(s) to the 
patient 

verifying that instructions are followed properly

maintaining accurate records of IP dispensing and collection

at the end of the study returning all unused medication to Lilly, or its designee, 
unless the sponsor and sites have agreed all unused medication is to be destroyed 
by the site, as allowed by local law
Clinical study materials will be labeled according to the country’s regulatory requirements.
6.1.1.
Selection and Timing of Doses
For patients randomly assigned to LY3209590, a loading dose will be determined using Table 1
in Algorithm 1 (see Section 10.8). The weekly dose adjustment thereafter will be based on 
guidance provided in Section 10.8.  The doses will be administered at approximately the same 
time and day each week.  The actual date, time and dose of each dose administrations
(LY3209590 and insulin degludec) will be recorded in the participant’s diary (and participant’s 
medical record when administered at the site).
If a patient misses a scheduled dose of LY3209590, it should be administered a soon as possible, 
but no later than 3 days after the scheduled administration.  If more than 3 days have elapsed 
since the scheduled administration, the dose should be skipped and the next injection will occur 
at the next scheduled day and time.
Insulin degludec should be administered at the same time each day adjusted per the modified 
Riddle algorithm (Section 10.8). 
Patients who miss a dose of insulin degludec should inject their daily dose during waking hours 
upon discovering the missed dose.  Instruct patients to ensure that at least 8 hours have elapsed 
between consecutive insulin degludec injections (Tresiba® USPI).
For details on the titration algorithms to be used, refer to Section 10.8.
6.1.2.
Special Treatment Considerations 
6.1.2.1.
Standards of Medical Care
Investigators and other study team members are expected to treat patients according to the 
nationally established standards of care for diabetes management in respective participating 
countries, except where that treatment would be in conflict with the protocol-provided treatment 
requirements. If there are no local standards of care for diabetes, the investigators should follow 
current published standards of care from the American Diabetes Association (2016) and the 
European Association for Study of Diabetes (Inzucchi et al. 2015) during their patients’ 
participation in this study. Standards of prevention of persistent hyperglycemia and ketone 
monitoring must be followed during the course of the study to prevent DKA.
Patients will continue their short acting insulin treatment throughout the duration of the study. 
Investigators are responsible to adapt mealtime and correction bolus dosing according to 

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standards of medical care. When titrating basal insulin a reduction of the mealtime insulin is 
necessary in most cases and should be considered by investigators to prevent hypoglycemia.
This section provides guidance on management of episodes of hypoglycemic events and events 
of severe, persistent hyperglycemia. For effective implementation of measures described here, it 
is important that patients, and their caregivers, if applicable, be well-educated about the signs 
and symptoms of hyperglycemia (e.g., severe thirst, dry mouth, frequent micturition, or dry skin) 
and hypoglycemia (e.g., intense hunger, sweating, tremor, restlessness, irritability, depression, 
headaches, disturbed sleep, or transient neurological disorders). Patients should be instructed to 
contact the investigative site in the event of severe, persistent hyperglycemia or severe 
hypoglycemia between study visits.
6.1.2.2.
Management of Increased Hypoglycemia Risk
To date, effects of LY3209590 on hypoglycemia in patients with T2DM are not different as 
compared to other basal insulins. An objective of the study is to assess the risk of hypoglycemia 
in T1DM patients receiving LY3209590 as compared to insulin degludec.
In this study, increased risk of hypoglycemia is defined as having a single episode of severe 
hypoglycemia or having more than 1 episode of documented hypoglycemia with BG <54 mg/dL 
within a 1-week period at any time during the treatment period. Documented hypoglycemia is 
defined as any time a participant reports a SMBG ≤70 mg/dL (<3.9 mmol/L) or any investigator 
confirmed case of severe hypoglycemia.  
In cases where a patient experiences hypoglycemia as described above, to confirm the increased 
risk, the study sites must ensure that the patient has been fully compliant with the assigned 
therapeutic regimen and also that there is no evidence of other possible causes of hypoglycemia 
(e.g., omission of meal, inadequate meal or correction bolus, unexpected increase in exercise).
Patients fulfilling the definition of increased risk of hypoglycemia should first correct their bolus 
dosing, then decrease their dose of IP per the respective dosing algorithm, followed by 
discontinuation of IP, if needed.  
6.1.2.3.
Management of Patients with Severe, Persistent Hyperglycemia during the 
Treatment Period
Transient hyperglycemia may be observed during the first 1 to 2 weeks of treatment with 
LY3209590 and additional correction doses of rapid acting insulin may be used to manage 
hyperglycemia during this transition period.
An additional therapeutic intervention should be considered in patients who develop severe, 
persistent hyperglycemia after randomization based on the following criteria (FDA 2008):
a) average fasting glucose (FG) >270 mg/dL (>15.0 mmol/L) over any 2-week period or 
longer during the first 6 weeks postrandomization; or
b) average FG >240 mg/dL (>13.3 mmol/L) over any 2-week period or longer from Week 6 
to Week 12 postrandomization; or
c) average FG >200 mg/dL (>11.1 mmol/L) over any 2-week period or longer after Week 
12.

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Investigators should first confirm that the patient does not have an acute condition causing severe 
hyperglycemia, and after the first 12 weeks of the study, that the patient is fully compliant with 
the assigned therapeutic regimen.  The investigator will decide, in consultation with the patient, 
on an appropriate intensification of insulin therapy after considering relevant clinical criteria.  
Patients who receive a new intervention for hyperglycemia management should also continue 
administering IP for the remaining period in the trial.
6.1.3.
Medical Devices
The sponsor will provide syringes for subcutaneous injection.
6.2.
Preparation/Handling/Storage/Accountability
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are reported 
and resolved before use of the study intervention.
Only participants enrolled in the study may receive study intervention and only authorized site 
staff may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the investigator and authorized site 
staff.
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records).
Further guidance and information for the final disposition of unused study interventions will be
provided by the sponsor.
The study site must store all study intervention in a locked and secure environment.  
Investigators should consult the study drug information provided in the Pharmacy Instructions or 
label for the specific administration information (including warnings). 
6.3.
Measures to Minimize Bias: Randomization and Blinding
This is an open-label study; thus, it will be unblinded.  However, the specific intervention to be 
taken by a participant will be assigned using an Interactive Web Response System (IWRS). The
site will contact the IWRS prior to the start of study intervention administration for each 
participant. The site will record the intervention assignment in the appropriate data capture tool.  
Potential bias will be reduced by the following steps: central randomization, stratification, 
blinded adjudication for CV endpoints.
Patients who meet all criteria for enrollment will be randomized to treatment at Visit 3.  
Assignment to treatment groups will be determined by a computer-generated random sequence 
using the IWRS.  The IWRS will be used to assign IP to each patient.  Site personnel will 
confirm that they have located the correct IP by entering a confirmation number found on the IP 
label into the IWRS.

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To achieve between-group comparability for site factor, the randomization will be stratified by 
baseline HbA1c (<8.5%, ≥8.5%), and country.  The randomization scheme will be performed 
using IWRS, which will ensure balance between treatment groups.
6.4.
Study Intervention Compliance
The assessment of treatment compliance with IP (LY3209590 or insulin degludec) will be 
determined by the following:

Information about the once weekly IP injections administered at home by the patient will 
be entered into the patient diary by the patient and reviewed by the site personnel at each 
study visit; this information will be collected in the electronic study diary;

IP accountability will be checked according to the Schedule of Activities (Section 1.3).  
Study participants will be instructed to return all dispensed vials, any unused pens, and/or 
all empty cartons at the next visit to the study site for the purpose of performing drug 
accountability.  
Other aspects of compliance will also be assessed at each visit, including the patient’s adherence 
to the visit schedule, compliance with the concomitant short acting insulin requirements and 
other medication guidances (Section 6.5), completion of study diaries, results of SMBG through
CGM, and any other parameters the investigator considers necessary.  Patients considered to be 
poorly compliant with their medications and/or study procedures (e.g., missed visits or specific 
diagnostic tests) will receive additional training and instructions, as required.
When participants are dosed at the site, they will receive IP directly from the investigator or 
designee, under medical supervision.  The date and time of each dose administered in the clinic 
will be recorded in the source documents and recorded in the diary.  
When participants administer study treatment at home, compliance with study treatment will be 
assessed at each visit. Compliance will be assessed by direct questioning, reviewing eCOA 
documentation, counting returned pens, etc. during the site visits.
A record of the number of the pens and study medications dispensed to and taken by each 
participant must be maintained and reconciled with study intervention and compliance records.  
Intervention start and stop dates, including dates for intervention delays and/or dose reductions 
will also be recorded in the electronic case report form (eCRF).
6.5.
Concomitant Therapy
Any medication or vaccine (including OTC or prescription medicines, vitamins, and/or herbal 
supplements) or other specific categories of interest) that the participant is receiving at the time 
of enrollment or receives during the study must be recorded in the eCRF along with:

Reason for use

Dates of administration including start and end dates, and

Dosage information including dose and frequency for concomitant therapy of special 
interest.

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Lilly Medical should be contacted if there are any questions regarding concomitant or prior 
therapy.
Participants will be permitted to use concomitant medications that they require during the study, 
except prohibited medications described in Section 5.2 and Sections 6.5.1 and 6.5.2 below.  In 
addition, certain permitted medications (e.g., treatments for blood pressure or dyslipidemia) 
described in Sections 6.5.3 and 6.5.4 should be continued, but not changed, during the study.
Participants will continue to use concomitant short-acting insulin throughout the treatment 
period.  Discontinuation or changes to regimen are not permitted, except in situations where dose 
adjustment is required for medical reasons or when allowed per study protocol. 
Investigative site staff will inform patients that they must consult with the investigator or a 
designated site staff member upon being prescribed any new medications during the study, 
except when initiated for treatment of medical emergencies.  
Non-study medications taken by patients who are screened but not randomized will not be 
reported to Lilly unless an SAE or AE occurs that the investigator believes may have been 
caused by a study procedure.
6.5.1.
Medications that Promote Weight Loss
Prescription or OTC medications that promote weight loss are exclusionary if used within the 
3 months prior to screening, or any time after screening (see Section 6.5).  If started after 
screening, these medications should be stopped immediately.  In addition, patients should not 
receive an intensive diet/exercise program with the intent of reducing body weight at any time 
during the study, other than the lifestyle and dietary measures for diabetes treatment (see 
Section 5.3).
6.5.2.
Systemic Glucocorticoids
Chronic systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, or inhaled 
preparations) is exclusionary if used >14 consecutive days during the 1-month period before 
screening or between screening and randomization at Visit 3.  
Patients treated with these medications after randomization will be excluded from the efficacy 
evaluable population for analyses if they receive: 

>14 days consecutive days of therapy, or

More than 1 course of therapy during the study.
6.5.3.
Antihypertensive Medications
If used, anti-hypertensive therapy should be kept stable throughout the trial to allow assessments
of the effect of randomized therapies on blood pressure. 
6.5.4.
Dyslipidemia Medication
If used, dyslipidemia therapy should be kept stable throughout the trial to allow assessments of 
the effect of randomized therapies on lipid endpoints. 

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
4 4
6. 6.
D ose M o dific ati o n
D osi n g of  basal ins uli n will  be i n di vi d ualize d base d o n F G.  See Secti o n 1 0. 8 f or details of d ose 
m o dificati o n. 
6. 7.
I nter ve nti o n after t he E n d of t he St u d y
After t he e n d of t he treat me nt peri o d patie nts s h o ul d c o nti n ue t o m o nit or t heir F G le vels.  T he 
treati n g p h ysicia n s h o ul d t he n ma ke t he decisi on base d o n l ocal cli nical pract ice, if a n d w hat 
a d ditio nal  a nti h y per gl yce mic treat me nt nee ds t o be a d mi nistere d.
I n vesti gati onal p r o d uct will n ot be m a de a vaila ble t o patie nts after c o ncl usi o n of t he st u d y .  After 
I P is disc o nti n ue d, a n a p pr o priate dia betes treat me nt re gi me n will be i nitiate d b y t he i n vestig at or.
6. 7. 1. 
Tre at me nt after St u d y C o m pleti o n 
T he l ast st u d y tr e at me nt a d mi nistrati o n f or patie nts treate d wit h L Y 3 2 0 9 5 9 0 will be at W ee k 2 5 
a n d f or patie nts treate d wit h i ns uli n de gl u dec t he e ve ni n g bef ore t he last st u d y visit at W ee k 2 6 .  
T he was h o ut of L Y 3 2 0 9 5 9 0 ma y ta ke u p t o 1 0 wee ks t o c o m plete. A n y a p pr o priate basal i ns uli n 
treat me nt must t heref ore be i nst itut e d sl o wl y a n d u n der re g ular s u per visi o n of B G pr ofiles after 
di sc o nti n uati on of L Y 3 2 0 9 5 9 0 . Si nce
 
  T heref ore, a sl o w u p-titratio n of  a n ot her basal 
i ns uli n is necessar y t o pre ve nt h y p o gl yce mia d ue t o o verla p pi n g i ns uli n act i on. F or e xa m ple, n o 
i ns uli n w o uld be re q uire d u nt il t he st u d y partici pa nt’s F G i ncreases t o > 1 0 0 m g/ d L, a n d t he n 
dail y  basal i ns uli n w o uld be i ni tiate d a n d a dj uste d base d o n F G. 
St u d y  p artici pa nts assi g ne d t o t he i ns uli n de gl u dec treat me nt gr o u p will s witc h t o t he basal 
i ns uli n use d bef ore e nteri n g t he st u d y. If i ns uli n de gl u dec was t he pre-st u d y basal ins uli n, t he y  
ca n c o nt i n ue wit h t he sa me d ose use d u ntil Visit 2 0 of t he st u d y.  If t he y s witc h t o a n ot her basal 
i ns uli n (e. g., i ns uli n g lar gi ne), st u d y partici pa nts s h o uld i nject a dail y  d ose, w hic h is 2 0 % l o wer 
t ha n t he last d ose of i ns uli n de gl u dec use d bef ore Visit 2 0 a n d t itrate u n der s u per visi on of t he 
i n vesti gat or usi n g t he c o u ntr y-s pecific la bel f or t heir pre -st u d y basal i ns uli n.
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7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
7.1.
Discontinuation of Study Intervention
Study drug may be permanently discontinued or temporarily withheld during the study.  
Participants who permanently discontinue study drug early will undergo ET procedures, which 
include

an ET visit or,

post-treatment follow-up visits (ED 1, ED 2).
The investigator will complete any AE reporting and necessary follow-up.
7.1.1.
Permanent Discontinuation from Study Treatment
Possible reasons leading to permanent discontinuation of investigational product include, but are 
not limited to:

Participant decision
o
the patient or the patient’s designee, for example, parents or legal guardian 
requests to discontinue IP.

Hepatic event or liver test abnormality: Participants who are discontinued from IP due 
to a hepatic event or liver test abnormality should have additional hepatic safety data 
collected via eCRF
Discontinuation of the IP for abnormal liver tests should be considered by the 
investigator when a participant meets one of the following conditions after consultation 
with Lilly Medical
o
ALT or AST >8x ULN
o
ALT or AST >5X ULN for more than 2 weeks
o
ALT or AST >3X ULN and TBL >2X ULN or international normalized 
ratio (INR) >1.5
o
ALT or AST >3X ULN with the appearance of fatigue, nausea, vomiting, 
right upper-quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5%)
o
ALP >3X ULN
o
ALP >2.5X ULN and TBL >2X ULN
o
ALP >2.5X ULN with the appearance of fatigue, nausea, vomiting, right 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)
In addition, participants will be discontinued from the IP in the following circumstances:

If a patient is inadvertently enrolled and it is determined that continued treatment with IP 
would not be medically appropriate (see Section 7.2.1)

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
if a patient is diagnosed with an active or untreated malignancy (other than basal or 
squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) 
after randomization

if the investigator or sponsor decides that the patient should be withdrawn from IP; if the 
investigator decides to permanently discontinue IP because of an SAE or a clinically 
significant laboratory value, Lilly or its designee should be alerted immediately

if the investigator, after consultation with Lilly Medical, determines that a systemic
hypersensitivity reaction has occurred related to study drug administration, the participant 
should be permanently discontinued from IP.
See the Schedule of Activities (Section 1.3) for data to be collected at the time of intervention 
discontinuation and follow-up and for any further evaluations that need to be completed.
Patients who stop the IP permanently may receive another glucose-lowering intervention, if 
appropriate, and will continue participating in the trial according to the protocol to collect all 
planned efficacy and safety measurements.
7.1.2.
Temporary Discontinuation
In certain situations after randomization, the investigator may need to temporarily discontinue 
(interrupt) IP (e.g., due to an AE or a clinically significant laboratory value). The maximum time 
allowed for a temporary interruption of IP is 14 days. If IP interruption is due to an AE, the 
event is to be documented and followed according to the procedures in Section 8.3 of this 
protocol.  Investigators should inform the sponsor that IP has been temporarily interrupted.  
Every effort should be made by the investigator to maintain patients on IP and to restart IP after 
any temporary interruption, as soon as it is safe to do so.  The data related to temporary 
interruption of IP and use of non-study insulin will be documented in source documents and 
entered in the eCRF.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant will be discontinued (withdrawn) from the study in the following circumstances: 

if he or she is diagnosed with any type of diabetes mellitus other than T1DM

at any time at his/her own request 

at the discretion of the investigator for safety, behavioral, compliance, or administrative 
reasons

if the participant becomes pregnant during the study 

if enrollment in any other clinical study involving an investigational product or 
enrollment in any other type of medical research judged not to be scientifically or 
medically compatible with this study

participation in the study needs to be stopped for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and good clinical practice (GCP)

investigator decision
o
the investigator decides that the participant should be discontinued from 
the study

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o
if the participant, for any reason, requires treatment with another 
therapeutic agent that has been demonstrated to be effective for treatment 
of the study indication, discontinuation from the study occurs prior to 
introduction of the new agent

participant decision:
o
the patient or the patient’s designee, for example, parents or legal guardian 
requests to be withdrawn from the study
Discontinuation is expected to be uncommon.
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the Schedule of Activities (Section 1.3). See Schedule of Activities for 
data to be collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed.  The participant will be permanently discontinued both 
from the study intervention and from the study at that time.
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent.  If a participant 
withdraws from the study, he/she may request destruction of any samples taken and not tested, 
and the investigator must document this in the site study records.
7.2.1.
Discontinuation of Inadvertently Enrolled Participants
If the sponsor or investigator identify a participant who did not meet enrollment criteria and was 
inadvertently enrolled, then the participant should be discontinued from study treatment unless 
there are extenuating circumstances that make it medically necessary for the participant to 
continue on study treatment.  If the investigator and the sponsor clinical research physician 
(CRP) agree it is medically appropriate to continue, the investigator must obtain documented 
approval from the sponsor CRP to allow the inadvertently enrolled participant to continue in the 
study with or without treatment with IP. Safety follow up is as outlined in Section 1.3 (Schedule 
of Activities), Section 8.3 (Adverse Events and Serious Adverse Events), and Section 8.2 (Safety 
Assessments) of the protocol.
7.3.
Lost to Follow up
A study participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study.

Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 

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equivalent methods). These contact attempts should be documented in the participant’s 
medical record.

Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
Discontinuation of specific sites or of the study as a whole are handled as part of Section 10.1.

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8.
Study Assessments and Procedures
Study procedures and the study visits at which they are performed, including tolerance limits for 
the study visits, are listed in the Schedule of Activities (Section 1.3).  Adherence to the study 
design requirements, including those specified in the Schedule of Activities, is essential and 
required for study conduct.
Efficacy and safety assessments included in this study are generally regarded as reliable and 
accurate with respect to the efficacy and safety assessments in individuals and populations with 
T1DM.
8.1.
Efficacy Assessments
8.1.1.
Primary Efficacy Assessment
The primary efficacy measure is HbA1c change from baseline to Week 26.
8.1.2.
Secondary Efficacy Assessments
Secondary efficacy assessments for this study are:
•
HbA1c change from baseline to Week 12
•
FG change from baseline to Weeks 12 and 26
•
Bolus insulin dose change from baseline to Weeks 12 and 26
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities
(Section 1.3).
The following safety assessments will be evaluated as secondary objectives:  

Incidence and rate of hypoglycemia 

Incidence of treatment-emergent SAEs

Clinical laboratory assessments with specific focus on liver aminotransferase changes
8.2.1.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the CV, 
Respiratory, Gastrointestinal and Neurological systems.  Height and weight will also be 
measured and recorded.
Investigators should pay special attention to clinical signs related to previous serious illnesses.
Additionally, investigators should inspect injection sites during the physical examination.  
8.2.2.
Vital Signs
For each participant, vital signs measurements should be conducted according to the Schedule of 
Activities (Section 1.3).
Sitting blood pressure (BP) and pulse rate will be measured using automated electronic 
sphygmomanometer according to the Schedule of Activities (Section 1.3).  Vital sign 

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measurements should be taken before obtaining an ECG tracing and before collection of blood 
samples for laboratory testing, at visits where required (see Schedule of Activities, Section 1.3).
The participant should be required to sit quietly for 5 minutes before vital sign measurements are 
taken.  An appropriately sized cuff (cuff bladder encircling at least 80% of the arm) should be 
used to ensure the accuracy of BP measurements.  The arm used for the BP measurement should 
be supported at heart level.  Blood pressure should be measured consistently using the same arm 
throughout the study.  For each parameter (pulse rate, systolic BP, and diastolic BP), 3 
measurements will be taken using the same arm; the recordings should be taken at least 1 minute 
apart, and each measurement of sitting pulse rate and BP will be recorded in the eCRF.
8.2.3.
Electrocardiograms
For each patient, triplicate 12-lead digital ECGs and single safety ECGs will be collected 
according to the Schedule of Activities (Section 1.3).  Patients must be supine for approximately 
5 to 10 minutes before ECG collection and remain supine but awake during ECG collection.
ECGs will be performed prior to collection of any blood samples.
ECGs will be interpreted by a qualified physician (the investigator or qualified designee) at the 
site as soon as possible after the time of ECG collection, and ideally while the patient is still 
present, to determine whether the patient meets entry criteria at the relevant visit(s) and for 
immediate patient management should any clinically relevant findings be identified.  
Digital ECGs will be electronically transmitted to a central ECG laboratory designated by Lilly.  
The central ECG laboratory will perform a basic quality control check (e.g., demographics and 
study details) then store the ECGs in a database.  At a future time, the stored ECG data may be 
overread at the central ECG laboratory for further evaluation of machine-read measurements or 
to meet regulatory requirements.  
The machine-read ECG intervals and heart rate may be used for data analysis and report writing 
purposes unless an overread of the ECGs is conducted prior to completion of the final study 
report (in which case the overread data would be used).
8.2.4.
Self-monitoring of Blood Glucose (SMBG)
At Visit 2, patients will receive the Dexcom G6 CGM device and training on its use, sensor 
placement, interpretation of CGM values and alarms, and the requirements for CGM.  SMBG 
will be performed through this CGM device. In the receiver of the CGM device 2 alarm settings 
are mandatory: an hypoglycemia alarm at 70mg/dl and a hypoglycemia alarm at 55mg/dl.
Glucose readings should be obtained for monitoring patient safety (hypoglycemia) and may be 
checked as frequently as necessary.  Patients should record 6-point glucose profiles in the eDiary
provided, prior to the visits indicated by the Schedule of Activities (Section 1.3).  Patients with 
missing eDiary glucose entries should be retrained on the importance of glucose reporting in the 
eDiary.
Patients will be instructed to record a prebreakfast (fasting) reading every morning and to record 
all results in the eDiary. Patients will also review BG using the CGM device as needed to 
evaluate symptoms of hypoglycemia.
Patients will be instructed to record 6-point glucose profiles over a 24-hour period on 
2 nonconsecutive days during the 7-day period prior to visits indicated in the Schedule of 

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Activities (Section 1.3) using their CGM sensor.  The 6-point profile consists of pre-meal and 
2-hour postprandial glucose readings for the morning, midday, and evening meals in 1 day.  Pre-
meal measurements should be taken before the patient begins eating the meal.  Patients should 
record their glucose measurements in their eDiaries and bring the diary to the investigative site at 
each study visit.  
Participants are permitted to use a personal glucose meter for additional monitoring if deemed 
necessary or by personal choice.  This data, however, should not be used for dosing decisions 
within the study as long as the CGM system is functional. In case of technical issues or during 
the calibration period of the CGM system a personal BG meter can be used for therapeutic 
decision making.
8.2.5.
Clinical Safety Laboratory Assessments
See Section 10.2 for the list of clinical laboratory tests to be performed and the Schedule of 
Activities (Section 1.3) for the timing and frequency.
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those, which are not associated with the underlying disease, unless judged 
by the investigator to be more severe than expected for the participant's condition.
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 6 weeks after the last dose of study intervention (i.e., within the follow up 
period) should be repeated until the values return to normal or baseline or are no longer 
considered clinically significant by the investigator or Lilly medical.

If such values do not return to normal/baseline within a period of time judged reasonable 
by the investigator, the etiology should be identified and the sponsor notified.

All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities.

If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded in the eCRF.
8.2.6.
Safety Monitoring
The principal investigator will monitor safety and laboratory data throughout the study and 
should discuss safety concerns with the sponsor immediately upon occurrence or awareness of 
the concern to determine whether the participant should continue or discontinue study drug.
8.2.6.1.
Hepatic Safety Monitoring
If a study patient experiences elevated ALT ≥3X ULN, ALP ≥2X ULN, or elevated TBL ≥2X 
ULN, liver testing (Section 10.5) should be repeated within 3 to 5 days including ALT, AST, 
ALP, TBL, direct bilirubin, gamma-glutamyl transferase, and creatine kinase to confirm the 
abnormality and to determine if it is increasing or decreasing.  If the abnormality persists or 

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worsens, clinical and laboratory monitoring should be initiated by the investigator and in 
consultation with the study Lilly Medical.  Monitoring of ALT, AST, TBL, and ALP should 
continue until levels normalize or return to approximate baseline levels. 
Hepatic Safety Data Collection
Additional safety data should be collected via the eCRF if 1 or more of the following conditions 
occur: 

elevation of ALT to ≥5X ULN on 2 or more consecutive blood tests

elevated TBL to ≥2X ULN (except for cases of known Gilbert’s syndrome)

elevation of ALP to ≥2X ULN on 2 or more consecutive blood tests

patient discontinued from treatment due to a hepatic event or abnormality of 
liver tests

hepatic event considered to be a SAE
8.2.7.
Body Weight
Body weight will be measured at prespecified time points (see Schedule of Activities, 
Section 1.3).  Patients will be weighed in a light hospital gown or standard clinical research site 
scrubs at approximately the same time in the morning after an overnight fast and after evacuation 
of bowel and bladder contents, if possible.  
Weight will be measured once at screening (non-fasting) and recorded in the source document 
and eCRF.  At lead-in and randomization (Visit 2 and Visit 3, respectively) and all subsequent 
visits indicated in the Schedule of Activities (Section 1.3), weight will be measured twice, with 
the patient stepping off the scale between measurements.  
Both weight measurements will be recorded in the source document and the eCRF.  Calibrated 
(within 6 months prior to study start) scales should be used.  The same scale should be used for 
all weight measurements throughout the study and should not be moved during the conduct of 
the study.
8.3.
Adverse Events and Serious Adverse Events
All AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or 
the participant's legally authorized representative).
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, are considered related to the study intervention or study procedures, or 
that caused the participant to discontinue the study intervention or the study (see Section 7).
8.3.1.
Time Period and Frequency for Collecting AE and SAE Information
All AEs occurring after signing the ICF are recorded in the eCRF and assessed for serious 
criteria.

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The SAE reporting to sponsor begins after the patient has signed the ICF and has received study 
drug.  However, if an SAE occurs after signing the ICF, but prior to receiving LY3209590, it 
needs to be reported ONLY if it is considered reasonably possibly related to study procedures.
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Section 10.3. The investigator will 
submit any updated SAE data to the sponsor within 24 hours of it being available.  
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time after 
a participant has been discharged from the study, and he/she considers the event to be reasonably 
related to the study intervention or study participation, the investigator must promptly notify the 
sponsor.
8.3.2.
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.
8.3.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each participant 
at subsequent visits/contacts. All SAEs, and AEs of special interest (as defined in Section 8.3.7), 
will be followed until resolution, stabilization, the event is otherwise explained, or the participant 
is lost to follow-up (as defined in Section 7.3). Further information on follow-up procedures is 
provided in Section 10.3.
8.3.4.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the sponsor will review and then file 
it along with the IB and will notify the IRB/IEC, if appropriate according to local requirements.

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8.3.5.
Pregnancy
Pregnancy (maternal or paternal exposure to IP) does not meet the definition of an AE.  
However, to fulfill regulatory requirements, any pregnancy should be reported following the 
SAE process described in Section 10.4 and to collect data on the outcome for both mother and 
fetus.
Details of all pregnancies in female participants and, if indicated, female partners of male 
participants will be collected after the start of study intervention and until 90 days after the last 
dose.
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of learning 
of the pregnancy and should follow the procedures outlined in Section 10.4.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs.
8.3.6.
Cardiovascular Events
Deaths and nonfatal CV AEs will be adjudicated by a committee of physicians external to Lilly 
with cardiology expertise.  The nonfatal CV AEs to be adjudicated include:  myocardial 
infarction; hospitalization for unstable angina; hospitalization for heart failure; coronary 
interventions (such as coronary artery bypass graft or percutaneous coronary intervention); and 
cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic 
attack.
8.3.7. Adverse Events of Special Interest 
Adverse events of special interest (AESIs) for this program include:
a.
Hypoglycemia
b. Allergic/hypersensitivity reactions
If any of these AESIs are reported, sites will be prompted to collect additional details/data.
8.3.7.1.
Hypoglycemia
Patients will collect information on episodes of hypoglycemia starting from Visit 2 until the last 
study visit (Visit 801 or ET visit).  For that purpose, patients will be trained about signs and 
symptoms of hypoglycemia, how to treat hypoglycemia, and how to collect in study diaries 
appropriate information for each episode of hypoglycemia according to the Schedule of 
Activities (Section 1.3).  
Participants will be instructed to report hypoglycemia in the eDiary any time he/she experiences 
signs or symptoms of hypoglycemia with or without a SMBG ≤70 mg/dL (<3.9 mmol/L).
Severe hypoglycemia is defined as an event requiring assistance of another person to actively 
administer carbohydrate, glucagon, or other resuscitative actions.  During these episodes, the 
participant has an altered mental status and cannot assist in his/her own care, may be
semiconscious or unconscious, or experience coma with or without seizures and may require 
parenteral therapy.  Glucose measurements may not be available during such an event, but 
neurological recovery attributable to the restoration of BG concentration to normal is considered 

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sufficient evidence that the event was induced by a low BG concentration (≤70 mg/dL [<3.9 
mmol/L]). 
If a hypoglycemic event meets the criteria of severe as confirmed by the investigator, it needs to 
be recorded as serious on the AE eCRF and reported to Lilly as an SAE.
In each case of suspected or confirmed hypoglycemia, it is important that the event be properly 
categorized, the effect of the intervention be assessed, and the frequency and duration of 
hypoglycemia be evaluated.  The role of dietary changes and physical exercise (or any other 
contributing factor) in the development of an event should be established.  The patient should 
receive additional education, if deemed appropriate.  Management of increased risk of 
hypoglycemia is described in Section 6.1.2.2.
8.3.7.2.
Allergic/Hypersensitivity Reactions
All allergic or hypersensitivity reactions, including injection site reactions (ISR), will be reported 
by the investigator as either AEs or, if any serious criterion is met, as SAEs.  Symptoms of a 
local ISR may include erythema, induration, pain, pruritus, and edema.  If an injection site event 
is reported, the AE will be recorded, and additional data will be provided to the sponsor in the 
eCRF.
Additional data, such as type of reaction and treatment received, will be collected on any AEs or 
SAEs that the investigator deems related to IP via an eCRF created for this purpose.  IP should 
be temporarily interrupted in any individual suspected of having a severe or serious allergic 
reaction to IP (Section 7.1.2).  IP may be restarted when/if it is safe to do so, in the opinion of the 
investigator.  If IP is permanently discontinued, see Section 7.1.1 for procedures required in this 
situation.
If an ISR is reported, the information will be provided to the sponsor in the eCRF.  If criteria for 
a SAE are met, the investigator will also complete the SAE form and urgently report the SAE.
8.3.7.3.
Systemic Hypersensitivity Reactions 
Many drugs, but particularly biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data describing each symptom should be provided
to the sponsor in the eCRF.  
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving study drug. It is recommended that participants
who experience a systemic hypersensitivity reaction be treated per the local standard of care.  
In the case of generalized urticaria or anaphylaxis, additional samples should be collected as 
described in Appendix 9 (Recommended Laboratory Testing for Hypersensitivity Events). 
Laboratory results are provided to the sponsor via the central laboratory.
8.3.8. Product Complaints
A product complaint is any written, electronic, or oral communication that alleges a deficiency
related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a 
Lilly product after it is released for distribution. When the ability to use the product safely is 
impacted, the following are also product complaints: 

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a.
Deficiencies in labeling information, and
b. Use errors for device or combination products due to ergonomic design elements of the 
product.
Sponsor collects product complaints on investigational products, medical devices, and drug 
delivery systems used in clinical studies in order to ensure the safety of study participants, 
monitor quality, and to facilitate process and product improvements.
Complaints are also collected on comparators and other materials supplied, as required and 
instructed for the study.
Participants will be instructed to contact the investigator as soon as possible if he or she has a 
complaint or problem with the investigational product, medical device, or delivery system, so 
that the situation can be assessed.
Product complaints will be reported by the investigator to the sponsor per instructions provided 
on the study specific Product Complaint Form.
With each complaint related to a medical device or delivery system, the investigator will assess 
and indicate on the complaint form whether the product complaint could have led to an SAE had 
precautions not been taken.
8.4.
Treatment of Overdose
In the case of an accidental overdose, contact the sponsor in regards to patient management. 
For patients with suspected or confirmed overdose of LY3209590, there is no specific antidote.  
The participant should monitor or be monitored for hypoglycemia.  Treatment is supportive, 
depending on the participant’s symptoms. The management of hypoglycemia should take into 
account the long duration of action of LY3209590, and if there is any concern regarding 
sustained glucose monitoring or nutrient access, the investigative staff should consider imposing 
close medical monitoring (e.g., hospitalization).  
In the event of an overdose with insulin degludec, refer to the Product Label.
8.5.
Pharmacokinetics
At the visits and times specified in the Schedule of Activities (Section 1.3), venous blood 
samples will be collected to determine the plasma concentrations of LY3209590.  After Visit 3, 
PK samples can be taken at any time during the visit.  Note:  PK sample collection is not 
intended for participants randomized to insulin degludec treatment.
Instructions for the collection and handling of blood samples will be provided by the sponsor.  
The actual date and time (24-hour clock time) of each sampling will be recorded.
All the samples will be analyzed at a laboratory designated by the sponsor and stored at a facility 
designated by the sponsor. 
Plasma concentrations of LY3209590 will utilize a validated enzyme-linked immunosorbent 
assay (ELISA) method.  

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Bioanalytical samples collected to measure IP concentration will be retained for a maximum of 
1 year following last patient visit for the study.
8.6.
Pharmacodynamics
In addition to PD parameters discussed in the efficacy and safety sections, fasting free fatty acids 
(FFA) and triglycerides will be evaluated as PD biomarkers of lipolysis, which is a sensitive 
measure of peripheral insulin activity.
Samples collected to measure FFA will be identified by the patient number (coded) and retained 
at a facility selected by Lilly or its designee for a maximum of 2 years following last patient visit 
for the study at a facility selected by Lilly or its designee.
8.7.
Genetics
A blood sample for deoxyribonucleic acid (DNA) isolation will be collected from participants. 
See Section 10.7 for information regarding genetic research and Section 10.1.7 for details about 
sample retention and custody.
8.8.
Biomarkers
Biomarker research is performed to address questions of relevance to drug disposition, target 
engagement, PD, mechanism of action, variability of patient response (including safety), and 
clinical outcome.  Sample collection is incorporated into clinical studies to enable examination of 
these questions through measurement of biomolecules including DNA, ribonucleic acid, 
proteins, lipids, and other cellular elements.
Serum and plasma samples for non-pharmacogenetic biomarker research will be collected at the 
times specified in the Schedule of Activities (Section 1.3) where local regulations allow.
Samples will be used for research on the drug target, disease process, variable response to 
LY3209590 pathways associated with T1DM, mechanisms of action of LY3209590 and/or 
research methods or in validating diagnostic tools or assay(s) related to T1DM.
All samples will be coded with the patient number.  These samples and any data generated can 
be linked back to the patient only by the investigator site personnel.  
Samples will be retained for a maximum 15 years after the last patient visit for the study, or for a 
shorter period if local regulations and ethic review boards impose shorter time limits, at a facility 
selected by Lilly.  This retention period enables use of new technologies, response to regulatory 
questions, and investigation of variable response that may not be observed until later in the 
development of LY3209590 or after LY3209590 become(s) commercially available.
8.9.
Immunogenicity Assessments
At the visits and times specified in the Schedule of Activities (Section 1.3), venous blood
samples will be collected for analysis to determine antibody production against LY3209590.  
Antibodies may be further characterized for cross-reactive binding to insulin. In vivo laboratory 
indicators for glycemic control (e.g., BG, HbA1c, and/or daily insulin dose) may be utilized to 
detect a potential neutralizing effect of antidrug antibodies (ADAs) against LY3209590. To 

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interpret the results of immunogenicity, a venous blood sample will be collected at the same time 
points to determine the plasma concentrations of LY3209590.  All samples for immunogenicity 
should be taken predose when applicable and possible.
Treatment-emergent (TE) ADAs are defined in Section 9.4.8. If the immunogenicity sample at 
the last scheduled assessment or discontinuation visit is TE-ADA positive, additional samples 
may be taken until the signal returns to baseline (i.e., no longer TE-ADA positive) or for up to 1 
year after last dose.  
Samples will be retained for a maximum of 15 years after the last patient visit, or for a shorter 
period if local regulations and Ethical Review Boards (ERBs) allow, at a facility selected by the 
sponsor.  The duration allows the sponsor to respond to future regulatory requests related to 
LY3209590.  Any samples remaining after 15 years will be destroyed. 
8.10.
Health Economics
No health economic outcomes are planned.

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9.
Statistical Considerations
9.1.
Statistical Hypotheses
The primary hypothesis is to test whether LY3209590 treatment is non-inferior to insulin 
degludec in HbA1c change from baseline to Week 26 in study participants who are MDI treated 
T1DM, using a non-inferiority margin (NIM) of 0.4%.
9.2.
Sample Size Determination
Approximately 238 participants will be randomized to study treatment (LY3209590 Algorithm 1, 
and insulin degludec) such that approximately 119 participants will be randomized to each 
treatment. Assuming a 20% dropout rate, approximately 190 participants will complete the 
study (approximately 95 participants per treatment group).  
The 190 participants who complete the treatment will provide at least 80% statistical power to 
demonstrate the noninferiority in the change in HbA1c from baseline to 26 weeks for 
LY3209590 Algorithm 1 versus insulin degludec, based on the following assumptions:

True mean difference = 0%

SD of 1.1%

NIM of 0.4%

Using 2-sided alpha level of 0.1

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9.3.
Populations for Analyses
The following populations are defined:
Population
Description
Entered/Enrolled
Population
All participants who sign the ICF
Randomized Population
All participants assigned to treatment, regardless of whether they 
take any doses of study treatment, or if they took the correct 
treatment.  The participants previously randomized to Algorithm 
2 will be pooled with the participants randomized to Algorithm 1
and all of these participants will be analyzed as one treatment 
group of LY3209590.
Efficacy Population
Participants in randomization population excluding the 
participants previously randomized to Algorithm 2. 
Safety Population
All participants randomly assigned to study treatment and who 
take at least 1 dose of study treatment. The participants 
previously randomized to Algorithm 2 will be pooled with the 
participants randomized to Algorithm 1 and all of these 
participants will be analyzed as one treatment group of 
LY3209590.
Pharmacokinetic 
Population
All randomized participants who received at least 1 dose of 
LY3209590 and have at least 1 evaluable PK sample.
Abbreviations:  ICF = informed consent form; PK = pharmacokinetics.
9.4.
Statistical Analyses
Statistical analysis of this study will be the responsibility of sponsor or its designee.
All tests of treatment effects will be conducted at a 2-sided alpha level of 0.1, unless otherwise 
stated, and all confidence intervals (CIs) will be given at a 2-sided 90% level.
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol.  Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the statistical analysis plan (SAP) and the clinical study report.  Additional exploratory 
analyses of the data will be conducted as deemed appropriate.
The SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of the 
most important endpoints including primary and key secondary endpoints.

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9.4.1. General Considerations
Unless otherwise stated, the efficacy analyses will be conducted on efficacy analyses set (EAS) 
based on the Efficacy Population using the data up to the study treatment discontinuation 
(defined as the observed data with collection date before or at the last dose date +10 days).
Sensitivity analyses for selected efficacy measures may be conducted on the Randomized 
Population using the data up to the study treatment discontinuation.
Unless otherwise stated, the safety analyses except for hypoglycemia will be conducted on the 
safety analyses set based on the Safety Population using all data collected during the study 
including treatment and follow-up period regardless of the treatment disposition status. The 
details for analyses of hypoglycemia will be documented in the SAP.
Unless otherwise specified, the baseline value used for the analyses will be the last nonmissing 
value obtained for each participant prior to or on the date of first study IP dose (or randomization
visit date if first dose date is missing). The baseline liver enzyme lab measures will be the 
average of all assessments prior to and at randomization visit.
9.4.2.
Treatment Group Comparability
9.4.2.1.
Patient Disposition
All randomized participants who discontinue the study/treatment will be identified, and a reason 
for their discontinuation will be given.  The reasons for study/treatment discontinuations will be 
listed and will be summarized by treatment. The discontinuation due to an AE will be 
summarized by AE and treatment. The percentage of participants discontinuing from each 
treatment will be compared using the Fisher’s exact test.
Reasons for discontinuation prior to randomization will also be summarized.
9.4.2.2.
Patient Characteristics
Demographic and baseline characteristics will be summarized by treatment group for 
Randomized Population and Efficacy Population.  Categorical variables will be summarized by 
frequencies and percentages, and comparisons between treatment groups will be assessed using a 
Pearson Chi-Square test.  Continuous variables will be summarized by mean and standard 
deviation, and comparisons between the treatment groups will be performed using a 1-way 
analysis of variance with treatment as the fixed effect.
9.4.2.3.
Concomitant Therapy
Summary of concomitant therapies will be provided by treatment group for all randomized 
participants.
9.4.2.4.
Treatment Compliance
Treatment compliance will be assessed using the EAS and summarized by treatment. The 
incidence of missed dose and the percentage of missed dose will be evaluated.
Adherence to the dosing algorithm will be assessed based on the number and percentage of 
investigator prescribed doses that did not follow the investigator-calculated algorithm dose and 

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the number and percentage of participant actual administration dose that did not follow the 
investigator prescribed dose.
9.4.3.
Primary endpoint(s)
The primary objective is to compare the HbA1c change from baseline to Week 26 between 
LY3209590 treatment and insulin degludec.  It is intended to estimate the treatment differences 
in the change in HbA1c from baseline to 26 weeks if participants adhered to the treatment 
without intercurrent events (stop of the study medication).  It is a type of hypothetical estimand 
based on International Council for Harmonisation (ICH) E9(R1). Only data before the 
occurrence of the intercurrent events (stop of the study medication) will be included in the 
analysis and the resulting missing values will be imputed implicitly in the mixed-effect model for 
repeated measurements (MMRM) analysis. The MMRM model will include treatment, country, 
visit, and treatment by visit interaction as fixed factors and the baseline of the dependent variable 
as a continuous covariate. 
As a sensitivity analysis, the treatment differences in HbA1c change from baseline to Week 26,
only if patients could complete the treatment, will also be estimated. More details will be 
specified in the SAP. 
9.4.4.
Secondary endpoint(s)
The following secondary efficacy outcomes will be analyzed:

HbA1c change from baseline to 12 weeks

FG and change from baseline at 12 and 26 weeks

Bolus insulin dose change from baseline to 12 and 26 weeks
9.4.5.
Tertiary/exploratory endpoint(s)
Refer to the SAP for analyses related to tertiary/exploratory endpoints.
9.4.6.
Safety Analyse(s)
Unless otherwise stated, all safety analyses will be based on the safety analysis set.  Safety 
measures include treatment exposure, AEs, vital signs, hypoglycemic episodes, laboratory 
measurements, ECG and immunogenicity.
9.4.6.1.
Adverse Events
AEs will be summarized as TEAEs (defined as events that are newly reported after 
randomization or reported to worsen in severity from baseline).  The incidence of participants
with at least 1 TEAE and the incidence of TEAEs by preferred term and system organ class will 
be presented by treatment group.  The frequency and percentage of participants for each 
preferred team will be presented.  The incidence of participants with at least 1 TEAE assessed as 
possibly related to the investigational drug will be summarized by treatment group, in addition to 
the incidence of these possibly related TEAEs by preferred term.  In addition, a summary of 
TEAEs by severity will be presented descriptively by treatment group.
Reported and adjudicated CVs will be listed by participant, and if there are a sufficient number 
of cases they may be summarized by treatment group.

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All SAEs will be listed by participant.  If a sufficient number of SAEs are reported, incidence 
summaries similar to incidence of TEAEs will be included.
Discontinuations due to AE will be summarized by treatment group and preferred term.
9.4.6.2.
Vital Signs
Descriptive statistics for the actual measurements and changes from baseline will be presented 
by treatment group and visit.  Corresponding figures may be presented. Vital signs will be 
analyzed using a MMRM model.
9.4.6.3.
Hypoglycemia Episodes
The incidence and rate per year of hypoglycemia will be presented for the periods between 
0-12 weeks, 12-26 weeks, 0-26 weeks, and the follow-up period and analyzed according to the 
hypoglycemia definitions described in the American Diabetes Association classification system
(ADA 2019). The analyses for hypoglycemia will be performed on Efficacy Population and 
additionally the severe (level 3) hypoglycemia analysis will also be performed for the Safety 
Population.
9.4.6.4.
Laboratory Measures
Summary statistics will be provided for laboratory measures by treatment group and by visit. An 
additional listing will be presented for all laboratory measurements that are outside the normal 
range.
Descriptive statistics for the laboratory analyses will be presented by treatment group and visit.
Laboratory analyses with categorical responses will be summarized by visit and treatment group 
using frequency and percentage.
The maximum/minimum post-baseline observation (as applicable for a lab) will be compared to 
the baseline observation by examining the proportion of participants whose test values are within 
and outside the reference ranges.
9.4.6.5.
Electrocardiograms
ECG is mainly for participant safety monitoring. Exploratory analysis may be conducted as 
necessary.
9.4.6.6.
Adverse Events of Special Interest
Hypoglycemia and allergic/hypersensitivity reactions are defined as AESIs (Section 8.3.7).
Descriptive statistics for the AESIs will be presented by treatment group.  
9.4.7.
Pharmacokinetic/Pharmacodynamic Analyses
LY3209590 concentration data will be analyzed using a population PK approach via nonlinear 
mixed-effects modeling with the NONMEM software. The relationships between LY3209590
dose and/or concentration and efficacy, tolerability, and safety as well as biomarker endpoints 
will be characterized if exploratory analyses of the PD data warrant further PK/PD analyses upon 

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
6 4
re vie w. S uc h a nal yses ma y i ncl u de, b ut are n ot necessaril y li mite d t o, gl uc ose, H b A 1c, Q Tc, 
h y p o gl yce mia, a n d vital si g ns.
I n a d diti on, if p o p ulat i on P K a n d P K/ P D m o dels ca n be esta blis he d , t he i m pact of a d dit i on al 
parti ci pa nt fact ors, s uc h as a ge, wei g ht, ge n der a n d re nal f u nct i on o n P K a n d/ or P D para meters,
ma y be e xa mi ne d. S h o ul d a nt i dr u g a nti b o d y be detecte d fr o m i m m u n o ge nicity testi n g, its 
i m pact o n L Y 3 2 0 9 5 9 0 P K or a n y  r ele va nt P D para meters will als o be e xa mi ne d.
9. 4. 8. 
E v al u ati o n of I m m u n o ge nicit y
T he fre q ue nc y a n d perce nta ge of pa rtici pa nt s wi t h pree xisti n g A D A a n d wit h T E -A D A t o 
L Y 3 2 0 9 5 9 0 ma y be ta b ulate d.
Treat me nt -e mer ge nt A D As are defi ne d as t h ose wit h a titer 
2- f ol d ( 1 dil uti o n) greater t ha n t he mi ni m u m re q uire d dilut i on if n o A D As were detecte d at 
baseli ne (treat me nt -i n d uce d A D A) or t h ose wit h a 4-f ol d ( 2 dil uti o ns) i ncrease i n titer c o m pare d 
t o baseli ne if A D As were detecte d at baseli ne (treat me nt-b o oste d A D A).
T he fre q ue nc y of cr oss -reacti ve bi n di n g t o i ns uli n ma y als o be ta b ulate d i n T E A D A + s u bjects, 
w he n a vaila ble.
T he rel at i ons hi p bet wee n t he prese nce of a nt i b o dies a n d t he P K para meters a n d P D res p o nse 
i ncl u di n g safety a n d efficac y t o L Y 3 2 0 9 5 9 0 ma y be assesse d.
9. 4. 9.
Ot her A n al yses
Detaile d a nal ysis pla n f or C G M will be d oc u me nte d i n t he S A P.
9. 5.
I nteri m A n al yses 
9. 6.
D at a M o nit ori n g C o m mittee ( D M C)
N o D M C i s pla n ne d f or t his st u d y.
C CI

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10.
Supporting Documentation and Operational Considerations
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations
10.1.1.
Regulatory and Ethical Considerations
This study will be conducted in accordance with the protocol and with the following:
o
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines
o
Applicable ICH GCP Guidelines
o
Applicable laws and regulations
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., advertisements) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC
before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Under emergency circumstances, deviations from this protocol to protect the rights, safety, or 
well-being of participants are allowed without prior approval of Lilly and the IRB/IEC. The site 
shall document and report these emergent deviations to Lilly and the IRB/IEC within 5 working 
days after the emergency occurred.
Deviation(s) from this protocol, signed 1572, applicable regulations, and any conditions of 
approval imposed by an IRB/IEC or applicable regulators shall be documented (including date of 
and reason for deviation).  Site personnel must identify and report deviations to the sponsor 
within 5 working days.
If appropriate, actions to secure compliance may be taken by Lilly.  These actions may include 
removal or discontinuation of study intervention materials, removal/disposal of devices from the 
investigator, or termination of an investigator’s participation in the study.
The investigator will be responsible for the following:
o
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC
o
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures
o
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations

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10.1.2.
Financial Disclosure
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study.
10.1.3.
Informed Consent Process
The investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant or his/her legally authorized representative and answer all
questions regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representative will be required to sign a statement of informed consent that meets the 
requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study center.
The medical record must include a statement that written informed consent was obtained before 
the participant was entered in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
Participants must be re-consented to the most current version of the ICF(s) during their 
participation in the study.
A copy of the ICF(s) must be provided to the participant or the participant’s legally authorized 
representative and is kept on file.
Participants who are rescreened are required to sign a new ICF.
10.1.4.
Data Protection
Participants will be assigned a unique identifier by the sponsor. Any participant records, datasets
or tissue samples that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by the 
sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
10.1.5.
Dissemination of Clinical Study Data
Reports
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
Data

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The sponsor provides access to all individual participant data collected during the trial, after 
anonymization, with the exception of PK or genetic data.  Data are available to request 6 months 
after the indication studied has been approved in the United States (US) and European Union 
(EU) and after primary publication acceptance, whichever is later.  No expiration date of data 
requests is currently set once data are made available. 
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data sharing agreement. Data and 
documents, including the study protocol, statistical analysis plan, clinical study report, blank or 
annotated case report forms, will be provided in a secure data sharing environment for up to 2 
years per proposal. 
For details on submitting a request, see the instructions provided at 
www.clinicalstudydatarequest.com.  
10.1.6.
Data Quality Assurance
All participant data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (e.g., laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the CRF.
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
The investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents.
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the contracts.
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.
The sponsor assumes accountability for actions delegated to other individuals (e.g., Contract 
Research Organizations).
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements.
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be transferred to 
another location or party without written notification to the sponsor.

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In addition, the sponsor or its representatives will periodically check a sample of the participant 
data recorded against source documents at the study site.  The study may be audited by the 
sponsor or its representatives, and/or regulatory agencies at any time.  Investigators will be given 
notice before an audit occurs.  
Data Capture System
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data.  The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system.  The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF.
Additionally, eCOA data (participant-focused outcome instrument) will be directly recorded by 
the participant, caregiver, and/or investigator site personnel, into an instrument (e.g., handheld
smart phone or tablet).  The eCOA data will serve as the source documentation and the 
investigator does not maintain a separate, written or electronic record of these data.  
The investigator will have continuous access to the data during the study and until 
decommissioning of the data capture system.  Prior to decommissioning, the investigator will 
receive an archival copy of pertinent data for retention.
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system and reports/electronic transfers will be provided to the 
investigator for review and retention.  Data will subsequently be transferred from the central 
vendor to the sponsor data warehouse.
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system.
Study Procedures
Electronic Clinical Outcomes Assessment
The use of eCOA eDiaries should also allow more complete and accurate capturing of 
hypoglycemic events, correction boluses and dosing, as well as more frequent and timely 
interactions between investigator and patients as the intensity of their individual diabetes 
management increases.  
Physicians and designated clinical staff will have access via the eCOA portal (secured web-based 
site) to BG readings, hypoglycemic events, correction boluses and dosing information for each 
patient once transferred.  It is recommended that investigators review patient data via the eCOA 
portal at least once weekly for clinical decision making and safety monitoring. More frequent 
reviews may be necessary for individual patient management.
An instruction manual will be provided to patients and investigative sites. Additional instruction 
and training will be provided to the investigative sites regarding data collection, review, 
retention, and archival processes. In the event of eCOA eDiary malfunction or loss, the patient 
will be instructed to immediately contact the investigative site for instructions regarding 
replacement of the equipment.

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Correction Boluses
Patients will be instructed to enter all non-meal-related correction bolus doses (those not 
associated with a meal or combined with a meal bolus) into the eCOA diary.
Hypoglycemia
Hypoglycemic events will be entered by the patient throughout the clinical study in eCOA along 
with date and time of the BG level if measured and hypoglycemia treatment and outcome data. 
Self-Monitoring Blood Glucose
Patients will be instructed to perform Daily Fasting BG values are expected as well as 6-point 
SMBG according to the Schedule of Activities (Section 1.3).  
10.1.7.
Source Documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
10.1.8.
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the participant and should 
assure appropriate therapy and/or follow-up

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10.1.9.
Publication Policy
In accordance with the sponsor’s publication policy the results of this study will be submitted for 
publication by a peer-reviewed journal.
10.1.10.
Investigator Information
Principal investigators who are a diabetologist, internal medicine specialist, or primary care 
physician with experience in the care of type 1 diabetes patients using MDI and CGM will 
participate as investigators in this clinical trial.
10.1.11.
Long-Term Sample Retention
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of 
LY3209590 or after LY3209590 becomes commercially available.  
The following table lists the maximum retention period for sample types.  The retention period 
begins after the last participant visit for the study. Any samples remaining after the specified 
retention period will be destroyed.
Sample Type
Custodian
Retention Period After 
Last Patient Visit*
Long-term storage samples
Sponsor or Designee
15 years
Biomarkers
Sponsor or Designee
15 years
PK
Sponsor or Designee
1 year
Genetics
Sponsor or Designee
15 years
PD
Sponsor or Designee
2 years
Immunogenicity
Sponsor or Designee
15 years
Abbreviations:  PD = pharmacodynamics; PK = pharmacokinetics.
* Retention periods may differ locally.

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10.2.
Appendix 2: Clinical Laboratory Tests
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations.
Investigators must document their review of each laboratory safety report.
Refer to Section 10.9 for recommended laboratory testing for hypersensitivity events.

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Clinical Laboratory Testsa
Hematology
Clinical Chemistry
Hemoglobin
Sodium
Hematocrit
Potassium
Erythrocyte count (RBC)
Chloride
Mean cell volume (MCV)
Bicarbonate
Mean cell hemoglobin (MCH)
Total bilirubin
Mean cell hemoglobin concentration (MCHC)
Direct bilirubin
Leukocytes (WBC)
Alkaline phosphatase
Neutrophils, segmented
Alanine aminotransferase (ALT)
Lymphocytes
Aspartate aminotransferase (AST)
Monocytes
Gamma glutamyltransferase (GGT)
Eosinophils
Blood urea nitrogen (BUN)
Basophils
Creatinine
Platelets
Uric acid
Calcium
Urinalysis
Phosphorus
Protein
Glucose
Nitrite
Total protein
Blood
Albumin
Urine leukocyte esterase
Creatine kinase (CK)
Cholesterol
Hormones
Pregnancy test serum and urine (females only)b
Triglycerides
Pancreatic amylase
Follicle stimulating hormone 
Lipase
Endocrine
Lipid Panel
C-Peptide
HDL cholesterol
LDL cholesterol
Hemoglobin A1c
Free Fatty Acid
Hepatitis B
Hepatitis B Core Antibody
Hepatitis B Surface Antigen
Hepatitis B Surface Antibody
Immunogenicityc
Drug concentrationc
Anti-LY3209590
Calculation
eGFR (Calculated by CKD-EPI equation)
LY3209590
Pharmacogenetic samplec
Non-pharmacogenetic samplesc
Serum
EDTA Plasma
Abbreviations:  CKD-EPI = chronic kidney disease epidemiology collaboration;
EDTA = Ethylenediaminetetraacetic acid; eGFR = estimated glomerular filtration rate; HDL = high density 
lipoprotein; LDL = low density lipoprotein; RBC = red blood cells; WBC = white blood cells.

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a
All tests will be performed by a Lilly-designated central laboratory, unless otherwise noted.
b
Urine pregnancy tests (analyzed on-site) to be performed at Visits 3 and 801/ED2, and serum pregnancy test 
(analyzed by central laboratory) to be performed at Visits 1 for women of childbearing potential.  Additional
pregnancy tests may be performed at the investigator’s discretion during the study.
c
Results will not be provided to the investigative sites.

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10.3.
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting
10.3.1.
Definition of AE
AE Definition

An AE is any untoward medical occurrence in a patient or clinical study participant, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of study intervention.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.

Note:  “Lack of efficacy” or “failure of expected pharmacological action” per se will 
not be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfil the definition of an AE or 
SAE.

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Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE.

Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.
10.3.2.
Definition of SAE
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease).
A SAE is defined as any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant 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 were more severe.
c.
Requires inpatient hospitalization or prolongation of existing hospitalization

In general, hospitalization signifies that the participant has been admitted to hospital
for observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.

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d.
Results in persistent disability/incapacity

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.

This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g., sprained ankle) which may interfere with or prevent 
everyday life functions but do not constitute a substantial disruption.
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered 
serious.

Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.
10.3.3.
Recording and Follow-Up of AE and/or SAE
AE and SAE Recording

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event.

The investigator will then record all relevant AE/SAE information in the CRF.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records in lieu of completion of the AE/SAE CRF page.

There may be instances when copies of medical records for certain cases are requested 
by sponsor. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to 
sponsor.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE.

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Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to 1 of the following categories:

Mild: An event that is easily tolerated by the participant, causing minimal discomfort 
and not interfering with everyday activities.

Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities.

Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe.
Assessment of Causality

The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE.

A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated.

The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment.

For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.

There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to the sponsor. However, it is very 
important that the investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to sponsor.

The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.

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Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include 
additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.

If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide sponsor with a copy of any post-mortem findings 
including histopathology.

New or updated information will be recorded in the originally completed CRF.

The investigator will submit any updated SAE data to sponsor within 24 hours of 
receipt of the information.
10.3.4.
Reporting of SAEs
SAE Reporting to Sponsor via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE to sponsor will be the electronic data 
collection tool.

If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours.

The site will enter the SAE data into the electronic system as soon as it becomes 
available.

After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data.

If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form (see next 
section) or to the Lilly Medical by telephone.
SAE Reporting to Sponsor or designee via Paper CRF

Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the Lilly Medical.

In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by overnight 
mail or courier service.

Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames.

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10.4.
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information
Definitions:
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below).
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Women in the following categories are not considered WOCBP
1. Premenarchal
2. Premenopausal female with 1 of the following:

Documented hysterectomy

Documented bilateral salpingectomy

Documented bilateral oophorectomy
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (e.g., mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview.
3. Postmenopausal female is defined as, women with:
i. A woman at least 40 years of age with an intact uterus, not on hormone therapy, 
who has cessation of menses for at least 1 year without an alternative medical 
cause, AND a follicle-stimulating hormone >40 mIU/mL; or
ii. A woman 55 or older not on hormone therapy, who has had at least 12 months of 
spontaneous amenorrhea; or
iii. A woman at least 55 years of age with a diagnosis of menopause prior to starting 
hormone replacement therapy.
The investigator will attempt to collect pregnancy information on any male participant’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male participants who receive study intervention.
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be 
followed to determine the outcome of the pregnancy. Information on the status of the mother 
and child will be forwarded to the sponsor. Generally, the follow-up will be no longer than 6 to 
8 weeks following the estimated delivery date. Any termination of the pregnancy will be 
reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 

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Female Participants who become pregnant
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. The initial information will be recorded on the 
appropriate form and submitted to the sponsor within 24 hours of learning of a participant's 
pregnancy. 
The participant will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow-up information on the participant and the neonate and the information will be 
forwarded to the sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks 
beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
A spontaneous abortion (occurring at <22 weeks gestational age) or still birth (occurring at 
>22 weeks gestational age) is always considered to be an SAE and will be reported as such. 
Any post-study pregnancy related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the sponsor as described in Section 8.3.4. While the 
investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention or be withdrawn from the study.

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10.5.
Appendix 5: Liver Safety: Suggested Actions and Follow-up 
Assessments
Hepatic Monitoring Tests
Hepatic Hematologya
Haptoglobina
Hemoglobin
Hematocrit
Hepatic Coagulationa
RBC
Prothrombin Time
WBC
Prothrombin Time, INR
Neutrophils, segmented
Lymphocytes
Hepatic Serologiesa,b
Monocytes
Hepatitis A antibody, total
Eosinophils
Hepatitis A antibody, IgM
Basophils
Hepatitis B surface antigen
Platelets
Hepatitis B surface antibody
Hepatitis B Core antibody
Hepatic Chemistrya
Hepatitis C antibody
Total bilirubin
Hepatitis E antibody, IgG
Direct bilirubin
Hepatitis E antibody, IgM
Alkaline phosphatase
ALT
Anti-nuclear antibodya
AST
GGT
Alkaline Phosphatase Isoenzymesa
CPK
Anti-smooth muscle antibody (or anti-actin antibody)a
Abbreviations:  ALT = alanine aminotransferase; AST = aspirate aminotransferase; CPK = creatinine 
phosphokinase; GGT = gamma-glutamyl transferase; Ig = immunoglobulin; INR = international normalised 
ratio; RBC = red blood cells; WBC = white blood cells.
a
Assayed by sponsor-designated or local laboratory.
b
Reflex/confirmation dependent on regulatory requirements and/or testing availability.

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10.6.
Appendix 6: New York Heart Association Cardiac Disease 
Classification
Functional Capacity
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.
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.
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.
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 increases.
1994 Revisions to Classification of Functional Capacity and Objective Assessment of Patients 
with Diseases of the Heart
Reprinted with permission
www.americanheart.org
© 2011, American Heart Association, Inc.

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10.7.
Appendix 7: Genetics
Use/Analysis of DNA
Genetic variation may impact a participant’s response to study intervention, susceptibility to, and 
severity and progression of disease. Variable response to study intervention may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease being 
treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis from consenting participants.
DNA samples will be used for research related to study intervention or T1DM and related 
diseases.  They may also be used to develop tests/assays including diagnostic tests related to 
study intervention and/or interventions of this drug class and T1DM.  Genetic research may 
consist of the analysis of one or more candidate genes or the analysis of genetic markers 
throughout the genome or analysis of the entire genome (as appropriate).
The samples may be analyzed as part of a multi-study assessment of genetic factors involved in 
the response to study intervention or study interventions of this class to understand study disease 
or related conditions.
The results of genetic analyses may be reported in the clinical study report (CSR) or in a separate 
study summary.
The sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
The samples will be retained as described in Section 10.1.11.  

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10.8.
Appendix 8: Dosing Guidance for LY3209590 and Insulin Degludec
10.8.1.
LY3209590 Algorithm 1 (paper algorithm) 
In Study BDCP, a paper dosing Algorithm 1 will be used by investigators for initiating and 
adjusting LY3209590 to achieve the target FG ≤100 mg/dL (<5.6 mmol/L). 
In situations where study participant safety is a concern, investigators may make adjustments to 
the dose of LY3209590 recommended by the dose-adjustment algorithm in Table 2; however, 
clinical rationale must be documented in the eCRF and Lilly Medical must be informed about 
this deviation and associated medical rationale. If the investigator has safety concerns about the 
algorithm, the investigator is to contact the Lilly CRP.
At the time of site visit, the investigator will assess the study participant’s glycemic control for 
the previous week and, if necessary, inform the study participant about any needed dose 
adjustment. The dose will be based on the study participant’s FG value obtained from the CGM 
system prior to the morning meal and hypoglycemia documented in the electronic diary in the 
previous week. Adherence to the dosing algorithm provided for this study is required from 
Visit 3 (randomization) up to Week 25 and will be monitored periodically by the study team.  
General Algorithm Considerations:

The treat-to-target FG in the algorithm is ≤100 mg/dL (<5.6 mmol/L).  LY3209590 dose 
adjustments will be determined based on the median of the FG (determined from SMBG
obtained from the CGM system, referred to as SMBG below) of at least 3 days (up to 7 
days) obtained in the previous week leading up to the visit.

The LY3209590 dose may not be increased if any SMBG reading was documented at 
≤70 mg/dL (<3.9 mmol/L) at any time in the preceding week. Dose decreases of 0.5 mg 
adjustment may be permitted if multiple episodes of hypoglycemia with SMBG ≤70 
mg/dL (<3.9 mmol/L) were recorded, or dose decrease of 1 mg if severe hypoglycemia 
(requiring assistance) occurred, or if any SMBG was documented at ≤54 mg/dL (≤3.0 
mmol/L) in the preceding week.

In dosing calculations where rounding is required, round to the nearest 0.25 mg.
The starting LY3209590 dose is determined based on both the prior basal insulin dose and 
baseline fasting glucose.  Participants may enter the study using insulin glargine, detemir, or 
degludec.  Consistent with product labeling these insulins may be transitioned on a unit-for-unit 
basis and for the purposes of this protocol are considered equivalent.  Because of the long half-
life of LY3209590, the change in fasting glucose response may take several weeks to reach a 
steady-state response; therefore, to minimize the time needed to achieve the desired target 
glycemic response, a loading dose strategy will be used for the first dose only.  Directions are 
provided below to convert current basal insulin dose (in Units, U) to the dose of LY3209590 (in 
mg) for determination of the starting weekly dose and for dose adjustments at subsequent Visits.  
Examples for Visits 3-6 are provided in italic text.
Visit 3 (Randomization Visit): 
1. Obtain the prior daily basal insulin dose of insulin glargine, detemir, or degludec assessed 
during the lead-in period.  Calculate the “basal insulin equivalent dose” of LY3209590 

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
8 5
(in m g) b y di vi di n g t he t otal dail y  d ose of basal i ns uli n ( U) b y t he c o n versi o n fact or of 
7 U/ m g.  
F or ex a m ple, if a p artici p a nt uses 3 5 U of de gl u dec e ac h d ay, 3 5 U ÷ 7 U/ m g = 5 
m g of L Y 3 2 0 9 5 9 0 .
2.
T he d ose of L Y 3 2 0 9 5 9 0 m g is t he n f urt her a djuste d acc or di n g t o me dia n baseli ne fasti n g 
gl uc ose a n d t he parti ci pa nt ’s c urre nt basal i ns uli n d ose (U ) cate g or y as s h o w n i n Ta ble 1.
F or a p artici p a nt wi t h a me di a n B G v al ue of 1 5 5 m g/ d L, t he d ose a dj ust me nt f or 
t his p artici p a nt c urre ntly usi n g a 3 5 U d ose of de gl u dec wo ul d be + 1. 5 m g.
3.
T he l oa di n g d ose i s o btai ne d b y m ulti pl yi n g t he starti n g t otal L Y 3 2 0 9 5 9 0 wee kl y d ose 
(s u m of basal i ns uli n e q ui vale nt d ose a n d t he d ose a djust m e nt fr o m Ta ble 1)
I n t his ex a m ple, 5 m g + 1. 5 m g = L Y 3 2 0 9 5 9 0 t ot al we ekly d ose of 6. 5 m g 
f or 
a t ot al first d ose of  
.  T his first d ose, i ncl u di n g t he l o a di n g d ose , is use d 
at Visit 3 o nly .
T a bl e 1.
L Y 3 2 0 9 5 9 0 D o s e A dj u st m e nt ( m g) U s i n g t h e M e di a n of B a s eli n e 
F a sti n g Gl u c o s e a n d Pri or B a s al I n s uli n D o s e (I nt er n ati o n al U nit s, U) 
Me di a n B aseli ne
F asti n g Gl uc ose 
( m g/ d L)
Me di a n B aseli ne
F asti n g Gl uc ose b
( m m ol/ L)
L Y 3 2 0 9 5 9 0 D ose A dj ust me nt ( m g) a
B as al I ns uli n D ose
≤1 5 U
B as al I ns uli n 
D ose
1 6 – 3 0 U
B as al I ns uli n 
D ose
> 3 0 U
< 8 0
< 4. 4
- 0. 2 5 
- 1 
- 1. 5 
8 0 - 1 0 0
4. 4 – 5. 5
N o c ha n ge
N o c ha n ge  
N o c ha n ge
1 0 1 – 1 4 0 
5. 6 – 7. 7
+ 0. 2 5 
+ 0. 5 
+ 0. 7 5 
1 4 1 – 1 8 0 
7. 8 – 1 0. 0
+ 0. 5
+ 1
+ 1. 5 
1 8 1 – 2 2 0 
1 0 . 1 – 1 2. 2
+ 0. 7 5
+ 1. 5
+ 2 
> 2 2 0
> 1 2. 2
+ 1 
+ 2 
+ 3 
a
T his d ose a dj ust me nt is a d de d t o t he Basal I ns uli n E q ui vale nt D ose t o o btai n t he t otal wee kl y d ose of 
L Y 3 2 0 9 5 9 0 i n m g.  T he starti n g t otal wee kl y d ose of L Y 3 2 0 9 5 9 0 is i ncrease d 
t o o btai n 
t he first l oa di n g d ose of L Y 3 2 0 9 5 9 0 necessar y t o re d uce t he ti me t o ac hie ve tar get gl yce mic res p o nse.  
b
C o n versi o ns fr o m m g/ d L t o m m ol/ L were r ou n d e d off t o pre ve nt o verla p bet wee n t hres h ol d ra n ges a n d t o 
a d dress t hat t he gl uc ose meter dis pla ys 1 si g nifica nt di git after t he deci mal w h e n re p orti n g m m ol/ L rea di n gs.
Vi sit 4 ( W e e k 1)
1.
O btai n t he starti n g t otal wee kl y d ose L Y 3 2 0 9 5 9 0 m g deter mi ne d at Visit 3. ( This is 1/ 3r d
t he d ose a d mi nistere d at Visit 3 .)
Fr o m t he Visit 3 ex a m ple, t he st arti n g L Y 3 2 0 9 5 9 0 t ot al we ekly d ose w a s 6. 5 m g.
2.
Use Ta ble 2 t o deter mi ne t he d ose a dj ust me nt  nee de d f or Visit 4 after caref ull y 
re vie wi n g parti ci pa nt’s fasti n g gl uc ose ( 3-7 da ys pri or t o visit) a n d h y p o gl yce mia 
d oc u m e nte d si nce t he last L Y 3 2 0 9 5 9 0 d ose.
C CI
C CI
C CI
C CI

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
8 6
T he p artici p a nt re p orte d n o hy p o glyce mi a si nce t he l ast d ose of L Y 3 2 0 9 5 9 0 a n d 
h a d a me di a n F G of 1 5 0 m g/ d L.  Usi n g t he Week 1 ( Visit 4) c ol u m n, t he 
L Y 3 2 0 9 5 9 0 weekly d ose s h o ul d be i ncre ase d by 1 m g.
6. 5 m g + 1 m g = 7. 5 m g L Y 3 2 0 9 5 9 0 s h o ul d be a d mi nistere d at Visit 4. 
T a bl e 2.
W e e kl y D o s e A dj u st m e nt of L Y 3 2 0 9 5 9 0 U si n g t h e Pr e vi o u s W e e k’ s 
D o s e ( D) u si n g t h e M e di a n F a sti n g Gl u c o s e a n d H y p o gl y c e mi c 
E pi s o d e s   
Me di a n F asti n g 
gl uc ose
( m g/ d L)a
Me di a n F asti n g 
gl uc ose 
( m m ol/ L)a , e
Wee k 1 
( Visit 4)
( 2n d d ose)
Wee k 2 
( Visit 5)
( 3r d d ose)
S u bse q ue nt
Wee k
c
< 8 0 m g/ d L or
ha ve a n y n oct ur nal 
h y p o gl yce mia or 
m ulti ple ( ≥3) e pis o des 
of h y p o gl yce mia d
< 4. 4 m m ol/ L or 
h a ve a n y n oct ur nal 
h y p o gl yce mia or 
m ulti ple ( ≥3) e pis o des 
of h y p o gl yce mia d
D b – 1. 5 m g
D b – 1 m g
D c – 0. 5 m g
8 0 – 1 0 0 m g/ d L
4. 4 – 5. 5
D b – 1 m g
D b – 0. 5 m g
N o c ha n ge
1 0 1 – 1 4 0 m g/ d L
5. 6 – 7. 7
N o c ha n ge 
N o c ha n ge
D c + 0. 2 5 m g 
1 4 1 – 1 8 0 m g/ d L
7. 8 – 1 0. 0
D b + 1 m g
D b + 0. 5 m g
D c + 0. 2 5 m g 
> 1 8 0 m g/ d L
> 1 0. 0
D b + 2 m g 
D b + 1 m g 
D c + 0. 5 m g 
a
Base d o n me dia n fasti n g gl uc ose fr o m at least 3 fasti n g gl uc ose rea di n gs fr o m pre vi o us wee k.
b
D f or Wee k 1 ( Visit 4) is  
 of t he d ose a d mi nistere d at ( Wee k 0, Visit 3).  D f or Wee k 2 ( Visit 5) is t he d ose 
a d mi nistere d at Wee k 1 ( Visit 4).  
c
D f or S u bse q ue nt Visits is t he d os e a d mi nistere d o ne wee k pri or t o t he c urre nt visit.
d
T he L Y 3 2 0 9 5 9 0 d ose ma y n ot be i ncrease d if a n y S M B G rea di n g was d oc u me nte d at ≤7 0 m g/ d L ( < 3. 9 m m ol/ L) 
at a n y ti me i n t he prece di n g wee k.  If m ulti ple e pis o des of hy p o gl yce mia wit h S M B G ≤7 0 m g/ d L ( < 3. 9 m m ol/ L) 
were rec or de d, f oll o w g ui da nce f or d ose re d ucti o n acc or di n g t o t he a p plica ble Visit n u m ber.  D ose decreases of 1 
m g s h o ul d be ma de w he n se vere h y p o gl yce mia (re q uiri n g assista nce) occ urre d, or if a n y S M B G was d oc u me nte d 
at ≤5 4 m g/ d L ( ≤3. 0 m m ol/ L) i n t he prece di n g wee k.
e
C o n versi o ns fr o m m g/ d L t o m m ol/ L were r ou n d e d off t o pre ve nt o verla p bet wee n t hres h ol d ra n ges a n d t o 
a d dress t hat t he gl uc ose meter dis pla ys 1 si g nifica nt di git after t he deci mal w h e n re p orti n g m m ol/ L rea di n gs.
Vi sit 5 ( W e e k 2)
1.
C o nfir m t he d ose of  L Y 3 2 0 9 5 9 0 m g a d mi nistere d at Visit 4.
Fr o m t he Visit 4 ex a m ple, t he L Y 3 2 0 9 5 9 0 weekly d ose w a s 7. 5 m g.
2.
Use Ta ble 2 t o deter mi ne t he d ose a dj ust me nt  nee de d f or Visit 5 after caref ull y 
re vie wi n g partici pa nt’s fasti n g gl uc ose ( 3-7 da ys pri o r t o visit) a n d h y p o gl yce mia 
d oc u m e nte d si nce t he last L Y 3 2 0 9 5 9 0 d ose.
C CI

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The participant reported no hypoglycemia since the last dose of LY3209590 and 
had a median FG of 153 mg/dL.  Using the Week 2 (Visit 5) column, the 
LY3209590 weekly dose should be increased by 0.5 mg.
7.5 mg + 0.5 mg = 8.0 mg LY3209590 should be administered at Visit 5. 
Visit 6 (Week 3)
1. Confirm the dose of LY3209590 administered at Visit 5 (Week 2).
From the Visit 5 example, the LY3209590 weekly dose was 8.0 mg.
2. Use Table 2 to determine the dose adjustment needed for Visit 6 after carefully 
reviewing participant’s fasting glucose (3-7 days prior to visit) and hypoglycemia 
documented since the last LY3209590 dose.
The participant reported one episode of nocturnal hypoglycemia since the last 
dose of LY3209590 and had a median FG of 133 mg/dL.  Using the Subsequent 
Week column in Table 2, and because of the case of nocturnal hypoglycemia, 
LY3209590 dose should be reduced by 0.5 mg.
8.0 – 0.5 = 7.5 mg of LY3209590 should be administered at Visit 6.
Subsequent visits are managed using the same approach as for Visit 6 (Week 3), always 
confirming the LY3209590 dose administered at the prior visit, the median fasting glucose 
during the week prior to the visits, and hypoglycemia status since the last dose of study drug.
10.8.2.
Insulin Degludec
A dosing algorithm (adapted from Riddle et al. 2003) will be used by investigators for initiating 
and adjusting insulin degludec to target an FG ≤100 mg/dL (<5.6 mmol/L) for patients to achieve
glycemic goal. 
In situations where patient safety is a concern or where dose adjustments have not had the 
desired therapeutic effect, investigators may make increased or decreased adjustments to the 
dose of insulin degludec recommended by the dose-adjustment algorithm and have to document 
the clinical rationale for the deviation as well as inform Lilly medical per email.
At the time of site visit or telephone visit, the investigator will assess the patient’s glycemic 
control for the previous week and, if necessary, inform the patient about any needed dose 
adjustment.  The dose will be based on the patient’s BG value.  Adherence to the dosing 
algorithm provided for this study is mandatory from Visit 3 (randomization) up to Visit 20 
(Week 26), inclusive.  Dose increases may be made at weekly intervals and no sooner than 5 
days following the last dose increase.  In some cases, patient visits could occur sooner than 5 
days apart due to the allowable visit window; however, there should be no dose increase if at 
least 5 days have not elapsed since the previous dose increase.  In contrast, the insulin degludec 
dose may be reduced at any time on the judgment of the investigator.  Any deviations from this 
guidance must be supported by clinical evidence and after consultation with Lilly Medical.  
Insulin dose algorithms have been reviewed by Strange (2007).  The insulin degludec dose 
increase algorithm is adapted from Riddle et al. 2003 and will be determined based on the 
definition of what is termed the “Algorithm FG.”  The Algorithm FG is the median of the FG 
(determined from SMBG) of Days 5, 6, and 7 since the last insulin dose increment.  If the 

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interval since the last dose adjustment has been longer than 7 days, the dose increase is 
determined by the median of the FG of the last 3 days.  If the patient only measured their FG on 
2 of the last 3 days, then the lesser of those 2 FG values should be used as the Algorithm FG.  If 
only 1 FG measurement is available for the last 3 days, then the investigator should use his/her 
discretion in determining whether there should be a dose adjustment based on that single FG 
value.
As it is desired to achieve glycemic goals in as many patients as possible, contingencies are 
provided to accommodate prespecified protocol visits and to increase the dose of insulin 
degludec in a timely manner.  Therefore, if the last dose increment was 5 days previous, then the 
dose increment is determined by the Algorithm FG, which is the lesser of the 2 FG values from 
Day 4 and Day 5.  If the dose increment was 6 days previous, then the Algorithm FG is the lesser 
of the 2 FG values from Day 5 and Day 6.  In both of these cases, if only 1 of the 2 FG values is 
available, then the investigator should use his/her discretion in determining whether there should 
be a dose adjustment based on that single FG value.
The dose increase algorithm is defined as follows:

If the Algorithm FG is 101 to 120 mg/dL (5.6 to 6.7 mmol/L), increase the dose by 2 U

If the Algorithm FG is 121 to 140 mg/dL (6.8 to 7.8 mmol/L), increase the dose by 4 U 

If the Algorithm FG is 141 to 180 mg/dL (7.9 to 10.0 mmol/L), increase the dose by 6 U 

If the Algorithm FG is 180 mg/dL (10.0 mmol/L), increase the dose by 8 U 
The treat-to-target FG is ≤100 mg/dL (<5.6 mmol/L).  The insulin degludec dose will not be 
increased if any SMBG was documented at ≤70 mg/dL (<3.9 mmol/L) at any time in the 
preceding week.  Dose decreases of 2 to 4 U per adjustment may be permitted if multiple 
episodes of hypoglycemia with SMBG ≤70 mg/dL (<3.9 mmol/L) were recorded, if severe 
hypoglycemia (requiring assistance) occurred, or if any SMBG was documented at ≤54 mg/dL 
(≤3.0 mmol/L) in the preceding week.

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10.9.
Appendix 9:  Recommended Laboratory Testing for Hypersensitivity 
Events
Guidance for laboratory assessments for hypersensitivity events:
Laboratory assessments should be performed if the participant experiences generalized urticaria 
or if anaphylaxis is suspected.

Collect sample after the participant has been stabilized, and within 1 to 2 hours of the 
event; however, samples may be obtained as late as 12 hours after the event as analytes 
can remain altered for an extended period of time.  Record the time at which the sample 
was collected.

Obtain a follow-up sample at the next regularly scheduled visit or after 4 weeks, 
whichever is later.

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
9 0
T a bl e 3.
Cli ni c al L a b T e st s f or H y p er s e n siti vit y E v e nt s
C CI

C O N FI D E N TI A L
I 8H- M C -B D C P ( d)
L Y 3 2 0 9 5 9 0
9 1
1 0. 1 0.
A p pe n di x 1 0 :  C h a n ges t o St u d y Pr oce d ures d ue t o t he C O VI D - 1 9 
P a n de mic or N at ur al Dis asters
Re m ote Visits d uri n g t he St u d y
If C O VI D 1 9- or nat ural disaster -relate d tra vel or s helter-i n place restricti o ns are re q ueste d b y 
l ocal/re gio n al a ut h orities or f or ot her reas o ns relate d t o t he pa n de mic or nat ural disasters w hic h 
ma ke it i m p ossi ble f or t he partici pa nt t o tra vel t o t he st u d y sit e for t he m a n dat or y titratio n visi ts, 
mit i gati ons are re q uire d t o e ns ure safe a n d ti mel y d osi n g of st u d y partici p a n ts. 
T he st u d y  sit e must recei ve pri or a p pr o val  b y Lill y f or eit her site m o bile visits perf or me d b y  
trai ne d site pers o n nel or visits perf or me d b y a q ualifie d h o me n ursi n g ser vice pr o vi der or ga nize d 
b y t he s p o ns or, wit h vi de o -c o nfere nci n g a bilit y,  t o r e place t he o n-site visits.  
Pr ot oc ol  pr oce d ures, i ncl u di n g bl o o d dra ws, data-d o w nl oa ds, partici pa nt (re -) e d ucati o n, st u d y 
dr u g d ose select io n a n d st u d y  dr u g d osi n g ma y be perf or me d at t he partici pa nts’ h o me b y 
q ualifie d pers o n nel u nt il tra vel or ot her restricti ons are lift e d. 
T he all o we d visit wi n d o ws ca n be e xte n de d base d o n a d vice fr o m Lill y Me dical i n t his 
e xce pti o nal case t o all o w m ore f le xi bility i n perf or mi n g t he h ome vis its. 
E arl y Disc o nti n u ati o n Pr oce d ures:
If a partici pa nt is q uara nti ne d or c o ntracts C O VI D-1 9 or i s u na ble t o atte n d t he visit f or ot her 
reas o ns d uri n g t he c o urse of t he st u d y a n d t heref ore mo bile visit s ca n n ot be or ga nize d, st u d y 
treat me nt must be di sc o nti n ue d earl y a n d d osi n g decisi ons f or t he alter nati ve treat me nt are 
all o we d t o be perf or me d b y tele p h o ne. 
St u d y  s u p plies f or bl o o d gl uc ose m o nit ori n g as well as alter nati ve treat me nts will be pr o vi de d t o 
t he partici pa nt u nt il t he e n d of t he safety f oll ow- u p peri o d ( 6 wee ks after t he last d ose of 
L Y 3 2 0 9 5 9 0 or 5 wee ks after t he last d ose of i ns uli n d e gl u dec). If circ u msta nces per mit, eff orts 
ma y be ma d e t o o btai n a n i m m u n o ge nicit y bl o o d sa m ple after t his f oll o w -u p. After t he e n d of 
t he safet y f oll ow -u p peri o d, st u d y  s u p plies ha ve t o be ret ur ne d or dis p ose d as directe d b y t he 
st u d y t e a m.
P arti cip a nt s ha ve t o c o nti n ue t o e nter t heir bl o o d gl uc ose, h y p o gl yce mia a n d i ns uli n d ose 
i nf or mat i on i nto t hei r ele ctr o nic diaries t o give t he i n vesti gat i ve site c o nti n ue d re m ote access t o 
t hese data.  After ter mi nati o n o f st u d y tr e at me nt , L Y 3 2 0 9 5 9 0 /ins uli n d e gl u dec s h o uld be 
r e place d b y t he pre vi o usl y use d basal i ns uli n. 
 
 
  T heref ore, a sl o w u p-titr atio n 
of  a n ot her basal i ns uli n is necessar y t o pre ve nt h y p o gl yce mia d ue t o o verla p pi n g i ns uli n acti on
after t he disc o nti n uati on of L Y 3 2 0 9 5 9 0 . D uri n g t his re m ote u p -titratio n , n o i ns uli n s h o uld be 
d ose d u ntil t he st u d y parti ci pa nt’s me d ia n fasti n g gl uc ose o ver a n y  7-da y peri o d i ncreases t o 
> 1 2 0 m g/ d L, a n d t he n dail y basal i ns uli n w o ul d be i nit iate d a n d a dj uste d base d o n fasti n g 
gl uc ose . St u d y  p artici pa nts assi g ne d t o t he i ns uli n de gl u dec treat me nt gr o u p will s witc h t o t he 
basal i ns uli n use d bef ore e nteri n g t he st u d y . If i ns uli n de gl u dec was t he pre-st u d y basal i ns uli n, 
t he y ca n c o nti n ue wit h t he sa me d ose use d u ntil t he st u d y i nter ve nt i on disc o nt i n uati on .  If t he y 
s witc h t o a n ot her basal i ns uli n (e. g., i ns uli n glar gi ne), st u d y partici pa nts s h o uld i nject a dail y 
d ose w hic h is 2 0 % l o wer t ha n t he last d ose of i ns uli n de gl u dec use d bef ore t he st u d y i nter ve ntio n
di sc o nti n uati on a n d titrate u n der r e mote s u per visi on of t he i n vest i gat or usi n g t he c o u ntr y-
C CI

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specific label for their pre-study basal insulin. In case remote visits are impossible, the 
participant must be hospitalized for a safe transition to an alternative antidiabetic treatment.
Replacement of Study Participants
The dropout rate will be monitored regularly during the study. If the dropout rate is over 15%
prior to completion of 12 weeks of treatment, additional participants may be enrolled to ensure 
approximately 190 participants complete 12 weeks of treatment.
Documentation
The sites must identify and document the details of how all participants and visits were affected 
by the COVID-19 pandemic restrictions.

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10.11.
Appendix 11: Abbreviations
Term
Definition
ADA
anti-drug antibodies
AE
adverse event:  Any untoward medical occurrence in a patient or clinical investigation 
participant administered a pharmaceutical product that does not necessarily have a 
causal relationship with this treatment.  An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, 
or disease temporally associated with the use of a medicinal (investigational) product, 
whether or not related to the medicinal (investigational) product.
AESI
adverse events of special interest
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BG
blood glucose
blinding/masking
A single-blind study is one in which the investigator and/or his staff are aware of the 
treatment but the participant is not, or vice versa, or when the sponsor is aware of the 
treatment but the investigator and/his staff and the participant are not.
A double-blind study is one in which neither the participant nor any of the investigator 
or sponsor staff who are involved in the treatment or clinical evaluation of the 
participants are aware of the treatment received.
BMI
body mass index
BP
blood pressure
CGM
continuous glucose monitoring
CI
confidence interval
CIOMS
Council for International Organizations of Medical Sciences
Companion diagnostic 
An in vitro diagnostic device (assay or test) that provides information that is essential 
for the safe and effective use of a corresponding therapeutic product
complaint
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system.
compliance
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements.
CONSORT
Consolidated Standards of Reporting Trials
CRP
clinical research physician: Individual responsible for the medical conduct of the study.  
Responsibilities of the CRP may be performed by a physician, clinical research 
scientist, global safety physician or other medical officer.

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CV
cardiovascular
DKA
diabetic ketoacidosis
DMC
data monitoring committee
DNA
deoxyribonucleic acid
EAS
efficacy analyses set
ECG
electrocardiogram
ED
early discontinuation
EDC
electronic data capture system
eDiary
electronic diary
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
enroll
The act of assigning a participant to a treatment.  Participants who are enrolled in the 
study are those who have been assigned to a treatment.
enter
Participants entered into a study are those who sign the informed consent form directly 
or through their legally acceptable representatives.
ERB
ethical review board
ET
Early termination
FFA
free fatty acids
FG
fasting glucose
GCP
good clinical practice
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonization
IMP
Investigational Medicinal Product
Informed consent
A process by which a participant voluntarily confirms his or her willingness to 
participate in a particular study, after having been informed of all aspects of the study 
that are relevant to the participant’s decision to participate.  Informed consent is 
documented by means of a written, signed and dated informed consent form.
INR
international normalized ratio

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interim analysis
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created/locked.
IP: investigational 
product
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to 
gain further information about the authorized form.
IRB/IEC
Institutional Review Boards/Independent Ethics Committees
ISR
injection site reaction
ITT
intention to treat:  The principle that asserts that the effect of a treatment policy can be 
best assessed by evaluating on the basis of the intention to treat a participant (i.e., the 
planned treatment regimen) rather than the actual treatment given.  It has the 
consequence that participant allocated to a treatment group should be followed up, 
assessed, and analyzed as members of that group irrespective of their compliance to the 
planned course of treatment.
IWRS
interactive web-response system
MAD
multiple-ascending dose
MDI
multiple daily injections
MMRM
mixed-effect model for repeated measurements
NAFLD
non-alcoholic fatty liver disease
NIM
non-inferiority margin
NIMP
Non-investigational Medicinal Product
OTC
over the counter
participant
Equivalent to CDISC term “subject”: an individual who participates in a clinical trial, 
either as recipient of an investigational medicinal product or as a control
PC
product complaint
PK/PD
pharmacokinetics/pharmacodynamics
PPS
per-protocol set:  The set of data generated by the subset of participant who sufficiently 
complied with the protocol to ensure that these data would be likely to exhibit the 
effects of treatment, according to the underlying scientific model.
PRO/ePRO
patient-reported outcomes/electronic patient-reported outcomes
QTc
corrected QT interval
SAD
single-ascending dose
SAE
serious adverse event

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SAP
statistical analysis plan
SC
subcutaneous
screen
The act of determining if an individual meets minimum requirements to become part of 
a pool of potential candidates for participation in a clinical study. 
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SMBG
self-monitoring blood glucose
SOA
schedule of activities
SUSARs
suspected unexpected serious adverse reactions
T1DM
type 1 diabetes mellitus
T2DM
type 2 diabetes mellitus
TBL
total bilirubin level
TEAE
Treatment-emergent adverse event:  An untoward medical occurrence that emerges 
during a defined treatment period, having been absent pretreatment, or worsens relative 
to the pretreatment state, and does not necessarily have to have a causal relationship 
with this treatment.
TE
treatment-emergent
ULN
upper limit of normal
UK
United Kingdom
US
United States
WOCBP
woman of childbearing potential

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10.12.
Appendix 12: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC).
Amendment [c]: 14 August 2020
This amendment is considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
The amendment provides information to reflect and reinforce investigational medical device 
requirements absent in the initial study protocol for Algorithm 2.  These requirements are 
consistent with country regulations where Algorithm 2 will be used.
Section # and Name
Description of Change
Brief Rationale
Section 1.1. Synopsis
Section 1.2. Schema
Section 4.1.1. Study Visits
Section 6.1. Study 
Interventions(s) Administered
Addition of language regarding 
randomization
Clarify that randomization distribution may 
vary based on country due to removal of 
randomization into LY3209590 Algorithm 2 
(digital) treatment for the European Union 
(EU)
Section 1.3 Schedule of 
Activities
Addition of product complaint 
review in AE/SAE review
Product complaint review was added to 
ensure alignment with Lilly guidance
Section 2.3. Benefit/Risk 
Assessment
Addition of language related to 
LY3209590 Algorithm 1 
(paper) and LY3209590 
Algorithm 2 (digital)
Additions to clarify regulatory designation of 
LY3209590 Algorithm 1 (paper) and 
LY3209590 Algorithm 2 (digital)
Section 2.3.1. Protocol Risk 
Mitigation Features for 
Investigational Algorithm 2
Addition of language for 
protocol risk mitigation 
Summarization of key risk mitigations for the 
protocol including investigational medical 
device
Section 4.1.1. Study Visits
Updated wording describing 
Algorithm 2
Clarification of Algorithm 2 as an 
investigational individualized accruing data 
algorithm
Section 6.1. Study 
Interventions(s) Administered
Addition of language describing 
Algorithm 1 and Algorithm 2
Clarification and description of algorithms 
Section 6.1.2.3. Management 
of Patients with Severe, 
Persistent Hyperglycemia 
during Treatment Period
Addition of language related to 
transient hyperglycemia
Provide acknowledgment of the potential for 
transient hyperglycemia and guidance for 
management during transition period from 
prestudy basal to LY3209590
Section 6.1.3. Medical 
Devices
Addition of language for 
Algorithm 2
Algorithm 2 was added based on regulatory 
feedback and classification as a medical 
device
Section 6.2. 
Preparation/Handling/Storage/
Accountability
Addition of language for 
accountability and access
Description of labeling and appropriate 
access controls by authorized trained 
personnel to meet regulatory requirements
Section 8.3.8. Product 
Complaints
Addition of required section 
Product complaint section added to align 
with Lilly template and guidance

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Section # and Name
Description of Change
Brief Rationale
Section 9. Statistical 
Considerations
Clarifications throughout
Clarifications and corrections provided to 
ensure consistency with the statistical 
analysis plan
Section 9.2 Sample Size 
Determinations
Revised language related to 
statistical power 
Language added to reflect the change in 
statistical power resulting from removal of 
Algorithm 2 from  the EU
Section 10.1.1. Regulatory 
and Ethical Considerations
Addition of language related to 
emergency circumstances
Clarification of guidance during emergency 
circumstances requiring prior approval of 
Lilly for regulatory compliance
Section 10.3.3. Definition of 
an Unanticipated Adverse 
Device Effect (UADE)
Addition of section related to 
unanticipated adverse device 
effect (UADE)
Guidance on definitions and procedures for 
handling UADEs
Section 10.8.1. LY3209590 
Algorithm 1 (paper algorithm)
Addition of language for 
investigators
Clarified guidance for investigators 
contacting Lilly Medical to be consistent 
with guidance provided for Algorithm 2
Section 10.8.2 LY3209590 
Algorithm 2 (digital 
algorithm)
Addition of language related to 
dosing and input of data for 
Algorithm 2
Clarification for investigators on the use of 
Algorithm 2
Throughout
Minor editorial and document 
formatting revisions
These are minor changes; therefore, they 
have not been summarized
Amendment [b]: 12 June 2020
This amendment is considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
This provides guidance if COVID-19 related local restrictions impact the participant’s ability to 
attend their onsite study visits as originally scheduled.
Section # and 
Name
Description of Change
Brief Rationale
Section 10.10 
Appendix 10
Added Appendix 10: Changes to Study 
Procedures due to the COVID-19 
Pandemic or Natural Disasters
Mitigation if COVID-19 related restrictions 
make it impossible for the participant to travel to 
sites for originally scheduled visits.
Amendment [a]: 08 April 2020
This amendment is considered substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.
Overall Rationale for the Amendment:
This amendment addresses Food and Drug Administration (FDA) feedback.

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Section # and Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities
Moved text from under ‘Notes’ for the 12-
lead ECG to footnote d
To include all information relevant to 
the ECG assessment under one 
footnote
1.3. Schedule of 
Activities
Updated text specifying PK sample 
collection in participants randomized to 
LY3209590
To better reflect that PK samples 
were only collected for participants 
randomized to the LY3209590 group
1.3. Schedule of 
Activities
Added text regarding the assessment of 
C-peptide under ‘Notes’ section
To better reflect the assessment of C-
peptide during screening and lead-in
1.3. Schedule of 
Activities
Added ‘X’ at Visit 3 for the procedure 
‘Review diary data and make dose 
individualization assessment’
Corrected an error:  initial dose 
selection based on the diary entries 
between V2 and V3 has to be done at 
V3
1.3. Schedule of 
Activities
Updated footnotes d and e to accommodate 
the language in the notes section for the 12-
lead ECG and to indicate that PK samples 
were not to be collected for participants in 
the insulin degludec treatment group
To streamline presentation of all 
relevant information under the 
footnotes and to better reflect that PK 
samples were only collected for 
participants randomized to the 
LY3209590 group
1.3. Schedule of 
Activities
Added footnote f to ‘Study participant CGM 
training’ to specify that the patients will be 
fitted with Dexcom G6® for CGM 
monitoring
Per regulatory feedback
3. Objectives
Deleted ‘recurrence’ for hypoglycemic 
events from the endpoints for the 
tertiary/exploratory objective of exploring 
the quality of glycemic control of 
LY3209590 compared with insulin degludec 
using CGM
Correction of an error
4.1.1. Study Visits,
5.1. Inclusion Criteria,
8.2.4. Self-monitoring 
of Blood Glucose 
(SMBG)
Included the CGM system name ‘Dexcom 
G6’
Per regulatory feedback
4.3. Justification for 
Dose
Deleted ‘after consultation with Lilly 
Medical’ in the statement regarding dose 
alterations recommended by dose 
adjustments algorithms, under the discretion 
of investigators.  Added text regarding 
documentation required in case of deviation 
from the algorithm-recommended dose
Corrected an error:  prior consultation 
with Lilly Medical is not required for 
the investigator for dose alterations of 
LY3209590
5.1. Inclusion Criteria
Added that C-peptide needs to be assessed to 
be ≤0.30 nmol/L at screening or before 
randomization
To clarify that an additional C-peptide 
evaluation can also be performed, if 
required, at Visit 2, before 
randomization
5.1. Inclusion Criteria
Changed ‘insulin levemir’ to ‘insulin 
detemir’ in inclusion criterion 6 in the current 
protocol
For consistency with using the 
generic name

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Section # and Name
Description of Change
Brief Rationale
5.1. Inclusion Criteria
Added the lower threshold of 5.6% to the 
HbA1c range for inclusion in the study
Per regulatory feedback
5.1. Inclusion Criteria
Added text to specify the dosing regimen of 
insulin prior to screening
Per regulatory feedback
5.2. Exclusion Criteria
Updated the exclusion criteria to explicitly 
exclude women of childbearing potential 
who are not using adequate contraception, 
pregnant women, women intending to 
become pregnant, or lactating women
Per regulatory feedback
5.2. Exclusion Criteria
Updated the exclusion criterion regarding 
glucocorticoid use (exclusion criterion 29 in 
the current protocol) to correct the duration 
of systemic therapy to be considered chronic 
to 14 days. This is consistent with Section 
6.5.2
Corrected text to be consistent with 
Section 6.5.2
5.2. Exclusion Criteria
Updated exclusion criteria numbering due to 
the addition of the exclusion criteria per 
regulatory feedback
Update in formatting
6.1.2.1. Standards of 
Medical Care
Added the statement, “Standards of 
prevention of persistent hyperglycemia and 
ketone monitoring must be followed during 
the course of the study to prevent DKA”
Per regulatory feedback, to further 
clarify the steps/mitigate the risk of 
hyperglycemia and DKA when 
starting LY3209590 or transitioning 
to other therapies (at the end of the 
trial)
6.1.2.2. Management of 
Increased 
Hypoglycemia Risk
Replaced ‘confirmed’ with ‘documented’ 
hypoglycemia from the definition of 
increased risk of hypoglycemia
Added the definition of documented 
hypoglycemia
Per regulatory feedback
6.4 Study Intervention 
Compliance
Updated text regarding IP accountability
To better reflect the process for IP 
accountability
7.1.1 Permanent 
Discontinuation from 
Study Treatment
Added text for discontinuation from 
following occurrence of a systemic 
hypersensitivity reaction
To clarify better the circumstances 
under which participants will be 
discontinued from the IP
8.3.7.1 Hypoglycemia
Deleted ‘ED2’ as one of the last visits
ED2 is not necessarily the last study 
visit if patient continues the study 
without IP
8.3.7.1. Hypoglycemia
Amended text regarding the reporting of 
hypoglycemia
To clarify how information regarding 
hypoglycemia is to be collected
8.3.7.1. Hypoglycemia
Deleted text describing the thresholds for 
analysis.
These thresholds will be used for 
analyses, and do not need to be 
included in the protocol.  The 
thresholds for algorithms are updated 
in Section 10.8.1.
8.3.7.3. Systemic 
Hypersensitivity 
Reactions
Added a section on systemic hypersensitivity 
as adverse events of special interest
To update the protocol with systemic 
hypersensitivity as an adverse event 
of special interest

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Section # and Name
Description of Change
Brief Rationale
8.4. Treatment of 
Overdose
Updated the text to provide guidance 
regarding the management of overdose with 
LY3209590
Per regulatory feedback
8.5. Pharmacokinetics
Updated the text to clarify that PK samples 
were not to be collected for participants 
randomized to insulin degludec
To better reflect that PK samples 
were only collected for participants 
randomized to the LY3209590 group
9.3. Populations for 
Analyses
Updated the description of the 
pharmacokinetic population to indicate that 
these participants have at least 1 evaluable 
PK sample
To clarify better the inclusion pf 
patients in the pharmacokinetic 
population
9.4.6.3. Hypoglycemia 
Episodes
Amended text to clarify that hypoglycemia 
will be analyzed according to the definitions 
in the American Diabetes Association 
classification system
To explain the analysis of 
hypoglycemia
10.1.6. Data Quality 
Assurance
Replaced ‘captured’ with ‘entered by patient’ 
to clarify that hypoglycemic events will be 
entered by patients in the eCOA
To clarify the text regarding data 
collection for hypoglycemic events
10.2.
Appendix 2
Updated the text to clarify that the 
investigators must document their review of 
each laboratory safety report and updated the 
footnotes
To correct errors, add information, 
and improve readability
10.8.1.
Appendix 8
Updated the text regarding the LY3209590 
algorithm 1 (paper algorithm)
Per regulatory feedback
10.9. Appendix 9
Added an appendix to describe recommended 
laboratory testing for hypersensitivity events
To update the protocol with systemic 
hypersensitivity as an adverse event 
of special interest
Throughout the protocol
Minor editorial and formatting changes
Minor, therefore not described
Abbreviations:  ECG = electrocardiogram; eCOA = electronic Clinical Outcome Assessment; ED2 (visit) = Early 
Discontinuation 2 (visit); IP = investigational product; PK = pharmacokinetic.

CONFIDENTIAL
I8H-MC-BDCP(d)
LY3209590
102
11.
References
[ADA] American Diabetes Association. Standards of medical care in diabetes—2016. Diabetes 
Care. 2016;39(suppl 1):S4-S108.
[ADA] American Diabetes Association. Standards of medical care in diabetes—2019. Diabetes 
Care. 2019;42(suppl 1):S4-S193.
[FDA] Food and Drug Administration. Guidance for Industry. Diabetes Mellitus:  Developing 
Drugs and Therapeutic Biologics for Treatment and Prevention. 2008. Available at:
https://www.fda.gov/media/71289/download. Accessed: December 3, 2019.
Heise T, Nosek L, Bøttcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a 
flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 
2012;14(10):944-950.
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas 
A, Wender R, Matthews DR. Management of Hyperglycemia in Type 2 Diabetes, 2015: A 
Patient-Centered Approach: Update to a Position Statement of the American Diabetes 
Association and the European Association for the Study of Diabetes. Diabetes Care. 
2015;38(1):140-149.
[NDA] National Diabetes Audit. National Diabetes Audit Report: 1 Care Processes and 
Treatment Targets 2016-17. Available at: https://digital.nhs.uk/data-and-
information/publications/statistical/national-diabetes-audit/national-diabetes-audit-report-1-
care-processes-and-treatment-targets-2016-17. Published 10 November 2017.  Accessed:
November 1, 2019.  
Riddle MC, Rosenstock J, Gerich J, Insulin Glargine 4002 Study Investigators. The Treat-to-
Target Trial: Randomized addition of glargine or human NPH insulin to oral therapy of type 2 
diabetic patients. Diabetes Care. 2003;26:3080–3086.
Strange P. Treat-to-target insulin titration algorithms when initiating long or intermediate acting 
insulin in type 2 diabetes. J Diabetes Sci Technol. 2007;1(4):540-548.
Tresiba® prescribing information [USPI 2015]. Available at: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203314lbl.pdf. Accessed: January 
11, 2018.

L e o  D o c u m e n t  I D  =  8 f 5 2 b c 1 3 - 7 c 8 6 - 4 b 9 6 - b 7 f 0 - 8 f 2 a 2 5 c c a 0 4 8
A p p r o v e r :
A p p r o v a l  D a t e  &  T i m e :  2 8 - O c t - 2 0 2 0  1 4 : 3 3 : 5 1  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
A p p r o v e r :
A p p r o v a l  D a t e  &  T i m e :  2 8 - O c t - 2 0 2 0  1 5 : 3 7 : 5 2  G M T
S i g n a t u r e  m e a n i n g :  A p p r o v e d
P P D
P P D