A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo and Once-Weekly Dulaglutide in Participants With Type 2 Diabetes Mellitus
Phase: PHASE2
Conditions: Type 2 Diabetes
Sponsor: Eli Lilly and Company

 
 
 
Protocol J2A-MC-GZGE(b) 
 
 
A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo and Once-Weekly 
Dulaglutide in Participants with Type 2 Diabetes Mellitus 
 
NCT05048719 
 
Approval Date: 27-Oct-2021 
 
 
 
 
 
 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
1
Title Page
Confidential Information
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3502970, unless such persons are bound by a confidentiality agreement with Eli Lilly and Company or its 
subsidiaries. 
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries.
Protocol Title: A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo and Once-
Weekly Dulaglutide in Participants with Type 2 Diabetes Mellitus
Protocol Number: J2A-MC-GZGE
Amendment Number: b
Compound: LY3502970
Brief Title: Effect of LY3502970 Versus Placebo and Dulaglutide in Participants with Type 2 
Diabetes Mellitus
Study Phase: 2
Sponsor Name: Eli Lilly and Company
Legal Registered Address: Indianapolis, Indiana, USA 46285
Regulatory Agency Identifier Number(s)
IND: 142842
EudraCT: 2021-002806-29
Approval Date: Protocol Amendment (b) Electronically Signed and Approved by Lilly on date 
provided below.
Approval Date: 27-Oct-2021 GMT

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
2
Medical Monitor Name and Contact Information will be provided separately.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
3
Protocol Amendment Summary of Changes Table
DOCUMENT HISTORY
Document
Date
Protocol amendment [a]
30-Jun-2021
Original Protocol
15-Jun-2021
Amendment [b]
This amendment is considered to be nonsubstantial.
Overall Rationale for the Amendment:
Section # and Name
Description of Change
Brief Rationale
1.3. Schedule of 
Activities 
Modified frequency of 
blood pressure collections at 
a visit from 3 to 2.
Typographical error. It was always 
planned that there would be only 2 
collections and the eCRF allows for 
only 2 collections.
1.3. Schedule of 
Activities 
Corrected the visit numbers 
for distribution of single 
dose pens.
Typographical error.
3. Objectives, 
Endpoints, and 
Estimands
Adjusted the wording for 
safety estimand.
To more precisely define safety 
estimand for the study.
4.1.1. Overview of 
Study Periods
Corrected visit number for 
dose escalations.
Typographical error. Dose 
escalations occur at Visits 4 through 
10.
5.1. Inclusion Criteria
Added a note to Inclusion 
Criterion #3 that 
participants from some 
countries may be required to 
be on metformin.
To address a regulatory agency 
concern.
6.5. Dose Modification
Replaced text referring to 
contacting the IWRS help 
desk for dose modification.
The investigator should now work 
through the IWRS web site portal for 
dose modifications.
6.8. Concomitant 
Therapy
Added language stating that 
drugs that may be affected 
by an increase in gastric pH 
should be separated from 
study drug administration 
by at least 2 to 4 hours.
Oversight in original protocol.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
4
Section # and Name
Description of Change
Brief Rationale
Added prohibition of taking 
CYP3A inducers.
To address regulatory agency 
request.
Added language stating that 
orally administered drugs 
with a narrow therapeutic 
index should not be taken 
simultaneously with 
LY3502970 due to delayed 
gastric emptying. Also 
provided examples of these 
drugs commonly taken by 
the participants with T2DM.
To address regulatory agency 
request.
7.1.3. Temporary 
Discontinuation
Removed the sentence 
regarding eCRF recording.
The eCRF was designed to capture 
any missed doses, including those 
associated with noncompliance. It 
also allows for the reason as “subject 
decision”.
7.1.4. Restarting Study 
Drug after Interruption
Replaced text referring to 
contacting the IWRS help 
desk for restarting study 
drug.
The investigator should now work 
through the IWRS web site portal for 
restarting study drug.
8.2.3.
Electrocardiograms
Deleted text referencing 
waiting 30 minutes between 
ECG and blood collection. 
Also, deleted text 
referencing ECG collection 
immediately prior to PK 
specific visit collection.
Typographical errors. There is no 
reason to wait 30 minutes between 
ECG and blood collection. Also, 
there are no ECG collections 
immediately prior to PK specific 
visit collection.
9.3.1. Statistical 
Analyses: General 
Considerations
Clarified HbA1c stratum.
Fixed the language to be less 
cumbersome.
HbA1c stratum will be 
included in the model for 
the analysis of HbA1c. 
Inclusion of discretized strata based 
on the continuous variable.
Removed language about 
SAS computation 
procedure.
The analysis software may not be 
limited to SAS.
Added that additional 
supplemental estimands 
may be explored for the 
primary and secondary 
efficacy endpoints. 
Oversight in original protocol.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
5
Section # and Name
Description of Change
Brief Rationale
Changed longitudinal 
logistic regression model to 
logistic regression model. 
A simulation has shown that logistic 
regression with missing values 
imputed with multiple imputations 
can lead to smaller variance 
estimates than longitudinal logistic 
regression and the analysis was 
updated accordingly.
9.3.2. Primary 
Endpoint(s)/Estimand(s) 
Analysis
Corrected visit number for 
Week 26.
Typographical error. Visit number 
for Week 26 is Visit 15.
9.3.3. Secondary 
Analyses
Changed longitudinal 
logistic regression to 
logistic regression with 
multiple imputation.
A simulation has shown that logistic 
regression with missing values 
imputed with multiple imputations 
can lead to smaller variance 
estimates than longitudinal logistic 
regression and the analysis was 
updated accordingly.
9.3.7. Subgroup 
Analyses
Corrected “efficacy stand” 
to “estimand” 
Typographical error.
HbA1c stratum will be 
included in the model for 
the subgroup analysis of 
HbA1c.
Inclusion of discretized strata based 
on the continuous variable.
10.10. Appendix 10: 
Provisions for Changes 
in Study Conduct 
During Exceptional 
Circumstances
Corrected visit numbers that 
need centralized laboratory 
collections rather than local 
laboratory collections.
Typographical error. Visits 3, 10, 
and 15 need to have blood collection 
through the central laboratory.
Corrected table with 
adjustments to visit 
windows.
Typographical error.
Throughout the protocol
Minor editorial changes 
made throughout the 
protocol.
Correction.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
6
Table of Contents
1.
Protocol Summary......................................................................................................9
1.1.
Synopsis.......................................................................................................................9
1.2.
Schema.......................................................................................................................11
1.3.
Schedule of Activities (SoA) ......................................................................................12
2.
Introduction..............................................................................................................21
2.1.
Study Rationale ..........................................................................................................21
2.2.
Background ................................................................................................................21
2.3.
Benefit/Risk Assessment ............................................................................................23
2.3.1.
Risk Assessment.........................................................................................................23
3.
Objectives, Endpoints, and Estimands ....................................................................25
4.
Study Design .............................................................................................................28
4.1.
Overall Design............................................................................................................28
4.1.1.
Overview of Study Periods .........................................................................................28
4.2.
Scientific Rationale for Study Design .........................................................................31
4.3.
Justification for Dose..................................................................................................32
4.4.
End of Study Definition..............................................................................................33
5.
Study Population ......................................................................................................34
5.1.
Inclusion Criteria........................................................................................................34
5.2.
Exclusion Criteria.......................................................................................................35
5.3.
Lifestyle Considerations .............................................................................................39
5.4.
Screen Failures...........................................................................................................40
5.5.
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant ...........................................................................................................41
6.
Study Intervention(s) and Concomitant Therapy ...................................................42
6.1.
Study Intervention(s) Administered ............................................................................43
6.1.1.
Medical Devices.........................................................................................................44
6.2.
Preparation, Handling, Storage, and Accountability....................................................44
6.3.
Measures to Minimize Bias: Randomization and Blinding..........................................44
6.4.
Study Intervention Compliance...................................................................................45
6.5.
Dose Modification......................................................................................................46
6.6.
Continued Access to Study Intervention after the End of the 
Study..........................................................................................................................46
6.7.
Treatment of Overdose ...............................................................................................46
6.8.
Concomitant Therapy .................................................................................................47
6.8.1.
Management of Participants with Gastrointestinal Symptoms.....................................49
6.8.2.
Hyperglycemia Rescue Medicine................................................................................50
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal....................................................................................51
7.1.
Discontinuation of Study Intervention ........................................................................51
7.1.1.
Liver Chemistry Stopping Criteria ..............................................................................52
7.1.2.
QTc Stopping Criteria.................................................................................................52

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
7
7.1.3.
Temporary Discontinuation ........................................................................................52
7.1.4.
Restarting Study Drug after Interruption.....................................................................53
7.2.
Participant Discontinuation/Withdrawal from the Study .............................................53
7.2.1.
Discontinuation of Inadvertently Enrolled Participants ...............................................54
7.3.
Lost to Follow-up .......................................................................................................54
8.
Study Assessments and Procedures .........................................................................55
8.1.
Efficacy Assessments .................................................................................................55
8.2.
Safety Assessments ....................................................................................................55
8.2.1.
Physical Examinations................................................................................................56
8.2.2.
Vital Signs..................................................................................................................56
8.2.3.
Electrocardiograms.....................................................................................................56
8.2.4.
Clinical Safety Laboratory Tests.................................................................................57
8.2.5.
Pregnancy Testing ......................................................................................................58
8.2.6.
Safety Monitoring.......................................................................................................58
8.3.
Adverse Events, Serious Adverse Events, and Product 
Complaints .................................................................................................................60
8.3.1.
Timing and Mechanism for Collecting Events ............................................................60
8.3.2.
Pregnancy...................................................................................................................62
8.3.3.
Adverse Events of Special Interest..............................................................................63
8.4.
Pharmacokinetics........................................................................................................68
8.5.
Pharmacodynamics.....................................................................................................69
8.6.
Genetics .....................................................................................................................69
8.7.
Biomarkers.................................................................................................................69
8.8.
Immunogenicity Assessments.....................................................................................69
8.9.
Health Economics.......................................................................................................69
9.
Statistical Considerations.........................................................................................70
9.1.
Statistical Hypotheses.................................................................................................70
9.1.1.
Multiplicity Adjustment..............................................................................................70
9.2.
Analyses Sets .............................................................................................................70
9.3.
Statistical Analyses.....................................................................................................71
9.3.1.
General Considerations...............................................................................................71
9.3.2.
Primary Endpoint(s)/Estimand(s) Analysis .................................................................72
9.3.3.
Secondary Analyses....................................................................................................72
9.3.4.
Tertiary/Exploratory Analysis.....................................................................................73
9.3.5.
Safety Analyses ..........................................................................................................73
9.3.6.
Pharmacokinetic/Pharmacodynamic Analyses ............................................................74
9.3.7.
Subgroup Analyses.....................................................................................................74
9.4.
Interim Analysis .........................................................................................................74
9.5.
Sample Size Determination.........................................................................................75
10.
Supporting Documentation and Operational Considerations ................................76
10.1.
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations............................................................................................................76
10.1.1.
Regulatory and Ethical Considerations........................................................................76
10.1.2.
Informed Consent Process ..........................................................................................76
10.1.3.
Data Protection...........................................................................................................77

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
8
10.1.4.
Dissemination of Clinical Study Data .........................................................................77
10.1.5.
Data Quality Assurance ..............................................................................................78
10.1.6.
Source Documents......................................................................................................79
10.1.7.
Study and Site Start and Closure.................................................................................79
10.1.8.
Publication Policy.......................................................................................................81
10.1.9.
Investigator Information .............................................................................................81
10.2.
Appendix 2: Clinical Laboratory Tests........................................................................82
10.3.
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting .......................................................................................................86
10.3.1.
Definition of AE.........................................................................................................86
10.3.2.
Definition of SAE.......................................................................................................87
10.3.3.
Definition of Product Complaints ...............................................................................88
10.3.4.
Recording and Follow-Up of AE and/or SAE and Product 
Complaints .................................................................................................................89
10.3.5.
Reporting of SAEs......................................................................................................91
10.3.6.
Regulatory Reporting Requirements ...........................................................................91
10.4.
Appendix 4: Contraceptive and Barrier Guidance .......................................................93
10.4.1.
Definitions..................................................................................................................93
10.4.2.
Contraception Guidance..............................................................................................93
10.5.
Appendix 5: Liver Safety: Suggested Actions and Follow-up 
Assessments ...............................................................................................................96
10.6.
Appendix 6: World Health Organization Classification of 
Diabetes and Diagnostic Criteria.................................................................................98
10.7.
Appendix 7: New York Heart Association Functional 
Classification of Heart Failure ....................................................................................99
10.8.
Appendix 8: Protocol GZGE Standardized Protocols for the 
Measurement of Height, Weight, Waist Circumference, Vital 
Signs and 7-Point Self-Monitoring Blood Glucose (SMBG) .....................................100
10.9.
Appendix 9: Patient-Reported Outcomes ..................................................................102
10.10.
Appendix 10: Provisions for Changes in Study Conduct During 
Exceptional Circumstances.......................................................................................104
10.11.
Appendix 11: Abbreviations and Definitions ............................................................108
10.12.
Appendix 12: Protocol Amendment History .............................................................113
11.
References...............................................................................................................114

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
9
1.
Protocol Summary
1.1.
Synopsis
Protocol Title: A Phase 2 Study of Once-Daily LY3502970 Compared with Placebo and Once-
Weekly Dulaglutide in Participants with Type 2 Diabetes Mellitus
Brief Title: Effect of LY3502970 Versus Placebo and Dulaglutide in Participants with Type 2 
Diabetes Mellitus
Rationale:
LY3502970 is a non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist that is being 
developed as a daily oral adjunct therapy to diet and exercise to improve glycemic control in 
adults with type 2 diabetes mellitus (T2DM). Unlike the peptide GLP-1 receptor agonists 
approved by regulators to-date, LY3502970 is a small molecule being developed for daily oral 
administration.  
Study J2A-MC-GZGE (GZGE) is a Phase 2, multicenter, randomized, double-blind, parallel, 
placebo- and active comparator (1.5 mg dulaglutide QW) -controlled 26-week study that will 
investigate glucose-lowering and body weight-lowering efficacy, as well as tolerability and 
safety of LY3502970 in participants with T2DM who failed to achieve adequate glycemic 
control on diet and exercise alone or when treated with a stable dose of metformin. This study is 
designed to inform dose selection and dose escalation scheme for Phase 3.
Objectives and Endpoints:
Objectives
Endpoints
Primary
To demonstrate that at least one dose level of QD oral 
doses of LY3502970 is superior in change from 
baseline for HbA1c relative to placebo at Week 26, in 
participants with T2DM inadequately controlled with 
diet and exercise alone or treated with a stable dose of 
metformin.
Difference between LY3502970 and placebo in change 
from baseline in HbA1c at Week 26
Secondary
To compare the effect of QD LY3502970 versus 
placebo and versus dulaglutide on glucose control at 
Week 26

Difference between LY3502970 and 
dulaglutide in change from baseline in HbA1c 
at Week 26 

Percentage of participants with HbA1c ≤6.5% 
and of <7.0% at Week 26

Change from baseline in fasting blood glucose 
at 26 weeks
To compare the effect of QD LY3502970 versus 
placebo and versus dulaglutide on body weight at 
Week 26

Change from baseline in body weight at Week 
26

Percent change in body weight from baseline 
at Week 26

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
10
Objectives
Endpoints

Percentage of participants with ≥5%, ≥10% 
body weight loss from baseline at Week 26
To assess safety and tolerability of LY3502970

Adverse events overall

Adverse events of special interest

Laboratory parameters

Electrocardiogram

Vital signs 
To assess the PK of LY3502970 and potential 
participant factors that may influence its PK

Population PK Parameters
Abbreviations: HbA1c = hemoglobin A1c; PK = pharmacokinetics; QD = once daily; T2DM = type 2 diabetes 
mellitus.
Overall Design
Brief Summary:
The purpose of this study is to measure the change in hemoglobin A1c (HbA1c) with oral daily 
LY3502970 compared with placebo and compared with once-weekly subcutaneously delivered 
dulaglutide 1.5 mg in participants with T2DM who failed to achieve adequate glycemic control 
on diet and exercise alone or when treated with a stable dose of metformin.
Study details include:
●
The study duration will be up to 30 weeks.
●
The treatment duration will be up to 26 weeks.
Number of Participants:
Approximately 530 participants will be screened to achieve 370 randomly assigned to study 
intervention.
Intervention Groups and Duration:
The duration of study participation for each participant will be approximately 30 weeks. The 
study will consist of an approximately 2-week screening/lead in period followed by a 26-week 
treatment period. There will also be a 2-week off-drug safety follow-up period.
During the treatment period, LY3502970 doses will be escalated for some treatment groups. The 
dose escalation period will range from 0 to 12 weeks depending on the dose group. LY3502970 
or matching placebo will be administered daily by oral capsule and dulaglutide 1.5 mg or 
matching placebo will be administered once weekly by subcutaneous injection.
Please see Section 6.5 regarding dose adjustments for participants who are having difficulty 
tolerating a specific dose.
Data Monitoring Committee: No

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
11
1.2.
Schema
Abbreviations: DPBO = dulaglutide placebo; LY = LY3502970; LY1 = LY 3 mg; LY2 = LY 12 mg; LY3 = LY 24 mg; LY4 = LY 36 mg; LY5 = LY 45 mg.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
12
1.3.
Schedule of Activities (SoA)
The Schedule of Activities (SoA) described below should be followed for all participants enrolled in Study GZGE. However, for those 
participants whose participation in this study is affected by exceptional circumstances (such as pandemics or natural disasters), please 
refer to Section 10.10 (Appendix 10) for additional guidance.
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Administrative
Informed 
consent
X
Inclusion and 
exclusion 
criteria review 
X
X
Demographics
X
Preexisting 
conditions and 
medical history, 
including 
surgical history
X
X
Concomitant 
medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Anti-diabetic 
medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
13
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Substance use 
(alcohol, 
caffeine, 
tobacco use)
X
X
Adverse events 
(AEs) and 
Product 
Complaints
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical Evaluation
Height
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Waist 
circumference
X
X
X
X
X
X
X
X
X
Vital signs (2
sitting BP and PR 
measurements)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vital signs include pulse rate, blood pressure, and temperature.  Vital sign measurements should be measured after participant has been sitting for 
at least 5 minutes and before obtaining ECG tracings and before collection of blood samples for laboratory testing (See Section 8.2.2).
Physical 
examination
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
14
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Symptom-
directed 
physical 
examination
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
As indicated based on participant status and standard of care. May be performed by qualified personnel per local regulations.
12-Lead ECGs 
X
X
X
X
X
X
X
X
X
Central ECGs should be collected prior to collection of blood samples, including PK samples. ECG measurements should be obtained per the 
instructions in Section 8.2.3.
Participant Education and Supplies
Blood glucose 
(BG) meter, 
instructions
X
Dispense BG 
meter/supplies 
(if needed)
X
X
X
X
X
X
X
X
X
X
X
X
X
Diabetes 
education
X
X
Diabetes education to be performed by site personnel to educate participants on symptoms and management of hyperglycemia and hypoglycemia, 
SMBG, self-injection, and diabetes management. All trainings should be repeated as needed to ensure participant compliance.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
15
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood Glucose Monitoring
Remind 
participants 
about 7-point 
SMBG
X
X
X
X
X
The 7-point SMBG will be required prior to randomization and randomization can occur any time after the 7-point SMBG is completed. At all other 
times, the participant should be instructed to collect the 7-point SMBG during the week prior to the visit in which the 7-point SMBG is required. All 
7-points of the SMBG should be completed in a single day.
7-point SMBG
X
X
X
X
X
Baseline 7-point SMBG to be explained to the participant at Visit 2 with participant completing the 7-point SMBG during the week prior to Visit 3.  
All other 7-point SMBGs should be completed during the week prior to the visit in which the 7-point SMBG is required.
Review SMBG 
values and 
hypoglycemic 
events collected 
in the diary
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Participant diary 
dispensed
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Diary 
compliance 
check
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Diary return
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
16
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient-Reported Outcomes (paper)
SF-36 v2 acute 
form
X
X
X
X
DTSQs
X
X
X
X
DTSQc
X
X
X
Participant 
Survey
X
X
Laboratory Tests and Sample Collections
Hematology
X
X
X
X
X
X
Hemoglobin A1c 
(HbA1c)
X
X
X
X
X
X
X
X
X
X
Clinical 
chemistry
X
X
X
X
X
X
X
Glucose
X
X
X
X
X
X
X
X
X
X
Glucagon
X
X
Lipid panel
X
X
X
X
X
Calcitonin
X
X
X
X
Pancreatic 
Amylase
X
X
X
X
X
X
X
Lipase
X
X
X
X
X
X
X
Urinalysis
X
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
17
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
pregnancy
X
Follicle 
stimulating 
hormone (FSH)
X
Collect serum estradiol, FSH, and LH in women whose menopausal status needs to be determined. For participants known to be either 
premenopausal or postmenopausal, these tests do not need to be collected.
Luteinizing 
Hormone (LH)
X
Estradiol
X
Insulin
X
X
X
X
C-peptide
X
X
X
X
HIV screening 
tests
X
Hepatitis C Virus 
(HCV) screening 
tests
X
Hepatitis B Virus 
(HBV) screening 
tests
X
Cytokeratin 18
X
X
X
Pro-C3
X
X
X
eGFR (CKD-EPI)
X
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
18
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urinary 
albumin/creatini
ne ratio (UACR)
X
X
X
X
Pharmacokinetic 
(PK) sample
Predose
X
X
X
X
Postdose
X
X
X
X
X
PK Predose sample should be collected predose (~up to 1 hour predose).
PK Postdose sample time windows: 3-6 hours postdose (Week 4), 6-12 hours postdose (week 8), 1-3 hours postdose (Week 16), 3-6 hours postdose 
(Week 20). Participants may need to return to clinical site for additional PK-specific visits to provide Postdose PK samples.
Stored Samples
Exploratory 
biomarker 
samples 
X
X
X
X
X
Randomization and Dosing
IWRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization
X
Injection 
training
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
19
Study Period I
Screening/Lead-in
Study Period II
Treatment period
For early terminations that occur before the last visit in treatment period, see the activities 
listed for ET in this table. Shaded columns represent the dose escalation period Weeks 0-12.
Study 
Period 
III 
Safety 
Follow
-Up
Screening
Lead-
In
Visit number
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
ET
801
Week Relative 
to 
Randomization
-2
-1
0
1
2
4
6
8
10
12
13
16
20
24
26
-
2 Wks 
post 
end of 
TXP
Allowable 
interval 
tolerance (days)
-
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
±3
-
±3
Fasting Visit
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study 
intervention 
capsules
X
X
X
X
X
X
X
X
X
X
X
One bottle of capsules is to be dispensed at Visits 3 and 4. Two bottles of capsules 
are to be dispensed at Visits 5-9 (during the dose escalation period). The site 
pharmacy should clearly label which bottle to take first. At Visits 10-13, 4 bottles of 
capsules should be dispensed. At Visit 14, 2 bottles should be dispensed.
Dispense study 
intervention 
injection and 
supplies
X
X
X
X
X
X
X
One package of 4 single dose pens should be dispensed at Visits 3-14.
Participant 
returns unused 
study 
intervention and 
injection 
supplies
X
X
X
X
X
X
X
X
X
X
X
X
Assess drug 
compliance
X
X
X
X
X
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
20
Abbreviations: AEs = adverse events; BG = blood glucose; BP = blood pressure; CKD-EP I =chronic kidney disease epidemiology; DTSQc = Diabetes 
Treatment Satisfaction Questionnaire-Change Version; DTSQs = Diabetes Treatment Satisfaction Questionnaire-Status Version; ECG = electrocardiogram; 
eGFR = estimated glomerular filtration rate; ET = early termination; FSH = follicle stimulating hormone; GLP-1 = glucagon-like peptide-1; HbA1c = 
hemoglobin A1c; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IWRS = interactive web response systems; PK = 
pharmacokinetic; LH = luteinizing hormone; PR = pulse rate; Pro-C3 = biomarker for liver fibrosis; SF-36 v2 acute form = Short Form 36 version 2 health 
survey acute form; SMBG = self-monitoring of blood glucose; TXP = treatment; UACR = urinary albumin creatinine ratio; Wks = weeks.
Note: If the time between Visit 1 (Screening), Visit 2 (Lead In) and Visit 3 (Randomization) takes longer or less time than 2 weeks, it is not considered a 
protocol deviation.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
21
2.
Introduction
2.1.
Study Rationale
LY3502970 is an oral non-peptide GLP-1 receptor agonist that is being developed as a daily oral 
adjunct therapy to diet and exercise to improve glycemic control in adults with T2DM. Unlike 
the peptide GLP-1 receptor agonists approved by regulators to-date, LY3502970 is a small 
molecule being developed for daily oral administration.  
Study J2A-MC-GZGE (GZGE) is a Phase 2, multicenter, randomized, double-blind, parallel, 
placebo- and active comparator (1.5 mg dulaglutide QW) -controlled 26-week study that will 
investigate glucose-lowering and body weight-lowering efficacy, as well as tolerability and 
safety of LY3502970 in participants with T2DM who failed to achieve adequate glycemic 
control on diet and exercise alone or when treated with a stable dose of metformin. This study is 
designed to inform dose selection and dose escalation scheme for Phase 3.
2.2.
Background
LY3502970 is being investigated for its potential use in the treatment of T2DM. LY3502970 is a 
chemically synthesized molecule that shows agonist activity for GLP-1 receptor. To date no off-
target toxicity has been identified in clinical trials.
The GLP-1 receptor agonists (GLP-1 RA) are highly effective peptide drugs that mimic the 
incretin hormone GLP-1 (Werner et al. 2010; Lau et al. 2015; Scheen 2017). The hormone is 
secreted from the intestine upon food consumption, and its effects include augmented glucose-
dependent insulin secretion, prolonged satiety, reduced glucagon release, and delayed gastric 
emptying (Bayless et al. 1902; Baggio et al. 2007; Nauck et al. 1997). The GLP-1RAs have good 
glucose-lowering effects with the additional benefits of low risk of hypoglycemia and weight 
loss (Pratley et al. 2018).
Dulaglutide was chosen as the active comparator in this study. It is a subcutaneously delivered 
QW GLP-1 RA, which is indicated as an adjunct to diet and exercise to improve glycemic 
control in adults with T2DM. Dulaglutide 1.5 mg treatment alone is also associated with modest 
weight loss (approximately 2.3 kg mean weight loss at 26 weeks) in T2DM patients (Trulicity
United States Package Insert [USPI], 2020; TrulicitySummary of Product Characteristics 
[SmPC], 2021).
The safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of LY3502970 have
been evaluated in 2 Phase 1 clinical pharmacology studies, J2A-MC-GZGA and J2A-MC-
GZGC. Study GZGA was a single ascending dose (SAD) and a 4-week multiple ascending dose 
(MAD) study in healthy volunteers that evaluated the safety, tolerability, PK, and PD of 
LY3502970. Study GZGC was a multiple dose study in participants with T2DM designed to 
evaluate the safety, tolerability, PK, and PD of LY3502970 following 12 weeks of treatment.
In Study GZGA the SAD part of the study evaluated single oral doses 0.3-, 1-, 3-, and 6 mg. 
The MAD part of the study evaluated 28 daily LY3502970 doses of 2 mg and weekly dose 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
22
escalation evaluating different dose escalation schemes that ranged from 2 mg through 24 mg 
with terminal doses of 6-, 16-, or 24-mg. In both the SAD and MAD, gastrointestinal 
(GI)-related adverse events (AEs) were the most commonly reported AEs, consistent with GLP-1 
receptor agonist pharmacology (Nauck et al. 2009; Dungan et al. 2014; Giorgino et al. 2015; 
Jendle et al. 2016; Nauck et al. 2016). All AEs were mild to moderate in severity. The incidence 
of GI AEs decreased with continued dosing in the MAD, thus demonstrating tachyphylaxis to the 
GI AEs. The MAD showed that LY3502970 initially delayed gastric emptying, an effect that was 
greatly diminished with continued LY3502970 exposure. Furthermore, LY3502970 showed a 
decrease in glucose and body weight. All the findings were similar to those observed with 
marketed GLP-1 receptor agonist peptide drugs.
This study also assessed the effect of food on the PK of LY3502970. The effect of food on the 
PK of LY3502970 was a slight decrease in the area under the curve (AUC) and the maximum 
plasma concentration Cmax.
There has been no apparent concentration-dependent increase in systolic or diastolic blood 
pressure (BP) after single or multiple doses or pulse rate (PR) after single doses. There has been 
a trend in concentration-dependent increase in PR after multiple doses of LY3502970, similar to 
that observed with other GLP-1 receptor agonists.
LY3502970 PK was studied across a range of doses administered as single doses or multiple 
doses (28 doses) via a once daily (QD) dosing regimen. LY3502970 PK appeared approximately 
dose proportional over the dose range studied after a single and multiple doses from 0.3 to 24
mg. Peak concentrations were observed at approximately 4-12 hours postdose, and the half-life 
was approximately 24.6-67.5 hours.
Study GZGC evaluates LY3502970 treatment for 12 weeks in participants with T2DM 
controlled with diet and exercise with or without a stable dose of metformin. Study GZGC 
included 5 dosing cohorts evaluating different target doses and dose escalations. Dose 
escalations occurred weekly until the target dose was reached and then maintained at the target 
dose for the duration of the study. The following were the dosing cohorts :

Cohort A:  3, 6, 12, and 21 mg

Cohort B:  3, 6, and 9 mg

Cohort C:  3, 6, 12, and 15 mg

Cohort D:  3, 6, 12, 21, and 27 mg

Cohort E:  3, 6, 9, 21, 36, and 45 mg
Preliminary data indicate that the most frequently reported AEs in Study GZGC are nausea, 
decreased appetite, and vomiting. Consistent with other GLP-1 receptor agonists, the AEs are 
more frequent early in the study and at the initiation of each dose escalation but diminished with 
continued dosing. No off-target AEs have been observed to date. LY3502970 treatment has also
demonstrated a decrease in fasting plasma glucose and a decreased in 7-point self-monitoring 
blood glucose levels. There has been a decrease in HbA1c and body weight. An increase in PR
has been observed, which is of a similar magnitude as seen in other early phase studies of GLP-1 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
23
RAs. There have been no clinically significant effects on electrocardiogram (ECG) parameters or 
other laboratory parameters.
2.3.
Benefit/Risk Assessment
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of LY3502970 may be found in the Investigator’s Brochure (IB) and Development 
Safety Update Reports.
2.3.1.
Risk Assessment
Study Intervention
The Sponsor has evaluated the preclinical and clinical risks associated with LY3502970.
Nonclinical safety of LY3502970 was evaluated in 6-month and 9-month repeat-dose toxicology 
studies in rats and monkeys, respectively. Monkey doses were 0, 1.35, and 3 mg/kg/day and were 
administered via oral gavage QD at a volume of 1 mL/kg. Rat doses were 0, 5, 30, and 200
mg/kg/day given by oral gavage QD at a volume of 10 mL/kg. Important LY3502970-related
findings in the monkey included vomiting, decreased body weight, and decreased food 
consumption. Additional findings from the monkey studies include changes in CV parameters 
(such as increases in HR and decreased blood pressure), and ECG changes (PR interval 
prolongation). The No-observed-adverse-effect level (NOAEL for target organ toxicity in the 
monkey 9-month toxicology study was 3.0 mg/kg. The monkey exposure multiples for the 
LY3502970 45-mg dose:  males = 0.773-fold; females = 0.875-fold.
The only clinically relevant observation in the rat 6-month repeat toxicology study was 
LY3502970 dose-related minimally higher total bilirubin in both sexes at ≥30 mg/kg, and 
minimally higher bile acid in both sexes at 200 mg/kg/day. These differences likely indicated a 
hepatobiliary effect but lacked any correlative microscopic findings in the liver. The NOAEL for 
target organ toxicity in the 6-month rat toxicology study was 200 mg/kg. The rat exposure 
multiples for the LY3502970 45-mg dose:  males = 16.5-fold; females = 31.1-fold.
In the Phase 1 Study GZGA, most findings were associated with the pharmacology of 
LY3502970 and include:

nausea

vomiting

loss of appetite, and

increased HR.
Of note, there have not been any liver transaminase or bilirubin changes observed in any of the 
Phase 1 clinical trials.
All identified risks from preclinical and clinical studies to date are associated with LY3502970 
pharmacology and are considered monitorable and manageable at the planned dose range of 2 to 
45 mg of LY3502970. These risks are similar to those noted during development of marketed
GLP-1 receptor agonists. Participants will be closely monitored with scheduled medical 
assessments, vital signs, laboratory evaluations, and triplicate ECG measurements.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
24
For the dulaglutide comparator, refer to the Prescribing Information for Trulicity (Trulicity 
United States Prescribing Information, 2021, TrulicitySummary of Product Characteristics 
[SmPC], 2021) for more information about the known and expected benefits and risks of 
dulaglutide.
Benefit Assessment
Data from the Phase 1 studies indicate that LY3502970 may lower glucose, which should result 
in lowered HbA1c in participants with T2DM. The data also showed that LY3502970 treatment 
resulted in a decrease in body weight. Taken together these data support improved glycemic 
control in participants with T2DM.
Overall Benefit Risk Conclusion
LY3502970 is being investigated as a daily oral therapy as an adjunct to diet and exercise to 
improve glycemic control in adults with T2DM who may or may not be taking metformin. At 
this time, no safety or efficacy issues that would reflect a significant risk to clinical trial subjects 
have been identified which would constitute undue risk to study participants. The safety profile 
continues to be refined as more clinical safety data become available. The benefit-risk profile 
continues to support further development of LY3502970.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
25
3.
Objectives, Endpoints, and Estimands
Objectives
Endpoints
Primary
To demonstrate that at least one dose level of QD oral 
doses of LY3502970 is superior in change from 
baseline for HbA1c relative to placebo at Week 26, in 
participants with T2DM inadequately controlled with 
diet and exercise alone or treated with a stable dose of 
metformin.
Difference between LY3502970 and placebo in change 
from baseline in HbA1c at Week 26 
Secondary
To compare the effect of QD LY3502970 versus 
placebo and versus dulaglutide on glucose control at 
Week 26

Difference between LY3502970 and 
dulaglutide in change from baseline in HbA1c 
at Week 26 

Percentage of participants with HbA1c ≤6.5% 
and of <7.0% at Week 26

Change from baseline in fasting blood glucose 
at 26 weeks
To compare the effect of QD LY3502970 versus 
placebo and versus dulaglutide on body weight at 
Week 26

Change from baseline in body weight at Week 
26

Percent change in body weight from baseline 
at Week 26

Percentage of participants with ≥5%, ≥10% 
body weight loss from baseline at Week 26
To assess safety and tolerability of LY3502970

Adverse events overall

Adverse events of special interest

Laboratory parameters

Electrocardiogram

Vital signs 
To assess the PK of LY3502970 and potential 
participant factors that may influence its PK

Population PK Parameters
Exploratory
To assess the relationship between QD LY3502970
dose and/or exposure and key efficacy and safety 
measures and potential participant factors that may 
influence these relationships 

Dose-response and concentration-response 
analyses for key efficacy and safety 
parameters
To evaluate the effect of QD LY3502970 versus 
placebo and versus dulaglutide on body weight as 
measured by BMI and waist circumference at Week 26

Change from baseline in BMI at 26 weeks

Change from baseline in waist circumference 
at 26 weeks
To evaluate the effects of QD LY3502970 versus 
placebo and versus dulaglutide on 7-point SMBG 
profile

Change from baseline in 7-point SMBG 
values at Week 26

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
26
Objectives
Endpoints
To evaluate the effects of QD LY3502970 versus 
placebo and versus dulaglutide on biomarkers

Change from baseline in mechanistic 
biomarkers (Section 1.3) at Week 26
To evaluate the effects of QD LY3502970 versus 
placebo and versus dulaglutide on patient-reported 
outcomes

Health-related quality of life

Change from baseline in SF-36v2 acute form 
domains and summary scores at Week 24

Diabetes treatment satisfaction

Change from baseline in DTSQs at Week 24 

Actual responses to DTSQc at Week 24

Participant experience

Summary statistics of actual responses to 
Participant survey at Week 24
Abbreviations: BMI = body mass index; DTSQc = Diabetes Treatment Satisfaction Questionnaire-Change Version; 
DTSQs = Diabetes Treatment Satisfaction Questionnaire-Status Version; HbA1c = hemoglobin A1c; PK = 
pharmacokinetics; QD = once daily; SF-36v2 = Short Form 36 version 2 health survey acute form; SMBG = self-
monitoring of blood glucose; T2DM = type 2 diabetes mellitus.
Primary Estimand
The primary clinical question of interest is: What is the treatment difference in HbA1c change 
from baseline after 26 weeks of treatment in participants who meet the inclusion criteria and 
would have completed the treatment period without additional anti-hyperglycemic rescue 
medication?
The “efficacy estimand” is described by the following attributes:

Population: participants who meet the inclusion criteria. Further details can be found in 
Section 5 and Section 9.

Endpoint: change from baseline in HbA1c at Week 26.

Treatment condition: the randomized treatment with allowance for down-titration based 
on GI tolerability. 
The two intercurrent events “permanent discontinuation of study drug” and “initiation of rescue 
medication” are handled by the hypothetical strategy and the potential outcome of interest is the 
response in the efficacy measurement if participants had adhered to the randomized treatment 
without using additional anti-hyperglycemic rescue medication. There are no other defined
intercurrent events. Down-titration will not be considered as intercurrent events for the definition 
of estimand in this study. Further details on study interventions and concomitant, including 
rescue, interventions may be found in Section 6.
Population-level summary: difference in mean changes in HbA1c at Week 26 between QD 
LY3502970 and placebo.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
27
Rationale for “efficacy estimand”: This phase 2 study aims to study the efficacy of LY3502970
under the ideal condition that all participants adhere to the randomized treatment without using 
additional anti-hyperglycemic rescue medication.
Estimand(s) for Secondary Objectives
The same estimand for the primary objective will be used for the following efficacy endpoints 
for the secondary objectives: 

Difference between LY3502970 and dulaglutide in change from baseline in HbA1c at 
Week 26 

percentage of participants with HbA1c ≤6.5% and of <7.0% at Week 26

change from baseline in fasting blood glucose at 26 weeks

Change from baseline in body weight at Week 26

Percent change in body weight from baseline at Week 26

Percentage of participants with ≥5%, ≥10% body weight loss from baseline at Week 26
Unless specified otherwise, safety and tolerability assessments will be guided by an estimand 
comparing safety of LY3502970 doses with placebo and dulaglutide for the entire study period 
(the treatment period plus safety follow-up period) irrespective of adherence to study 
intervention for all study population (including advertently enrolled participants).

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
28
4.
Study Design
4.1.
Overall Design
Study GZGE is a Phase 2, multicenter, randomized, double-blinded, parallel, placebo- and active 
comparator (1.5 mg dulaglutide QW)-controlled 26-week study, to investigate the safety and 
efficacy of LY3502970 in participants with T2DM who failed to achieve adequate glycemic 
control on diet and exercise alone or on a stable dose of metformin for at least 3 months prior to 
Visit 1) (see Section 1.2).
4.1.1.
Overview of Study Periods
Screening Period
Visit 1 
The purpose of screening procedures at Visit 1 is to establish initial eligibility and to obtain 
blood samples for laboratory assessments needed to confirm eligibility. The participant must sign 
the informed consent form (ICF) before the study procedures are performed, as outlined in the 
SoA, Section 1.3. Screening procedures will be performed according to the SoA (Section 1.3). 
Visit 2 
At Visit 2, the screening laboratory results will be reviewed to confirm eligibility. 
Participants will be provided with paper diaries and will be trained on how to record key study 
information, as appropriate. Participants will start recording their self-monitoring of blood 
glucose (SMBG) values and hypoglycemic events immediately after Visit 2 and will perform 
these procedures until the last study visit. 
Participants will receive training on the routine BG monitoring and paper diary completion 
required during the study. Participants should follow the investigator’s instructions related to 
frequency of SMBG but should test their glucose a minimum of 3 times per week and as 
specified for determination of 7-point glucose profiles (see Section 10.8). Eligible participants
will return to the site for some baseline procedures during the lead-in phase (Visit 2) and again 
for randomization to treatment and to receive their first dose of study drug at Visit 3.
Diabetes education will be performed by site personnel to educate participants on symptoms and 
management of hyperglycemia and hypoglycemia, SMBG, self-injection, and diabetes 
management according to American Diabetes Association Standards of Medical Care in Diabetes 
(ADA 2020) or local standards. Participants will be trained on how to utilize BG meters and how 
to collect SMBG, including 7-point measurements as appropriate. Blood glucose meters or 
supplies will be provided to measure SMBG values (see Section 10.8).
Of note, if the screening period between Visit 1 and Visit 3 (randomization) takes less or more 
time than 2 weeks, it is not a protocol deviation.
Randomization 
Visit 3 
At Visit 3, eligible participants, those who meet all applicable inclusion criteria and none of the 
applicable exclusion criteria, will perform all required study procedures prior to randomization.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
29
Patient-reported outcomes questionnaires should be administered according to the SoA (Section 
1.3), as early as possible during the visit. Preferred administration order of these questionnaires 
throughout the trial is
1. SF-36 v2 acute form
2. DTSQs
Following randomization, study site personnel will train participants on how to use the single-
dose pen and observe the study participant inject the first dose of study comparator/placebo 
according to the randomized treatment group. Site personnel will also observe the study 
participant take the first oral dose of study drug capsule. The date and time of the first dose of 
study drugs will be recorded on the electronic case report form (eCRF). Beginning at 
randomization, all participants will receive study drugs according to the randomized treatment 
arm for the duration of the 26-week treatment period as per the SoA (Section 1.3). 
Treatment Period 
During the Treatment Period, study drugs and injection supplies will be returned per the SoA 
(Section 1.3) and according to local requirements. New supplies will be dispensed as needed. 
Participants should be instructed to contact the investigative site for assistance as soon as 
possible if they experience any difficulties taking or administering their study drugs. Whenever 
possible, participants should take their study medication (both capsule and injection) at the study 
site during a visit.
Participants should also be advised about the appropriate course of action if study drugs are not 
taken at the required time (late/missing doses) (see Section 6.5). Study participants will be 
permitted to use concomitant medications that they require during the study, except certain 
excluded medications (see Section 6.8) that may interfere with the assessment of efficacy and 
safety characteristics of the study treatments. 
Dose-Escalation Period (Visits 4-10)
For maintenance doses of LY3502970 starting at 3 mg, the initial dose will be 2 or 3 mg 
followed by additional escalation steps as appropriate. The dose will be increased until the 
maintenance dose is achieved (see Section 1.2 for dosing details and the LY3502970 Treatment 
Group Dose Escalation Regimen table below).
The maintenance doses of LY3502970 or dulaglutide 1.5 mg will be continued for the remainder 
of the study. For participants who experience intolerable GI symptoms or may need dose 
adjustment for other reasons, the dose modification procedures are described in Section 6.5.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
30
LY3502970 Treatment Group Dose Escalation Regimen
W
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
V
3
4
5
6
7
8
9
10
11
12
13
14
15
LY1
2
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
LY2
2
2
6
6
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
LY3
3
3
6
8
12
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
LY4-1
2
3
6
8
12
24
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
36
LY4-2
3
3
3
6
6
6
12
12
12
24
24
24
36
36
36
36
36
36
36
36
36
36
36
36
36
36
LY5-1
3
3
6
6
8
8
12
12
24
24
36
36
45
45
45
45
45
45
45
45
45
45
45
45
45
45
LY5-2
2
2
3
3
6
6
12
12
24
24
36
36
45
45
45
45
45
45
45
45
45
45
45
45
45
45
Abbreviations: LY = LY3502970; V = Visit; W = week.
Note: Gray area represents the dose escalation period.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
31
Maintenance Period (Visits 11-15)
During the maintenance period, visits will occur approximately every 3-4 weeks until 24 weeks 
and then 2 weeks from Weeks 24 to 26. Visit procedures should be conducted according to the 
SoA (Section 1.3).
Patient-reported outcomes questionnaires should be administered at Week 16 (Visit 12) and 
Week 24 (Visit 14), as early as possible during the visit. Preferred administration order of these 
questionnaires is
1. SF-36v2 acute form
2. DTSQs
3. DTSQc
4. Participant survey (Week 24)
Early Termination Visit
Participants unable or unwilling to continue the study for any reason will perform an early 
termination (ET) of treatment visit (Section 7.1). If the participant is discontinuing during an 
unscheduled visit or a scheduled visit, that visit should be performed as an ET visit. Procedures 
should be completed according to the SoA (Section 1.3). Participants who withdrawal from the 
study after signing the informed consent but who have not taken a dose of study drug prior to 
randomization do not need to complete ET procedures.
Patient-reported outcomes questionnaires should be administered at ET visit. Preferred 
administration order of these questionnaires is
1. SF-36v2 acute form
2. DTSQs
3. DTSQc
4. Participant survey 
Safety Follow-up Period
Visit 801
A safety follow-up visit will occur approximately 2 weeks following the last treatment period 
visit. All participants who have taken at least one dose of study drug should complete a safety 
follow-up visit (Visit 801), according to the SoA (Section 1.3).
For participants who discontinue from investigational product (IP) early but remain in the study, 
all remaining visits should be completed per SoA (Section 1.3).
For participants who discontinue from the study early (regardless of whether they discontinue IP 
at the same time or have discontinued IP at an earlier visit), an ET visit followed by the safety 
follow-up visit (Visit 801) should be completed as per the SoA (Section 1.3).
Participants are also required to return any remaining study diaries to the study site at the end of 
this period.
4.2.
Scientific Rationale for Study Design
Study GZGE is a Phase 2 study designed to examine the efficacy on glycemic control, 
decreasing body weight, and safety of QD LY3502970 compared with placebo and QW 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
32
dulaglutide 1.5 mg in participants with T2DM who have inadequate glycemic control with diet 
and exercise alone or in combination with a stable dose of metformin.
Inclusion of an active comparator (dulaglutide 1.5 mg) in Study GZGE will allow for a direct 
comparison of the safety and efficacy of QD LY3502970 to an injectable GLP-1 RA (as well as 
to placebo) over a 6-month time period. In addition, effects of the medication on other 
parameters such as other measures of glycemic control and various other safety-related 
assessments will also be determined. The planned duration of 6 months will allow for a more 
robust evaluation of the body weight effects of the 2 drugs, as the putative mechanism of action 
of LY3502970 suggests that treatment with LY3502970 will result in continued weight loss over 
a 6-month period. The data from this trial will form the primary basis to assess dose/exposure–
response of LY3502970 efficacy for selection of doses to be included in Phase 3 testing. The 
data will also provide information to select the dose escalation scheme to reach the target doses 
in Phase 3. In addition, safety and tolerability over a wide dose range of LY3502970 versus 
placebo and dulaglutide 1.5 mg will be assessed to enable robust benefit–risk characterization in 
T2DM.
The placebo arm is included to determine whether any efficacy or safety effects of LY3502970 
are different in magnitude from those of dulaglutide 1.5 mg, equivalent to or are also different 
from no treatment (i.e., placebo).
Dulaglutide 1.5 mg was chosen to be the active comparator because it is a marketed GLP-1RA 
and has a great deal of data on its effects on HbA1c, glucose, body weight, and AEs in the 
population chosen for this study.
The current study will enroll participants with inadequate glycemic control based on HbA1c
values ranging from 7.0% to 10.5%, inclusive. The study population, as defined by inclusion and 
exclusion criteria, is expected to include participants with modestly advanced T2DM and 
partially preserved pancreatic cell function, the key prerequisite for glucose-lowering efficacy 
of incretins.
To minimize the potential confounding effect of changes in concomitant medications, 
participants will be permitted to use concomitant medications that do not interfere with the 
assessment of efficacy or safety characteristics of the study treatments.
4.3.
Justification for Dose
LY3502970 maintenance doses of 3, 12, 24, 36, and 45 mg administered orally QD, were 
selected based on the points below.  

In the single and a 4-week multiple dose study in healthy volunteers, GZGA, LY3502970 
doses through 24 mg were safe and well tolerated following dose escalation.

Although data are limited, in the 12-week study, GZGC, in participants with T2DM, 
LY3502970 doses through 45 mg appear to be safe and tolerated following dose 
escalation. Furthermore, LY3502970 treatment through 45 mg appears to reduce glucose, 
HbA1c, and body weight in the 12-week study.

The selected dose levels and dose range will evaluate various dose escalation schemes 
and support dose exposure-response analysis of multiple safety and efficacy measures to 
support selection of dose(s) of LY3502970 with optimal benefit-risk ratio for further 
clinical development.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
33
High acute doses of GLP-1 RAs, including LY3502970 are often poorly tolerated due to GI 
symptoms, whereas a more gradual dose escalation scheme to reach a high dose has been shown 
to improve GLP-1RA tolerability. Therefore, different dose escalation schemes are also being 
evaluated within dose groups to provide information on starting doses, dose increments and 
duration of increments, on tolerability to support a dose escalation scheme in further clinical 
development.
4.4.
End of Study Definition
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the SoA (Section 1.3) for the last participant in the trial 
globally.
A participant is considered to have completed the study if the participant has completed all 
periods of the study including the last visit or the last scheduled procedure shown in the SoA
(Section 1.3).

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
34
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:
Age
1. Participant must be 18 or the legal age of consent in the jurisdiction in which the study is 
taking place to 75 years of age inclusive, at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Have been diagnosed with T2D based on the World Health Organization (WHO) 
classification (see Section 10.6) or other locally applicable diagnostic standards for at 
least 6 months prior to screening 
3. Have an HbA1c value at screening of 7.0% and 10.5% and treated with diet and 
exercise alone or with a stable dose of metformin (and not more than the locally approved 
dose) for at least 3 months prior to screening/Visit 1. Note: Participants from some 
countries may be required to be on metformin in order to enroll in this study.
Weight
4. Have a body mass index (BMI) of ≥ 23 kg/m2 at Visit 1
5. Have had a stable body weight for the 3 months prior to randomization (≤5 % body 
weight gain and/or loss)
Sex and Contraceptive/Barrier Requirements
6.
Male and/or female
Contraceptive use by participants should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.
Women not of childbearing potential (for definitions, see Section 10.4) and men can participate 
in this study considering the following:

Male participants:
o
Males who agree to use highly effective/effective methods of contraception may 
participate in this trial.  
o
Please refer Section 10.4 to for definitions and additional guidance related to 
contraception. 

Female participants:
o
Women not of childbearing potential (WNOCBP) may participate in this trial.  
o
Please refer to Section 10.4 for definitions and additional guidance related to 
contraception.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
35
Note: Hormone replacement therapy in post-menopausal women is allowed but women must be 
on stable therapy for 3 months prior to screening/Visit 1.
Informed Consent
7. Capable of giving signed informed consent as described in Section 10.1 (Appendix 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
Diabetes Related
8. Have type 1 diabetes mellitus (T1DM) or history of ketoacidosis or hyperosmolar coma 
9. Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-
proliferative diabetic retinopathy that requires immediate treatment intervention
10. Have had more than 1 episode of severe hypoglycemia, as defined by the 
occurrence of neuroglycopenic symptoms requiring the assistance of another 
person for recovery, within 6 months prior to Visit 1, or has a history of 
hypoglycemia unawareness or poor recognition of hypoglycemic symptoms. Any 
participant that the investigator feels will not be able to communicate an 
understanding of hypoglycemic symptoms and the appropriate treatment of 
hypoglycemia should also be excluded.
11. Have a history of acute or chronic pancreatitis or elevation in serum 
lipase/amylase (greater than 3 times the upper limit of normal [ULN]) or fasting 
serum triglyceride level of >500 mg/dL at screening
Obesity Related
12. Have obesity induced by other endocrine disorders (such as Cushing’s syndrome or 
Prader-Willi syndrome)
Other Medical
13. Have a known clinically significant gastric emptying abnormality (for example, severe 
diabetic gastroparesis or gastric outlet obstruction), have undergone gastric bypass 
(bariatric) surgery or restrictive bariatric surgery (for example, Lap-Band®), or 
chronically take medications that directly affect GI motility
14. Have poorly controlled hypertension (in other words, mean seated systolic BP
160 mm Hg or mean seated diastolic BP 100 mm Hg) at screening, renal artery 
stenosis, or symptomatic postural hypotension. For participants with uncontrolled 
hypertension at the screening visit, antihypertensive medication may be started,
and BP must meet the protocol criterion for hypertension control by the 
randomization visit.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
36
15. Have a known self or family history (first-degree relative) of multiple endocrine 
neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid 
carcinoma
16. Evidence of hypothyroidism or hyperthyroidism based on clinical evaluation 
and/or an abnormal thyroid-stimulating hormone that, in the opinion of the 
investigator, would pose a risk to participant safety. Participants on a stable dose 
of thyroid replacement therapy for at least the prior 3 months who are clinically 
euthyroid and who are anticipated to remain on this dose throughout the trial 
period may be eligible if they meet the other criteria.
17. Have had any of the following within the last 6 months prior to screening:

myocardial infarction (MI), 

unstable angina, 

coronary artery bypass graft, 

percutaneous coronary intervention (diagnostic angiograms are 
permitted), 

transient ischemic attack (TIA), 

cerebrovascular accident (stroke) or decompensated congestive 
heart failure, or 

currently have New York Health Association Class III or IV heart 
failure. 
18. Have an ECG considered by the investigator indicative of abnormalities that may 
interfere with the interpretation of changes in ECG intervals at screening  
19. Medical history of significant autonomic neuropathy as evidenced by urinary 
retention, resting tachycardia, orthostatic hypotension, or diabetic diarrhea
20. Have a personal or family history of long QT syndrome, family history of sudden 
death in a first-degree relative (parents, sibling, or children) before the age of 
40 years, or a personal history of unexplained syncope within the last year. Use of 
prescription or over-the-counter medications known to significantly prolong the 
QT or QTc interval at screening.
21. Have an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, as 
determined by the central laboratory at Visit 1, or a level of eGFR that would 
contraindicate the use of metformin per the label in the respective country.
Participants on metformin must meet local label requirements.
22. Have signs and symptoms of any other liver disease other than nonalcoholic fatty liver 
disease (NAFLD), or any of the following, as determined by the central laboratory during 
screening 

Alanine aminotransferase (ALT) level >3.0X upper limit of normal (ULN) for 
the reference range (as determined by the central laboratory at study entry)

alkaline phosphatase (ALP) level >1.5X ULN for the reference range, or

total bilirubin level (TBL) >1.5X ULN for the reference range (except for 
cases of known Gilbert’s Syndrome)

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
37
23. Have a serum calcitonin level (at Visit 1) of 

≥20 ng/L, if eGFR ≥60 mL/min/1.73 m2 or 

≥35 ng/L if eGFR < 60 mL/min/1.73 m2 (as determined by central 
laboratory at Visit 1)
24. Have an active or untreated malignancy or have been in remission from a 
clinically significant malignancy (other than basal or squamous cell skin cancer, 
in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
prior to screening
25. Have evidence of human immunodeficiency virus (HIV) and/or positive HIV 
antibodies historically or at screening
26. Evidence of hepatitis B and/or positive hepatitis B surface antigen.
27. Hepatitis C as defined by presence of hepatitis C virus (HCV) ribonucleic acid 
(RNA) or positive hepatitis C antibody (anti-HCV). Participants treated for 
hepatitis C (and diagnosed as cured) must have an RNA test at screening and also 
be RNA negative for at least 3 years prior to screening in order to be eligible for 
the study.
28. Have a history of a transplanted organ (corneal transplants [keratoplasty] 
allowed).
29. Have any other condition (including known drug or alcohol abuse or psychiatric 
disorder) that, in the opinion of the investigator, may preclude the participant
from following and completing the protocol
30. Have had a blood donation of 500 mL within the previous 8 weeks of study screening or 
a blood transfusion or severe blood loss within the prior 3 months, or have known 
hemoglobinopathy (for example, hemolytic anemia or sickle cell anemia), or have a 
hemoglobin value <11 g/dL (males) or <10 g/dL (females), or any other condition known 
to interfere with HbA1c measurements
31. Have evidence of a significant, active autoimmune abnormality (for example, 
lupus or rheumatoid arthritis) that, in the opinion of the investigator, is likely to 
require concurrent treatment with systemic glucocorticoids in the next 6 months
32. Have evidence of a significant active, uncontrolled medical condition or a history of any 
medical problem capable of constituting a risk when taking the study medication or 
interfering with the interpretation of data, as judged by the screening investigator at 
screening
33. Have difficulty swallowing capsules
Prior/Concomitant Therapy
34. Unless otherwise specified, all concomitant medications should be at a stable dose 
for at least 3 months prior to randomization

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
38
35. With the exception of stable doses of metformin, participants on another OAM 
(including, but not limited to, sulfonylureas, DPP-4i, sodium–glucose 
cotransport 2 inhibitors, alpha-glucosidase inhibitors, meglitinides) may be 
randomized if the additional OAM treatment was discontinued at least 3 months 
prior to screening
36. Have used insulin for diabetic control within the prior year. However, short-term 
use of insulin for acute conditions is allowed (14 days) in certain situations, such 
as during a hospitalization or perioperatively.
37. Have had any exposure to dulaglutide, other GLP-1 analogs, or other related 
compounds within the prior 3 months or any prior history of 
hypersensitivity/allergies to these medications. Have known or suspected 
hypersensitivity to trial product(s), to selective GLP-1 RAs or GIP/GLP-1 or 
GLP-1/GCG dual receptor agonists. 

Participants who previously took GLP-1 analogs or related compounds 
and who discontinued those medications for intolerability or lack of 
efficacy should not be randomized.
38. Have taken within 3 months prior to screening medications (prescribed or over the 
counter) or alternative remedies (including herbal/nutritional supplements) intended to 
promote weight loss
Examples include, but are not limited to:

Saxenda® [liraglutide 3.0 mg] or other GLP-1RA

Xenical® [orlistat] 

Meridia® [sibutramine] 

Acutrim® [phenylpropanolamine] 

Sanorex® [mazindol] 

Adipex® [phentermine] 

BELVIQ® [lorcaserin] 

Qsymia™[phentermine/topiramate combination] 

Contrave® [naltrexone/bupropion]

WegovyTM (semaglutide 2.4 mg), and

other similar body weight loss medication, including over-the-counter 
(OTC) medications, for example, allī®
39. Are receiving or have received within 3 months prior to screening chronic (>2 
weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, 
single intraarticular injection, or inhaled preparations) or have received such 
therapy within 4 weeks immediately prior to screening
40. Are receiving strong CYP3A inhibitors and drugs that are P-glycoprotein/breast 
cancer resistant protein (P-gp/BCRP) substrates with narrow therapeutic index. 
Please see Section 6.8 concomitant medications for details.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
39
41. Have a history of use of marijuana or tetrahydrocannabinol (THC)-containing products 
within 3 months of enrollment or unwillingness to abstain from marijuana or THC-
containing products use during the trial
Note: If a participant has used cannabidiol oil during the past 3 months but agrees to 
refrain from use for the duration of the study, the participant can be enrolled.
42. Are currently taking a central nervous system stimulant (for example, Ritalin-
SR) with the exception of caffeinated beverages at screening
43. Have an average weekly alcohol intake that exceeds 21 units per week (males) 
and 14 units per week (females) [1 unit = 12 oz or 360 mL of beer; 5 oz or 
150 mL of wine; 1.5 oz or 45 mL of distilled spirits].
44. Evidence of regular use of known drugs of abuse in the opinion of the investigator
Prior/Concurrent Clinical Study Experience
45. Are currently enrolled in a clinical study involving an IP or any other type of medical 
research judged not to be scientifically or medically compatible with this study
46. Have participated, within the last 90 days, in a clinical study and received treatment, 
whether active or placebo. If the study involved an IP; at least 5 elimination half-lives or 
90 days, whichever is longer, should have passed
47. Have previously completed or withdrawn from this study or any other study 
investigating LY3502970
Other Exclusions
48. Are women of child-bearing potential
49. Are women, acting as a surrogate, who are currently pregnant or breastfeeding, or who 
intend to become pregnant or to breastfeed at any time during the study or within 20 
weeks after receiving the last dose of study drug
50. Are investigative 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.
51. Are employees of Eli Lilly and Company (Lilly) or are employees of a third-party 
organization involved in the study which requires exclusion of their employees
52. Are, in the opinion of the investigator or sponsor, unsuitable for inclusion in the 
study
5.3.
Lifestyle Considerations
Throughout the study, participants may undergo medical assessments and review of compliance 
with requirements before continuing in the study. Participants will report to the clinical research 
site for safety assessments and will remain in the clinic until all procedures for that visit are 
complete and the investigator has deemed it safe to release the participant from the clinic. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
40
Per the SoA (Section 1.3), personnel will provide diabetes management counseling, which will 
include instructions on diet and exercise and education about the signs, symptoms, and
management of hyperglycemia and hypoglycemia, SMBG, and self-injection.
Prescription or OTC medications that promote weight loss are exclusionary if used within 
3 months prior to screening or between screening and randomization. These medications are also 
not allowed at any time during the treatment period. If started after randomization, the 
medications should be immediately withdrawn. Participants who refuse to withdraw the weight 
loss medications must be discontinued from study drug.  
Throughout the study, participants may undergo medical assessments and review of compliance 
with requirements before continuing in the study.
Meals/Diet-Participants should not initiate a structured diet and/or exercise program for weight 
reduction during the study other than the lifestyle and dietary measures for diabetes treatment.
For certain assessments, the participants will be required to come to the site in a fasting state, 
after an overnight fast (except for water) of at least 8 hours when clinical laboratory assessments 
and/or weight measures are performed as specified in the SoA (Section 1.3). 
Caffeine, Alcohol, and Tobacco-Participants will be allowed to maintain their regular caffeine 
consumption throughout the study period.
Alcohol will not be permitted at least 24 hours prior to the study site visits, until the participant 
has been discharged from the clinical research site. Daily alcohol should not exceed 3 units for 
males and 2 units for females.
Participants should consume no more than 10 cigarettes or equivalent vaping products per day. 
Physical Activity-Participants will be advised to maintain their regular levels of physical 
activity/exercise during the study; strenuous exercise within 24 hours prior to all visits should be 
avoided if possible. When certain study procedures are in progress at the site, participants may 
be required to remain recumbent or seated.
Blood Donation –Study participants should be instructed not to donate blood or blood products 
during the study and for 8 weeks following the study. 
5.4.
Screen Failures
A screen failure occurs when a participant who consents to participate in the clinical study is 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 serious adverse event (SAE).
If, in the opinion of the investigator, an ineligible lab test result is the result of an error or 
extenuating circumstance, then that parameter can be retested without the participant having to 
be rescreened. However, screen failures for HbA1c may not be retested or rescreened.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
41
5.5.
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention of 
a Participant
Not applicable.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
42
6.
Study Intervention(s) and Concomitant Therapy
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol.
All participants will take one capsule orally each day and one subcutaneous injection each week. 
All capsules are the same size and placebo capsules match LY3502970 capsules. Furthermore, 
the dulaglutide placebo injection device matches the active dulaglutide injection device. 
Therefore, participants will not know whether they are receiving active LY3502970 or 
LY3502970 placebo to match, the dose of LY3502970, or dulaglutide 1.5 mg or dulaglutide 
placebo to match.  
LY3502970 will be supplied in weekly bottles with 10 capsules per bottle. Bottles contain 10 
capsules to account for visit windows and preventing participants from missing doses even if it 
delays the dose escalation. Participants should be instructed to return unused capsules.  
Disposition of Study Drug Bottles
Visit
Number of Bottles of 
Capsules to be Dispensed
3
1
4
1
5-9*
2
10-13
4
14
2
*Visits 5-9 take place during the dose escalation period. The site pharmacy should clearly label which bottle to take 
first. 
Dulaglutide or matching placebo will be supplied at the monthly visits as 4 single-dose pens.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
43
6.1.
Study Intervention(s) Administered
ARM Name
LY3502970
LY-Placebo
Dulaglutide
Dulaglutide-
Placebo
Intervention 
Name
LY3502970
LY3502970-Placebo
dulaglutide
dulaglutide-
placebo
Type 
Drug
Drug
Dose 
Formulation
capsule
capsule
Injectable
Injectable
Unit Dose 
Strength(s)
2 mg capsule LY
3 mg capsule LY
6 mg capsule LY
8 mg capsule LY
12 mg capsule 
LY
24 mg capsule 
LY
36 mg capsule 
LY
45 mg capsule 
LY
capsule of LY-placebo 
to match
1.5 mg/0.5 mL 
single-dose pen
placebo to 
match 
dulaglutide in a 
0.5 mL single-
dose pen
Route of 
Administration
oral
oral
SC
SC
Use
experimental
placebo
active-comparator
placebo- active-
comparator
Abbreviations: LY = LY3502970; SC = subcutaneous.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
44
6.1.1.
Medical Devices
The medical devices provided for use in the study are marketed prefilled single-use pens for 
dulaglutide and prefilled single-dose placebo pens for dulaglutide placebo. Any medical-device 
incidents, including those resulting from malfunctions of the device, must be detected, 
documented, and reported by the investigator throughout the study (see Section 10.3.3).
6.2.
Preparation, Handling, Storage, and Accountability

The investigator or designee must confirm appropriate storage 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. Only 
authorized study personnel may supply, prepare, 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 study personnel.

The investigator or authorized study personnel are 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 are provided in the study training materials.
The study site must store the study drug in a locked and secure environment. The study drug 
capsules may be stored at room temperature. Participants will also be provided with single dose 
pens (SDPs) containing dulaglutide or dulaglutide placebo at clinic visits according to the Study 
Schedule. Dulaglutide/matching placebo SDPs should be stored refrigerated (not frozen) at 2C 
to 8C. Dry ice should not be used for cooling. Participants will also receive insulated bags with 
cooling gel packs for use in transporting the SDPs from the site to the home. Study drug in each 
participating country will be labeled according to the country’s regulatory requirements.
6.3.
Measures to Minimize Bias: Randomization and Blinding
All participants will be centrally assigned to randomized study intervention using an interactive 
web-response system (IWRS). Before the study is initiated, the log in information and directions 
for the IWRS will be provided to each site.
Participants will be randomly assigned to study intervention in a randomization ratio of 
5:5:5:5:5:3:3:3:3, including 50 participants per treatment group to placebo, dulaglutide, LY1, 
LY2 and LY3 treatment groups, and 30 participants per treatment group to LY4-1, LY4-2, LY5-
1 and LY5-2 treatment groups.
This is a double-blind study. All participants will take daily oral blinded study drug and weekly 
subcutaneously injected study drug. Participants will not know if they are receiving active or 
matching placebo oral study drug or active or matching placebo injectable study drug.
Stratification will be by country and HbA1c stratum (≤8.0%, >8.0%) at Visit 1.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
45
Study intervention will be dispensed at the study visits summarized in SoA (Section 1.3). 
Returned study interventions should not be re-dispensed to the participants.
Blinding will be maintained throughout the conduct of the study as described in the separate 
Blinding Plan.
Emergency codes will be available to the investigator and pharmacy. A code, which reveals the 
study intervention (group) for a specific study participant, may be opened during the study only 
if the participant’s well-being requires knowledge of the participant’s treatment assignment.
If a participant’s study treatment assignment is unblinded, the participant must be discontinued 
from the study, unless the investigator obtains specific approval from a Lilly clinical research 
physician/clinical research scientist (CRP/CRS) for the study participant to continue in the study. 
During the study, emergency unblinding should occur only by accessing the study participant’s 
emergency code.
In case of an emergency, the investigator has the sole responsibility of determining if unblinding 
of a participant’s treatment assignment is warranted for medical management of the event. The 
participant’s safety must always be the first consideration in making such a determination. 
Where feasible and when timing of the emergent situation permits, the investigator should 
attempt to contact the Lilly medical monitor before unblinding a participant’s treatment 
assignment. If the investigator decides that unblinding is warranted, it is the responsibility of the 
investigator to promptly document the decision and rationale and notify Lilly as soon as possible.
6.4.
Study Intervention Compliance
Participant compliance with study drug will be assessed at each visit. Compliance will be 
assessed by direct questioning and counting of unused study drug (capsules/single dose pens). 
Study drug compliance will be determined by the following: 

Study drug administration data will be recorded by the participant and reviewed 
by the investigator at each study visit.

The participants will be instructed to return any unused study drug and/or empty 
vials at the next visit to the study site for the purpose of performing drug 
accountability.
In addition to the assessment of a participant’s compliance with the study drug administration, 
other aspects of compliance with the study treatments will be assessed at each visit based on the 
participant’s adherence to the visit schedule, completion of study, study drug administration logs, 
and any other parameters the investigator considers necessary.
Participants considered to be poorly compliant with their medication, and/or the study 
procedures will receive additional training and instruction, as required, and will be reminded of 
the importance of complying with the protocol. Additional unscheduled visits may be scheduled 
if study site personnel determine that a participant requires additional training for the study drug 
preparation and injection techniques. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
46
6.5. Dose Modification
Participants who do not tolerate the first capsule dose escalation, in other words from 2 mg or 3 
mg to 6 mg (or placebo equivalent), will need to discontinue from study treatment. If a 
participant does not tolerate a dose level higher than 6 mg for 1 week (for example, moderate-to-
severe nausea, vomiting, or diarrhea) and the investigator does not believe that the participant 
will tolerate the dose with further exposure, then the investigator may reduce the dose to the next 
lower target dose (for example, 3 mg, 12 mg, 24 mg, or 36 mg). If this dose is tolerated after 2
weeks, the dose should be increased per original protocol dose escalation until the target dose is 
achieved. If this dose escalation is not tolerated, the dose should be reduced to the next lower 
target dose that was tolerated (for example, 3 mg, 12 mg, 24 mg, or 36 mg). The participant will 
remain at that dose level for the duration of the study. Maintenance doses of 2 mg, 6 mg, or 8 mg
will not be allowed. The injectable study treatment should be maintained during dose 
modification of the capsule treatment.
Participants who do not tolerate the injectable study treatment, such as participants who have 
moderate to severe nausea and/or vomiting following 2 injections (2 weeks of treatment) and the 
investigator believes the participant will not tolerate the injectable treatment with further dosing 
will need to discontinue the injectable study treatment. The participant should continue taking 
the capsule study treatment.
In order to maintain blinding to study drug, the site should work through the IWRS web site 
portal for dose modifications.
6.6.
Continued Access to Study Intervention after the End of the Study
LY3502970 will not be made available to participants after conclusion of the study.
6.7.
Treatment of Overdose
Capsule Study Drug
For this study, any total dose estimated from where the participant is in the dose-escalation 
regimen or treatment-maintenance regimen within a 48-hour time period that is greater than 100 
mg will be considered an overdose and should be reported per criteria described in Section 
10.3.1. For example, if a participant takes 3 45-mg capsules within 48 hours or all of the capsules 
in a bottle at one time for dose escalations beginning with the 12 mg dose, those would be 
considered overdoses. The investigator should assume that all participants are assigned to LY 4-1 
treatment group if the event occurs during Week 2 through Week 11, and to the LY 5 treatment 
group after Week 11 considering where the participant would be in the dose escalation and how 
many capsules were taken for calculation of the potential overdose.
Injectable Study Drug
For this study, taking more than 1 injection within a 72-hour period is considered an overdose.
Overdose Treatment
In the event of an overdose for either the capsule or the injectable study treatment, the 
investigator should

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
47

Contact the medical monitor immediately.

Evaluate the participant to determine, in consultation with the medical monitor, whether 
study intervention should be interrupted or whether the dose should be reduced.

Closely monitor the participant for any AE/SAE and laboratory abnormalities for at least 
1 week. Based on the known AE profile of LY3502970, the following are the possible 
AEs related to an overdose:
o
Severe GI events that lead to dehydration and require medical intervention 
o
CV abnormalities such as increase in heart rate, decrease in BP, 
supraventricular arrhythmias/cardiac conduction disorders
o
Hypoglycemia
Implement medical intervention/monitoring according to the clinical presentation.
Obtain a plasma sample for PK analysis as soon as possible from the date of the last dose of 
study intervention if requested by the Medical Monitor (determined on a case-by-case basis).
Document the quantity of the excess dose as well as the duration of the overdose in the case 
report form (CRF).
6.8.
Concomitant Therapy
Allowed concomitant medications should be taken according to label instructions. 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 along with

reason for use

dates of administration including start and end dates

dosage information including dose and frequency for concomitant therapy 
of special interest
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.  
Drugs that may be affected by an increase in gastric pH should be separated from study drug 
administration by at least 2 to 4 hours.
Participants cannot be taking strong CYP3A inducers or inhibitors and drugs that are sensitive P-
glycoprotein/breast cancer resistant protein (P-gp/BCRP) substrates with a narrow therapeutic 
index. In order to be eligible for screening into this study, those drugs need to be washed out for 
at least 2 weeks and the participant should be on a stable dose of alternative medications for at 
least 2 weeks prior to screening.
The FDA has provided a list of strong CYP3A4 inhibitors, which are listed below:

boceprevir

cobicistat

danoprevir and ritonavir

elvitegravir and ritonavir 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
48

grapefruit juice

indinavir and ritonavir 

itraconazole 

ketoconazole 

lopinavir and ritonavir 

paritaprevir and ritonavir  

ombitasvir and/or dasabuvir

posaconazole 

ritonavir 

saquinavir and ritonavir 

telaprevir

tipranavir and ritonavir 

telithromycin

troleandomycin 

voriconazole 

clarithromycin

nefazodon, 

nelfinavir
In order to be eligible for screening into this study, participants taking the following anti-fungal 
agents 

ketoconazole 

itraconazole 

voriconazole, or 

posaconazole
should discontinue taking these medications for at least 2 weeks prior to screening. However, if
the participant is unable to wash out these drugs, then, if appropriate, the participant could switch 
to 

miconazole

clotrimazole, or 

fluconazole. 
For participants prescribed clarithromycin or telithromycin, azithromycin may be considered as 
an alternative option. Participants who chronically use these drugs should be excluded.
Examples of sensitive P-gp substrates are: 

digoxin 

fexofenadine 

loperamide 

quinidine 

talinolol, and

vinblastine
Participants taking these drugs are excluded from being screened for this study.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
49
Examples of sensitive BCRP substrates are:

coumestrol, 

daidzein, 

genistein, 

prazosin, and 

sulphasalazine.
Participants taking these drugs are excluded from being screened for this study.
Initial doses of LY3502970 may delay gastric emptying and have the potential to transiently 
impact the rate of absorption of concomitantly administered oral medicinal products. If an orally 
administered drug has a narrow therapeutic index and its oral absorption is sensitive to gastric 
emptying time, then LY3502970 and that drug should not be administered simultaneously 
because exposure to the non-study drug may be affected. It is recommended that the drugs are 
administered at least 2 to 4 hours apart. 
Examples of drugs with narrow therapeutic indexes that may have increased exposure due to 
delayed gastric emptying and are commonly used in participants with T2DM:

levothyroxine

sulfonylureas

warfarin/coumarins

ethinyl estradiol

oxycodone
6.8.1.
Management of Participants with Gastrointestinal Symptoms
In the Phase 1 program, the most commonly reported treatment-emergent adverse events 
(TEAEs) for participants receiving LY3502970 were nausea, vomiting, and diarrhea. To mitigate 
GI symptoms and manage participants with intolerable GI AEs, the investigator should:  

Advise participants to eat smaller meals, for example, splitting 3 daily meals into 4, or 
more smaller meals, and to stop eating when they feel full. Also, participants may be 
informed that lower-fat meals could be better tolerated.

Prescribe symptomatic medication (for example, anti-emetic or antidiarrheal medication)
per local country availability and individual participant needs. Use of symptomatic
medication should be captured as concomitant medication in the eCRF.

Temporarily interrupt study drug (omit 1 to 3 doses). The data related to temporary 
interruption of study treatment should be documented in source documents and entered 
on the eCRF.

After the interruption, restart at the same dose with the participant taking medication to
alleviate their GI symptoms.
If intolerable GI symptoms or events persist despite the above measures, see Section 6.5.  

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
50
6.8.2.
Hyperglycemia Rescue Medicine
Investigators will be trained on how to apply decision criteria for the timing and method of 
intervention in participants who do not reach glycemic targets during the 26-week treatment 
period. An additional therapeutic intervention should be considered in participants who meet the 
following criteria:

The participants are fully compliant with assigned therapeutic regimen.
AND

In the absence of any acute condition that raises BG either of the following occurs:
o
During the first 6 weeks post-randomization: An average fasting glucose 
level above 270 mg/dL (15.0 mmol/L) occurs over at least a 2-week period 
(at least 4 values/week must be available); 
Or
o
Average FBG >240 mg/dL (>13.3 mmol/L) over any 2-week period or 
longer from Week 6 to Week 12 postrandomization;
Or
o
Average FBG >200 mg/dL (>11.1 mmol/L) over any 2-week period or 
longer after Week 12.
If these conditions are met, then participants may begin treatment with another 
antihyperglycemic agent as determined by their physician. If treatment with another 
antihyperglycemic agent is instituted, then study drug (both oral and injectable) should be 
permanently discontinued. Participants may remain in the study for safety follow-up, but the date 
at which they begin rescue therapy will be the last date for collection of efficacy measures.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
51
7.
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1
(Section 10.1).
7.1.
Discontinuation of Study Intervention
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. If study intervention is permanently discontinued, the participant will remain in the 
study to be evaluated for all planned efficacy and safety measures. See the SoA (Section 1.3) for 
data to be collected at the time of discontinuation of study intervention and follow-up and for any 
further evaluations that need to be completed.
Possible reasons leading to permanent discontinuation of IP:

Participant Decision

The participant or the participant’s designee (for example, parents or legal guardian) 
requests to discontinue IP.

Investigator Decision
o
the investigator decides that the participant should be discontinued from the 
study medication

Any medication for weight loss is given for more than 1 week

Participants will be discontinued from the IP in the following circumstances:
o
Diagnosis of cirrhosis after randomization (refer to Section 8.3.3.7 for details)
o
Pancreatitis or pancreatic cancer (refer to Section 8.3.3.2 for details) 
o
Diagnosis of medullary thyroid carcinoma (MTC) after randomization
o
Diagnosis of 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  
o
Any TEAE, SAE, or clinically significant laboratory value for which the 
investigator believes that permanent study drug discontinuation is the appropriate 
measure to be taken
o
A female participant becomes pregnant
o
Diagnosis of T1DM or latent autoimmune diabetes in adults

If the participant develops any exclusion criteria during the course of the study, the 
investigator should call the sponsor to determine whether discontinuation of study drug is 
necessary

Significant non-compliance with the protocol
Study drug should be temporarily discontinued in any individual suspected of having a severe or 
serious allergic reaction to study drug or other serious safety concerns. Study drug may be 
restarted when/if it is safe to do so, in the opinion of the investigator.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
52
If study drug is permanently discontinued, the participant should remain in the study. The 
participant should continue participation in the study, attend all visits, and undergo most protocol 
procedures.  
Participants discontinuing from the IP prematurely for any reason should complete AE and other 
follow-up procedures per Section 1.3 (SoA), Section 8.3 (Adverse Events and Serious Adverse 
Events), and Section 8.2 (Safety Assessments) of the protocol.  
7.1.1.
Liver Chemistry Stopping Criteria
The study drug should be interrupted or discontinued if one or more of these conditions occur:
Elevation
Exception
ALT or AST >8x ULN
ALT or AST >5x ULN for more than 2 weeks
ALT or AST >3x ULN and either TBL >2x ULN or INR >1.5 
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL>2x ULN.
ALT or AST >3x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%)
ALP >3x ULN, when the source of increased ALP is the liver
ALP >2.5x ULN and TBL > 2x ULN 
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL>2x ULN.
ALP >2.5x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%)
Source: FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009 
and other consensus guidelines, with minor modifications.
Resumption of the study drug can be considered only in consultation with the Lilly-designated 
medical monitor and only if the liver test results return to baseline and if a self-limited non-drug 
etiology is identified.
7.1.2.
QTc Stopping Criteria
If a clinically significant finding is identified (including, but not limited to changes from baseline 
in QT interval corrected using Fridericia’s formula [QTcF]) after enrollment, the investigator or 
qualified designee will determine if the participant can continue in the study and if any change in 
participant management is needed. This review of the ECG printed at the time of collection must 
be documented. Any new clinically relevant finding should be reported as an AE.
7.1.3.
Temporary Discontinuation
After randomization, the investigator may interrupt study drug, for example, due to an AE (for 
example, nausea of moderate severity or vomiting), or a clinically significant laboratory value. If 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
53
study drug interruption is due to an AE, the event is to be followed and documented. Every effort 
should be made by the investigator to maintain participants in the study and to restart study drug 
promptly after any interruption, as soon as it is safe to do so (See Section 7.1.4 for restarting 
study drug). The dates of study drug interruption and restart must be documented. The data 
related to interruption of study treatment will be documented in source documents and entered on 
the eCRF.
7.1.4.
Restarting Study Drug after Interruption
Capsule Study Drug
If the number of consecutive missed capsule doses is ≤7, the treatment can be restarted at the 
same dose.
Participants who have missed >7 days of capsule study drug will need to restart the study drug at 
the 8 mg dose (LY3502970 treatment groups 2, 3, 4-1, 4-2, 5-1, and 5-2) and dose escalate 
according to the protocol. LY3502970 treatment group 1 (2/3 mg group) will restart study drug 
at 3 mg and remain at that level for the duration of the study. 
In order to maintain blinding of the investigator and participant, the investigator should work 
through the IWRS web site portal for restarting study drug and IWRS will provide dispensing 
information. Dose reductions may occur at unscheduled visits.
Injectable Study Drug
Participants who have missed any amount of injectable study drug may restart the injectable 
study drug at any time. There is no dose escalation procedure associated with the injectable study 
drug.
The investigator will use the IWRS web site portal to receive the appropriate study drug 
dispensing information to preserve blinding of the study drug.
7.2.
Participant Discontinuation/Withdrawal from the Study
A participant may withdraw from the study:
●
at any time at his/her own request 
●
at the request of his/her designee (for example, parents or legal guardian)
●
at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons
●
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
●
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 drug occurs prior to introduction of the new agent.
Discontinuation is expected to be uncommon.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
54
At the time of discontinuing from the study, if possible, an early discontinuation visit should be 
conducted, as shown in the SoA. See the SoA (Section 1.3) 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 from both the study intervention and 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 identifies 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 advisable for the participant to 
continue on study treatment. If the investigator and the Lilly CRP/CRS agree it is medically 
appropriate to continue, the investigator must obtain documented approval from the Lilly
CRP/CRS to allow the inadvertently enrolled participant to continue in the study with or without 
treatment with IP. Safety follow-up should be performed as outlined in Section 1.3 (SoA), 
Section 8.2 (Safety Assessments), and Section 8.3 (Adverse Events, Serious Adverse Events, and 
Product Complaints) of the protocol.
7.3.
Lost to Follow-up
A 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. Site personnel or designee are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
55
8.
Study Assessments and Procedures

Study procedures and their timing are summarized in the SoA (Section 1.3).

Immediate safety concerns should be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study intervention.

Adherence to the study design requirements, including those specified in the SoA
(Section 1.3), is essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.
8.1.
Efficacy Assessments
Primary:
The primary efficacy measure is change from baseline in HbA1c, as determined by the central 
laboratory.
Secondary:
The following secondary efficacy measures will be collected at the times shown in the SoA
(Section 1.3).

HbA1c as determined by the central laboratory

Fasting blood glucose (FBG) as determined by the central laboratory

Body weight (see Section 10.8 for measurement procedure) 
Exploratory:

BMI (see Section 10.8 for measurement procedure)

Waist circumference (see Section 10.8 for measurement procedure)

Seven-point SMBG (see Section 10.8 for measurement procedure)

Mechanistic biomarkers: to explore potential mechanisms of action related to changes in 
glucose, lipid, and/or nutrient metabolism, markers will be assessed.

Patient-reported outcomes (see Section 10.9 for details)
o
Short Form-36 version 2 Health Survey acute form, 1-week recall version
o
Diabetes Treatment Satisfaction Questionnaire-Status Version 
o
Diabetes Treatment Satisfaction Questionnaire-Change Version 
o
Participant Survey
8.2.
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.3).

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
56
8.2.1.
Physical Examinations
A complete physical examination will include, at a minimum, assessments of the CV, 
respiratory, GI, and neurological systems. Height and weight will also be measured and recorded
as per the SoA Section 1.3. Refer to Section 10.8 for further details on weight measurements.
A brief physical examination will include, at a minimum, assessments of the skin, lungs, CV
system, and abdomen (liver and spleen).
Investigators should pay special attention to clinical signs related to previous serious illnesses.
8.2.2.
Vital Signs
For each participant, vital signs measurements should be conducted according to the 
Schedule of Activities (Section 1.3) and following the study-specific recommendations 
included in Section 10.8).
Any clinically significant findings from vital signs measurement that result in a diagnosis and
that occur after the participant receives the first dose of study intervention should be reported to
Lilly or its designee as an AE via eCRF.
8.2.3.
Electrocardiograms
For each participant, 12-lead ECGs should be collected according to Section 1.3.

All digital ECGs will be obtained using centrally provided ECG machines and will be 
electronically transmitted to a designated central ECG laboratory.

12-lead ECGs should be obtained after the subject has rested in a supine position for 
at least 10 minutes.
Electrocardiograms should be collected prior to collection of blood samples for laboratory 
testing, including PK trough level samples.
Screening and early termination ECGs may be collected as single ECGs.  All other ECGs are to 
be recorded in triplicate; consecutive replicate ECGs will be obtained at approximately 1-minute 
intervals.  
Electrocardiograms may be obtained at additional times, when deemed clinically necessary.  
Collection of more ECGs than expected at a particular time point is allowed when needed to 
ensure high-quality records.
Electrocardiograms will initially be interpreted by a qualified physician (the investigator or 
qualified designee) at the site as soon after the time of ECG collection as possible, and ideally 
while the participant is still present, to determine whether the participant meets entry criteria and 
for immediate participant management, should any clinically relevant findings be identified. Any 
clinically significant findings from ECGs that result in a diagnosis and that occur after the 
participant receives the first dose of the investigational treatment should be reported to Lilly or 
its designee as an AE. The investigator (or qualified designee) is responsible for determining if 
any change in participant management is needed, and must document his/her review of the ECG 
printed at the time of evaluation.
After enrollment, if a clinically significant increase in the QT/QTc interval from baseline or 
other clinically significant quantitative or qualitative change from baseline is identified, the 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
57
participant will be assessed by the investigator for symptoms (for example, palpitations, near 
syncope, and syncope) and to determine whether the participant can continue in the study. The 
investigator or qualified designee is responsible for determining if any change in participant.
management is needed and must document his/her review of the ECG printed at the time of 
evaluation from at least 1 of the replicate ECGs from each time point.
All digital ECGs will be obtained using centrally provided ECG machines and will be 
electronically transmitted to a designated central ECG laboratory. The central ECG laboratory 
will perform a basic quality control check (for example, demographics and study details) and 
then store the ECGs in a database. At a future time, the stored ECG data may be over-read by a 
cardiologist at the central ECG laboratory for further evaluation of machine-read measurements 
or to meet regulatory requirements.
The machine-read ECG intervals and HR may be used for data analysis and report-writing 
purposes, unless a cardiologist over-reading of the ECGs is conducted prior to completion of the 
final study report (in which case, the over-read data would be used).
Any treatment-emergent clinically significant ECG finding resulting in a diagnosis should be 
reported as an AE in the eCRF.
8.2.4.
Clinical Safety Laboratory Tests
●
See Section 10.2 (Appendix 2) for the list of clinical laboratory tests to be 
performed and the SoA (Section 1.3) for the timing and frequency.
●
The investigator must review the laboratory results, document this review, and 
report any clinically relevant changes occurring during the study as an AE. The
laboratory results must be retained with source documents unless a Source 
Document Agreement or comparable document cites an electronic location that 
accommodates the expected retention duration. 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 2 weeks after the last dose of study 
intervention should be repeated until the values return to normal or baseline or are 
no longer considered clinically significant by the investigator or medical monitor.
○
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 Appendix 2
(Section 10.2), must be conducted in accordance with the SoA (Section 1.3), 
standard collection requirements.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
58
●
If laboratory values from non-protocol specified laboratory assessments 
performed at an investigator-designated local laboratory require a change in 
participant management or are considered clinically significant by the investigator 
(for example, SAE or AE or dose modification), then report the information as an 
AE.
8.2.5.
Pregnancy Testing 
Female participants will undergo a serum pregnancy test at screening.
8.2.6.
Safety Monitoring
Lilly will periodically review evolving aggregate safety data within the study by appropriate 
methods. The study team will review safety reports in a blinded fashion (for applicable blinded 
study period) according to the schedule provided in the Trial-Level Safety Review plan. Lilly 
will also review SAEs within time frames mandated by company procedures. The Lilly 
CRP/CRS will, as appropriate, consult with the functionally independent Global Patient Safety 
(GPS) therapeutic area physician or clinical scientist. Safety monitoring will include review of 
hepatic, pancreatic, CV, thyroid c-cell function, and renal safety data. The hepatic safety 
monitoring plan is provided below; for additional information, please see also Section 10.5.
8.2.6.1.
Hepatic Safety Monitoring
Close hepatic monitoring
Laboratory tests (Section 10.2), including ALT, AST, ALP, TBL, D. Bil, GGT, and CK, should be 
repeated within 48 to 72 hours to confirm the abnormality and to determine if it is increasing or 
decreasing, if one or more of these conditions occur:
If a participant with baseline results 
of ... 
develops the following elevations:
ALT or AST <1.5X ULN
ALT or AST ≥3X ULN
ALP <1.5X ULN
ALP ≥2X ULN
TBL <1.5X ULN
TBL ≥2X ULN (except for participants with Gilbert’s 
syndrome)
ALT or AST ≥1.5X ULN
ALT or AST ≥2X baseline
ALP ≥1.5X ULN
ALP ≥2X baseline
TBL ≥1.5X ULN
TBL ≥1.5X baseline (except for participants with 
Gilbert’s syndrome)
If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor. At a minimum, this evaluation should include physical 
examination and a thorough medical history, including symptoms, recent illnesses (for example, 
heart failure, systemic infection, hypotension, or seizures), recent travel, history of concomitant 
medications (including OTC), herbal and dietary supplements, history of alcohol drinking and 
other substance abuse. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
59
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and lab results stabilize. Monitoring of ALT, AST, ALP, and TBL 
should continue until levels normalize or return to approximate baseline levels.
Comprehensive hepatic evaluation  
A comprehensive evaluation should be performed to search for possible causes of liver injury if 
one or more of these conditions occur:
If a participant with baseline 
results of... 
develops the following elevations:
ALT or AST <1.5X ULN
ALT or AST ≥3X ULN with hepatic signs/symptoms*, or
ALT or AST ≥5X ULN
ALP <1.5X ULN
ALP ≥3X ULN
TBL <1.5X ULN
TBL ≥2X ULN (except for participants with Gilbert’s syndrome)
ALT or AST ≥1.5X ULN
ALT or AST ≥2X baseline with hepatic signs/symptoms*, or
ALT or AST ≥3X baseline
ALP ≥1.5X ULN
ALP ≥2X baseline
TBL ≥1.5X ULN
TBL ≥2X baseline (except for participants with Gilbert’s syndrome) 
* Hepatic signs/symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%.
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for PT-INR; tests for viral hepatitis A, B, C, or E; tests 
for autoimmune hepatitis; and an abdominal imaging study (for example, ultrasound or 
computerized tomography [CT] scan). 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus 
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and blood phosphatidylethanol. Based on the circumstances and the 
investigator’s assessment of the participant’s clinical condition, the investigator should consider 
referring the participant for a hepatologist or gastroenterologist consultation, magnetic resonance 
cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), 
cardiac echocardiogram, or a liver biopsy.  
Additional hepatic data collection (hepatic safety CRF) in study participants who have 
abnormal liver tests during the study 
Additional hepatic safety data collection in hepatic safety CRFs should be performed in study 
participants who meet 1 or more of the following 5 conditions:
1. Elevation of serum ALT to ≥5X ULN on 2 or more consecutive blood tests (if baseline 
ALT <1.5X ULN)

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
60

In participants with baseline ALT ≥1.5X ULN, the threshold is ALT ≥3X baseline 
on 2 or more consecutive tests
2. Elevated TBL to ≥ 2X ULN (if baseline TBL <1.5X ULN) (except for cases of known 
Gilbert’s syndrome)

In participants with baseline TBL ≥1.5X ULN, the threshold should be TBL ≥2X
baseline
3. Elevation of serum ALP to ≥2X ULN on 2 or more consecutive blood tests (if baseline 
ALP <1.5X ULN)

In participants with baseline ALP ≥1.5X ULN, the threshold is ALP ≥2X baseline 
on 2 or more consecutive blood tests
4. Hepatic event considered to be a SAE
5. Discontinuation of study drug due to a hepatic event 
Note: the interval between the two consecutive blood tests should be at least 2 days.
8.3.
Adverse Events, Serious Adverse Events, and Product Complaints
The definitions of the following events can be found in Appendix 3 (Section 10.3):

AEs

SAEs

Product complaints (PCs)
These events 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 these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study drug. (see Section 7).
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences.
For some studies, participants are not always able to provide valid verbal responses to 
open-ended questions. In these circumstances, another method of detecting events must be 
specified.
After the initial 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 8.3.3) 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). For PCs, the investigator is responsible for ensuring 
that follow-up includes any supplemental investigations as indicated to elucidate the nature 
and/or causality. Further information on follow-up procedures is provided in Appendix 3
(Section 10.3).
8.3.1.
Timing and Mechanism for Collecting Events
This table describes the timing, deadlines, and mechanism for collecting events.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
61
Event
Collection 
Start
Collection 
Stop
Timing for Reporting to 
Sponsor or Designee
Mechanism for 
Reporting
Back-up 
Method 
of 
Reporting
Adverse Event
AE
start of 
study drug
participation 
in study has 
ended
Should be recorded in the 
eCRF as soon as possible.  
The sponsor will 
periodically evaluate 
safety data in the eCRF.
AE eCRF
N/A
Serious Adverse Event
SAE and 
SAE updates 
– prior to 
start of study 
intervention 
and deemed 
reasonably 
possibly 
related with 
study 
procedures
signing of 
the informed 
consent 
form (ICF) 
start of 
intervention
Within 24 hours of 
awareness
SAE eCRF 
SAE 
paper 
form
SAE and 
SAE updates
– after start 
of study 
intervention
start of 
intervention
participation 
in study has 
ended
Within 24 hours of 
awareness
SAE eCRF 
SAE 
paper 
form
SAE*– after 
participant’s 
study 
participation 
has ended 
and the 
investigator 
becomes 
aware
After 
participant’s 
study 
participation 
has ended
N/A
Promptly
SAE paper form
N/A

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
62
Event
Collection 
Start
Collection 
Stop
Timing for Reporting to 
Sponsor or Designee
Mechanism for 
Reporting
Back-up 
Method 
of 
Reporting
Pregnancy
Pregnancy 
in female 
participants 
and female 
partners of 
male 
participants
After the 
start of 
study 
intervention
90 days or 3 
months after 
last 
participant 
visit
Within 24 hours (see 
Section 8.3.2)
Pregnancy paper 
form
SAE 
paper 
form
Product Complaints
PC
associated 
with an SAE
or might 
have led to 
an SAE
Start of 
study 
intervention
End of study 
intervention
Within 24 hours of 
awareness
Product Complaint 
form
N/A
PC not 
associated 
with an SAE
Start of 
study 
intervention
End of study 
intervention
Within 1 business day of 
awareness
Product Complaint 
form
N/A
Updated PC 
information
—
—
As soon as possible upon 
site awareness
Originally completed 
Product Complaint 
form with all changes 
signed and dated by 
the investigator
N/A
PC (if 
investigator 
becomes 
aware)
Participation 
in study has 
ended
N/A
Promptly
Product Complaint 
form
*Serious adverse events should not be reported unless the investigator deems them to be possibly related to study 
treatment or study participation.
8.3.2.
Pregnancy
Collection of pregnancy information
Male participants with partners who become pregnant

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
63
●
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 drug.
●
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 gestational age, fetal status (presence or absence of 
anomalies) or indication for the procedure. 
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 gestational age, 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 <20 weeks gestational age) or still birth 
(occurring at ≥20 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 
protocol Section 8.3.1. 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. If the participant is discontinued from the 
study, follow the standard discontinuation process and continue directly to the 
follow-up phase. The follow-up on the pregnancy outcome should continue 
independent of intervention or study discontinuation. 
8.3.3. Adverse Events of Special Interest 
The following are AEs that will be adjudicated by an external adjudication committee

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
64

pancreatitis (see Section 8.3.3.2)

major adverse CV events (see Section 8.3.3.4), 

supraventricular arrhythmias and cardiac conduction disorders (Section 8.3.3.5)

drug-induced liver injury, and

deaths.
The following are additional adverse events of special interest (AESI)

hypoglycemia (Level 2 and 3)

severe persistent hyperglycemia

thyroid malignancies and C-cell hyperplasia

hepatobiliary disorders

severe GI AEs, and

acute renal events.
Sites should collect additional details and data regarding these AEs, as instructed on the 
applicable eCRFs, and detailed below.
8.3.3.1.
Hypoglycemia 
Upon ICF signing, all participants will be educated about signs and symptoms of hypoglycemia,
how to treat hypoglycemia, and how to collect appropriate information for each episode of
hypoglycemia.
Participants who develop persistent or recurrent unexplained hypoglycemia during the treatment 
period will be asked to reduce the dose or discontinue any concomitant glucose-lowering agents 
other than study drug. Study drug discontinuation for recurrent hypoglycemia should be 
considered only if these events continue despite complete discontinuation of concomitant 
medications.
All hypoglycemic episodes will be recorded on a specific eCRF and should not be recorded as 
AEs unless the event meets serious criteria. If a hypoglycemic event meets severe criteria (see 
definition below), it should be recorded as serious on the AE and SAE eCRFs, and reported to 
Lilly as an SAE.
Investigators should use the following definitions and criteria when diagnosing and categorizing 
an episode considered to be related to hypoglycemia (the BG values in this section refer to values 
determined by a laboratory or International Federation of Clinical Chemistry and Laboratory 
Medicine blood-equivalent glucose meters and strips) in accordance with the 2020 American 
Diabetes Association position statement on glycemic targets (ADA 2020) as below. Level 2 and 
Level 3 hypoglycemia events are considered as safety topics of special interest:
Level 1 hypoglycemia: 
Glucose <70 mg/dL (3.9 mmol/L) and ≥ 54 mg/dL (3.0 mmol/L): Level 1 hypoglycemia 
can alert a person to take action such as treatment with fast-acting carbohydrates. Providers 
should continue to counsel participants to treat hypoglycemia at this glucose alert value.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
65
Level 2 hypoglycemia: 
Glucose <54 mg/dL (3.0 mmol/L): This is also referred to as documented or BG confirmed 
hypoglycemia with glucose <54 mg/dL (3.0 mmol/L). This glucose threshold is clinically 
relevant regardless of the presence of absence of symptoms of hypoglycemia. 
Level 3 hypoglycemia: 
Severe hypoglycemia (in adults): A severe event characterized by altered mental and/or 
physical status requiring assistance for treatment of hypoglycemia. For example, participants
had altered mental status, and could not assist in their own care, or were semiconscious or 
unconscious, or experienced coma with or without seizures, and the assistance of another 
person was needed to actively administer carbohydrate, glucagon, or other resuscitative
actions. Glucose measurements may not be available during such an event, but neurological 
recovery attributable to the restoration of glucose concentration to normal is considered
sufficient evidence that the event was induced by a low glucose concentration.

The determination of a hypoglycemic event as an episode of severe 
hypoglycemia, as defined above, is made by the investigator based on the 
medical need of the participant to have required assistance and is not 
predicated on the report of a participant simply having received assistance.

If a hypoglycemic event meets the criteria of severe hypoglycemia, the 
investigator must record the event as serious on the AE CRF and report it to 
Lilly as an SAE.
Nocturnal hypoglycemia:
Nocturnal hypoglycemia is a hypoglycemia event (including severe hypoglycemia) that 
occurs at night and presumably during sleep.
8.3.3.2.
Pancreatitis 
Diagnosis of acute pancreatitis
Acute pancreatitis is an AE of interest in all studies with LY3502970, including this study. The 
diagnosis of acute pancreatitis requires 2 of the following 3 features (Banks and Freeman 2006): 

abdominal pain, characteristic of acute pancreatitis (that is, epigastric pain 
radiating to the back, often associated with nausea and vomiting)

serum amylase (total, pancreatic, or both) and/or lipase ≥3X ULN

characteristic findings of acute pancreatitis on CT scan or magnetic resonance 
imaging (MRI)
If acute pancreatitis is suspected, the investigator should

obtain appropriate laboratory tests, including pancreatic amylase and lipase

perform imaging studies, such as abdominal CT scan with or without contrast, 
or abdominal MRI, and

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
66

evaluate for possible causes of acute pancreatitis, including alcohol use, 
gallstone or gall bladder disease, hypertriglyceridemia, and concomitant 
medications.
Discontinuation for acute pancreatitis
If acute pancreatitis is suspected by the investigator, the participant must temporarily discontinue 
use of the IP. In this case, the participant needs to receive an appropriate alternative glucose 
lowering regimen. Afterwards, if pancreatitis is confirmed by the adjudication committee, the IP 
must be permanently discontinued, and the participant needs to be followed throughout the 
duration of the study. If the case is not confirmed, then the participant can restart the IP if the 
investigator deems as clinically appropriate as described in Section 6.5 (Dose Modification).
Case adjudication and data entry
An independent clinical endpoint committee (CEC) will adjudicate all suspected cases of acute 
pancreatitis. Relevant data from participants with acute pancreatitis will be entered into a 
specifically designed eCRF page. The adjudication committee representative will enter the 
results of adjudication in a corresponding eCRF page.
Asymptomatic elevation of pancreatic amylase and/or lipase
Serial measures of pancreatic enzymes have limited clinical value for predicting episodes of 
acute pancreatitis in asymptomatic participants (Nauck et al. 2017; Steinberg et al. 2017a, 
2017b). Therefore, further diagnostic follow-up of cases of asymptomatic elevation of pancreatic 
enzymes (lipase and/or pancreatic amylase ≥3X ULN) is not mandated but may be performed 
based on the investigator’s clinical judgment and assessment of the participant’s overall clinical 
condition.
8.3.3.3.
Thyroid Malignancies and C-Cell Hyperplasia 
Individuals with personal or family history of MTC and/or MEN2 will be excluded from the 
study. Participants who are diagnosed with MTC and/or MEN2 during the study will have study 
drug stopped and should continue follow-up with an endocrinologist. Additionally, participants 
who have a serum calcitonin level of ≥20 ng/L, if eGFR ≥ 60 mL/min/1.73 m2 or ≥35 ng/L if 
eGFR < 60 mL/min/1.73 m2, as determined by central laboratory at Visit 1, will also be 
excluded.
The assessment of thyroid safety during the trial will include reporting of any case of thyroid 
neoplasms (including MTC, papillary carcinoma, and others) and measurements of calcitonin. 
These data will be captured in specific eCRFs. The purpose of calcitonin measurements is to 
assess the potential of LY3502970 to affect thyroid C-cell function, which may indicate 
development of C-cell hyperplasia and neoplasms.
If an increased calcitonin value (see definitions below) is observed in a participant who has been 
administered a medication that is known to increase serum calcitonin, then this medication 
should be stopped, and calcitonin levels should be measured after an appropriate washout period.
For participants who require additional endocrine assessment because of increased calcitonin 
concentration as defined in this section, data from the follow-up assessment will be collected in 
the specific section of the eCRF.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
67
Calcitonin Measurements in Participants with eGFR ≥60 mL/min/1.73 m2
A significant increase in calcitonin for participants with eGFR ≥60 mL/min/1.73 m2 is defined 
below. If a participant’s laboratory results meet these criteria, these clinically significant 
laboratory results should be recorded as an AE. 

Serum calcitonin value ≥20 ng/L and <35 ng/L AND ≥50% increase from the screening 
value. These participants will be requested to repeat the measurement within 1 month. If 
this repeat value is increasing (≥10% increase), the study drug should be discontinued, 
and the participant should undergo additional endocrine assessment and longer-term 
follow-up by an endocrinologist to exclude adverse effects on the thyroid gland.

Serum calcitonin value ≥35 ng/L AND ≥50% over the screening value. In these 
participants, study drug should be discontinued, and the participant should be 
recommended to immediately undergo additional endocrine assessments and longer-term 
follow-up by an endocrinologist.
Calcitonin Measurement in Participants with eGFR <60 mL/min/1.73 m2
A significant increase in calcitonin for participants with eGFR <60 mL/min/1.73 m2 is defined as 
a serum calcitonin value ≥35 ng/L AND ≥50% over the screening value. If a participant’s labs 
meet these criteria, these clinically significant labs should be recorded as an AE. 
In these participants, if the increased concentration of calcitonin is confirmed, the participant 
must be recommended to immediately undergo additional endocrine assessments and longer-
term follow-up by an endocrinologist to exclude adverse effects on the thyroid gland.
8.3.3.4.
Major Adverse Cardiovascular Events 
Nonfatal CV AEs will be adjudicated by a committee of physicians external to Lilly with 
cardiology expertise. This committee will be blinded to treatment assignment. 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.
8.3.3.5.
Supraventricular Arrhythmias and Cardiac Conduction Disorders
Treatment-emergent cardiac conduction disorders will be further evaluated. Participants who 
develop any event from these groups of disorders should undergo an ECG, which should be 
submitted to the central reading center. Additional diagnostic tests to determine exact diagnosis 
should be performed, as needed. The specific diagnosis will be recorded as an AE. Events that 
meet criteria for serious conditions as described in Section 10.3.2 must be reported as SAEs. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
68
8.3.3.6.
Deaths
All deaths will be adjudicated by a committee of physicians external to Lilly. This committee 
will be blinded to treatment assignment.
8.3.3.7.
Hepatobiliary Disorders
All events of TE biliary colic, cholecystitis, cholelithiasis or other suspected events related to 
acute gallbladder disease should be evaluated and additional diagnostic tests performed, as 
needed. In cases of elevated liver markers, hepatic monitoring should be initiated as outlined in 
Section 8.2.6.1.
8.3.3.8.
Severe Gastrointestinal Adverse Events 
LY3502970 and dulaglutide may cause severe GI AEs, such as nausea, vomiting, and diarrhea. 
Information about severe GI AEs as well as antiemetic or antidiarrheal use will be collected in 
the AE and concomitant medications eCRFs, respectively. For detailed information concerning 
the management of GI AEs, please refer to Section 6.8.1.
8.3.3.9.
Acute Renal Events
Renal safety will be assessed based on repeated renal functional assessment as well as 
assessment of AEs suggestive of acute renal failure or worsening of preexisting chronic renal 
failure. Gastrointestinal AEs have been reported with LY3502970 including nausea, diarrhea, 
and vomiting. This is consistent with other GLP-1R agonists (Aroda and Ratner 2011). The 
events may lead to dehydration, which could cause a deterioration in renal function, including 
acute renal failure. Participants should be advised to notify investigators in case of severe nausea, 
frequent vomiting, or symptoms of dehydration.
8.4.
Pharmacokinetics
Blood samples will be collected from all randomized participants in accordance with schedule 
provided in Section 1.3 and at ET for measurement of plasma concentrations of LY3502970. 
Participants may need to return to the clinical site for PK-specific visits to provide post-dose PK 
samples dependent on the time window of PK sampling. Only samples from participants 
assigned to treatment with LY3502970 will be analyzed for drug concentration. 
Date and time of each sample and the most recent LY3502970 dose prior to PK blood draw must 
be recorded. Drug concentration information that would unblind the study will not be reported to 
study sites or blinded personnel while the study is blinded. 
Samples will be analyzed at a laboratory approved by the sponsor and stored at a facility 
designated by the sponsor. Concentrations of LY3502970 will be assayed using a validated 
liquid chromatography mass spectrometry method. Analyses of samples collected from 
participants who received placebo or dulaglutide are not planned. Bioanalytical samples 
collected to measure IP concentrations will be retained for a maximum of 1 year following the 
last participant visit for the study. During this time, samples remaining after the bioanalyses may 
be used for exploratory analyses such as additional metabolism, protein binding, or exploratory
analyses including bioanalytical assay validation or cross-validation exercises.
Instructions for the collection and handling of blood samples will be provided by the sponsor.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
69
8.5.
Pharmacodynamics
Efficacy measures will be used as indicators of pharmacodynamic response.
8.6.
Genetics
Not applicable.
8.7.
Biomarkers
In addition to the planned biomarker research as indicated in the SoA (Section 1.3), biomarker 
research on stored nonpharmacogenetic samples may be performed to address questions of 
relevance to drug disposition, target engagement, PD, mechanism of action, variability of 
participant response (including safety), and clinical outcome. Sample collection is incorporated 
into clinical studies to enable examination of these questions through measurement of 
biomolecules including proteins, lipids, and other cellular elements.
Serum and plasma samples for nonpharmacogenetic biomarker research will be collected at the 
times specified in the SoA (Section 1.3) where local regulations allow.
Samples may be used for research on the drug target, disease process, variable response to 
LY3502970, pathways associated with diabetes mellitus and related clinical traits or 
complications, including nonalcoholic steatohepatitis or obesity, mechanism of action of 
LY3502970, and/or research method, or for validating diagnostic tools or assay(s) related to 
diabetes mellitus, related clinical traits, or complications.
All samples will be coded with the participant number. These samples and any data generated 
can be linked back to the participant only by the investigative site personnel. 
Samples will be retained at a facility selected by Lilly or its designee for a maximum 15 years 
after the last participant visit for the study, or for a shorter period if local regulations and ERBs 
impose shorter time limits. 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 LY3502970 or after LY3502970 becomes commercially available.
8.8.
Immunogenicity Assessments
Not applicable.
8.9.
Health Economics
Not applicable.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
70
9.
Statistical Considerations
9.1.
Statistical Hypotheses
The study hypothesis for the primary objective is that at least one dose level of QD oral doses of 
LY3502970 is superior in change from baseline for HbA1c relative to placebo at Week 26, in 
participants with T2DM inadequately controlled with diet and exercise alone or treated with a 
stable dose of metformin.
9.1.1.
Multiplicity Adjustment
Treatment comparisons will be performed for the primary objective at the full significance level 
of 0.05. No multiplicity adjustments will be made for the analysis of secondary and exploratory 
objectives.
9.2.
Analyses Sets
For the purposes of analysis, the following analysis population and datasets are defined:
Participant Analysis 
Population/Datasets
Description
Entered Participants
All participants who sign informed consent.
Randomized
All participants who are randomly assigned a study drug. 
Efficacy Analysis Set (EAS)
Data obtained during the treatment period from all randomized participants 
who are exposed to at least 1 dose of study drug. Excludes data after 
permanent discontinuation of study drug or initiation of rescue medication. 
Participants will be included in the treatment group to which they were 
randomly assigned.  
Full Analysis Set (FAS)
Data obtained during the treatment period from all randomized participants 
who are exposed to at least 1 dose of study drug, regardless of adherence to 
study drug or initiation of rescue medication. Participants will be included in 
the treatment group to which they were randomly assigned.  
Safety Analysis Set (SS)
Data obtained during the treatment period plus safety follow-up from all 
randomized participants who are exposed to at least 1 dose of study drug, 
regardless of adherence to study drug or initiation of rescue medication. 
Participants will be included in the treatment group to which they were
randomly assigned.  

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
71
9.3.
Statistical Analyses
9.3.1.
General Considerations
Statistical analysis of this study will be the responsibility of Lilly or its designee. 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) or the clinical study report (CSR). Additional exploratory analyses 
of data will be conducted, as deemed appropriate.
Unless otherwise noted, all tests of treatment effects will be conducted at a 2-sided alpha level of 
0.05, and confidence intervals (CIs) will be calculated at 95%, 2-sided. All tests of interactions 
between treatment groups and other factors will be conducted at a 2-sided alpha level of 0.10.  
Baseline is defined as the last non-missing measurement at or before randomization visit (prior to 
first dosing of study drug) unless otherwise specified. 
The primary estimand (a precise definition of the treatment effect to be estimated) of interest in 
comparing efficacy of LY3502970 doses with placebo is the “efficacy estimand” (Section 2.3.1).
The primary efficacy assessment guided by the “efficacy estimand” will be conducted using the 
EAS (Section 9.2). To estimate the “efficacy estimand”, when change from baseline is included 
as a response variable of analysis models, the participants will be included in the analysis only if 
a baseline and at least 1 postbaseline measurement are available. A restricted maximum 
likelihood-based, mixed-effect model repeated measures (MMRM) analysis will be used to 
analyze continuous longitudinal variables. All the longitudinal observations at each scheduled 
postbaseline visit will be included in the analysis. The model for the analysis of the primary 
efficacy endpoint of change from baseline in HbA1c will include the fixed class effects of 
treatment (placebo, dulaglutide, LY1, LY2, LY3, LY4-1, LY4-2, LY5-1, LY5-2), strata
(country, HbA1c stratum [≤8%, >8%]), visit, and treatment-by-visit interaction, as well as the 
continuous, fixed covariate of baseline value. An unstructured covariance structure will be used 
to model the within-participant errors. Significance tests will be based on least squares (LS) 
means and Type III tests. If this analysis fails to converge, the following covariance structures 
will be tested in order:

Toeplitz with heterogeneity

Autoregressive with heterogeneity 

Compound symmetry with heterogeneous variances 

Toeplitz 

Autoregressive

Compound symmetry without heterogeneous variances 
The first covariance structure that converges will be used. The Kenward-Roger approximation 
will be used to estimate denominator degrees of freedom.
Additional supplemental estimands may be explored for the primary and secondary efficacy 
endpoints.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
72
Unless specified otherwise, safety assessments will be guided by an estimand comparing safety 
of LY3502970 doses with placebo and dulaglutide irrespective of adherence to study drug. Thus, 
safety analyses will be conducted using the SS.
For continuous measures, summary statistics will include sample size, mean, SD, median, 
minimum, and maximum for both the actual and the change from baseline measurements. LS 
means and standard errors derived from the analysis models will also be displayed for the change 
from baseline measurements. Treatment comparisons will be displayed showing the treatment 
difference LS means and the 95% CIs for the treatment differences, along with the p-values for 
the treatment comparisons. 
For categorical measures, summary statistics will include sample size, frequency, and 
percentages. A logistic regression model with treatment and strata as fixed effects and the 
continuous baseline value as a covariate will be used to examine the treatment difference in 
binary efficacy outcomes. Fisher’s exact test or Pearson’s chi-square test will be used for 
treatment comparisons in other categorical outcomes.
Other statistical methods may be used, as appropriate, and details will be described in the SAP.
9.3.2.
Primary Endpoint(s)/Estimand(s) Analysis
The primary efficacy assessment, guided by the “efficacy estimand”, will be conducted using the 
EAS for the primary endpoint (change from baseline in HbA1c at Week 26). 
For the “efficacy estimand”, the hypothetical strategy is used to handle the intercurrent events 
(permanent discontinuation of study drug or initiation of rescue medication), so only data 
collected before the occurrence of any intercurrent events will be used in the MMRM analysis
(Section 9.3.1) through which the potential efficacy measures (after the intercurrent events) had 
participants had not intercurrent events will be implicitly imputed. 
The primary efficacy comparison will be based on the contrast between each treatment group of 
LY3502970 and placebo at Week 26 (Visit 15) from the MMRM analysis of change from 
baseline in HbA1c using the EAS (Section 9.2). The analysis model and selection of covariance 
structure is described in Section 9.3.1. To confirm efficacy of LY3502970 with adequate 
statistical power, the evaluation of the primary endpoint for LY4 (36 mg) and LY5 (45 mg) will 
be made by pooling two dose escalation regimens, i.e., combine LY4-1 and LY4-2 for LY4, and 
combine LY5-1 and LY5-2 for LY5.
Treatment comparisons will be performed for the primary objective at the full significance level 
of 0.05.
9.3.3.
Secondary Analyses
The following secondary study objectives will be analyzed on the EAS: 

Difference between LY3502970 and dulaglutide in change from baseline in HbA1c at 
Week 26 

Percentage of participants with HbA1c ≤6.5% and of <7.0% at Week 26

Change from baseline in fasting BG at 26 weeks

Change from baseline in body weight at Week 26

Percent change in body weight from baseline at Week 26

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
73

Percentage of participants with ≥5%, ≥10% body weight loss from baseline at Week 26
Actual and change from baseline in HbA1c, FBG, and body weight, and percent change in body 
weight will be analyzed by the MMRM model for the “efficacy estimand” as described in 
Section 9.3.1.
Treatment comparisons for the percentage of participants with HbA1c <7.0% and ≤6.5% and 
percentage of participants with ≥5%, ≥10% body weight loss will be analyzed using a logistic 
regression with treatment and strata as fixed effects and the continuous baseline value as a 
covariate.  
9.3.4.
Tertiary/Exploratory Analysis
A Bayesian approach will be used as the dose–response model for change in HbA1c and body 
weight from baseline to the 26-week endpoint. The placebo group will be modeled with 
LY3502970 doses. Details of the prior distribution specifications along with other analyses with 
regards to the exploratory objectives will be provided in the SAP.
9.3.5.
Safety Analyses
Unless specified otherwise, safety assessments will be guided by an estimand comparing safety 
of LY3502970 doses with placebo and dulaglutide 1.5 mg irrespective of adherence to study 
drug. Thus, safety analyses will be conducted using the SS.
Adverse events will be coded from the actual term using the Medical Dictionary for Regulatory 
Activities (MedDRA) and reported with preferred terms and system organ class. Selected notable 
AEs of interest may be reported using high-level terms or Standardized MedDRA Queries. 
Summary statistics will be provided for incidence of TEAEs, SAEs, study discontinuation due to 
AEs, study drug discontinuation due to AEs, deaths, and other CV endpoints. Counts and 
proportions of participants experiencing AEs will be reported for each treatment group, and 
Fisher’s exact test will be used to compare the treatment groups.
9.3.5.1.
Adverse Event of Special Interest
Summaries and analyses for incidence of AESIs will be provided by treatment. The details of 
analysis of AESI (as defined in Section 8.3) will be provided in the SAP.
9.3.5.2.
Other Adverse Event Assessments 
9.3.5.2.1. Gastrointestinal Events
Summaries and analyses for incidence and severity of nausea, vomiting, and diarrhea will be 
provided by each treatment.
9.3.5.2.2. Hypoglycemia Events 
Hypoglycemic events will be analyzed. Incidence and rate of hypoglycemia will be reported. 
Some analyses may be conducted excluding data after introducing another antihyperglycemic 
therapy.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
74
9.3.5.3.
Central Laboratory Measures, Vital Signs, and Electrocardiograms 
Actual and change from baseline to postbaseline values of central laboratory measures, vital 
signs, and selected ECG parameters will be summarized at each scheduled visit. Continuous 
variables, as well as the change from baseline for these variables, will be analyzed by MMRM 
models as described in Section 9.3.1. The percentages of participants with treatment-emergent 
(TE) abnormal, high, or low measures (including laboratory, vital, and ECG parameters) will be 
summarized and compared between treatment groups using Fisher’s exact test.
9.3.6.
Pharmacokinetic/Pharmacodynamic Analyses
LY3502970 concentration data will be summarized and analyzed using a population PK 
approach via nonlinear mixed-effects modeling. The relationships between LY3502970 dose 
and/or concentration and selected efficacy, tolerability, and safety endpoints may be 
characterized. Additionally, the impact of intrinsic and extrinsic factors, such as age, weight, 
gender, and renal function on PK and/or PD parameters, may be examined as needed. Additional 
analyses may be conducted if they are deemed appropriate. 
9.3.7.
Subgroup Analyses 
Subgroup analyses of the primary endpoint will be made to assess consistency of the intervention 
effect across the following subgroups using the “efficacy estimand”:

Age group: < 65 vs ≥ 65 years

Sex: female vs male

HbA1c stratum (≤8.0%, >8.0%)

BMI (≤30 kg/m2, >30 kg/m2)

Race

Ethnicity

Country/Region
If the number of participants is too small (less than [10%]) within a subgroup, then the subgroup 
categories may be redefined prior to unblinding the study. Further details on the statistical 
analysis will be provided in the SAP.
Analyses for HbA1c and change from baseline in HbA1c will be performed using an MMRM 
model that includes the same fixed effects given for the primary analysis model plus factors of 
subgroup, 2-way interaction of subgroup and treatment, 2-way interaction of subgroup and visit, 
and 3-way interaction of treatment, visit and subgroup. The interaction of subgroup and 
treatment at the primary endpoint (Week 26) will be evaluated to assess the treatment by 
subgroup interaction. Additional subgroup analyses may also be performed.
9.4.
Interim Analysis 
An interim efficacy and safety assessment after all participants complete Visit 12 (Week 16) of 
the treatment period may be conducted to provide information for dose escalation schemes and 
clinical trial material packaging for future studies. If conducted, an internal Assessment 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
75
Committee (AC) will be formed to review the interim analyses for the safety and efficacy reports 
in an unblinded manner. Additional interim analyses may be conducted. Details on the timing of 
the interim analyses, operational support, and unblinding will be specified in the AC charter and 
in the study unblinding plan. Information that may unblind the study during the analyses will not 
be reported to study sites or blinded study team members before the study has been unblinded for 
the final data base lock. Study sites will receive information about interim results only if deemed 
necessary for the safety of the participants. The trial will not be stopped based on the superiority 
of LY3502970 versus placebo or dulaglutide 1.5 mg. Therefore, there will be no inflation of the 
type 1 error rate and no need to employ an alpha spending function or multiplicity adjustment. 
The database lock and primary data analysis for Study GZGE will occur when all participants 
have completed the study. Participants and investigators will remain blinded until the completion 
of the study. 
The cancellation or addition of an interim analysis can be determined at any time during the 
study and will not require a protocol amendment.
Unblinding details are specified in the unblinding plan section of the SAP or in a separate 
unblinding plan document. The SAP will describe the planned interim analyses in greater detail.
9.5.
Sample Size Determination
Approximately 370 participants will be randomly assigned to study drug in a randomization ratio 
of 5:5:5:5:5:3:3:3:3, including 50 participants per treatment group to placebo, dulaglutide, LY1, 
LY2 and LY3 treatment groups, and 30 participants per treatment group to LY4-1, LY4-2, LY5-
1 and LY5-2 treatment groups.
The sample size calculation is based on the primary efficacy estimand and its endpoint (change 
from baseline to Week 26 in HbA1c). Assuming a SD of 1.1%, a 2-sided alpha level of 0.05, 40
completers for one LY3502970 treatment group and 40 completers for the placebo group can 
provide >90% power to detect a treatment difference of -0.9% between the LY3502970
treatment group and placebo (LY3502970– Placebo) in change from baseline HbA1c at Week 
26.  Taking into consideration a potentially higher dropout rate due to gastrointestinal events in 
the higher doses of LY, 50 participants for placebo arm and 60 participants per treatment group
(or 30 participants per dose escalation regimen) for LY4 and LY5 should be randomized. 
Assuming a same 20% dropout rate for dulaglutide, LY1, LY2, and LY3, 50 participants per 
treatment group should be randomized. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
76
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:
○
Consensus ethical principles derived from international guidelines including 
the Declaration of Helsinki and Council for International Organizations of 
Medical Sciences (CIOMS) International Ethical Guidelines
○
Applicable ICH Good Clinical Practice (GCP) Guidelines
○
Applicable laws and regulations
●
The protocol, protocol amendments, ICF, IB, and other relevant documents (for 
example, advertisements) must be submitted to an Institutional Review 
Board/Independent Ethics Committee (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.
●
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants.
●
The investigator will be responsible for the following:
○
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
○
Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures
○
Providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations
●
Investigator sites are compensated for participation in the study as detailed in the 
clinical trial agreement.
10.1.2.
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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
77
●
Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representatives will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, privacy and data protection 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 reconsented 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.
10.1.3.
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 his/her 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.
●
The sponsor has processes in place to ensure data protection, information security 
and data integrity. These processes include appropriate contingency plan(s) for 
appropriate and timely response in the event of a data security breach.
10.1.4.
Dissemination of Clinical Study Data
Report Preparation
An investigator will sign the final CSR for this study, indicating agreement that, to the best of his 
or her knowledge, the report accurately describes the conduct and results of the study.
Public Access to Reports and Data
Reports
The sponsor will disclose a summary of study information, including tabular study results, on 
publically available websites where required by local law or regulation.
Data

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
78
The sponsor provides access to all individual participant data collected during the trial, after 
anonymization, with the exception of PK data. Data are available to request 6 months after the 
indication studied has been approved in the US and European Union (EU) and after primary 
publication acceptance, whichever is later. No expiration date of data requests is currently set 
once they 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, SAP, CSR, blank or 
annotated CRFs, 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.
Publications/Publication Policy
The publication policy is described in the letters of agreement between the sponsor and the 
investigators and institutions.  
10.1.5.
Data Quality Assurance
●
All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically (for example, 
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 (for example, 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 are 
provided in the Monitoring Plan.
●
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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
79
●
Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the investigator for the time period outlined in the 
Clinical Trial Agreement (CTA) 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.
●
In addition, 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 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.
Data collected via the sponsor-provided data capture system will be stored at a third party. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture system(s). 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 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 sponsor will be encoded and stored in the global 
product complaint management system.
10.1.6.
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.
●
Definition of what constitutes source data can be found in Section 10.1.5.
10.1.7.
Study and Site Start and Closure
First Act of Recruitment
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first participant to enter screening and will be the study start 
date.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
80
Study or Site Termination
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:
For study termination:
●
Discontinuation of further study intervention development
For site termination:
●
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 (evaluated after a reasonable amount of time) of 
participants by the investigator
●
Total number of participants included earlier than expected.
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 participant therapy and/or follow-up.
Discontinuation of the Study
The study will be discontinued if Lilly or its designee judges it necessary for medical, safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and GCP.
A safety investigation will be triggered to determine if the study should be terminated early 
based on the following criteria:

Three study participants develop the same TEAE or SAE considered possibly or probably 
related to study drug that is severe or medically significant, but not immediately life 
threatening; or where hospitalization or prolongation of hospitalization is indicated; or is 
disabling; or limits self-care activities of daily living 
OR

Two study participants develop any TEAE or SAE regardless of attribution to study drug 
that has life-threatening consequences or requires urgent intervention
OR

Death of any study participant at any time related to AE that is considered possibly or 
probably related to study drug study drug.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
81
10.1.8.
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.
10.1.9.
Investigator Information
Researchers with appropriate education, training, and experience, as determined by the sponsor,
will participate as investigators in this clinical trial.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
82
10.2.
Appendix 2: Clinical Laboratory Tests
●
The tests detailed in the table below will be performed by the central laboratory.
●
Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample 
for central analysis is obtained at the same time. Additionally, if the local 
laboratory results are used to make either a study intervention decision or 
response evaluation, the results must be recorded.
●
In circumstances where the sponsor approves local laboratory testing in lieu of 
central laboratory testing (in the table below), the local laboratory must be 
qualified in accordance with applicable local regulations.
●
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol.
●
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 the laboratory safety results.
Laboratory/analyte results that could unblind the study will not be reported to investigative sites 
or other blinded personnel until the study has been unblinded.
Clinical Laboratory Tests
Comments 
Hematology
Assayed by Lilly-designated laboratory
Hemoglobin
Hematocrit
Erythrocyte count (RBCs - red blood cells)
Mean cell volume 
Mean cell hemoglobin
Mean cell hemoglobin concentration 
Leukocytes (WBCs - white blood cells) 
Differential
   Neutrophils, segmented
   Lymphocytes
   Monocytes
   Eosinophils
   Basophils
Platelets
Cell morphology (RBCs and WBCs)

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
83
Clinical Chemistry
Assayed by Lilly-designated laboratory
Sodium
Potassium
Chloride
Bicarbonate
Total bilirubin
Direct bilirubin
Alkaline phosphatase (ALP)
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Gamma-glutamyl transferase (GGT)
Blood urea nitrogen (BUN)
Creatinine 
Creatine kinase (CK)
Uric acid
Total protein
Albumin
Calcium
Phosphorus
Glucose
Lipid Panel 
Assayed by Lilly-designated laboratory
High-density lipoprotein cholesterol (HDL-C)
Low-density lipoprotein cholesterol (LDL-C)
Very low-density lipoprotein cholesterol 
(VLDL-C)
Total cholesterol 
Triglycerides
Urinalysis
Assayed by Lilly-designated laboratory
Specific gravity
pH
Protein
Glucose
Ketones
Bilirubin
Urobilinogen
Blood
Nitrite
Urine leukocyte esterase
Microscopic examination of sediment (as 
indicated)

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
84
Hormones (female)
Assayed by Lilly-designated laboratory
Serum pregnancy 
Follicle stimulating hormone (FSH)
Estradiol
Urine Chemistry
Assayed by Lilly-designated laboratory
Albumin
Creatinine
Calculations
Generated by Lilly-designated 
laboratory
eGFR (CKD-EPI) 
Urinary albumin/creatinine ratio (UACR)
Pharmacokinetic Samples – LY3502970
concentration
Assayed by Lilly-designated laboratory. 
Results will not be provided to the
investigative sites.
Exploratory samples 
Assayed by Lilly-designated laboratory. 
Results will not be provided to the 
investigative sites.
Exploratory storage samples: 
Serum
Plasma (EDTA)
   Plasma (P800)
Whole blood (EDTA) 
LY3502970 concentrations (PK)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the 
investigative sites.
Hypersensitivity Tests
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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
85

Tryptase
Assayed by Lilly-designated 
laboratory. Results will not be 
provided to the investigative sites.
Note: If a tryptase sample is obtained 
more than 2 hours after the event (that 
is, within 2 to 12 hours), or is not 
obtained because more than 12 hours 
have lapsed since the event, obtain urine 
sample for N-methylhistamine testing. 
Note that for tryptase serum samples 
obtained within 2 to 12 hours of the 
event, urine N-methylhistamine testing 
is performed in addition to tryptase 
testing. Collect the first void urine 
following the event. Obtain a follow-up 
urine for N-methylhistamine testing at 
the next regularly scheduled visit or 
after 4 weeks, whichever is later.

Drug-specific IgE
Will be performed if a validated assay 
is available.
Assayed by Lilly-designated laboratory. 
Results will not be provided to the 
investigative sites.

Basophil activation test
Will be performed if a validated assay 
is available.
Assayed by Lilly-designated 
laboratory. Results will not be 
provided to the investigative sites.
Note: The basophil activation test is an 
in vitro cell-based assay that only 
requires a serum sample. It is a surrogate 
assay for drug-specific IgE, but is not 
specific for IgE.

Complement (C3, C3a, and C5a)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the 
investigative sites.

Cytokine panel (IL‐6, IL‐1β, and 
IL‐10)
Assayed by Lilly-designated laboratory. 
Results will not be provided to the 
investigative sites.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
86
10.3.
Appendix 3: Adverse Events and Serious Adverse Events: Definitions
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting

The definitions and procedures detailed in this appendix are in accordance with 
International Organization for Standardization (ISO) 14155.

Both the investigator and the sponsor will comply with all local medical device 
reporting requirements.

The detection and documentation procedures described in this protocol apply to all 
sponsor medical devices provided for use in the study. See Section 6.1.1 for the list of 
sponsor medical devices).
10.3.1.
Definition of AE
AE Definition
a.
An AE is any untoward medical occurrence in a participant administered a pharmaceutical 
product and which does not necessarily have a causal relationship with the study 
intervention. 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 a medicinal (investigational) product, whether or not related to 
the medicinal (investigational) product.
b.
An AE is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory finding) in study participants, users, or other 
persons, whether or not related to the investigational medical device. This definition 
includes events related to the investigational medical device or comparator and events 
related to the procedures involved except for events in users or other persons, which only 
include events related to investigational devices.
Events Meeting the AE Definition

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (that is, 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 condition 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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
87

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 fulfill the definition of an AE or SAE.
Events NOT Meeting the AE Definition

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that 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 (for example, 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
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or 
more of the criteria listed:
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 or emergency ward (usually involving at least an overnight stay) 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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
88

Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
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 (for example, 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

Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs.
f.
Other situations:

Medical or scientific judgment should be exercised by the investigator 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.
g.
Resulted in medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function.
10.3.3.
Definition of Product Complaints
Product Complaint
a.
A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness or 
performance of a study intervention. When the ability to use the study intervention safely 
is impacted, the following are also product complaints:
b.
Deficiencies in labeling information, and
c.
Use errors for device or drug-device combination products due to ergonomic design 
elements of the product.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
89
d.
Product complaints related to study interventions used in clinical trials are collected in 
order to ensure the safety of participants, monitor quality, and to facilitate process and 
product improvements.
e.
Investigators will instruct participants to contact the site as soon as possible if he or she 
has a product complaint or problem with the study intervention so that the situation can be 
assessed.
f.
An event may meet the definition of both a product complaint and an AE/SAE. In such 
cases, it should be reported as both a product complaint and as an AE/SAE.
10.3.4.
Recording and Follow-Up of AE and/or SAE and Product Complaints
AE, SAE, and Product Complaint Recording

When an AE/SAE/product complaint occurs, it is the responsibility of the investigator 
to review all documentation (for example, hospital progress notes, laboratory reports, 
and diagnostics reports) related to the event.

The investigator will then record all relevant AE/SAE/product complaint information 
in the participant’s medical records, in accordance with the investigator’s normal 
clinical practice. AE/SAE information is reported on the appropriate (e)CRF page and 
product complaint information is reported on the Product Complaint Form.
Note: An event may meet the definition of both a product complaint and an AE/SAE. 
In such cases, it should be reported as both a product complaint and as an AE/SAE.

It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the (e)CRF page for AE/SAE 
and the Product Complaint Form for product complaints.

There may be instances when copies of medical records for certain cases are requested 
by Sponsor or designee. 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 or designee.

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.
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories:

Mild: A type of adverse event that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with usual 
activities of daily living.

Moderate: A type of adverse event that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
90
causing discomfort but poses no significant or permanent risk of harm to the research 
participant.

Severe: A type of adverse event that interrupts usual activities of daily living, or 
significantly affects clinical status, or may require intensive therapeutic intervention. 
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 one 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. The investigator will use clinical judgment to 
determine the relationship/

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.

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) 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 Sponsor or designee. 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 or designee.

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.
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 by Sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
91
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 or designee with a copy of any 
post-mortem findings including histopathology. 
10.3.5.
Reporting of SAEs
SAE Reporting via an Electronic Data Collection Tool

The primary mechanism for reporting an SAE will be the electronic data collection 
tool.

If the electronic system is unavailable, then the site will use the SAE paper form 
(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 SAE paper form (see 
next section) or to the medical monitor by telephone.

Contacts for SAE reporting can be found in study start up materials and from the 
study CRA.
SAE Reporting via Paper Form

Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the medical monitor or Lilly Global Patient Safety.

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.

Contacts for SAE reporting can be found in study start up materials.
10.3.6.
Regulatory Reporting Requirements
SAE Regulatory Reporting
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.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
92
●
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.
●
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information (for example, summary or listing of SAEs) 
from the sponsor will review and then file it along with the Investigator’s 
Brochure and will notify the IRB/IEC, if appropriate according to local 
requirements.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
93
10.4.
Appendix 4: Contraceptive and Barrier Guidance
10.4.1.
Definitions
Word/Phrase
Definition
Women of child 
bearing potential
Females are considered a woman of childbearing potential if

they have had at least one cycle of menses, or

they have Tanner 4 breast development.
Any amount of spotting should be considered menarche.  If Tanner Staging of 
breasts is performed as part of study procedures, please refer to the Reproductive, 
Pregnancy and Pediatrics Safety Committee Safety Guidance for Children in 
Clinical Trial regarding Tanner staging.
Women not of 
childbearing 
potential
Females are considered women not of childbearing potential if

they have a congenital anomaly such as Mullerian agenesis, 

they are infertile due to surgical sterilization, or 

they are post-menopausal.
Examples of surgical sterilization include 

hysterectomy, 

bilateral oophorectomy, and 

tubal ligation.
Postmenopausal 
state
The postmenopausal state should be defined as:
1.
A woman at any age at least 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative note; or 
2.
A woman at least 40 years of age and up to 55 years old with an intact 
uterus, not on hormone therapy*, who has had cessation of menses for at 
least 12 consecutive months without an alternative medical cause, AND 
With a follicle-stimulating hormone >40 mIU/mL; or 
3.
A woman 55 or older not on hormone therapy, who has had at least 12 
months of spontaneous amenorrhea, or
4.
A woman at least 55 years of age with a diagnosis of menopause prior to 
starting hormone replacement therapy
* Women should not be taking medications during amenorrhea such as oral 
contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, 
selective estrogen receptor modulators (SERMs), or chemotherapy that could 
induce transient amenorrhea.
Reproductive 
Toxicology 
Studies
Embryo-fetal studies are toxicity studies in pregnant animals designed to identify 
abnormalities in the development of fetuses, which could indicate potential for 
teratogenicity in humans.  The relevant dosing period is during organogenesis.
10.4.2.
Contraception Guidance
Women of childbearing potential are excluded from participation in this study.
The table below describes contraception guidance for men.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
94
Topic
Guidance
For all men
should refrain from sperm donation for the 
duration of the study and for 90 days or 3 months 
after last participant visit
Contraception for men with partners of 
childbearing potential 

either remain abstinent (if this is their 
preferred and usual lifestyle), or

must use condoms during intercourse 
for the duration of the study, and 

for 90 days or 3 months after last 
participant visit
Contraception for men in exclusively same sex 
relationships, as their preferred and usual lifestyle
Are not required to use contraception
Examples of highly effective, effective and unacceptable methods of contraception can be found below.
Methods
Examples
Highly effective contraception 

combination oral contraceptive pill and 
mini-pill

implanted contraceptives

injectable contraceptives

contraceptive patch (only women <198 
pounds or 90 kg)

total abstinence

vasectomy (if only sexual partner)

fallopian tube implants (if confirmed by 
hysterosalpingogram)

combined contraceptive vaginal ring, or 

intrauterine devices
Effective contraception 

male or female condoms with spermicide 

diaphragms with spermicide or cervical 
sponges

barrier method with use of a spermicide
o
condom with spermicide
o
diaphragm with spermicide, or
o
female condom with spermicide
Note:  The barrier method must include use of a 
spermicide (in other words, condom with 
spermicide, diaphragm with spermicide, female 
condom with spermicide) to be considered 
effective.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
95
Methods
Examples
Ineffective forms of contraception

spermicide alone 

immunocontraceptives

periodic abstinence

fertility awareness (calendar method, 
temperature method, combination of 
above 2, cervical mucus, symptothermal)

withdrawal,

post coital douche

lactational amenorrhea

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
96
10.5.
Appendix 5: Liver Safety: Suggested Actions and Follow-up 
Assessments 
See protocol Section 8.2.6.1 for guidance on appropriate test selection.
The Lilly-designated central laboratory must complete the analysis of all selected testing except 
for microbiology testing.
Local testing may be performed in addition to central testing, when necessary, for immediate 
participant management.
Results will be reported if a validated test or calculation is available.
Hematology
Clinical Chemistry
Hemoglobin
Total bilirubin
Hematocrit
Direct bilirubin
Erythrocytes (RBCs - red blood cells)
Alkaline phosphatase (ALP)
Leukocytes (WBCs - white blood cells)
Alanine aminotransferase (ALT)
Differential:
Aspartate aminotransferase (AST)
    Neutrophils, segmented
Gamma-glutamyl transferase (GGT)
    Lymphocytes
Creatine kinase (CK)
    Monocytes
Other Chemistry
    Basophils
Acetaminophen
    Eosinophils
Acetaminophen protein adducts
Platelets
Alkaline phosphatase isoenzymes
Cell morphology (RBC and WBC)
Ceruloplasmin
Coagulation
Copper
Ethyl alcohol (EtOH)
Prothrombin time, INR (PT-INR)
Haptoglobin
Serology
Immunoglobulin IgA (quantitative)
Hepatitis A virus (HAV) testing:
Immunoglobulin IgG (quantitative)
    HAV total antibody
Immunoglobulin IgM (quantitative)
    HAV IgM antibody
Phosphatidylethanol (PEth)
Hepatis B virus (HBV) testing:
Urine Chemistry
    Hepatitis B surface antigen (HBsAg)
Drug screen
    Hepatitis B surface antibody (anti-HBs)
Ethyl glucuronide (EtG)
    Hepatitis B core total antibody (anti-HBc)
Other Serology
    Hepatitis B core IgM antibody
Anti-nuclear antibody (ANA)
    Hepatitis B core IgG antibody
Anti-smooth muscle antibody (ASMA) a

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
97
Hematology
Clinical Chemistry
    HBV DNA d
Anti-actin antibody b
Hepatis C virus (HCV) testing:
Epstein-Barr virus (EBV) testing:
    HCV antibody
    EBV antibody
    HCV RNA d
    EBV DNA d
Hepatitis D virus (HDV) testing:
Cytomegalovirus (CMV) testing:
    HDV antibody
    CMV antibody
Hepatitis E virus (HEV) testing:
    CMV DNA d
    HEV IgG antibody
Herpes simplex virus (HSV) testing:
    HEV IgM antibody
    HSV (Type 1 and 2) antibody 
    HEV RNA d
    HSV (Type 1 and 2) DNA d
Microbiology c
Liver kidney microsomal type 1 (LKM-1) antibody
Culture:
    Blood
    Urine
Abbreviations: Ig = immunoglobulin; INR = international normalized ratio.
a
Not required if anti-actin antibody is tested.
b
Not required if anti-smooth muscle antibody (ASMA) is tested.
c
Assayed ONLY by investigator-designated local laboratory; no central testing available.
d
Reflex/confirmation dependent on regulatory requirements, testing availability, or both.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
98
10.6.
Appendix 6: World Health Organization Classification of Diabetes 
and Diagnostic Criteria
Type 1 Diabetes: Type 1 diabetes is judged to be present when the classical symptoms of 
diabetes (thirst, polyuria, wasting and stupor, or coma) are associated with readily detectable 
concentrations of glucose and ketone bodies in the blood and urine. Insulin treatment is 
necessary not only to control hyperglycemia but also to prevent spontaneous ketosis and death.
Type 2 Diabetes: Type 2 diabetes, although often asymptomatic, may also present with classical 
hyperglycemic symptoms (thirst, polyuria, weight loss), but despite hyperglycemia, ketone 
bodies are present in only low concentrations in the blood and urine. Coma is rare in type 2 
diabetes, but may result from extreme hyperglycemia and hyperosmolarity; lactic acidosis or 
ketoacidosis can also occur in fulminating illness (for example, severe infection or mesenteric 
artery thrombosis) due to an acute increase in insulin requirements, but spontaneous ketosis does 
not occur. Some patients with type 2 diabetes later progress to a state of absolute insulin 
deficiency (Alberti and Zimmet 1998). 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
99
10.7.
Appendix 7: New York Heart Association Functional Classification 
of Heart Failure
Class
Symptomatology 
I
No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, 
palpitation, dyspnea.
II
Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in 
fatigue, palpitation, dyspnea.
III
Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes 
fatigue, palpitation, or dyspnea.
IV
Unable to carry on any physical activity without discomfort.  Symptoms of heart failure at rest. 
If any physical activity is undertaken, discomfort increases.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
100
10.8.
Appendix 8: Protocol GZGE Standardized Protocols for the
Measurement of Height, Weight, Waist Circumference, Vital Signs 
and 7-Point Self-Monitoring Blood Glucose (SMBG)
The following information has been adapted from standardized physical measurement protocols 
for the WHO’s STEPwise approach to Surveillance (STEPS) (WHO 2017). 
Measuring Height
Step 1. Ask the participant to remove their footwear and any headgear (light headgear worn for 
religious reasons can remain, but this should be worn by the participant at every clinic visit when 
their height is measured).
Step 2. Ask the participant to stand on the calibrated height measuring board (stadiometer) or 
against a wall with their feet together and their knees straight with their heels against the 
backboard, the stadiometer, or the wall.
Step 3. Ask the participant to look straight ahead without tilting their head up.
Step 4. Ask the participant to breathe in and stand tall. Measure and record the participant’s 
height in centimeters to 1 decimal place. 
Measuring Weight
Body weight measurements should be done in a consistent manner using a calibrated 
electronic scale capable of measuring weight in kilograms to 1 decimal place.
All weights for a given participant should be measured using the same scale, whenever 
possible, at approximately the same time in the morning after evacuation of bladder 
contents.  
Body weight should be measured in fasting state. If the participant is not fasting, the 
participant should be called in for a new visit within the visit window to have the fasting 
body weight measured.
Step 1. Ask the participant to empty their pockets, remove their footwear, outerwear (coat, 
jacket, etc.), and any headgear (light headgear worn for religious reasons can remain, but this 
should be worn by the participant at every clinic visit when weight is measured).
Step 2. Make sure the scale is placed on a firm, flat, even surface (not on carpet, on a sloping 
surface, or a rough, uneven surface).
Step 3. Ask the participant to step onto the scale with 1 foot on each side of the scale.
Step 4. Ask the participant to stand still with arms by sides and then record weight in kilograms 
to the nearest one-tenth kilogram.
Measuring Waist Circumference

Waist circumference should be measured in the horizontal plane and at the midpoint 
between the lower margin of the last palpable rib and the top of the iliac crest.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
101

Measurements should be taken at the end of a normal expiration using a nonstretchable 
measuring tape. The tape should lie flat against the skin without compressing the soft 
tissue.

The waist circumference should be measured twice, rounded to the nearest 0.5 cm. The 
measuring tape should be removed between the 2 measurements. Both measurements 
will be recorded in the eCRF. If the difference between the 2 measurements exceeds 
1 cm, this set of measurements should be discarded and the 2 measurements repeated.
Step 1: Ask the participant to wear little clothing (if available, garments could also be used).
Step 2: Ask the participant to stand with their feet close together, arms at their side, body weight 
evenly distributed.
Step 3: Ask the participant to relax and measure the participant’s waist circumference.
Vital Sign Measurements

Vital sign measurements (blood pressure and heart rate, measured by pulse) should be 
taken before obtaining an ECG tracing and before collection of blood samples for 
laboratory testing.

The participant should sit quietly for 5 minutes before vital signs measurements are 
taken.

For each parameter, 2 measurements will be taken using the same arm, preferably the 
nondominant arm.

The recordings should be taken at least 1 minute apart. Each measurement of sitting 
pulse and BP needs to be recorded in the eCRF.

BP must be taken with an automated blood pressure instrument.

If blood pressure and pulse measurements are taken separately, pulse should be taken 
prior to blood pressure.
Note: In the event pulse measurement cannot be taken via an automated blood pressure 
instrument, the preferred location for measurement of pulse is the radial artery. 
7-Point Self-Monitoring Blood Glucose
Seven-point SMBG profiles consist of measurements obtained before each meal, approximately 
2 hours after each meal, and at bedtime on a day during the week before the scheduled clinic 
visit. Participants will record their SMBG levels in their diaries, according to instructions. The 
complete 7-point profile must be collected on a single day. If a participant does not complete the 
entire profile on a single day, all 7 points must be collected on a subsequent day.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
102
10.9.
Appendix 9: Patient-Reported Outcomes
Short Form-36 version 2 Health Survey acute form, 1 week recall version
The Short Form-36 version 2 Health Survey acute form (SF-36v2 acute), 1-week recall version is 
a 36-item generic, participant-completed measure designed to assess the following 8 domains
• Physical Functioning 
• Role Physical
• Bodily Pain
• General Health
• Vitality
• Social Functioning 
• Role Emotional, and
• Mental Health. 
The Physical Functioning domain assesses limitations due to health “now” while the remaining 
domains assess functioning “in the past week.” Each domain is scored individually and 
information from these 8 domains are further aggregated into 2 health component summary 
scores: Physical Component Summary and Mental Component Summary. Items are answered on 
Likert scales of varying lengths (3-point, 5-point, or 6-point scales). Scoring of each domain and 
both summary scores are norm based and presented in the form of T-scores, with a mean of 50 
and standard deviation of 10; higher scores indicate better levels of function and/or better health 
(Maruish 2011).
Diabetes Treatment Satisfaction Questionnaire-Status Version 
The Diabetes Treatment Satisfaction Questionnaire-Status Version (DTSQs) (Bradley and Lewis 
1990; Bradley 1994) is a diabetes-specific patient-reported outcome instrument that assesses the 
overall treatment satisfaction and perceived frequency of hyperglycemia and hypoglycemia. It is 
appropriate for use in both type 1 and type 2 diabetes.
The DTSQs consists of 8 items that assess treatment satisfaction as well as concerns about 
hyperglycemia and hypoglycemia over the past few weeks, prior to the visit. Each item is rated 
on a 7-point Likert scale. Items 1, 4, 5-7, and 8 are rated from 0 (very dissatisfied) to 6 (very 
satisfied) and can be summed up to produce a treatment satisfaction score. Items 2 and 3 evaluate 
the perceived frequency of hyperglycemia and hypoglycemia and are rated from 0 (none of the 
time) to 6 (most of the time).
Diabetes Treatment Satisfaction Questionnaire-Change Version
The Diabetes Treatment Satisfaction Questionnaire-Change Version (DTSQc) (Bradley 1999) 
was designed to overcome potential ceiling effects in the status version.  The DTSQc has the 
same 8 items as the status version, but is reworded slightly to measure the change in treatment 
satisfaction rather than absolute treatment satisfaction.
Each item is scored on a scale of -3 to +3.  For all items except items 2 (perceived frequency of 
hyperglycemia) and item 3 (perceived frequency of hypoglycemia): 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
103

the higher the score, the greater the improvement in treatment satisfaction

the lower the score, the greater the deterioration in treatment satisfaction, and

a score of 0 represents no change. 
For items 2 and 3: the lower the score, the better the perception.
Participant Survey
The Participant Survey is a participant-completed form, which includes questions to understand 
participant experience with and preference for study treatments (injectable vs. oral), and the 
factors influencing their preferences. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
104
10.10.
Appendix 10: Provisions for Changes in Study Conduct During 
Exceptional Circumstances
Implementation of this appendix
The changes to procedures described in this appendix are temporary measures intended to be 
used only during specific time periods as directed by the sponsor in partnership with the 
investigator.
Exceptional circumstances
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study.
Examples include pandemics or natural disasters. These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures.
Implementing changes under exceptional circumstances
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may 
implement changes if permitted by local regulations. 
After approval by local Ethical Review Boards, regulatory bodies and any other relevant local 
authorities, implementation of these exceptional circumstance changes will not typically require 
additional notification to these groups, unless they have specific requirements in which 
notification is required (for example, upon implementation and suspension of changes). All 
approvals and notifications must be retained in the study records.
If the sponsor grants written approval for changes in study conduct, the sponsor will also provide 
additional written guidance, if needed.
Considerations for making a change
The prevailing consideration for making a change is ensuring the safety of study participants.
Additional important considerations for making a change are compliance with GCP, enabling 
participants to continue safely in the study and maintaining the integrity of the study. 
Informed consent
Additional consent from the participant will be obtained, if required, for:

participation in remote visits, as defined in Section “Remote Visits,”

dispensation of additional study intervention during an extended treatment period, 

alternate delivery of study intervention and ancillary supplies, and

provision of their personal or medical information required prior to implementation of 
these activities. 
Changes in study conduct during exceptional circumstances
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed.
The following changes in study conduct will not be considered protocol deviations.
Remote visits
Types of remote visits

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
105
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Assessments to be completed in this manner include, but are 
not limited to, adverse events, SMBG values and concomitant medications 
Mobile healthcare:
Healthcare visits may be performed by a mobile healthcare provider at locations other than the 
study site when participants cannot travel to the site due to an exceptional circumstance if written 
approval is provided by the sponsor. Procedures performed at such visits include, but are not 
limited to, concomitant medications, SMBG values, vital signs (BP and PR), body weight, 
collection of blood samples, physical assessments, administration of PROs if validated for these 
types of visits, administration of study intervention, and collection of health information. 
Other alternative locations:  
During exceptional circumstances, laboratory samples may be drawn locally, if needed outside of 
mobile healthcare visits.
Data capture
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits.
Safety reporting
Regardless of the type of remote visits implemented, the protocol requirements regarding the 
reporting of AEs, SAEs, and PCs remain unchanged. 
Return to on-site visits
Every effort should be made to enable participants to return to on-site visits as soon as 
reasonably possible, while ensuring the safety of both the participants and the site staff.
Local laboratory testing option
Local laboratory testing may be conducted in lieu of central laboratory testing. However, central 
laboratory testing must be retained for: Visits 3, 10, and 15. The local laboratory must be 
qualified in accordance with applicable local regulations.
Study intervention and ancillary supplies (including participant diaries)
When a participant is unable to go to the site to receive study supplies during normal on-site 
visits, the site should work with the sponsor to determine appropriate actions. These actions may
include: 

asking the participant to go to the site and receive study supplies from site staff 
without completion of a full study visit, 

asking the participant’s designee to go to the site and receive study supplies on a 
participant’s behalf, and

arranging delivery of study supplies.
These requirements must be met before action is taken:

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
106

Alternate delivery of study intervention should be performed in a manner that does 
not compromise treatment blinding and ensures product integrity. The existing 
protocol requirements for product accountability remain unchanged, including 
verification of participant’s receipt of study supplies.

When delivering supplies to a location other than the study site (for example, 
participant’s home), the investigator, sponsor, or both should ensure oversight of the 
shipping process to ensure accountability and product quality (that is, storage 
conditions maintained and intact packaging upon receipt).

Instructions may be provided to the participant or designee on the final disposition of 
any unused or completed study supplies.
Screening period guidance
To ensure safety of study participants, laboratory values and other eligibility assessments taken 
at screening visit are valid for a maximum of 30 days. The following rules will be applied for 
active, nonrandomized participants whose participation in the study must be paused due to 
exceptional circumstances:

If screening is paused for less than 30 days from screening visits to randomization 
visit: the participant will proceed to the next study visit per the usual SoA, 
provided that randomization visit must be conducted within 30 days from first 
screening/lead-in visit.
o
The site should conduct the next visit if the participant’s eligibility criteria 
are confirmed, and the site should document the reason for delay.
o
Due to the pause in screening, sites should also reconfirm the impacted
participant’s consent and document this confirmation in the source 
documentation.

If screening is paused for more than 30 days from screening visits to 
randomization visit, the participant must be discontinued because of screening 
interruption due to an exceptional circumstance. This is documented as a screen 
failure in the CRF. The participant can reconsent and be rescreened as a new 
participant. The screening procedures per the usual SoA should be followed, 
starting at screening visit to ensure participant eligibility by randomization visit.
Adjustments to visit windows 
Whenever possible and safe to do so, as determined by the investigator’s discretion, participants 
should complete the usual SoA. To maximize the possibility that these visits can be conducted as 
on-site visits, the windows for visits may be adjusted, upon further guidance from the sponsor. 
This minimizes missing data and preserves the intended conduct of the study.
This table describes the allowed adjustments to visit windows.

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
107
Visit Number
Tolerance
Visit 4 through 
Visit 15
within 10 days before or after the intended date per the SoA
Visit 801
within 14 days before the intended date, or up to 28 days after the 
intended date per the SoA
For participants whose visits have extended windows, additional study intervention may need to 
be provided to avoid interruption and maintain overall integrity of the study.
Documentation
Changes to study conduct will be documented
Sites will identify and document the details of how participants, visit types, and conducted 
activities were affected by exceptional circumstances. Dispensing/shipment records of study 
intervention and relevant communications, including delegation, should be filed with site study 
records.
Source documents at alternate locations
Source documents generated at a location other than the study site should be part of the 
investigator’s source documentation and should be transferred to the site in a secure and timely 
manner. 

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
108
10.11.
Appendix 11: Abbreviations and Definitions
Term
Definition
AC
Assessment Committee
ADA
American Diabetes Association
AE
adverse event
AESI
adverse event of special interest
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANA
antinuclear antibody
ASMA
anti-smooth muscle antibody
AST
aspartate aminotransferase
AUC
area under the curve
BG
blood glucose
blinding/masking
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 subjects 
are aware of the treatment received.
BMI
body mass index
BP
Blood pressure
CEC
Clinical endpoint committee
CFR
Code of Federal Regulations
CI
Confidence interval
CIOMS
Council for International Organizations of Medical Sciences
CK
creatine kinase
CKD-EPI
chronic kidney disease epidemiology
Cmax
maximum concentration
CMV
cytomegalovirus

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
109
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
CRF
Case report form
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.
CRS
clinical research scientist
CSR
Clinical study report
CV
cardiovascular
D. bil.
Direct bilirubin
DTSQc
Diabetes Treatment Satisfaction Questionnaire-Change Version
DTSQs
Diabetes Treatment Satisfaction Questionnaire-Status Version
EAS
Efficacy analysis set
EBV
Epstein-Barr virus
ECG
Electrocardiogram
eCRF
Electronic case report form
eGFR
estimated glomerular filtration rate
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.
ERCP
endoscopic retrograde cholangiopancreatography
ET
Early termination
FAS
Full analysis set
FBG
fasting blood glucose
FSH
follicle stimulating hormone
GI
gastrointestinal

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
110
GCP
good clinical practice
GGT
gamma-glutamyl transferase
GLP-1
glucagon-like peptide-1
GLP-1 RA
glucagon-like peptide-1 receptor agonist
GPS
Global Patient Safety
HbA1c
hemoglobin A1c
HAV, HBV, HCV, HDV,
HEV
hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis E virus
HIV
human immunodeficiency virus
HR
heart rate
HSV
herpes simplex virus
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonization
IEC
Independent Ethics Committee
Ig
immunoglobulin
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.
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 is 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
Institutional Review Board
IWRS
interactive web-response system
LH
luteinizing hormone
LS
least squares
LY
LY3502970

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
111
MAD
multiple-ascending dose
MEN2
multiple endocrine neoplasia type 2
MMRM
mixed-effect model repeated measures
MRCP
magnetic resonance cholangiopancreatography
MTC
medullary carcinoma of the thyroid
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
PR
pulse rate
Pro-C3
biomarker for liver fibrosis
PRO/ePRO
patient-reported outcomes/electronic patient-reported outcomes
PT-INR
Prothrombin time
QD
once-daily
QTc
corrected QT interval
QW
once-weekly
OTC
over the counter
SAD
Single-ascending dose
SAE
serious adverse event
SAP
statistical analysis plan
SS
Safety analysis set
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. 
SF-36 v2 acute form
Short Form-36 version 2 health survey acute form
SDPs
single dose pens
SMBG
self-monitoring of blood glucose
SoA
schedule of activities

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
112
T1DM
Type 1 diabetes mellitus
T2DM
Type 2 diabetes mellitus
TBL
total bilirubin
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.
THC
tetrahydrocannabinol
TXP
treatment
UACR
Urinary albumin creatinine ratio
ULN
Upper limit of normal
WHO
World Health Organization
Wks
weeks
WNOCBP
women not of childbearing potential

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
113
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 a: 30 June 2021
This amendment is considered to be nonsubstantial 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 
because it neither significantly impacts the safety or physical/mental integrity of participants nor 
the scientific value of the study.
Overall Rationale for the Amendment
There was a typographical error in the Section 2.3 Benefit/Risk assessment. The section referred 
to ambulatory blood pressure monitoring (ABPM). ABPM is not being conducted in this study; 
however, it is being collected in a Phase 2 obesity study (J2A-MC-GZGI) that will be conducted 
at the same time as this study.
Section # and 
Name
Description of Change
Brief Rationale
2.3.1. Risk 
Assessment
Deleted reference to ABPM, as it 
will not be conducted in this 
study.
ABPM is not being conducted in this 
study but is being conducted in a Phase 
2 study evaluating the effects of 
LY3502970 in participants with obesity 
or overweight with comorbidities. 
Throughout the 
protocol
Minor editorial changes made 
throughout the protocol.
Correction

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
114
11.
References
[ADA] American Diabetes Association. 6. Glycemic targets: standards of medical care in 
diabetes-2020. Diabetes Care. 2020;43(suppl 1):S66-S76. https://doi.org/10.2337/dc20-S006
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its 
complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a 
WHO consultation. Diabet Med. 1998;15(7):539-553. https://doi.org/10.1002/(SICI)1096-
9136(199807)15:7<539:AID-DIA668>3.0.CO;2-S
Aroda VR, Ratner R. The safety and tolerability of GLP-1 receptor agonists in the treatment of 
type 2 diabetes: a review. Diabetes Metab Res Rev. 2011;27(6):528-542. 
https://doi.org/10.1002/dmrr.1202
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 
2007;132(6):2131–2157. https://doi.org/10.1053/j.gastro.2007.03.054
Banks PA, Freeman ML; Practice Parameters Committee of the American College of 
Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 
2006;101(10):2379-2400. https://doi.org/10.1111/j.1572-0241.2006.00856.x
Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiol. 1902;28:325–353.
https://doi.org/10.1113/jphysiol.1902.sp000920
Bradley C. (Ed). Handbook of psychology and diabetes: a guide to psychological measurement 
in diabetes research and practice; Harwood Academic Publishers, 1994. 
Bradley C. Diabetes Treatment Satisfaction Questionnaire: Change version for use alongside 
status version provides appropriate solution where ceiling effects occur. Diabetes Care. 
1999:22(3):530-532. https://doi.org/10.2337/diacare.22.3.530  
Bradley C, Lewis KS. Measures of psychological well-being and treatment satisfaction 
developed from the responses of people with tablet-treated diabetes. Diabet Med. 
1990;7(5):445-451. https://doi.org/10.1111/j.1464-5491.1990.tb01421.x
Dungan KM, Povedano ST, Forst T, et al. Once weekly dulaglutide versus once-daily liraglutide 
in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, 
phase 3, non-inferiority trial. Lancet. 2014; 384(9951):1349–1357.
https://doi.org/10.1016/S0140-6736(14)60976-4
Giorgino F, Benroubi M, Sun JH, et al. Efficacy and safety of once weekly dulaglutide versus 
insulin glargine in patients with type 2 diabetes on metformin and glimepiride (AWARD-2). 
Diabetes Care. 2015;38(12):2241–2249. https://doi.org/10.2337/dc14-1625
Jendle J, Grunberger G, Blevins T, et al. Efficacy and safety of dulaglutide in the treatment of 
type 2 diabetes: a comprehensive review of the dulaglutide clinical data focusing on the 
AWARD phase 3 clinical trial program. Diabetes Metab Res Rev. 2016;32(8):776–790.
https://doi.org/10.1002/dmrr.2810
Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) 
analogue semaglutide. J Med Chem. 2015;58:7370–80.   
https://doi.org/10.1021/acs.jmedchem.5b00726

CONFIDENTIAL
Protocol J2A-MC-GZGE (b)
115
Maruish ME, ed. User’s Manual for the SF-36v2 Health Survey. 3rd ed. Lincoln, RI: Quality 
Metric Incorporated; 2011.
Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric 
emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997;273(5 Pt 
1):E981–8. https://doi.org/10.1152/ajpendo
Nauck M, Frid A, Hermansen K, et al. for the and for the LEAD-2 Study Group. Efficacy and 
safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, 
in type 2 diabetes: the LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care. 
2009;32(1):84–90. https://doi.org/10.2337/dc08-1355
Nauck M. Incretin therapies: highlighting common features and differences in the modes of 
action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. 
Diabetes Obes Metab. 2016;18(3):203-216.  https://doi.org/10.1111/dom.12591
Nauck MA, Meier JJ, Schmidt WE. Incretin-based glucose-lowering medications and the risk of 
acute pancreatitis and/or pancreatic cancer: reassuring data from cardio-vascular outcome 
trials. Diabetes Obes Metab. 2017;19(9):1327-1328. https://doi.org/10.1111/dom.12981
Pratley RE, Aroda VR, Lingvay I, et al. SUSTAIN 7 investigators. Semaglutide versus 
dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-
label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275-286.  
https://doi.org/0.1016/S2213-8587(18)30024-X
Scheen AJ. Dulaglutide for the treatment of type 2 diabetes. Expert Opin Biol 
Ther. 2017;17(4):485-496. https://doi.org/10.1080/14712598.2017.1296131
Steinberg WM, Buse JB, Ghorbani MLM, et al.; LEADER Steering Committee; LEADER Trial 
Investigators. Amylase, lipase, and acute pancreatitis in people with type 2 diabetes treated 
with liraglutide: results from the LEADER randomized trial. Diabetes Care. 
2017a;40(7):966-972. https://doi.org/10.2337/dc16-2747
Steinberg WM, Rosenstock J, Wadden TA, et al. Impact of liraglutide on amylase, lipase, and 
acute pancreatitis in participants with overweight/obesity and normoglycemia, prediabetes, or 
type 2 diabetes: secondary analyses of pooled data from the SCALE clinical development 
program. Diabetes Care. 2017b;40(7):839-848. https://doi.org/10.2337/dc16-2684
Trulicity [summary of product characteristics]. Indianapolis, IN: Eli Lilly and Company; 2020.
Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; 2020.
Werner U, Haschke G, Herling AW, Kramer W. Pharmacological profile of lixisenatide. A new 
GLP-1 receptor agonist for the treatment of type 2 diabetes. Regul Pept. 2010;164:58–64.
https//doi.org/10.1016/j.regpep.2010.05.008
[WHO] World Health Organization. WHO STEPS surveillance manual: the WHO STEPwise 
approach to noncommunicable disease risk factor surveillance. Updated January 26, 2017. 
Accessed May 04, 2020. https://www.who.int/ncds/surveillance/steps/STEPS_Manual.pdf

Leo Document ID = 3a662cc0-d0a4-4912-b29e-a3a0309049de
Approver: 
Approval Date & Time: 27-Oct-2021 00:43:02 GMT
Signature meaning: Approved
Approver: 
Approval Date & Time: 27-Oct-2021 00:51:01 GMT
Signature meaning: Approved
PPD
PPD