A Study to Compare a New Drug for Type 2 Diabetes to Placebo and to a Treatment Already Available for Type 2 Diabetes

• Sponsor: OPKO Health, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02119819
• Collaborator: (none)
• Enrollment: 420
• Locations: 51
• Arms: 6
• Duration (Months): 18
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The main purpose of this study is to compare the safety and effectiveness of the study drug known as LY2944876 to exenatide extended-release and placebo in participants with type 2 diabetes mellitus. All drugs will be given by an injection under the skin. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry. Participants' involvement in the study is expected to last about 30 weeks.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: LY2944876; Drug: Exenatide extended-release; Drug: Placebo; Drug: Metformin	Phase 2

Detailed Description

The study will include a 12 week blinded treatment period, where neither the participant nor the investigator will know to which treatment each individual is assigned. Thereafter follows a 12 week period where participants and the investigator will know which treatment they are assigned to. Participants' on LY2944876 and on exenatide extended-release continue treatment in this period, those who received placebo will be followed without treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 420 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Comparison of the Oxyntomodulin Analog, LY2944876, to Once-Weekly Exenatide and to Placebo in Patients With Type 2 Diabetes
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 10 mg LY2944876 10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: LY2944876; Administered SC; Drug: Metformin; Oral
Experimental: 15 mg LY2944876 15 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: LY2944876; Administered SC; Drug: Metformin; Oral
Experimental: 30 mg LY2944876 30 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: LY2944876; Administered SC; Drug: Metformin; Oral
Experimental: 50 mg LY2944876 50 mg LY2944876 given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: LY2944876; Administered SC; Drug: Metformin; Oral
Experimental: Exenatide extended-release 2 mg exenatide extended-release given SC once weekly for 24 weeks. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Exenatide extended-release; Administered SC; Drug: Metformin; Oral
Placebo Comparator: Placebo Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study. Participants remain on stable doses of metformin, as prescribed by their personal investigator if they were on metformin at study entry.	Drug: Placebo; Administered SC; Drug: Metformin; Oral

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 [Baseline, Week 12]

   HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Secondary Outcome Measures

1. Change From Baseline in HbA1c at Week 24 [Baseline, Week 24]

   HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

2. Percent Change From Baseline in Body Weight [Baseline, Week 12; Baseline, Week 24]

3. Change From Baseline in Fasting Blood Glucose [Baseline, Week 12; Baseline, Week 24]

   Least square means (LSM) was calculated from mixed-effects model with repeated measures (MMRM) analysis using restricted maximum likelihood (REML) with metformin use, baseline body mass index (BMI) category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.

4. Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values [Baseline, Week (Wk) 12; Baseline, Week 24]

   SMBG 7-point profiles were measured at morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. LSM were calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.

5. Change From Baseline in Lipids [Baseline, Week 24]

   Change from baseline in high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C). LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant an a random effect.

6. Change From Baseline in Fasting Fibroblast Growth Factor 21 [Baseline, Week 12; Baseline, Week 24]

   LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

7. Percentage of Participants Requiring Rescue Therapy [Baseline through Therapy Completion (Week 24)]

   Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.

8. Percentage of Participants Developing Anti-Drug Antibodies to LY2944876 [Week 12 and Week 24]

   Percentage of participants developing anti-drug antibodies to LY2944876.

9. Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876 [Baseline, Week 8, Week 12, Week 16, Week 20, Week 24]

   Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.

10. Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876 [Baseline, Week 8, Week 12, Week 16, Week 20, Week 24]

    Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.

11. Change From Baseline in Adiponectin Levels [Baseline, Week 12; Baseline, Week 24]

    LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

12. Change From Baseline in Beta-Hydroxy Butyrate Levels [Baseline, Week 12; Baseline, Week 24]

    LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

13. Change From Baseline in Glucagon Levels [Baseline, Week 12; Baseline, Week 24]

    LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

14. Change From Baseline in Insulin Levels [Baseline, Week 12; Baseline, Week 24]

    LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men or women with diabetes mellitus Type 2

• Have screening HbA1c ≥7.0% and ≤10.5% either on diet and exercise alone or on a stable dose of metformin (≥1000 mg/day) for 3 months prior to screening

• Have body mass index (BMI) ≥23 and ≤45 kilograms per meter squared at screening

Exclusion Criteria:

• Women of child bearing potential

• Participants who have used thiazolidinediones within 3 months prior to screening, or any other drugs for treatment of hyperglycemia (except metformin) within the prior 2 months

• Participants who have used insulin for diabetic control for more than 6 consecutive days within the prior year

• Participants with impaired renal function (serum creatinine >124 micromole per liter (µmol/L) [1.4 milligrams per deciliter (mg/dL)] in women, >133 µmol/L [1.5 mg/dL] in men)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Muir Physician Network Clinical Research Center	Concord	California	United States	94520
2	Valley Endocrine, Fresno	Fresno	California	United States	93720
3	National Research Institute	Los Angeles	California	United States	90057
4	Desert Medical Group Inc	Palm Springs	California	United States	92262
5	Artemis Institute for Clinical Research	San Diego	California	United States	92103
6	Encompass Clinical Research	Spring Valley	California	United States	91978
7	Meridien Research	Bradenton	Florida	United States	34208
8	M & O Clinical Research, LLC	Fort Lauderdale	Florida	United States	33316
9	Suncoast Research Group, LLC	Miami	Florida	United States	33135
10	Suncoast Clinical Research	New Port Richey	Florida	United States	34652
11	Compass Research	Oviedo	Florida	United States	32765
12	Clinical Research of Central Florida	Winter Haven	Florida	United States	33880
13	University of Hawaii	Honolulu	Hawaii	United States	96813
14	East West Medical Institute	Honolulu	Hawaii	United States	96814
15	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
16	Iderc, P.L.C.	Des Moines	Iowa	United States	50314
17	Cotton O'Neil Diabetes and Endocrinology Center	Topeka	Kansas	United States	66606
18	St John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
19	Mercy Medical Research Institute	Springfield	Missouri	United States	65807
20	Mercy Health Research	Washington	Missouri	United States	63090
21	Southern New Hampshire Diabetes and Endocrinology	Nashua	New Hampshire	United States	03063
22	High Point Clinical Trials Center	High Point	North Carolina	United States	27265
23	Lillestol Research LLC	Fargo	North Dakota	United States	58103
24	The Corvallis Clinic P.C.	Corvallis	Oregon	United States	97330
25	Blair Medical Associates, Inc.	Altoona	Pennsylvania	United States	16602
26	Texas Diabetes and Endocrinology	Austin	Texas	United States	78731
27	Dallas Diabetes Endocrine Center	Dallas	Texas	United States	75230
28	San Gabriel Clinical Research	Georgetown	Texas	United States	78626
29	Oakwell Clinical Research	San Antonio	Texas	United States	78218
30	Southwest Health Associates, P.A.	Sugar Land	Texas	United States	77478
31	Wade Family Medicine	Bountiful	Utah	United States	84010
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ampelokipoi		Greece	11527
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Athens		Greece	11527
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Thessaloniki		Greece	57010
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chihuahua		Mexico	31238
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara		Mexico	44690
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tampico		Mexico	89000
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bialystok		Poland	15-351
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdansk		Poland	80-546
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gdynia		Poland	81-553
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz		Poland	90-242
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poznan		Poland	61-853
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Szczecin		Poland	70-506
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Warsaw		Poland	01-518
45	Manati Medical Center	Manati		Puerto Rico	00674
46	American Telemedicine Center	San Juan		Puerto Rico	00917-3104
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cluj-Napoca		Romania	400349
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Iaşi		Romania	700547
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ploiesti		Romania	100342
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Targu Mures		Romania	540098
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Timisoara		Romania	300456

Sponsors and Collaborators

• OPKO Health, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: OPKO Health, Inc.
• ClinicalTrials.gov Identifier: NCT02119819
• Other Study ID Numbers: 15062; 2013-003552-21; I7I-MC-XNAA
• First Posted: Apr 22, 2014
• Last Update Posted: May 27, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by OPKO Health, Inc.: Weight loss
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Exenatide

Study Results

Participant Flow

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks, plus background PO metformin.	15 mg LY2944876 given SC once weekly for 24 weeks, plus background PO metformin..	30 mg LY2944876 given SC once weekly for 24 weeks, plus background PO metformin..	50 mg LY2944876 given SC once weekly for 24 weeks, plus background PO metformin..	2 mg exenatide extended-release given SC once weekly for 24 weeks, plus background PO metformin..	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks,plus background PO metformin. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Period Title: Overall Study
STARTED	66	71	73	70	69	71
COMPLETED	57	66	69	63	62	56
NOT COMPLETED	9	5	4	7	7	15

Baseline Characteristics

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo	Total
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.	Total of all reporting groups
Overall Participants	66	71	73	70	69	71	420
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.1 (9.4)	59.0 (8.5)	56.1 (8.3)	55.6 (8.4)	57.6 (9.1)	56.5 (9.7)	57.1 (8.9)
Sex: Female, Male (Count of Participants)
Female	33 50%	40 56.3%	26 35.6%	33 47.1%	32 46.4%	35 49.3%	199 47.4%
Male	33 50%	31 43.7%	47 64.4%	37 52.9%	37 53.6%	36 50.7%	221 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 28.8%	21 29.6%	26 35.6%	19 27.1%	22 31.9%	22 31%	129 30.7%
Not Hispanic or Latino	42 63.6%	42 59.2%	42 57.5%	47 67.1%	44 63.8%	47 66.2%	264 62.9%
Unknown or Not Reported	5 7.6%	8 11.3%	5 6.8%	4 5.7%	3 4.3%	2 2.8%	27 6.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 1.5%	2 2.8%	1 1.4%	1 1.4%	2 2.9%	1 1.4%	8 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	4 6.1%	3 4.2%	5 6.8%	5 7.1%	2 2.9%	6 8.5%	25 6%
White	55 83.3%	59 83.1%	59 80.8%	58 82.9%	59 85.5%	58 81.7%	348 82.9%
More than one race	6 9.1%	6 8.5%	8 11%	6 8.6%	6 8.7%	6 8.5%	38 9%
Unknown or Not Reported	0 0%	1 1.4%	0 0%	0 0%	0 0%	0 0%	1 0.2%
Region of Enrollment (participants) [Number]
Greece	6 9.1%	6 8.5%	5 6.8%	4 5.7%	5 7.2%	6 8.5%	32 7.6%
Puerto Rico	1 1.5%	2 2.8%	2 2.7%	1 1.4%	3 4.3%	3 4.2%	12 2.9%
Romania	9 13.6%	10 14.1%	10 13.7%	9 12.9%	9 13%	10 14.1%	57 13.6%
United States	32 48.5%	33 46.5%	33 45.2%	34 48.6%	31 44.9%	30 42.3%	193 46%
Poland	9 13.6%	10 14.1%	12 16.4%	12 17.1%	12 17.4%	11 15.5%	66 15.7%
Mexico	9 13.6%	10 14.1%	11 15.1%	10 14.3%	9 13%	11 15.5%	60 14.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12
Description	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline HbA1c data at Week 12. Missing observations are imputed using the Bayesian simple linear regression longitudinal model.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	57	68	68	65	63	62
Mean (Standard Error) [percentage of HbA1c]	-1.07 (0.12)	-1.09 (0.11)	-1.44 (0.11)	-1.33 (0.11)	-1.42 (0.11)	-0.29 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	10 mg LY2944876, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.459
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.78
	Confidence Interval	(2-Sided) 90%; -1.05 to -0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	15 mg LY2944876, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.511
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 90%; -1.07 to -0.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	30 mg LY2944876, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.988
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.15
	Confidence Interval	(2-Sided) 90%; -1.41 to -0.89
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	50 mg LY2944876, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.934
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-1.04
	Confidence Interval	(2-Sided) 90%; -1.30 to -0.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	10 mg LY2944876, Exenatide Extended-release
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.373
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 90%; 0.08 to 0.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	15 mg LY2944876, Exenatide Extended-release
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.433
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 90%; 0.07 to 0.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	30 mg LY2944876, Exenatide Extended-release
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.978
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 90%; -0.28 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	50 mg LY2944876, Exenatide Extended-release
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.904
	Comments
	Method	Bayesian
	Comments
Method of Estimation	Estimation Parameter	Posterior Mean Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 90%; -0.17 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.16
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 24
Description	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline HbA1c data at Week 24. Missing observations are imputed using the Bayesian simple linear regression longitudinal model.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	55	66	68	62	60	51
Mean (Standard Error) [percentage of HbA1c]	-0.85 (0.14)	-1.14 (0.13)	-1.37 (0.13)	-1.29 (0.13)	-1.48 (0.13)	-0.38 (0.14)

3. Secondary Outcome

Title	Percent Change From Baseline in Body Weight
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for body weight. Missing observations are imputed using the Bayesian simple linear regression longitudinal model.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	57	68	68	65	63	63
Week 12	-1.09 (0.35)	-1.86 (0.33)	-2.01 (0.33)	-3.23 (0.34)	-2.04 (0.35)	-1.22 (0.34)
Week 24	-1.57 (0.47)	-2.13 (0.45)	-1.98 (0.45)	-3.41 (0.46)	-2.18 (0.47)	-1.70 (0.46)

4. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose
Description	Least square means (LSM) was calculated from mixed-effects model with repeated measures (MMRM) analysis using restricted maximum likelihood (REML) with metformin use, baseline body mass index (BMI) category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for fasting blood glucose. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	-20.881 (4.618)	-21.991 (4.371)	-31.309 (4.305)	-28.405 (4.506)	-39.074 (4.419)	-1.588 (4.519)
Week 24	-21.497 (4.919)	-30.186 (4.639)	-29.875 (4.548)	-31.390 (4.785)	-40.328 (4.726)	0.124 (4.973)

5. Secondary Outcome

Title	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values
Description	SMBG 7-point profiles were measured at morning pre-meal, morning 2 hours post-meal, mid-day pre-meal, mid-day 2 hours post-meal, evening pre-meal, evening 2 hours post-meal, and at bedtime. LSM were calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline fasting blood glucose as a covariate, and participant as a random effect.
Time Frame	Baseline, Week (Wk) 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for SMBG. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Morning pre-meal (Week 12)	-26.8 (3.9)	-28.4 (3.8)	-34.3 (3.7)	-34.8 (3.8)	-38.7 (3.8)	-7.4 (3.8)
Morning pre-meal (Week 24)	-23.5 (4.7)	-29.1 (4.5)	-29.6 (4.3)	-34.2 (4.5)	-36.8 (4.5)	-14.4 (4.9)
Morning 2 hours post-meal (Week 12)	-27.9 (6.7)	-34.2 (6.8)	-36.0 (6.3)	-26.4 (6.6)	-43.5 (6.5)	-1.5 (6.5)
Morning 2 hours post-meal (Week 24)	-29.9 (6.5)	-35.9 (6.5)	-37.1 (6.1)	-42.8 (6.4)	-42.7 (6.4)	-6.3 (6.8)
Mid-day pre-meal (Week 12)	-17.1 (5.1)	-19.6 (5.1)	-26.1 (4.8)	-24.2 (5.0)	-23.5 (5.0)	-2.3 (5.0)
Mid-day pre-meal (Week 24)	-16.3 (5.6)	-23.4 (5.6)	-22.4 (5.3)	-23.5 (5.4)	-23.9 (5.5)	-4.0 (6.0)
Mid-day 2 hours post-meal (Week 12)	-17.1 (6.4)	-20.7 (6.3)	-24.6 (6.0)	-22.2 (6.2)	-27.4 (6.2)	-8.9 (6.1)
Mid-day 2 hours post-meal (Week 24)	-12.2 (6.1)	-26.6 (5.9)	-21.9 (5.7)	-33.4 (5.9)	-37.2 (5.9)	-8.5 (6.4)
Evening pre-meal (Week 12)	-24.1 (5.3)	-24.8 (5.2)	-28.5 (4.9)	-30.1 (5.1)	-24.7 (5.1)	-1.5 (5.1)
Evening pre-meal (Week 24)	-24.9 (5.7)	-24.3 (5.6)	-33.0 (5.3)	-29.6 (5.4)	-36.4 (5.6)	-5.7 (6.0)
Evening 2 hours post-meal (Week 12)	-25.1 (5.9)	-26.5 (5.7)	-33.4 (5.4)	-32.8 (5.7)	-33.5 (5.7)	4.0 (5.6)
Evening 2 hours post-meal (Week 24)	-30.2 (5.9)	-27.9 (5.8)	-26.0 (5.5)	-37.2 (5.8)	-36.9 (5.8)	1.1 (6.2)
Bedtime (Week 12)	-19.3 (5.7)	-33.5 (5.8)	-33.2 (5.8)	-36.2 (5.6)	-41.6 (5.7)	5.6 (5.7)
Bedtime (Week 24)	-28.9 (6.0)	-25.4 (6.0)	-32.3 (5.7)	-38.5 (5.9)	-42.9 (6.0)	-6.9 (6.4)

6. Secondary Outcome

Title	Change From Baseline in Lipids
Description	Change from baseline in high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C). LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant an a random effect.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for lipids. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
HDL-C	1.56 (1.03)	0.92 (0.98)	0.90 (0.96)	1.04 (1.01)	2.35 (0.990)	2.17 (1.04)
Total Cholesterol	-1.26 (4.37)	-1.12 (4.16)	-1.46 (4.09)	-5.11 (4.24)	-0.12 (4.22)	7.32 (4.40)
Triglycerides	-14.63 (11.49)	-13.32 (10.93)	-15.40 (10.59)	-20.96 (11.16)	-11.83 (11.01)	10.61 (11.58)
LDL-C	-1.37 (3.75)	-0.40 (3.57)	-0.24 (3.56)	-0.04 (3.72)	0.37 (3.65)	4.55 (3.81)

7. Secondary Outcome

Title	Change From Baseline in Fasting Fibroblast Growth Factor 21
Description	LSM was calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for fasting fibroblast growth factor 21. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	-0.07 (0.071)	0.06 (0.068)	-0.03 (0.068)	-0.14 (0.069)	-0.09 (0.069)	-0.11 (0.071)
Week 24	0.06 (0.071)	-0.04 (0.068)	-0.07 (0.067)	-0.12 (0.070)	-0.06 (0.069)	-0.09 (0.073)

8. Secondary Outcome

Title	Percentage of Participants Requiring Rescue Therapy
Description	Participants who received rescue medication with non-study antihyperglycemic medications or change their stable dose of metformin.
Time Frame	Baseline through Therapy Completion (Week 24)

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for participants requiring rescue therapy.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Number [percentage of participants]	6.1 9.2%	2.8 3.9%	2.7 3.7%	4.3 6.1%	2.9 4.2%	11.3 15.9%

9. Secondary Outcome

Title	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876
Description	Percentage of participants developing anti-drug antibodies to LY2944876.
Time Frame	Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug and had evaluable immunogenicity.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	70	69	71
Week 12	1.7 2.6%	1.4 2%	1.5 2.1%	0 0%	1.6 2.3%	0 0%
Week 24	1.8 2.7%	0 0%	1.5 2.1%	0 0%	0 0%	0 0%

10. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876
Description	Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.
Time Frame	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug LY2944876 and had evaluable PK data.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.
Measure Participants	66	71	73	70
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	607 (282)	799 (368)	1690 (732)	2570 (1240)

11. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876
Description	Evaluable pharmacokinetic concentrations from the specified timepoints were combined and utilized in a population approach to determine the population mean estimate and standard deviation at steady-state.
Time Frame	Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug LY2944876 and had evaluable PK data.

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.
Measure Participants	66	71	73	70
Mean (Standard Deviation) [nanograms*hour per milliliter (ng*h/mL)]	88100 (40600)	117000 (50800)	247000 (106000)	381000 (187000)

12. Secondary Outcome

Title	Change From Baseline in Adiponectin Levels
Description	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for adiponectin levels. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	0.14 (0.168)	0.03 (0.160)	-0.10 (0.157)	0.12 (0.161)	0.04 (0.160)	0.03 (0.164)
Week 24	0.03 (0.245)	0.30 (0.226)	0.28 (0.221)	0.58 (0.235)	0.14 (0.231)	0.25 (0.250)

13. Secondary Outcome

Title	Change From Baseline in Beta-Hydroxy Butyrate Levels
Description	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for beta-hydroxy butyrate levels. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	-0.27 (0.13)	-0.28 (0.12)	-0.13 (0.12)	-0.31 (0.12)	-0.29 (0.12)	-0.23 (0.13)
Week 24	-0.33 (0.11)	-0.39 (0.10)	-0.34 (0.10)	-0.33 (0.10)	-0.19 (0.10)	-0.37 (0.11)

14. Secondary Outcome

Title	Change From Baseline in Glucagon Levels
Description	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for glucagon levels. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	-1.26 (0.82)	-2.65 (0.79)	-5.14 (0.79)	-6.21 (0.81)	-1.58 (0.79)	-0.04 (0.84)
Week 24	-2.30 (1.15)	-2.25 (1.05)	-4.40 (1.05)	-4.93 (1.11)	-0.19 (1.08)	0.66 (1.16)

15. Secondary Outcome

Title	Change From Baseline in Insulin Levels
Description	LSM are calculated from MMRM analysis using REML with metformin use, baseline BMI category, baseline HbA1c category, country, treatment, visit, and treatment-by-visit interaction as fixed effects, baseline parameter result as a covariate, and participant as a random effect.
Time Frame	Baseline, Week 12; Baseline, Week 24

Outcome Measure Data

Analysis Population Description

All randomized participants with baseline and at least one post-baseline data for insulin levels. Missing observations are imputed using last observation carried forward (LOCF).

Arm/Group Title	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	15 mg LY2944876 given SC once weekly for 24 weeks.	30 mg LY2944876 given SC once weekly for 24 weeks.	50 mg LY2944876 given SC once weekly for 24 weeks.	2 mg exenatide extended-release given SC once weekly for 24 weeks.	Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
Measure Participants	66	71	73	69	69	71
Week 12	0.30 (1.21)	0.97 (1.13)	0.03 (1.14)	0.96 (1.17)	2.78 (1.14)	-0.85 (1.16)
Week 24	-1.44 (1.51)	0.68 (1.39)	0.58 (1.40)	0.34 (1.48)	1.97 (1.40)	1.45 (1.51)

Adverse Events

Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug.
Arm/Group Title	10 mg LY2944876		15 mg LY2944876		30 mg LY2944876		50 mg LY2944876		Exenatide Extended-release		Placebo
Arm/Group Description	10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.		15 mg LY2944876 given SC once weekly for 24 weeks.		30 mg LY2944876 given SC once weekly for 24 weeks.		50 mg LY2944876 given SC once weekly for 24 weeks.		2 mg exenatide extended-release given SC once weekly for 24 weeks.		Placebo for LY2944876 and Exenatide given SC once weekly for 12 weeks. Participants assigned to placebo will have no injections during the second 12 weeks of the study.
All Cause Mortality
	10 mg LY2944876		15 mg LY2944876		30 mg LY2944876		50 mg LY2944876		Exenatide Extended-release		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	10 mg LY2944876		15 mg LY2944876		30 mg LY2944876		50 mg LY2944876		Exenatide Extended-release		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/66 (0%)		2/71 (2.8%)		2/73 (2.7%)		3/70 (4.3%)		3/69 (4.3%)		2/71 (2.8%)
Cardiac disorders
Acute myocardial infarction	0/66 (0%)	0	1/71 (1.4%)	1	0/73 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Angina unstable	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Congenital, familial and genetic disorders
Branchial cyst	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Eye disorders
Cataract	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Gastrointestinal disorders
Abdominal pain lower	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Pancreatitis	0/66 (0%)	0	0/71 (0%)	0	1/73 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Infections and infestations
Abscess limb	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Urinary tract infection	0/66 (0%)	0	0/71 (0%)	0	1/73 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Endometrial cancer	0/66 (0%)	0	1/71 (1.4%)	1	0/73 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/66 (0%)	0	0/71 (0%)	0	1/73 (1.4%)	1	0/70 (0%)	0	0/69 (0%)	0	0/71 (0%)	0
Skin and subcutaneous tissue disorders
Blood blister	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Surgical and medical procedures
Cataract operation	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	1/69 (1.4%)	1	0/71 (0%)	0
Vascular disorders
Vessel perforation	0/66 (0%)	0	0/71 (0%)	0	0/73 (0%)	0	0/70 (0%)	0	0/69 (0%)	0	1/71 (1.4%)	1
Other (Not Including Serious) Adverse Events
	10 mg LY2944876		15 mg LY2944876		30 mg LY2944876		50 mg LY2944876		Exenatide Extended-release		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/66 (51.5%)		47/71 (66.2%)		39/73 (53.4%)		46/70 (65.7%)		38/69 (55.1%)		16/71 (22.5%)
Gastrointestinal disorders
Abdominal pain upper	1/66 (1.5%)	1	1/71 (1.4%)	1	2/73 (2.7%)	7	3/70 (4.3%)	3	4/69 (5.8%)	5	1/71 (1.4%)	2
Constipation	3/66 (4.5%)	3	4/71 (5.6%)	4	4/73 (5.5%)	4	5/70 (7.1%)	8	2/69 (2.9%)	2	1/71 (1.4%)	1
Diarrhoea	7/66 (10.6%)	35	15/71 (21.1%)	24	13/73 (17.8%)	45	12/70 (17.1%)	25	18/69 (26.1%)	52	4/71 (5.6%)	16
Dyspepsia	0/66 (0%)	0	1/71 (1.4%)	1	2/73 (2.7%)	3	5/70 (7.1%)	8	1/69 (1.4%)	2	0/71 (0%)	0
Flatulence	1/66 (1.5%)	1	1/71 (1.4%)	1	4/73 (5.5%)	4	2/70 (2.9%)	2	1/69 (1.4%)	1	0/71 (0%)	0
Gastrooesophageal reflux disease	1/66 (1.5%)	1	1/71 (1.4%)	1	1/73 (1.4%)	1	4/70 (5.7%)	4	2/69 (2.9%)	2	0/71 (0%)	0
Nausea	11/66 (16.7%)	28	21/71 (29.6%)	33	20/73 (27.4%)	53	32/70 (45.7%)	90	17/69 (24.6%)	55	4/71 (5.6%)	4
Vomiting	8/66 (12.1%)	9	6/71 (8.5%)	6	10/73 (13.7%)	21	22/70 (31.4%)	37	6/69 (8.7%)	12	2/71 (2.8%)	3
Infections and infestations
Bronchitis	4/66 (6.1%)	4	1/71 (1.4%)	1	3/73 (4.1%)	3	2/70 (2.9%)	2	0/69 (0%)	0	0/71 (0%)	0
Influenza	1/66 (1.5%)	1	4/71 (5.6%)	5	1/73 (1.4%)	3	2/70 (2.9%)	2	1/69 (1.4%)	1	2/71 (2.8%)	3
Nasopharyngitis	8/66 (12.1%)	8	9/71 (12.7%)	11	5/73 (6.8%)	5	4/70 (5.7%)	4	6/69 (8.7%)	7	2/71 (2.8%)	3
Sinusitis	1/66 (1.5%)	1	5/71 (7%)	6	2/73 (2.7%)	2	0/70 (0%)	0	2/69 (2.9%)	2	2/71 (2.8%)	2
Upper respiratory tract infection	2/66 (3%)	3	10/71 (14.1%)	12	5/73 (6.8%)	5	3/70 (4.3%)	3	4/69 (5.8%)	4	1/71 (1.4%)	1
Viral upper respiratory tract infection	0/66 (0%)	0	0/71 (0%)	0	4/73 (5.5%)	6	1/70 (1.4%)	2	0/69 (0%)	0	0/71 (0%)	0
Injury, poisoning and procedural complications
Muscle strain	0/66 (0%)	0	4/71 (5.6%)	4	1/73 (1.4%)	1	1/70 (1.4%)	1	0/69 (0%)	0	0/71 (0%)	0
Investigations
Lipase increased	4/66 (6.1%)	4	2/71 (2.8%)	2	2/73 (2.7%)	2	5/70 (7.1%)	9	0/69 (0%)	0	0/71 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	3/66 (4.5%)	3	6/71 (8.5%)	6	6/73 (8.2%)	6	8/70 (11.4%)	9	2/69 (2.9%)	2	1/71 (1.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/66 (0%)	0	2/71 (2.8%)	2	0/73 (0%)	0	5/70 (7.1%)	5	1/69 (1.4%)	1	0/71 (0%)	0
Back pain	4/66 (6.1%)	4	6/71 (8.5%)	7	1/73 (1.4%)	1	2/70 (2.9%)	2	2/69 (2.9%)	3	2/71 (2.8%)	3
Nervous system disorders
Dizziness	4/66 (6.1%)	4	2/71 (2.8%)	2	1/73 (1.4%)	1	2/70 (2.9%)	2	1/69 (1.4%)	1	1/71 (1.4%)	1
Headache	5/66 (7.6%)	7	9/71 (12.7%)	13	5/73 (6.8%)	5	6/70 (8.6%)	11	9/69 (13%)	14	4/71 (5.6%)	4
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/66 (4.5%)	3	3/71 (4.2%)	3	1/73 (1.4%)	1	2/70 (2.9%)	2	4/69 (5.8%)	4	1/71 (1.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.