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

Comparison of the Oxyntomodulin Analog, LY2944876, to Once-Weekly Exenatide and to Placebo in Patients With Type 2 Diabetes

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02119819

Enrollment

420

Registered

2014-04-22

Start date

2014-04-30

Completion date

2015-10-31

Last updated

2021-05-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 2

Keywords

Weight loss

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.

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.

Interventions

DRUGLY2944876

Administered SC

DRUGExenatide extended-release

Administered SC

DRUGPlacebo

Administered SC

DRUGMetformin

Oral

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
Percent Change From Baseline in Body Weight	Baseline, Week 12; Baseline, Week 24	—
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12 and Week 24	Percentage of participants developing anti-drug antibodies to LY2944876.

Countries

Greece, Mexico, Poland, Puerto Rico, Romania, United States

Participant flow

Participants by arm

Arm	Count
10 mg LY2944876 10 milligrams (mg) LY2944876 given subcutaneously (SC) once weekly for 24 weeks.	66
15 mg LY2944876 15 mg LY2944876 given SC once weekly for 24 weeks.	71
30 mg LY2944876 30 mg LY2944876 given SC once weekly for 24 weeks.	73
50 mg LY2944876 50 mg LY2944876 given SC once weekly for 24 weeks.	70
Exenatide Extended-release 2 mg exenatide extended-release given SC once weekly for 24 weeks.	69
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.	71
Total	420

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005
Overall Study	Adverse Event	3	1	2	3	0	1
Overall Study	Jury Duty	0	0	1	0	0	0
Overall Study	Lack of Efficacy	0	0	0	0	0	1
Overall Study	Left the city to get a job	0	0	0	1	0	0
Overall Study	Lost to Follow-up	0	0	1	2	1	2
Overall Study	Physician Decision	1	1	0	0	0	1
Overall Study	Protocol Violation	0	0	0	1	0	0
Overall Study	Withdrawal by Subject	5	3	0	0	6	10

Baseline characteristics

Characteristic	10 mg LY2944876	15 mg LY2944876	30 mg LY2944876	50 mg LY2944876	Exenatide Extended-release	Placebo	Total
Age, Continuous	58.1 years STANDARD_DEVIATION 9.4	59.0 years STANDARD_DEVIATION 8.5	56.1 years STANDARD_DEVIATION 8.3	55.6 years STANDARD_DEVIATION 8.4	57.6 years STANDARD_DEVIATION 9.1	56.5 years STANDARD_DEVIATION 9.7	57.1 years STANDARD_DEVIATION 8.9
Ethnicity (NIH/OMB) Hispanic or Latino	19 Participants	21 Participants	26 Participants	19 Participants	22 Participants	22 Participants	129 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants	42 Participants	42 Participants	47 Participants	44 Participants	47 Participants	264 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants	8 Participants	5 Participants	4 Participants	3 Participants	2 Participants	27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	1 Participants	1 Participants	2 Participants	1 Participants	8 Participants
Race (NIH/OMB) Black or African American	4 Participants	3 Participants	5 Participants	5 Participants	2 Participants	6 Participants	25 Participants
Race (NIH/OMB) More than one race	6 Participants	6 Participants	8 Participants	6 Participants	6 Participants	6 Participants	38 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	55 Participants	59 Participants	59 Participants	58 Participants	59 Participants	58 Participants	348 Participants
Region of Enrollment Greece	6 participants	6 participants	5 participants	4 participants	5 participants	6 participants	32 participants
Region of Enrollment Mexico	9 participants	10 participants	11 participants	10 participants	9 participants	11 participants	60 participants
Region of Enrollment Poland	9 participants	10 participants	12 participants	12 participants	12 participants	11 participants	66 participants
Region of Enrollment Puerto Rico	1 participants	2 participants	2 participants	1 participants	3 participants	3 participants	12 participants
Region of Enrollment Romania	9 participants	10 participants	10 participants	9 participants	9 participants	10 participants	57 participants
Region of Enrollment United States	32 participants	33 participants	33 participants	34 participants	31 participants	30 participants	193 participants
Sex: Female, Male Female	33 Participants	40 Participants	26 Participants	33 Participants	32 Participants	35 Participants	199 Participants
Sex: Female, Male Male	33 Participants	31 Participants	47 Participants	37 Participants	37 Participants	36 Participants	221 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	34 / 66	47 / 71	39 / 73	46 / 70	38 / 69	16 / 71
serious Total, serious adverse events	0 / 66	2 / 71	2 / 73	3 / 70	3 / 69	2 / 71

Outcome results

Primary

Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12

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

Population: 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	Measure	Value (MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-1.07 percentage of HbA1c	Standard Error 0.12
15 mg LY2944876	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-1.09 percentage of HbA1c	Standard Error 0.11
30 mg LY2944876	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-1.44 percentage of HbA1c	Standard Error 0.11
50 mg LY2944876	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-1.33 percentage of HbA1c	Standard Error 0.11
Exenatide Extended-release	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-1.42 percentage of HbA1c	Standard Error 0.11
Placebo	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12	-0.29 percentage of HbA1c	Standard Error 0.11

p-value: 0.45990% CI: [-1.05, -0.52]Bayesian

p-value: 0.51190% CI: [-1.07, -0.54]Bayesian

p-value: 0.98890% CI: [-1.41, -0.89]Bayesian

p-value: 0.93490% CI: [-1.3, -0.78]Bayesian

p-value: 0.37390% CI: [0.08, 0.61]Bayesian

p-value: 0.43390% CI: [0.07, 0.59]Bayesian

p-value: 0.97890% CI: [-0.28, 0.24]Bayesian

p-value: 0.90490% CI: [-0.17, 0.35]Bayesian

Secondary

Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	-30.2 mg/dL	Standard Error 5.9
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-24.1 mg/dL	Standard Error 5.3
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-12.2 mg/dL	Standard Error 6.1
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-24.9 mg/dL	Standard Error 5.7
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-27.9 mg/dL	Standard Error 6.7
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-28.9 mg/dL	Standard Error 6
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-23.5 mg/dL	Standard Error 4.7
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	-19.3 mg/dL	Standard Error 5.7
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-26.8 mg/dL	Standard Error 3.9
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-17.1 mg/dL	Standard Error 5.1
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	-25.1 mg/dL	Standard Error 5.9
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-17.1 mg/dL	Standard Error 6.4
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-16.3 mg/dL	Standard Error 5.6
10 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-29.9 mg/dL	Standard Error 6.5
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-24.3 mg/dL	Standard Error 5.6
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-24.8 mg/dL	Standard Error 5.2
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	-27.9 mg/dL	Standard Error 5.8
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	-26.5 mg/dL	Standard Error 5.7
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-29.1 mg/dL	Standard Error 4.5
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	-33.5 mg/dL	Standard Error 5.8
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-28.4 mg/dL	Standard Error 3.8
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-25.4 mg/dL	Standard Error 6
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-34.2 mg/dL	Standard Error 6.8
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-35.9 mg/dL	Standard Error 6.5
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-26.6 mg/dL	Standard Error 5.9
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-19.6 mg/dL	Standard Error 5.1
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-23.4 mg/dL	Standard Error 5.6
15 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-20.7 mg/dL	Standard Error 6.3
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-24.6 mg/dL	Standard Error 6
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-32.3 mg/dL	Standard Error 5.7
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-37.1 mg/dL	Standard Error 6.1
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-28.5 mg/dL	Standard Error 4.9
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	-33.2 mg/dL	Standard Error 5.8
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	-33.4 mg/dL	Standard Error 5.4
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	-26.0 mg/dL	Standard Error 5.5
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-33.0 mg/dL	Standard Error 5.3
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-21.9 mg/dL	Standard Error 5.7
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-22.4 mg/dL	Standard Error 5.3
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-29.6 mg/dL	Standard Error 4.3
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-26.1 mg/dL	Standard Error 4.8
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-34.3 mg/dL	Standard Error 3.7
30 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-36.0 mg/dL	Standard Error 6.3
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-33.4 mg/dL	Standard Error 5.9
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-26.4 mg/dL	Standard Error 6.6
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-29.6 mg/dL	Standard Error 5.4
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	-36.2 mg/dL	Standard Error 5.6
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-38.5 mg/dL	Standard Error 5.9
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-22.2 mg/dL	Standard Error 6.2
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-34.8 mg/dL	Standard Error 3.8
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-42.8 mg/dL	Standard Error 6.4
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-34.2 mg/dL	Standard Error 4.5
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-23.5 mg/dL	Standard Error 5.4
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	-37.2 mg/dL	Standard Error 5.8
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-30.1 mg/dL	Standard Error 5.1
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-24.2 mg/dL	Standard Error 5
50 mg LY2944876	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	-32.8 mg/dL	Standard Error 5.7
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-42.9 mg/dL	Standard Error 6
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-23.9 mg/dL	Standard Error 5.5
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	-33.5 mg/dL	Standard Error 5.7
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-38.7 mg/dL	Standard Error 3.8
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-36.8 mg/dL	Standard Error 4.5
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-43.5 mg/dL	Standard Error 6.5
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-42.7 mg/dL	Standard Error 6.4
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-23.5 mg/dL	Standard Error 5
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-27.4 mg/dL	Standard Error 6.2
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-37.2 mg/dL	Standard Error 5.9
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-24.7 mg/dL	Standard Error 5.1
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-36.4 mg/dL	Standard Error 5.6
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	-36.9 mg/dL	Standard Error 5.8
Exenatide Extended-release	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	-41.6 mg/dL	Standard Error 5.7
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 12)	-8.9 mg/dL	Standard Error 6.1
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 24)	-4.0 mg/dL	Standard Error 6
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 12)	4.0 mg/dL	Standard Error 5.6
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening 2 hours post-meal (Week 24)	1.1 mg/dL	Standard Error 6.2
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day pre-meal (Week 12)	-2.3 mg/dL	Standard Error 5
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 24)	-6.3 mg/dL	Standard Error 6.8
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning 2 hours post-meal (Week 12)	-1.5 mg/dL	Standard Error 6.5
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Mid-day 2 hours post-meal (Week 24)	-8.5 mg/dL	Standard Error 6.4
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 12)	5.6 mg/dL	Standard Error 5.7
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 24)	-14.4 mg/dL	Standard Error 4.9
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Morning pre-meal (Week 12)	-7.4 mg/dL	Standard Error 3.8
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Bedtime (Week 24)	-6.9 mg/dL	Standard Error 6.4
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 24)	-5.7 mg/dL	Standard Error 6
Placebo	Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values	Evening pre-meal (Week 12)	-1.5 mg/dL	Standard Error 5.1

Secondary

Change From Baseline in Adiponectin Levels

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 12	0.14 µg/L	Standard Error 0.168
10 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 24	0.03 µg/L	Standard Error 0.245
15 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 12	0.03 µg/L	Standard Error 0.16
15 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 24	0.30 µg/L	Standard Error 0.226
30 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 12	-0.10 µg/L	Standard Error 0.157
30 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 24	0.28 µg/L	Standard Error 0.221
50 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 24	0.58 µg/L	Standard Error 0.235
50 mg LY2944876	Change From Baseline in Adiponectin Levels	Week 12	0.12 µg/L	Standard Error 0.161
Exenatide Extended-release	Change From Baseline in Adiponectin Levels	Week 24	0.14 µg/L	Standard Error 0.231
Exenatide Extended-release	Change From Baseline in Adiponectin Levels	Week 12	0.04 µg/L	Standard Error 0.16
Placebo	Change From Baseline in Adiponectin Levels	Week 12	0.03 µg/L	Standard Error 0.164
Placebo	Change From Baseline in Adiponectin Levels	Week 24	0.25 µg/L	Standard Error 0.25

Secondary

Change From Baseline in Beta-Hydroxy Butyrate Levels

Time frame: Baseline, Week 12; Baseline, Week 24

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.27 mg/dL	Standard Error 0.13
10 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.33 mg/dL	Standard Error 0.11
15 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.28 mg/dL	Standard Error 0.12
15 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.39 mg/dL	Standard Error 0.1
30 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.13 mg/dL	Standard Error 0.12
30 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.34 mg/dL	Standard Error 0.1
50 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.31 mg/dL	Standard Error 0.12
50 mg LY2944876	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.33 mg/dL	Standard Error 0.1
Exenatide Extended-release	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.29 mg/dL	Standard Error 0.12
Exenatide Extended-release	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.19 mg/dL	Standard Error 0.1
Placebo	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 12	-0.23 mg/dL	Standard Error 0.13
Placebo	Change From Baseline in Beta-Hydroxy Butyrate Levels	Week 24	-0.37 mg/dL	Standard Error 0.11

Secondary

Change From Baseline in Fasting Blood Glucose

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 12	-20.881 milligrams per deciliter (mg/dL)	Standard Error 4.618
10 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 24	-21.497 milligrams per deciliter (mg/dL)	Standard Error 4.919
15 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 12	-21.991 milligrams per deciliter (mg/dL)	Standard Error 4.371
15 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 24	-30.186 milligrams per deciliter (mg/dL)	Standard Error 4.639
30 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 12	-31.309 milligrams per deciliter (mg/dL)	Standard Error 4.305
30 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 24	-29.875 milligrams per deciliter (mg/dL)	Standard Error 4.548
50 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 24	-31.390 milligrams per deciliter (mg/dL)	Standard Error 4.785
50 mg LY2944876	Change From Baseline in Fasting Blood Glucose	Week 12	-28.405 milligrams per deciliter (mg/dL)	Standard Error 4.506
Exenatide Extended-release	Change From Baseline in Fasting Blood Glucose	Week 12	-39.074 milligrams per deciliter (mg/dL)	Standard Error 4.419
Exenatide Extended-release	Change From Baseline in Fasting Blood Glucose	Week 24	-40.328 milligrams per deciliter (mg/dL)	Standard Error 4.726
Placebo	Change From Baseline in Fasting Blood Glucose	Week 12	-1.588 milligrams per deciliter (mg/dL)	Standard Error 4.519
Placebo	Change From Baseline in Fasting Blood Glucose	Week 24	0.124 milligrams per deciliter (mg/dL)	Standard Error 4.973

Secondary

Change From Baseline in Fasting Fibroblast Growth Factor 21

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	0.06 microgram per liter (µg/L)	Standard Error 0.071
10 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	-0.07 microgram per liter (µg/L)	Standard Error 0.071
15 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	-0.04 microgram per liter (µg/L)	Standard Error 0.068
15 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	0.06 microgram per liter (µg/L)	Standard Error 0.068
30 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	-0.03 microgram per liter (µg/L)	Standard Error 0.068
30 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	-0.07 microgram per liter (µg/L)	Standard Error 0.067
50 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	-0.14 microgram per liter (µg/L)	Standard Error 0.069
50 mg LY2944876	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	-0.12 microgram per liter (µg/L)	Standard Error 0.07
Exenatide Extended-release	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	-0.06 microgram per liter (µg/L)	Standard Error 0.069
Exenatide Extended-release	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	-0.09 microgram per liter (µg/L)	Standard Error 0.069
Placebo	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 12	-0.11 microgram per liter (µg/L)	Standard Error 0.071
Placebo	Change From Baseline in Fasting Fibroblast Growth Factor 21	Week 24	-0.09 microgram per liter (µg/L)	Standard Error 0.073

Secondary

Change From Baseline in Glucagon Levels

Time frame: Baseline, Week 12; Baseline, Week 24

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Glucagon Levels	Week 24	-2.30 picomol per liter (pmol/L)	Standard Error 1.15
10 mg LY2944876	Change From Baseline in Glucagon Levels	Week 12	-1.26 picomol per liter (pmol/L)	Standard Error 0.82
15 mg LY2944876	Change From Baseline in Glucagon Levels	Week 24	-2.25 picomol per liter (pmol/L)	Standard Error 1.05
15 mg LY2944876	Change From Baseline in Glucagon Levels	Week 12	-2.65 picomol per liter (pmol/L)	Standard Error 0.79
30 mg LY2944876	Change From Baseline in Glucagon Levels	Week 12	-5.14 picomol per liter (pmol/L)	Standard Error 0.79
30 mg LY2944876	Change From Baseline in Glucagon Levels	Week 24	-4.40 picomol per liter (pmol/L)	Standard Error 1.05
50 mg LY2944876	Change From Baseline in Glucagon Levels	Week 12	-6.21 picomol per liter (pmol/L)	Standard Error 0.81
50 mg LY2944876	Change From Baseline in Glucagon Levels	Week 24	-4.93 picomol per liter (pmol/L)	Standard Error 1.11
Exenatide Extended-release	Change From Baseline in Glucagon Levels	Week 12	-1.58 picomol per liter (pmol/L)	Standard Error 0.79
Exenatide Extended-release	Change From Baseline in Glucagon Levels	Week 24	-0.19 picomol per liter (pmol/L)	Standard Error 1.08
Placebo	Change From Baseline in Glucagon Levels	Week 24	0.66 picomol per liter (pmol/L)	Standard Error 1.16
Placebo	Change From Baseline in Glucagon Levels	Week 12	-0.04 picomol per liter (pmol/L)	Standard Error 0.84

Secondary

Change From Baseline in HbA1c at Week 24

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

Population: 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	Measure	Value (MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in HbA1c at Week 24	-0.85 percentage of HbA1c	Standard Error 0.14
15 mg LY2944876	Change From Baseline in HbA1c at Week 24	-1.14 percentage of HbA1c	Standard Error 0.13
30 mg LY2944876	Change From Baseline in HbA1c at Week 24	-1.37 percentage of HbA1c	Standard Error 0.13
50 mg LY2944876	Change From Baseline in HbA1c at Week 24	-1.29 percentage of HbA1c	Standard Error 0.13
Exenatide Extended-release	Change From Baseline in HbA1c at Week 24	-1.48 percentage of HbA1c	Standard Error 0.13
Placebo	Change From Baseline in HbA1c at Week 24	-0.38 percentage of HbA1c	Standard Error 0.14

Secondary

Change From Baseline in Insulin Levels

Time frame: Baseline, Week 12; Baseline, Week 24

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Insulin Levels	Week 24	-1.44 micro-international units/milliliter	Standard Error 1.51
10 mg LY2944876	Change From Baseline in Insulin Levels	Week 12	0.30 micro-international units/milliliter	Standard Error 1.21
15 mg LY2944876	Change From Baseline in Insulin Levels	Week 24	0.68 micro-international units/milliliter	Standard Error 1.39
15 mg LY2944876	Change From Baseline in Insulin Levels	Week 12	0.97 micro-international units/milliliter	Standard Error 1.13
30 mg LY2944876	Change From Baseline in Insulin Levels	Week 24	0.58 micro-international units/milliliter	Standard Error 1.4
30 mg LY2944876	Change From Baseline in Insulin Levels	Week 12	0.03 micro-international units/milliliter	Standard Error 1.14
50 mg LY2944876	Change From Baseline in Insulin Levels	Week 12	0.96 micro-international units/milliliter	Standard Error 1.17
50 mg LY2944876	Change From Baseline in Insulin Levels	Week 24	0.34 micro-international units/milliliter	Standard Error 1.48
Exenatide Extended-release	Change From Baseline in Insulin Levels	Week 24	1.97 micro-international units/milliliter	Standard Error 1.4
Exenatide Extended-release	Change From Baseline in Insulin Levels	Week 12	2.78 micro-international units/milliliter	Standard Error 1.14
Placebo	Change From Baseline in Insulin Levels	Week 12	-0.85 micro-international units/milliliter	Standard Error 1.16
Placebo	Change From Baseline in Insulin Levels	Week 24	1.45 micro-international units/milliliter	Standard Error 1.51

Secondary

Change From Baseline in Lipids

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
10 mg LY2944876	Change From Baseline in Lipids	Total Cholesterol	-1.26 mg/dL	Standard Error 4.37
10 mg LY2944876	Change From Baseline in Lipids	LDL-C	-1.37 mg/dL	Standard Error 3.75
10 mg LY2944876	Change From Baseline in Lipids	Triglycerides	-14.63 mg/dL	Standard Error 11.49
10 mg LY2944876	Change From Baseline in Lipids	HDL-C	1.56 mg/dL	Standard Error 1.03
15 mg LY2944876	Change From Baseline in Lipids	LDL-C	-0.40 mg/dL	Standard Error 3.57
15 mg LY2944876	Change From Baseline in Lipids	HDL-C	0.92 mg/dL	Standard Error 0.98
15 mg LY2944876	Change From Baseline in Lipids	Total Cholesterol	-1.12 mg/dL	Standard Error 4.16
15 mg LY2944876	Change From Baseline in Lipids	Triglycerides	-13.32 mg/dL	Standard Error 10.93
30 mg LY2944876	Change From Baseline in Lipids	LDL-C	-0.24 mg/dL	Standard Error 3.56
30 mg LY2944876	Change From Baseline in Lipids	Triglycerides	-15.40 mg/dL	Standard Error 10.59
30 mg LY2944876	Change From Baseline in Lipids	Total Cholesterol	-1.46 mg/dL	Standard Error 4.09
30 mg LY2944876	Change From Baseline in Lipids	HDL-C	0.90 mg/dL	Standard Error 0.96
50 mg LY2944876	Change From Baseline in Lipids	HDL-C	1.04 mg/dL	Standard Error 1.01
50 mg LY2944876	Change From Baseline in Lipids	Total Cholesterol	-5.11 mg/dL	Standard Error 4.24
50 mg LY2944876	Change From Baseline in Lipids	LDL-C	-0.04 mg/dL	Standard Error 3.72
50 mg LY2944876	Change From Baseline in Lipids	Triglycerides	-20.96 mg/dL	Standard Error 11.16
Exenatide Extended-release	Change From Baseline in Lipids	Total Cholesterol	-0.12 mg/dL	Standard Error 4.22
Exenatide Extended-release	Change From Baseline in Lipids	HDL-C	2.35 mg/dL	Standard Error 0.99
Exenatide Extended-release	Change From Baseline in Lipids	Triglycerides	-11.83 mg/dL	Standard Error 11.01
Exenatide Extended-release	Change From Baseline in Lipids	LDL-C	0.37 mg/dL	Standard Error 3.65
Placebo	Change From Baseline in Lipids	LDL-C	4.55 mg/dL	Standard Error 3.81
Placebo	Change From Baseline in Lipids	HDL-C	2.17 mg/dL	Standard Error 1.04
Placebo	Change From Baseline in Lipids	Total Cholesterol	7.32 mg/dL	Standard Error 4.4
Placebo	Change From Baseline in Lipids	Triglycerides	10.61 mg/dL	Standard Error 11.58

Secondary

Percentage of Participants Developing Anti-Drug Antibodies to LY2944876

Percentage of participants developing anti-drug antibodies to LY2944876.

Time frame: Week 12 and Week 24

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

Arm	Measure	Group	Value (NUMBER)
10 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	1.7 percentage of participants
10 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	1.8 percentage of participants
15 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	1.4 percentage of participants
15 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	0 percentage of participants
30 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	1.5 percentage of participants
30 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	1.5 percentage of participants
50 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	0 percentage of participants
50 mg LY2944876	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	0 percentage of participants
Exenatide Extended-release	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	1.6 percentage of participants
Exenatide Extended-release	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	0 percentage of participants
Placebo	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 12	0 percentage of participants
Placebo	Percentage of Participants Developing Anti-Drug Antibodies to LY2944876	Week 24	0 percentage of participants

Secondary

Percentage of Participants Requiring Rescue Therapy

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)

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

Arm	Measure	Value (NUMBER)
10 mg LY2944876	Percentage of Participants Requiring Rescue Therapy	6.1 percentage of participants
15 mg LY2944876	Percentage of Participants Requiring Rescue Therapy	2.8 percentage of participants
30 mg LY2944876	Percentage of Participants Requiring Rescue Therapy	2.7 percentage of participants
50 mg LY2944876	Percentage of Participants Requiring Rescue Therapy	4.3 percentage of participants
Exenatide Extended-release	Percentage of Participants Requiring Rescue Therapy	2.9 percentage of participants
Placebo	Percentage of Participants Requiring Rescue Therapy	11.3 percentage of participants

Secondary

Percent Change From Baseline in Body Weight

Time frame: Baseline, Week 12; Baseline, Week 24

Population: 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	Measure	Group	Value (MEAN)	Dispersion
10 mg LY2944876	Percent Change From Baseline in Body Weight	Week 12	-1.09 Percentage change	Standard Error 0.35
10 mg LY2944876	Percent Change From Baseline in Body Weight	Week 24	-1.57 Percentage change	Standard Error 0.47
15 mg LY2944876	Percent Change From Baseline in Body Weight	Week 12	-1.86 Percentage change	Standard Error 0.33
15 mg LY2944876	Percent Change From Baseline in Body Weight	Week 24	-2.13 Percentage change	Standard Error 0.45
30 mg LY2944876	Percent Change From Baseline in Body Weight	Week 12	-2.01 Percentage change	Standard Error 0.33
30 mg LY2944876	Percent Change From Baseline in Body Weight	Week 24	-1.98 Percentage change	Standard Error 0.45
50 mg LY2944876	Percent Change From Baseline in Body Weight	Week 12	-3.23 Percentage change	Standard Error 0.34
50 mg LY2944876	Percent Change From Baseline in Body Weight	Week 24	-3.41 Percentage change	Standard Error 0.46
Exenatide Extended-release	Percent Change From Baseline in Body Weight	Week 12	-2.04 Percentage change	Standard Error 0.35
Exenatide Extended-release	Percent Change From Baseline in Body Weight	Week 24	-2.18 Percentage change	Standard Error 0.47
Placebo	Percent Change From Baseline in Body Weight	Week 12	-1.22 Percentage change	Standard Error 0.34
Placebo	Percent Change From Baseline in Body Weight	Week 24	-1.70 Percentage change	Standard Error 0.46

Secondary

Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876

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

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

Arm	Measure	Value (MEAN)	Dispersion
10 mg LY2944876	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876	88100 nanogramshour per milliliter (ngh/mL)	Standard Deviation 40600
15 mg LY2944876	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876	117000 nanogramshour per milliliter (ngh/mL)	Standard Deviation 50800
30 mg LY2944876	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876	247000 nanogramshour per milliliter (ngh/mL)	Standard Deviation 106000
50 mg LY2944876	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876	381000 nanogramshour per milliliter (ngh/mL)	Standard Deviation 187000

Secondary

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876

Time frame: Baseline, Week 8, Week 12, Week 16, Week 20, Week 24

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

Arm	Measure	Value (MEAN)	Dispersion
10 mg LY2944876	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876	607 nanogram per milliliter (ng/mL)	Standard Deviation 282
15 mg LY2944876	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876	799 nanogram per milliliter (ng/mL)	Standard Deviation 368
30 mg LY2944876	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876	1690 nanogram per milliliter (ng/mL)	Standard Deviation 732
50 mg LY2944876	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876	2570 nanogram per milliliter (ng/mL)	Standard Deviation 1240

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12

Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values

Change From Baseline in Adiponectin Levels

Change From Baseline in Beta-Hydroxy Butyrate Levels

Change From Baseline in Fasting Blood Glucose

Change From Baseline in Fasting Fibroblast Growth Factor 21

Change From Baseline in Glucagon Levels

Change From Baseline in HbA1c at Week 24

Change From Baseline in Insulin Levels

Change From Baseline in Lipids

Percentage of Participants Developing Anti-Drug Antibodies to LY2944876

Percentage of Participants Requiring Rescue Therapy

Percent Change From Baseline in Body Weight

Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2944876

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2944876