A Study of LY3437943 in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of LY3437943 in participants with type 2 diabetes (T2D) who failed to achieve adequate glycemic control on diet and exercise alone or on a stable dose of metformin. This study will last about 43 weeks.

Official Title
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A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo and Dulaglutide in Participants With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: LY3437943
* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have Type 2 Diabetes (T2D) Have an HbA1c value at screening of ≥7.0% and ≤10.5% and treated with diet and exercise alone or with a stable dose of metformin (either immediate release or extended release, 1000 milligram (mg)/day and not more than the locally approved dose) for at least 3 months prior to screening. Exclusion Criteria: Have type 1 diabetes mellitus (T1DM) Have ketoacidosis Have retinopathy, maculopathy Have history of pancreatitis Have obesity induced by other endocrine disorders Have uncontrolled hypertension Have acute or chronic hepatitis Have chronic kidney disease Have an autoimmune abnormality for example, lupus or rheumatoid arthritis Have an active or untreated malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 milligrams (mg) LY3437943<br>Participants received 0.5 mg LY3437943 administered as SC (subcutaneous) injection once weekly (QW). | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 4 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 4 mg LY3437943 (4 mg)<br>Participants received 4 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 8 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 and then 8 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 8 mg LY3437943 (4 mg)<br>Participants received 4 mg LY3437943 starting dose followed by 8 mg LY3437943 administered as a SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 12 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943, then 8 mg LY3437943, then 12 mg LY3437943 administered as a SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Active Comparator: 1.5 mg Dulaglutide<br>Participants received 1.5 mg dulaglutide administered as SC single-dose pen injection QW. | Drug: Dulaglutide<br>* Administered SC<br>|
| Placebo Comparator: Placebo<br>Participants received placebo administered as SC injection QW. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) | Change in HbA1c (%) from baseline in LY3437943 relative to placebo. HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Treatment*Time + Strata*Time + Baseline*Time. | Baseline, 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c | Change in HbA1c (%) from baseline in LY3437943 relative to dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Strata*Time + Baseline*Time. | Baseline, 24 Weeks | 
| Change From Baseline in HbA1c | Change in HbA1c (%) from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Baseline HbA1c Group (<=8.5%, >8.5%)*Time + Baseline Body Mass Index (BMI) Group (<30 kilograms/square meter (kg/m2), >=30 kg/m2)*Time + Baseline*Time. | Baseline, 36 Weeks | 
| Percentage of Participants Reaching HbA1c <7.0% | Percentage of participants reaching HbA1c <7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<30 kg/m2, ≥30 kg/m2] as fixed effects, and baseline HbA1c value as a covariate. | Week 24 | 
| Percentage of Participant Reaching HbA1c <7.0% | Percentage of participants reaching HbA1c <7.0% in LY3437943 relative to placebo and dulaglutide. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<30 kg/m2, ≥30 kg/m2] as fixed effects, and baseline HbA1c value as a covariate. | Week 36 | 
| Change From Baseline in Fasting Blood Glucose (FBG) | Change in FBG from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Strata*Time + Baseline*Time. | Baseline, 24 Weeks | 
| Change From Baseline in Fasting Blood Glucose (FBG) | Change in FBG from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Baseline HbA1c Group (<=8.5%, >8.5%)*Time + Baseline BMI Group (<30kg/m2, >=30kg/m2)*Time + Baseline*Time. | Baseline, 36 Weeks | 
| Change From Baseline in Body Weight | Change in body weight from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Strata*Time + Baseline*Time. | Baseline, 24 Weeks | 
| Change From Baseline in Body Weight | Change in body weight from baseline in LY3437943 relative to placebo and dulaglutide. LSMean was calculated using MMRM for post-baseline measures: Variable = Treatment*Time + Baseline HbA1c Group (<=8.5%, >8.5%)*Time + Baseline BMI Group (<30kg/m2, >=30kg/m2)*Time + Baseline*Time. | Baseline, 36 Weeks | 
| Population PK: Average Steady-State Plasma Concentration (Cav,ss) of LY3437943 | The average steady-state plasma concentration of LY3437943 was evaluated using sparse sampling methodology/Population PK (PopPK) modeling. | Predose: Week 0, 1, 4, 12, 24, 30; Postdose: Week 2, 8, 16, 20, 36 |