A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease

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 retatrutide once weekly in participants with obesity and established cardiovascular disease (CVD). The study will last about 113 weeks.

Official Title
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A Randomized, Double-Blind, Phase 3 Study to Investigate the Efficacy and Safety of LY3437943 Once Weekly Compared to Placebo in Participants With Severe Obesity and Established Cardiovascular Disease

Conditions
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Obesity, Cardiovascular Diseases

Intervention / Treatment
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* Drug: Retatrutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) ≥35.0 kilogram/square meter (kg/m²). Have established cardiovascular (CV) disease with at least 1 of the following: prior myocardial infarction prior ischemic or hemorrhagic stroke, or symptomatic peripheral arterial disease Have a history of at least 1 self-reported unsuccessful dietary effort to reduce body weight. Exclusion Criteria: Have had acute myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina, or hospitalization due to congestive heart failure within 90 days prior to screening. Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening. Have a prior or planned surgical treatment of obesity. Have a change in body weight greater than 5 kg (11 pounds) within 90 days prior to screening. Have Type 1 diabetes. Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) Have had pancreatitis.

Ages Eligible for Study
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Minimum Age: 18 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: Retatrutide Dose 1<br>Participants will receive retatrutide subcutaneously (SC). | Drug: Retatrutide<br>* Administered SC<br>* Other names: LY3437943;|
| Experimental: Retatrutide Dose 2<br>Participants will receive retatrutide SC. | Drug: Retatrutide<br>* Administered SC<br>* Other names: LY3437943;|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change from Baseline in Body Weight |  | Baseline, Week 80 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Body Mass Index (BMI) |  | Baseline, Week 80 | 
| Change from Baseline in Waist Circumference |  | Baseline, Week 80 | 
| Percent Change from Baseline in Total Cholesterol |  | Baseline, Week 80 | 
| Percent Change from Baseline in Triglycerides |  | Baseline, Week 80 | 
| Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 80 | 
| Change from Baseline in Diastolic Blood Pressure (DBP) |  | Baseline, Week 80 | 
| Change from Baseline in Hemoglobin A1c (HbA1c) |  | Baseline, Week 80 | 
| Percent Change from Baseline in Fasting Insulin |  | Baseline, Week 80 | 
| Change from Baseline in Short Form version 2 (SF-36v2) Acute Form Physical Function Domain Score |  | Baseline, Week 80 | 
| Pharmacokinetics (PK): Steady State Area Under the Concentration Time Cure (AUC) | AUC is presented as a single average measure of AUC across the study duration. | Baseline to Week 80 |