A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight

Study Overview
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Brief Summary
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The purpose of this study is to is to evaluate the efficacy and safety of retatrutide in participants with type 2 diabetes in participants who have obesity or overweight (J1I-MC-GZBK master protocol) including a subset of participants who have obstructive sleep apnea (OSA) (J1I-MC-GSA2). The study will last about 89 weeks and will include up to 24 visits.

Official Title
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A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight: A Randomized Double-Blind, Placebo-Controlled Trial

Conditions
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Type 2 Diabetes, Obesity, Overweight, Obstructive Sleep Apnea

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) greater than or equal to 27.0 kilogram/square meter (kg/m ²) Have Type 2 Diabetes (T2D) Are on stable treatment for T2D for at least 90 days Have a history of at least one unsuccessful dietary effort to lose body weight. GSA2 Inclusion Criteria Previously diagnosed with OSA Have AHI ≥15 on polysomnography at screening (definition of moderate-to-severe OSA) For participants not on positive airway pressure (PAP) therapy: unable or unwilling to use PAP therapy and have not used PAP for at least 4 weeks prior to screening. If on PAP therapy, have been on PAP therapy for at least 3 consecutive months prior to screening, and willing to temporarily stop using PAP therapy for approximately 7 days prior to each of the sleep study (PSG) visits. Exclusion Criteria: Have a self-reported or documented change in body weight >5 kg (11 pounds) within 90 days. Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening. Have a prior or planned surgical treatment for obesity. Have Type 1 diabetes Have a family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2) Have had pancreatitis GSA2 Exclusion Criteria Use stimulants (for example, modafinil, armodafinil, solriamfetol, pitolisant, amphetamine) less than 3 months prior to screening. Use hypnotics, mirtazapine, opioids, trazodone, and zonisamide less than 3 months prior to screening. Use a dental appliance or other device to treat OSA other than PAP therapy.

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;|
| Experimental: Retatrutide Dose 3<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 | 
| Change from Baseline in Apnea-Hypopnea Index (AHI) for GSA2 Subset |  | 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 | 
| Change from Baseline in Systolic Blood Pressure (SBP) |  | Baseline, Week 80 | 
| Change from Baseline in Diastolic Blood Pressure (DBP) |  | 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 Hemoglobin (A1c) HbA1c % |  | Baseline, Week 80 | 
| Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score |  | Baseline, Week 80 | 
| Change from Baseline in Fasting Glucose |  | Baseline, Week 80 | 
| Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) | AUC is presented as a single average measure of AUC across the study duration. | Baseline through Week 80 | 
| Percent Change from Baseline in Apnea-Hypopnea Index (AHI) for GSA2 Subset |  | Baseline, Week 80 | 
| A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score for GSA2 Subset | A hierarchical combination of change from baseline in the FOSQ 10 score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score will be assessed by the win ratio. The reported unit will be the total wins for each treatment group from performing a hierarchical comparison of the component. | Baseline to Week 80 | 
| Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA2 Subset |  | Baseline to Week 80 | 
| Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA2 Subset |  | Week 80 |