A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight

Phase 3

Active, not recruiting

• Conditions: Obesity; Overweight; Osteoarthritis, Knee; Obstructive Sleep Apnea
• Interventions: Drug: Retatrutide; Drug: Placebo

• Registration Number: NCT05929066
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of retatrutide in participants who have obesity or overweight (J1I-MC-GZBJ master protocol) including subsets of participants who have knee osteoarthritis (OA) (J1I-MC-GOA1) or who have obstructive sleep apnea (OSA) (J1I-MC-GSA1). This study will last about 89 weeks and will include up to 24 visits. Addendum (2) is optional and available to approximately 500 participants to continue treatment with retatrutide for up to an additional 24 weeks.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-26
• Study First Submitted QC: 2023-06-26
• Study First Posted: 2023-07-03
• Study Start: 2023-07-10
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-18
• Primary Completion: 2026-04
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 2300

Inclusion Criteria

• Have body mass index (BMI) ≥30.0 kilograms per square meter (kg/m²), or ≥27.0 kg/m² with at least one of the following:

  • hypertension
  • dyslipidemia
  • obstructive sleep apnea, or
  • cardiovascular disease

• History of of at least one unsuccessful dietary effort to reduce body weight

GOA1 Inclusion Criteria:

• Have index knee pain for >12 weeks prior to screening, and presence of index knee pain for >15 days over the previous month
• Have knee X-ray with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3) per central reading at screening
• Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA.

GSA1 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.

GZBJ Addenda (2) inclusion criteria:

• Have completed the final treatment visit of GZBJ Week 80.

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 diabetes mellitus.
• Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
• Have had pancreatitis.

GOA1 exclusion criteria

• Have had steroid joint injections within 90 days of screening.
• Have had other joint injections and procedures within 6 months of screening.
• Have joint disease other than osteoarthritis.

GSA1 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.

GZBJ Addenda (2) exclusion criteria

• Have had study intervention discontinuation.
• Have had permanent dose reduction.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Retatrutide Dose 3	Retatrutide	Participants will receive retatrutide SC.
Retatrutide Extension Period	Retatrutide	Participants will receive retatrutide after the placebo-controlled 80 week treatment period for an additional 24 weeks.
Retatrutide Dose 2	Retatrutide	Participants will receive retatrutide SC.
Retatrutide Dose 1	Retatrutide	Participants will receive retatrutide subcutaneously (SC).
Placebo	Placebo	Participants will receive placebo.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Body Weight	Baseline, Week 80
Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score for GOA1 Subset	Baseline, Week 80
Change from Baseline in Apnea-Hypopnea Index (AHI) Events Per Hour for GSA1 Subset	Baseline, Week 80
Percent Change from Baseline in Body Weight to	Baseline, Week 104

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in HbA1c	Baseline, Week 80
Change from Baseline in Body Mass Index (BMI)	Baseline, Week 80
Change from Baseline in Average Pain Intensity Numeric Rating Scale (API-NRS) Score for GOA1 Subset	Baseline, Week 80
Percent Change from Baseline in AHI for GSA1 Subset	Baseline, Week 80
Percent Change form Baseline in Fasting Insulin	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 Worst Pain Intensity Numeric Rating Scale (WPI-NRS) Score for GOA1 Subset	Baseline, Week 80
Change from Baseline in Waist Circumference	Baseline, Week 80
Change from Baseline in Systolic Blood Pressure (SBP)	Baseline, Week 80
Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA1 Subset	Baseline to Week 80
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)	Baseline through Week 80	AUC is presented as a single average measure of AUC across the study duration.
A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score for GSA1 Subset	Baseline to Week 80	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 components.
Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA1 Subset	Week 80
Change from Baseline in the WOMAC Physical Function Subscale Score for GOA1 Subset	Baseline, Week 80

Trial Locations

Locations (133)

Central Phoenix Medical Clinic; 🇺🇸 Phoenix, Arizona, United States

Arizona Research Center; 🇺🇸 Phoenix, Arizona, United States

Medical Investigations; 🇺🇸 Little Rock, Arkansas, United States

Neuro-Pain Medical Center; 🇺🇸 Fresno, California, United States

Valley Research; 🇺🇸 Fresno, California, United States

Artemis Institute for Clinical Research; 🇺🇸 San Diego, California, United States

University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Chase Medical Research, LLC; 🇺🇸 Waterbury, Connecticut, United States

Teradan Clinical Trials, LLC; 🇺🇸 Brandon, Florida, United States

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