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OpenTrials
Completed

NCT Number: NCT05929066

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

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.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Retatrutide

Drug

Administered SC

Other names: LY3437943

Placebo

Drug

Administered SC

Primary outcomes

  1. Percent Change From Baseline in Body Weight

    Time frame: Baseline, Week 80

  2. Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score for GOA1 Subset

    Time frame: Baseline, Week 80

  3. Change from Baseline in Apnea-Hypopnea Index (AHI) Events Per Hour for GSA1 Subset

    Time frame: Baseline, Week 80

  4. Percent Change from Baseline in Body Weight to

    Time frame: Baseline, Week 104

Secondary outcomes

  1. Change from Baseline in Body Mass Index (BMI)

    Time frame: Baseline, Week 80

  2. Change from Baseline in Waist Circumference

    Time frame: Baseline, Week 80

  3. Change from Baseline in Systolic Blood Pressure (SBP)

    Time frame: Baseline, Week 80

  4. Percent Change form Baseline in Fasting Insulin

    Time frame: Baseline, Week 80

  5. Change from Baseline in HbA1c

    Time frame: Baseline, Week 80

  6. Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score

    Time frame: Baseline, Week 80

  7. Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)

    Time frame: Baseline through Week 80

    AUC is presented as a single average measure of AUC across the study duration.

  8. Change from Baseline in the WOMAC Physical Function Subscale Score for GOA1 Subset

    Time frame: Baseline, Week 80

  9. Change from Baseline in Average Pain Intensity Numeric Rating Scale (API-NRS) Score for GOA1 Subset

    Time frame: Baseline, Week 80

  10. Change from Baseline in Worst Pain Intensity Numeric Rating Scale (WPI-NRS) Score for GOA1 Subset

    Time frame: Baseline, Week 80

  11. Percent Change from Baseline in AHI for GSA1 Subset

    Time frame: Baseline, Week 80

  12. 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

    Time frame: 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.

  13. Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA1 Subset

    Time frame: Baseline to Week 80

  14. Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA1 Subset

    Time frame: Week 80

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (TRIUMPH-1)

Acronym: TRIUMPH-1

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Jul 3, 2023
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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