Retatrutide TRIUMPH trials explained (US): what each study is testing (obesity, diabetes, CV disease, OSA, knee OA)

ByGLP1-Consultant

Short answer

The TRIUMPH program is Eli Lilly’s Phase 3 set of studies designed to show whether retatrutide (LY3437943) can deliver clinically meaningful weight loss—and whether that weight loss translates into measurable benefits for common obesity-related conditions, including type 2 diabetes, obstructive sleep apnea (OSA), knee osteoarthritis (OA), and major cardiovascular (CV) and kidney outcomes.

In plain terms, the TRIUMPH trials ask five big questions:

  1. Obesity/overweight (no diabetes): How much weight do people lose vs placebo over ~80 weeks? (TRIUMPH-1, NCT05929066)
  2. Obesity/overweight + type 2 diabetes: How much weight do people lose—plus how much does glucose control improve? (TRIUMPH-2, NCT05929079)
  3. Severe obesity + established cardiovascular disease: Does retatrutide work similarly in a higher-risk population with known CV disease? (TRIUMPH-3, NCT05882045)
  4. Obesity/overweight + knee osteoarthritis: Does it reduce knee pain and improve function, in addition to weight loss? (TRIUMPH-4, NCT05931367)
  5. Obesity + ASCVD and/or chronic kidney disease: Does it prevent “hard” outcomes like heart attack, stroke, CV death, heart failure hospitalization, and kidney failure/progression over ~5 years? (TRIUMPH-Outcomes, NCT06383390)

When results are posted, focus first on the primary endpoints. Then check: the placebo-adjusted difference, the timepoint (Week 68 vs Week 80 vs event-driven follow-up), dropout rates, GI side effects and discontinuations, and whether results are consistent across key subgroups.

What is retatrutide—and why TRIUMPH matters

Retatrutide (also known as LY3437943) is an investigational once-weekly injectable medicine that activates three hormone receptors involved in metabolism:

  • GLP-1 receptor
  • GIP receptor
  • Glucagon receptor

Phase 3 programs like TRIUMPH are where a drug has to prove it can deliver meaningful benefits—safely—across large groups of people and real-world comorbidities.

TRIUMPH at a glance (US-relevant trials + NCT numbers)

TRIUMPH-1 — NCT05929066

Primary endpoint: % body weight change at Week 80.
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05929066

TRIUMPH-2 — NCT05929079

Primary endpoint: % body weight change at Week 80 (plus OSA subset AHI endpoint).
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05929079

TRIUMPH-3 — NCT05882045

Primary endpoint: % body weight change at Week 80 in severe obesity + established CVD.
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05882045

TRIUMPH-4 — NCT05931367

Co-primary endpoints: WOMAC pain + % body weight change at Week 68.
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT05931367

TRIUMPH-Outcomes — NCT06383390

Primary endpoints: time-to-event CV composite + time-to-event kidney composite.
ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT06383390

Plain-English guide to the endpoints you’ll see

Percent change in body weight

Look for the difference vs placebo, the timepoint, and dropout/discontinuation.

AHI (sleep apnea)

AHI is events/hour. A meaningful drop can reflect fewer breathing disruptions.

WOMAC (knee OA)

WOMAC pain/function are patient-reported outcomes—look for clinically meaningful change.

CV and kidney “time-to-event” outcomes

Focus on hazard ratios (HR), confidence intervals, and absolute risk differences when available.

How to interpret results when they’re posted (quick checklist)

  1. Confirm the population (non-diabetes vs T2D; baseline BMI; comorbidities)
  2. Focus on the primary endpoint at the primary timepoint
  3. Use placebo-adjusted results
  4. Check tolerability (GI side effects, discontinuations)
  5. Avoid cross-trial “X% vs Y%” rankings unless head-to-head

References