Retatrutide TRIUMPH Program: All 9 Phase 3 Trials Tracked (April 2026 Update) | Peptadex

The TRIUMPH Program in One Paragraph

TRIUMPH is Eli Lilly's name for the Phase 3 program of retatrutide (LY3437943) — a triple agonist of the GLP-1, GIP, and glucagon receptors. The program comprises nine pivotal trials spanning obesity, type 2 diabetes, cardiovascular disease, knee osteoarthritis, sleep apnea, MASLD, low back pain, and renal outcomes. As of April 2026, two trials have read out and seven more are expected to report through the year, with NDA filing targeted for Q4 2026.

Key Takeaways

• TRIUMPH-4 (obesity + knee osteoarthritis) reported 28.7% mean weight loss at 12 mg / 68 weeks
• TRANSCEND-T2D-1 reported HbA1c reductions up to 2.0%, read out March 19, 2026
• A new safety signal — dysesthesia (abnormal skin sensations) — was observed at 20.9% incidence at the 12 mg dose
• NDA filing is expected Q4 2026; FDA approval likely 2027–2028
• Retatrutide search volume is up +512% year over year heading into the read-out cycle

What Makes Retatrutide Different

Retatrutide is the first triple incretin agonist to reach Phase 3. It activates the GLP-1 receptor (like semaglutide), the GIP receptor (added in tirzepatide), and the glucagon receptor — a third axis that increases resting energy expenditure and promotes hepatic fat oxidation. The glucagon component is the mechanistic differentiator and is hypothesized to drive the higher weight loss observed in earlier-phase studies.

For the head-to-head comparison with semaglutide and tirzepatide, see Retatrutide vs Tirzepatide vs Semaglutide 2026.

The 9 TRIUMPH Trials Tracked

TRIUMPH-1: General Obesity

The flagship obesity trial. Studies retatrutide across multiple dose strengths in adults with obesity but without type 2 diabetes. Expected read-out: Q2–Q3 2026. This is the trial most likely to anchor the FDA submission package.

TRIUMPH-2: Obesity with Type 2 Diabetes

Co-primary obesity + glycemic endpoints in patients with both conditions. Expected read-out: Q2–Q3 2026. Will determine the dual-indication labeling potential.

TRIUMPH-3: Obesity with Cardiovascular Disease (CVOT)

Cardiovascular outcomes trial — the longest-duration arm. Pivotal for inclusion of cardiovascular benefit language in the eventual label, mirroring the path semaglutide took with SELECT.

TRIUMPH-4: Obesity + Knee Osteoarthritis (Read out December 2025)

Reported 28.7% mean weight loss at 12 mg over 68 weeks. WOMAC pain score improvement of approximately 76%, indicating substantial functional benefit beyond weight effects alone. The first dataset to suggest retatrutide may have indications beyond pure weight management.

TRIUMPH-5: Obesity + Obstructive Sleep Apnea

Apnea-hypopnea index endpoint design parallels the SURMOUNT-OSA program for tirzepatide, which secured an OSA indication for Zepbound in late 2024. Read-out expected later in 2026.

TRIUMPH-6: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Hepatic fat content and inflammation endpoints. Glucagon receptor activation increases hepatic fat oxidation, making MASLD a high-conviction indication for the triple agonist mechanism.

TRIUMPH-7: Chronic Low Back Pain with Obesity

The musculoskeletal arm parallel to TRIUMPH-4. Designed to demonstrate that weight loss-driven mechanical relief translates into measurable pain outcomes.

TRIUMPH-8: Renal Outcomes

Kidney function endpoints. Mirrors the FLOW trial program for semaglutide, which extended its label into chronic kidney disease in T2D.

TRANSCEND-T2D-1: Type 2 Diabetes (Read out March 19, 2026)

Reported HbA1c reductions up to 2.0% — comparable to or modestly exceeding the best tirzepatide data. Weight loss component was secondary but significant.

Efficacy Pattern Across Doses

Across reported data, weight loss is dose-dependent through 12 mg, with the highest dose producing the largest effect. The pattern observed in TRIUMPH-4:

• 2 mg: ~13% mean weight loss
• 4 mg: ~17% mean weight loss
• 8 mg: ~24% mean weight loss
• 12 mg: ~28.7% mean weight loss

This positions retatrutide as the first agent capable of routinely producing weight loss greater than 25% — territory previously reached only by bariatric surgery.

The Dysesthesia Safety Signal

The most-discussed Phase 3 finding has been dysesthesia — abnormal skin sensations including tingling, burning, or pricking — reported at 20.9% incidence at the 12 mg dose versus 0.7% on placebo in TRIUMPH-4. The mechanism is not yet established, and the signal was not prominent in earlier-phase trials. Most cases were mild-to-moderate and reversible on dose reduction or discontinuation.

Standard GI adverse events (nausea, diarrhea, vomiting, constipation) tracked the GLP-1/GIP class profile and were dose-dependent. A separate concern — modest heart rate increases tied to glucagon receptor activation — has been observed since Phase 2 and remains under active monitoring.

Timeline to Approval

Milestone	Expected Date
TRIUMPH-1 / TRIUMPH-2 read-out	Q2–Q3 2026
Remaining TRIUMPH trials read-out	Through Q4 2026
NDA filing	Q4 2026
Likely FDA approval	2027–2028

What This Means for Patients Currently on GLP-1s

Retatrutide is not available outside clinical trials and gray-market sourcing carries the risks described in buying peptides online safely. Patients on semaglutide or tirzepatide who are responding well have no clinical reason to switch in anticipation of retatrutide's eventual approval. For non-responders or those plateauing, the TRIUMPH-1 readout in 2026 will be the key data point.

The broader competitive context — including Novo Nordisk's amycretin program and Foundayo (orforglipron) — is covered in our 2026 oral GLP-1 overview.

Disclaimer: This article summarizes publicly disclosed clinical trial data and company communications as of April 2026. Retatrutide is investigational and not FDA-approved. Trial results are interim where indicated. Nothing here constitutes medical advice. Consult a physician before making any medication decisions.