Retatrutide TRIUMPH-1: 28.3% Weight Loss at 80 Weeks in Phase 3

On 21 May 2026, Eli Lilly released topline results from TRIUMPH-1, the Phase 3 pivotal obesity trial of retatrutide, an investigational once-weekly triple hormone receptor agonist that activates GIP, GLP-1 and glucagon receptors from a single molecule. All three doses (4 mg, 9 mg, 12 mg) met the primary and key secondary endpoints. The 12 mg arm produced an average 28.3% body-weight reduction at 80 weeks and 30.3% (85.0 lbs / 38.5 kg) at 104 weeks in a pre-specified extension — the largest weight loss reported to date for a non-surgical obesity therapy.¹

Primary endpoint: 80-week efficacy estimand

TRIUMPH-1 randomised 2,339 adults with obesity or overweight plus at least one weight-related comorbidity (and without diabetes) 1:1:1:1 to retatrutide 4 mg, 9 mg, 12 mg, or placebo. Baseline mean body weight was 112.7 kg (248.5 lbs) at a mean BMI of 40.0.¹

Categorical responder rates on retatrutide 12 mg were striking: 62.5% of participants lost ≥25% of body weight, 45.3% lost ≥30%, and 27.2% lost ≥35%. 65.3% of 12 mg participants reached a BMI under 30 — moving below the obesity threshold entirely — including 37.5% of those who started in class 3 obesity (BMI ≥40).¹

Extension to 104 weeks: continued weight loss

532 participants with BMI ≥35 at baseline who completed 80 weeks entered a blinded extension to 104 weeks. Weight loss continued rather than plateauing: 12 mg → −30.3% (−85.0 lbs / −38.5 kg); 9 mg → −29.5%; 4 mg titrated to maximum tolerated dose → −27.9%. Even participants who crossed over from placebo to retatrutide MTD lost an average of −19.2% (−49.9 lbs) in just 24 weeks of active treatment.¹

The 4 mg dose: 19% weight loss with one escalation step

The most under-reported finding is the 4 mg arm. Reached with a single step-up from the 2 mg starting dose, 4 mg retatrutide delivered −19.0% weight loss at 80 weeks — roughly matching semaglutide 2.4 mg in STEP-1 (−14.9%) and approaching tirzepatide 15 mg in SURMOUNT-1 (−20.9%) — with a discontinuation rate (4.1%) lower than placebo (4.9%).¹ For protocols where tolerability and titration time matter, this is a clinically meaningful entry point.

Cardiometabolic markers

Beyond weight, retatrutide produced significant improvements from baseline across waist circumference (−24.1 cm on 12 mg), non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).¹ These are the markers we routinely include in pre- and post-protocol bloodwork panels.

Safety and tolerability

The adverse-event profile was consistent with the incretin class. Most common AEs on 12 mg (vs placebo) were nausea (42.4% vs 14.8%), diarrhoea (32.0% vs 13.5%), constipation (26.1% vs 10.9%) and vomiting (25.3% vs 4.8%). Two findings warrant specific mention:¹

Dysesthesia (altered sensation) occurred in 5.1%, 12.3% and 12.5% of the 4 mg, 9 mg and 12 mg arms respectively (vs 0.9% placebo). Events were generally mild-to-moderate and mostly resolved on treatment.

Urinary tract infections occurred in 7.5–8.8% of retatrutide arms vs 5.3% placebo. Most events were mild-to-moderate and resolved during treatment.

Discontinuation due to adverse events: 4.1% (4 mg), 6.9% (9 mg), 11.3% (12 mg), 4.9% (placebo). The 12 mg discontinuation rate is the meaningful trade-off for the additional weight loss — and is the reason a tolerability-led titration protocol matters.

How retatrutide compares to tirzepatide and semaglutide

Cross-trial comparison is not the same as a head-to-head trial, but the directional gap is large. Tirzepatide 15 mg in SURMOUNT-1 produced −20.9% at 72 weeks; semaglutide 2.4 mg in STEP-1 produced −14.9% at 68 weeks. Retatrutide 12 mg in TRIUMPH-1 produced −28.3% at 80 weeks, and −30.3% at 104 weeks. The mechanistic difference is the glucagon receptor — adding glucagon agonism to GIP/GLP-1 appears to drive additional energy expenditure on top of appetite suppression.

See our full tirzepatide vs semaglutide comparison for the dual- vs single-agonist data.

What this means for research-peptide protocols

Retatrutide remains an investigational molecule — Lilly has not yet filed for regulatory approval, and it is legally available only via Lilly's own clinical trials. In the research-peptide context, the TRIUMPH-1 dataset gives us, for the first time, a Phase 3-grade dose-response curve to anchor protocol design: a tolerable 4 mg entry point, a 9 mg sweet spot, and a 12 mg ceiling that comes with a real GI-tolerability tax.

Our standing position on retatrutide protocols has not changed: 12-week structured cycles, GP-led oversight, baseline and 12-week bloodwork (HbA1c, lipid panel, hsCRP, liver enzymes, eGFR), titration step every 4 weeks unless symptoms dictate otherwise, and a planned taper rather than an abrupt stop. The TRIUMPH-1 dysesthesia and UTI signals are now on our standard monitoring checklist.

What's next in the TRIUMPH programme

TRIUMPH-2 (retatrutide in obesity with type 2 diabetes) and TRIUMPH-3 (obesity with established cardiovascular disease) are due to report later in 2026. The basket trials for knee osteoarthritis pain and moderate-to-severe obstructive sleep apnoea from TRIUMPH-1 will be released subsequently. Full TRIUMPH-1 data are scheduled for presentation at the 86th ADA Scientific Sessions.¹