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, a Phase 3 obesity trial of retatrutide, an investigational once-weekly agonist of GIP, GLP-1 and glucagon receptors. All three doses met the reported primary and key secondary endpoints. The 12 mg arm showed an average 28.3% body-weight reduction at 80 weeks under the efficacy estimand.¹ These are sponsor-reported topline results; a complete peer-reviewed Phase 3 paper was not available when this article was updated.

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

Lilly reported the following categorical responder rates for retatrutide 12 mg: 62.5% of participants lost ≥25% of body weight, 45.3% lost ≥30%, and 27.2% lost ≥35%. 65.3% reached a BMI under 30, including 37.5% of those who started with class 3 obesity (BMI ≥40). Lilly notes that the overall BMI-under-30 analysis was not controlled for multiplicity and that the class 3 subgroup analysis was post hoc.¹

Extension to 104 weeks: continued weight loss

A pre-specified blinded extension enrolled 532 participants with baseline BMI ≥35 who completed 80 weeks on study drug without permanent dose reduction and met other extension criteria. In that selected subgroup, the 12 mg-to-maximum-tolerated-dose arm averaged −30.3% (−85.0 lbs / −38.5 kg) at 104 weeks; the 9 mg arm averaged −29.5% and the 4 mg arm, after escalation to a maximum tolerated dose, averaged −27.9%. The selection criteria mean these extension results should not be generalised to every participant or patient.¹

The 4 mg trial arm

The 4 mg randomised trial arm showed −19.0% weight reduction at 80 weeks under the efficacy estimand, with adverse-event discontinuation reported in 4.1% versus 4.9% for placebo.¹ This describes a controlled trial arm; it does not establish 4 mg as a safe starting dose, target or treatment plan outside the study.

Cardiometabolic markers

Lilly reported improvements from baseline in waist circumference (−24.1 cm with 12 mg), non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein (hsCRP).¹ The release did not provide complete effect estimates for every marker, so the clinical importance of those secondary findings requires fuller reporting.

Safety and tolerability

Lilly described the adverse-event types as generally consistent with other incretin-therapy trials. The most common events with 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 other reported observations warrant 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 was reported in 4.1% (4 mg), 6.9% (9 mg), 11.3% (12 mg) and 4.9% (placebo). The higher discontinuation percentage in the 12 mg arm is relevant to benefit–risk assessment; it does not supply a self-titration rule.

How retatrutide compares to tirzepatide and semaglutide

Tirzepatide 15 mg in SURMOUNT-1 reported −20.9% at 72 weeks, semaglutide 2.4 mg in STEP 1 reported −14.9% at 68 weeks, and Lilly's TRIUMPH-1 release reported −28.3% with retatrutide 12 mg at 80 weeks.^1,3,4 These are cross-trial figures with different populations, durations and analysis methods. They do not prove comparative superiority or show how much of any difference is caused by glucagon-receptor activity. The direct TRIUMPH-5 trial is active and has not reported results.⁵

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

What the topline results do—and do not—establish

Retatrutide remains investigational. Lilly states that it is legally available only to participants in its clinical trials.^1,6 A positive topline release does not establish an approved indication, a product specification, a public dose schedule or the identity and sterility of products sold online.

The study's dose escalation, laboratory schedule and 80-to-104-week follow-up belong to its controlled research protocol. They should not be converted into a shorter consumer 'cycle' or self-directed titration plan. In South Africa, SAHPRA warns against unregistered peptide products sold online and advises use of registered products through registered prescribers and licensed pharmacists.⁷

What's next in the TRIUMPH programme

Lilly announced topline TRIUMPH-2 and TRIUMPH-3 results in July 2026.⁶ The direct retatrutide-versus-tirzepatide TRIUMPH-5 study remains active and has not reported results.⁵ Complete peer-reviewed reports and regulatory review remain more informative than sponsor releases for judging benefits, harms and applicability.