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Retatrutide vs semaglutide
As of 23 September 2026 no head-to-head trial of retatrutide against semaglutide has reported. The trials below are set side by side from separate studies, which is not a head-to-head result.
Primara Labs sells some of the compounds covered here. Every figure on this page links to its source and the date it was checked.
Mechanism
How the two differ
Retatrutide
Retatrutide is a single peptide that activates three receptors: GIP, GLP-1 and glucagon. Lilly describes it as a first-in-class triple hormone receptor agonist.
Semaglutide
Semaglutide is a GLP-1 analogue that selectively binds to and activates the GLP-1 receptor, the target of native GLP-1.
Cross-trial
Separate trials, side by side
| TRIUMPH-1 | STEP 1 | |
|---|---|---|
| Compound | Retatrutide | Semaglutide |
| Phase | 3 | 3 |
| Population | Adults with obesity, or overweight with at least one weight-related condition, without diabetes | Adults with BMI of 30 or greater (27 or greater with at least one weight-related coexisting condition), without diabetes |
| n | 2,339 | 1,961 |
| Weeks | 80 | 68 |
| Estimand | efficacy | treatment-policy |
| Arms | 4 mg: -19.0%; 9 mg: -25.9%; 12 mg: -28.3% | 2.4 mg: -14.9% |
| Comparator | Placebo: -2.2% | Placebo: -2.4% |
| Stopped for adverse events | 4 mg: 4.1%; 9 mg: 6.9%; 12 mg: 11.3%; Placebo: 4.9% | Not published in the source read |
| Source | Eli Lilly topline release, 21 May 2026 | Wilding JPH et al. N Engl J Med 2021;384:989-1002 |
TRIUMPH-1: side effects reported
In TRIUMPH-1, discontinuation because of adverse events was 4.1% on 4 mg, 6.9% on 9 mg and 11.3% on 12 mg, against 4.9% on placebo. The most frequently reported adverse events were nausea in 28.6% on 4 mg, 38.4% on 9 mg and 42.4% on 12 mg against 14.8% on placebo, diarrhoea in 25.2% on 4 mg, 34.1% on 9 mg and 32.0% on 12 mg against 13.5% on placebo, constipation in 23.8% on 4 mg, 25.9% on 9 mg and 26.1% on 12 mg against 10.9% on placebo and vomiting in 10.6% on 4 mg, 22.8% on 9 mg and 25.3% on 12 mg against 4.8% on placebo.
STEP 1: side effects reported
STEP 1: Discontinuation for adverse events is not given in the abstract; discontinuation for gastrointestinal adverse events was 4.5% against 0.8% on placebo.
Figures from different trials are not a head-to-head comparison: the populations, durations and estimands differ. The head-to-head trials among these compounds are SURMOUNT-5, tirzepatide against semaglutide, completed, and TRIUMPH-5, retatrutide against tirzepatide, still running.
Questions
Questions
Has retatrutide been compared head to head with semaglutide?
No head-to-head trial of retatrutide against semaglutide is in the Research Desk trials dataset as of 23 September 2026. The figures on this page come from separate trials.
Why can the TRIUMPH-1 and STEP 1 figures not be compared directly?
Figures from different trials are not a head-to-head comparison: the populations, durations and estimands differ. The head-to-head trials among these compounds are SURMOUNT-5, tirzepatide against semaglutide, completed, and TRIUMPH-5, retatrutide against tirzepatide, still running. TRIUMPH-1 reports the efficacy estimand over 80 weeks. STEP 1 reports the treatment-policy estimand over 68 weeks.