Retatrutide phase 3: TRIUMPH-1 and TRIUMPH-2 results published
Prepared by: Research Desk. Sources are linked for verification.
Published 22 October 2026
At a glance
- Compound: retatrutide (LY3437943), a synthetic peptide that acts on three receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon
- Developer: Eli Lilly and Company, which funded both trials
- New records: two phase 3 papers published online on 29 September 2026, TRIUMPH-1 in the New England Journal of Medicine and TRIUMPH-2 in The Lancet
- Regulatory status: investigational. A search of FDA's drug approvals data (Drugs at FDA) through the openFDA interface on 22 October 2026 returned no record for retatrutide.
What was published
Retatrutide is described in both papers as an agonist of the GIP, GLP-1 and glucagon receptors, which is why it is often called a "triple agonist". Its earlier phase 2 obesity trial, a 48-week study of 338 adults, was published in 2023 (Jastreboff et al., 2023, PubMed).
The two new papers are the first full peer-reviewed reports from the TRIUMPH phase 3 programme in obesity:
- TRIUMPH-1 (Jastreboff et al., 2026, PubMed; registry entry NCT05929066) enrolled adults with obesity who did not have type 2 diabetes.
- TRIUMPH-2 (Bellido et al., 2026, PubMed; registry entry NCT05929079) enrolled adults with obesity or overweight and type 2 diabetes.
Both were randomised, double-blind and placebo-controlled, ran for 80 weeks and compared three retatrutide groups with placebo. ClinicalTrials.gov lists both trials as completed.
TRIUMPH-1: obesity without diabetes
TRIUMPH-1 randomised 2,339 participants. It had three primary outcomes, each tested in the two upper retatrutide groups against placebo:
- percent change in body weight in the whole trial population;
- change in the WOMAC knee pain score in a subgroup of 574 participants with knee osteoarthritis;
- change in the apnoea-hypopnoea index, a count of breathing interruptions per hour of sleep, in a subgroup of 243 participants with obstructive sleep apnoea.
According to the abstract, mean body-weight change at 80 weeks was −17.6%, −23.7% and −25.0% across the three retatrutide groups, compared with −3.9% with placebo. The authors report that both primary comparisons were statistically significant (P<0.001). The knee pain and sleep apnoea comparisons were also reported as significant in both of the analyses the paper presents. The most common adverse events were gastrointestinal.
TRIUMPH-2: obesity with type 2 diabetes
TRIUMPH-2 randomised 1,152 participants at 92 centres in eight countries, and 965 (84%) completed the study drug. The table summarises figures stated in the abstract.
| Measure (week 80) | Retatrutide groups | Placebo |
|---|---|---|
| Mean body-weight change, treatment-regimen estimand | −11.9%, −16.8%, −18.8% | −5.1% |
| Diarrhoea | 27%, 34%, 34% | 13% |
| Nausea | 14%, 21%, 28% | 8% |
| Hypotension | 1%, 5%, 6% | under 1% |
| Dysaesthesia (abnormal skin sensation) | 4%, 6%, 7% | 1% |
The authors also report improvements in glycaemic control. Permanent discontinuation of the study drug because of adverse events or death was more frequent in the two upper retatrutide groups (12% and 8%) than in the lowest group (4%) or with placebo (5%). Seven participants died during the trial, six in the retatrutide groups and one in the placebo group, and the investigators judged all deaths unrelated to the study intervention.
Why the two papers report different kinds of estimate
Large trials have to decide how to count participants who stop the study drug or start other measures. The rule chosen is called an estimand.
- The treatment-regimen estimand, used for the weight outcomes in both papers, counts every randomised participant whether or not they kept taking the study drug. It is close to what trial reports call an ITT analysis, in which participants are analysed in the group they were randomised to.
- TRIUMPH-1 used a different, hybrid estimand for the knee pain and sleep apnoea outcomes, and also reported ITT results alongside it.
- Company press releases often quote a third approach, an efficacy estimand, which estimates the result if everyone had stayed on the study drug. Those figures are typically larger.
When comparing headline numbers between sources, it matters which estimand each figure uses. The papers themselves are the reference for the primary analysis.
Regulatory status
Neither paper describes an approval, and the TRIUMPH-2 authors describe retatrutide as "currently under investigation". A query of FDA's drug approvals data through openFDA on 22 October 2026 returned no match for retatrutide. That is a database check on one date, not a statement of FDA's position. For how to weigh trial papers against press releases and regulator records, see our guide on how to read a research signal.
Research-grade retatrutide sold for laboratory use is not the investigational product used in these trials, and the trial results do not describe it.
Open research questions
- How the results hold up in the remaining TRIUMPH trials, including those not yet published in full.
- What longer follow-up shows about weight regain after the study drug stops.
- How each of the three receptor actions contributes to the reported effects.
- How the heart-rate increases reported in the phase 2 trial and the hypotension reported in TRIUMPH-2 develop over longer periods.
Limitations of the evidence
- Both trials were funded by the developer, and several authors are company employees.
- The results come from two trials in selected adult populations with defined entry criteria, and may not apply to other groups.
- The subgroup outcomes in TRIUMPH-1 rest on smaller numbers (574 and 243 participants).
- This summary is based on the published abstracts and registry records. Full methods and supplementary data are in the papers.
Key terms
- Agonist. A molecule that binds to a receptor and activates it.
- Estimand. A precise definition of the effect a trial sets out to measure, including how events such as stopping the study drug are handled.
- WOMAC. The Western Ontario and McMaster Universities Osteoarthritis Index, a questionnaire that scores knee and hip pain, stiffness and function.
- Apnoea-hypopnoea index. The number of complete or partial breathing interruptions per hour of sleep.
Where researchers source it
Purita is a store that lists retatrutide for laboratory research use only. Its product page labels the item for research use only and not for human or animal administration.
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