TRIUMPH-1 Is Now in the NEJM: Retatrutide’s 80-Week Obesity Results

Which numbers these are. Every figure below is from the paper’s published abstract, which reports the trial’s treatment-regimen (intention-to-treat) estimand unless a figure is labeled otherwise. The full text, which holds the adverse-event tables, was not available for this article. The earlier Prof. Peptide report on the May company release used Lilly’s own 104-week extension figures, which are a different measurement and are not comparable to these.

What the trial was

The abstract describes a phase 3, randomized, double-blind trial funded by Eli Lilly (ClinicalTrials.gov NCT05929066). Adults with obesity but without diabetes were assigned to once-weekly subcutaneous retatrutide at 4 mg, 9 mg or 12 mg, or to placebo, for 80 weeks. Retatrutide is a single molecule that activates the GIP, GLP-1 and glucagon receptors. In total, 2,339 participants were randomized.

There were three prespecified primary outcomes, each assessed for the 9 mg and 12 mg groups against placebo: percent change in body weight; change in the WOMAC knee-pain score in the subgroup of 574 participants with knee osteoarthritis; and change in the apnea-hypopnea index in the 243 participants with obstructive sleep apnea.

What it reported

• Body weight. Mean percent change was −17.6% (4 mg), −23.7% (9 mg) and −25.0% (12 mg) versus −3.9% with placebo. The differences from placebo were −19.8 and −21.0 percentage points for 9 mg and 12 mg (P<0.001 for both).
• Knee osteoarthritis pain. On the WOMAC pain score (1 to 10, higher is worse), the hybrid-estimand changes were −3.2, −3.5 and −3.6 in the retatrutide groups versus −1.9 with placebo, with differences of −1.6 and −1.8 points for 9 mg and 12 mg. On the intention-to-treat estimand the differences were −1.4 and −1.6 points. All P<0.001.
• Obstructive sleep apnea. The abstract reports differences in the apnea-hypopnea index of −24.4 and −21.9 events per hour for 9 mg and 12 mg on the hybrid estimand, and −24.7 and −22.5 on the intention-to-treat estimand, against changes of roughly −10 events per hour with placebo (both P<0.001).

The hybrid estimand is the paper’s way of handling participants who stopped treatment or began other therapy in the two subgroups; the abstract reports it alongside the intention-to-treat result. The figures here are the paper’s, not recalculated.

Adverse events

The abstract states that “the most common adverse events were gastrointestinal.” It gives no event rates, discontinuation figures or serious-adverse-event counts; those sit in the full text, which was not read for this article. The weight figures above are therefore only half of the report; for rates, the full paper and its supplement are the source. The companion TRIUMPH-2 paper in The Lancet, covered in a separate report, does give adverse-event rates in its abstract.

How this differs from the May release

In May, Lilly reported topline TRIUMPH-1 results, including a 104-week extension, in a company release; Prof. Peptide covered it in Retatrutide Hits 30.3% Average Weight Loss in TRIUMPH-1. The NEJM paper is the first peer-reviewed publication of the trial and reports the prespecified 80-week outcomes. The two use different time points and estimands, so the 30.3% figure and the 25.0% figure above are not in conflict; they measure different things.

Where the molecule stands

Retatrutide is investigational and has no approval anywhere. Lilly has said it plans to submit its application in the first quarter of 2027, and the FDA’s October 2 classification decision addresses which pathway applies; see the report on that decision. Reports of unapproved retatrutide sold online, and what clinicians and researchers have documented about it, are in a separate report.

What this is, and isn’t

This is reporting on a published clinical trial, taken from the paper’s abstract and the trial registry. It is not a review of the full paper, not a comparison with other drugs, and not a statement that retatrutide is safe or effective outside the trial. The trial assigned set doses to selected participants under its protocol; the figures describe that setting only. Retatrutide is investigational and is not approved for human use anywhere. Nothing here is medical advice or a usage recommendation.

Sources

• Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med, Sept. 29, 2026 (PubMed record and abstract) — primary: every figure above. DOI 10.1056/NEJMoa2604169.
• TRIUMPH-1, ClinicalTrials.gov NCT05929066 — primary: the trial registration.
• Lilly press release, Sept. 29, 2026 — company release: Q1 2027 application plan.