NEJM: retatrutide phase 3 TRIUMPH-1 shows ~25% mean weight loss at highest dose

Coverage dated 3 October 2026 (ScienceAlert) highlights a phase 3 New England Journal of Medicine report — TRIUMPH-1, led by Ania Jastreboff (Yale) — of once-weekly retatrutide, an investigational GLP-1 / GIP / glucagon receptor agonist from Eli Lilly, in adults with obesity or overweight without type 2 diabetes.

Key efficacy (80 weeks)

The randomised, double-blind, placebo-controlled trial enrolled 2,339 adults assigned to 4, 9 or 12 mg retatrutide or placebo. On the treatment-regimen estimand (effect regardless of discontinuation), mean weight change at 80 weeks was about −17.6%, −23.7% and −25.0% for 4, 9 and 12 mg versus −3.9% on placebo. Nested baskets also reported greater improvements in knee osteoarthritis pain and obstructive sleep apnea event rates versus placebo at higher doses. An extension of eligible participants toward week 104 showed further loss in those continuing higher doses (ScienceAlert cites ~29.9% average in one 12 mg extension path).

Limitations and safety

Retatrutide remains investigational; Lilly has said a U.S. biologics application is planned for early 2027. Gastrointestinal adverse events (nausea ~42% at 12 mg) were most common; adverse events led ~11% on 12 mg to stop treatment versus ~4.6% on placebo. The trial was not designed for cardiovascular outcome superiority, did not head-to-head compare retatrutide with semaglutide or tirzepatide, and was sponsor-funded with sponsor data handling. This summarises a peer-reviewed phase 3 trial — not personal medical advice.