- Lilly's TRIUMPH‑1 randomized 2,339 adults with overweight/obesity to retatrutide 4/9/12 mg or placebo with an 80‑week primary endpoint and a 104‑week extension (532 enrolled, BMI>=35).
- Retatrutide, a GIP/GLP‑1/glucagon triple agonist, produced dose‑related mean weight loss at 80 weeks: -19.0% (4 mg), -25.9% (9 mg), -28.3% (12 mg).
- At 80 weeks 45.3% on 12 mg achieved >=30% weight loss and 65.3% reached BMI<30; extension to 104 weeks in the BMI>=35 subgroup reached -30.3% (avg -85.0 lbs) on 12 mg.
- Safety: common GI adverse events (nausea, diarrhea, vomiting); discontinuations due to AEs were 4.1%/6.9%/11.3% for 4/9/12 mg versus 4.9% for placebo.
Trial design
TRIUMPH‑1 was an 80‑week, randomized, double‑blind, placebo‑controlled Phase 3 master trial that enrolled 2,339 adults with overweight/obesity to once‑weekly retatrutide (target doses 4, 9 or 12 mg) or placebo; dosing began at 2 mg with stepwise escalation; a pre‑specified blinded extension enrolled 532 participants with baseline BMI≥35 to continue treatment to 104 weeks with escalation to maximum tolerated dose (9 or 12 mg).
Efficacy at 80 weeks
Mean percent weight change at 80 weeks was −19.0% (4 mg, −47.2 lb), −25.9% (9 mg, −64.4 lb) and −28.3% (12 mg, −70.3 lb) versus −2.2% (placebo, −5.5 lb); waist circumference fell dose‑dependently (−16.3 cm to −24.1 cm vs −3.6 cm); proportions achieving ≥25% weight loss were 27.8%, 52.9% and 62.5% (placebo 2.2%), and ≥30% were 15.3%, 37.9% and 45.3% (placebo 0.5%); 65.3% on 12 mg reached BMI<30 (pre‑specified analysis; multiplicity not controlled).
Extension to 104 weeks
In the BMI≥35 extension, participants maintained or increased weight loss to 104 weeks with mean reductions up to −30.3% (12 mg to MTD; −85.0 lb); other MTD results were −27.9% (4 mg to MTD) and −29.5% (9 mg to MTD), with placebo→MTD at −19.2%.
Safety
Adverse events mirrored incretin‑class profiles: common events included nausea (28.6%–42.4% vs 14.8% placebo), diarrhea (25.2%–34.1% vs 13.5%), constipation and vomiting; dysesthesia (5.1%–12.5% vs 0.9%) and UTIs (7.5%–8.8% vs 5.3%) were reported; discontinuations for AEs were 4.1%, 6.9% and 11.3% (4/9/12 mg) versus 4.9% for placebo.
