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Tirzepatide Once Weekly for the Treatment of Obesity
SURMOUNT-1 randomized 2,539 adults with obesity without diabetes to once-weekly tirzepatide (5, 10, or 15 mg) versus placebo for 72 weeks: dose-dependent mean weight reductions and high responder rates on active doses versus placebo.
Design
- Phase 3 double-blind RCT; n = 2,539 randomized 1:1:1:1 to 5 mg, 10 mg, 15 mg tirzepatide weekly vs placebo (72 weeks inclusive of 20-week escalation)
- Population: BMI ≥30, or ≥27 with complications; excluded diabetes
- Coprimary estimands (treatment-regimen): % weight change and ≥5% weight loss
Key efficacy (week 72; treatment-regimen estimand in primary publication)
- Mean % weight change: −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) vs −3.1% (placebo) (P < 0.001 each vs placebo)
- ≥5% loss: 85% / 89% / 91% (5 / 10 / 15 mg) vs 35% (placebo)
- ≥20% loss (selected doses): 50% (10 mg) and 57% (15 mg) vs 3% (placebo) (P < 0.001)
Safety (headline)
- GI events predominated, mostly mild–moderate during escalation; discontinuation due to AE 4.3% / 7.1% / 6.2% vs 2.6% (placebo)
Publication
Jastreboff AM, Aronne LJ, Ahmad NN, et al. N Engl J Med. 2022 Jul 21;387(3):205–216. PMID 35658024.
Outcomes
- Mean % body-weight change at week 72: −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) vs −3.1% with placebo (P<0.001 for each active dose vs placebo).
- ≥5% weight loss at week 72: 85%, 89%, and 91% with 5 mg, 10 mg, and 15 mg tirzepatide, respectively, vs 35% with placebo.