Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1) — VialBase Research
22.5% mean body weight loss with tirzepatide 15mg at 72 weeks
- 22.5% mean body weight loss with tirzepatide 15mg at 72 weeks
- 96% of tirzepatide 15mg participants lost ≥5% body weight
- 63% lost ≥20% body weight with 15mg dose
- Highest weight loss reported for any anti-obesity medication at the time
- 2,539 adults without type 2 diabetes enrolled
Summary
SURMOUNT-1 was the pivotal Phase 3 trial that established tirzepatide as the most effective anti-obesity medication available. The study enrolled 2,539 adults with BMI ≥30 (or ≥27 with comorbidity) without type 2 diabetes. Participants were randomized to tirzepatide 5mg, 10mg, or 15mg weekly vs placebo, with lifestyle intervention, for 72 weeks.
Key Findings
- Mean weight loss at 72 weeks by dose:
- 5mg: -15.0% (vs -3.1% placebo)
- 10mg: -19.5%
- 15mg: -20.9% (treatment policy estimand) / -22.5% (efficacy estimand, on-treatment)
- Proportion achieving ≥5% weight loss: 85% (5mg), 89% (10mg), 91% (15mg) vs 35% placebo
- Proportion achieving ≥20% weight loss: 30% (5mg), 50% (10mg), 57% (15mg) vs 3% placebo
- Mean absolute weight loss: ~24 kg (~52 lbs) in the 15mg group
- Significant improvements in waist circumference, blood pressure, lipids, and fasting insulin
- GI adverse events: nausea 24-33%, diarrhea 18-23%, vomiting 6-13% — generally mild to moderate and transient
- Discontinuation due to adverse events: 4.3% (5mg), 7.1% (10mg), 6.2% (15mg) vs 2.6% placebo
Relevance to Tirzepatide
SURMOUNT-1 was the defining trial for tirzepatide in obesity, leading directly to FDA approval of Zepbound in November 2023. The 22.5% mean weight loss exceeded all prior anti-obesity medications and approached outcomes previously only achievable with bariatric surgery (typically 25-35% weight loss). It demonstrated that dual GIP/GLP-1 agonism provides meaningfully greater efficacy than GLP-1 agonism alone (Semaglutide STEP 1: 14.9% weight loss). The dose-response relationship (15% to 22.5% across 5-15mg doses) provided important dosing guidance.
Citation
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038.
See Also
- Parent compound: Tirzepatide
- Semaglutide