Tirzepatide for chronic weight management: SURMOUNT-1
Pivotal 72-week phase-3 RCT of tirzepatide in 2,539 adults with obesity. The 15 mg dose produced a mean total body weight reduction of 22.5%, and 36% of participants lost at least one quarter of their baseline body weight.
Design
Double-blind, placebo-controlled, randomized phase-3 trial in adults with BMI ≥ 30 (or ≥ 27 with at least one weight-related complication, excluding diabetes). Participants were assigned 1:1:1:1 to tirzepatide 5, 10, 15 mg subcutaneous weekly, or placebo, for 72 weeks alongside lifestyle counseling.
Primary outcome
Mean percentage change in body weight from baseline to week 72: tirzepatide 5 mg −15.0%, 10 mg −19.5%, 15 mg −20.9% to −22.5% (depending on analysis set), placebo −3.1%. All comparisons p < 0.001.
Secondary outcomes
Weight loss of ≥ 5% achieved by 85–91% of tirzepatide groups vs 35% placebo. Weight loss of ≥ 20% achieved by 50% of the 15 mg group. Improvements in waist circumference, systolic/diastolic blood pressure, fasting glucose, HbA1c, lipids, and SF-36 physical-function scores.
Safety
Most common adverse events were gastrointestinal (nausea, diarrhea, constipation), predominantly mild-to-moderate and during dose-escalation. Discontinuation due to AEs: 4.3–7.1% on tirzepatide vs 2.6% on placebo. No new safety signals.