SURMOUNT-1: A Study of Tirzepatide in Participants with Obesity or Overweight

Background + significance

SURMOUNT-1 established tirzepatide's class-leading effect size in chronic weight management. At the highest 15 mg dose, mean weight loss of 20.9% at 72 weeks substantially exceeded semaglutide's STEP-1 result and led to Zepbound FDA approval in 2023. The dual GIP/GLP-1 mechanism appears to be the structural reason for the larger effect vs GLP-1-only agents.

Trial design

Sponsor

Eli Lilly

Phase

Phase 3

Participants

2,539

Duration

72 weeks

ClinicalTrials.gov ID

NCT04184622 (opens in a new tab)

Drugs tested

• Zepbound (tirzepatide 5/10/15 mg)Active

Primary outcome

Percentage change in body weight from baseline to week 72

−15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) on tirzepatide vs −3.1% placebo

Secondary outcomes

• •~91% of 15 mg patients achieved ≥5% weight loss
• •~57% achieved ≥20% weight loss
• •~36% achieved ≥25% weight loss
• •Improvements in BP, lipids, A1C in patients with prediabetes

Why it matters

1. 1.Class-leading effect size: ~22% mean weight loss at 15 mg.
2. 2.Dose-dependent: even the lowest 5 mg dose (15% loss) exceeds Wegovy 2.4 mg.
3. 3.Most weight loss occurred during the 20-week titration; weight stable in the extension period.