Visual Abstract Summary: SURMOUNT-3 Phase 3 Trial
Objective: To evaluate the efficacy and safety of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, in achieving additional weight loss in adults with overweight or obesity who had already reduced their body weight by at least 5% through a 12-week intensive lifestyle intervention.
Study Design:
- Type: Double-blind, placebo-controlled, randomized clinical trial
- Participants: 579 adults with a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with at least one obesity-related complication (excluding diabetes)
- Intervention: Participants were randomized 1:1 to receive once-weekly subcutaneous injections of either tirzepatide (titrated up to 10 mg or 15 mg) or placebo for 72 weeks
- Primary Endpoints:
- Mean percentage change in body weight from randomization to week 72
- Proportion of participants achieving an additional weight reduction of ≥5%
Findings:
- Weight Reduction:
- Tirzepatide group: Mean additional weight loss of 18.4% (SE 0.7)
- Placebo group: Mean weight change of +2.5% (SE 1.0)
- Estimated treatment difference: -20.8 percentage points (95% CI: -23.2%, -18.5%; P < 0.001)
- Achievement of ≥5% Additional Weight Loss:
- Tirzepatide group: 87.5% (SE 2.2)
- Placebo group: 16.5% (SE 3.0)
- Odds ratio: 34.6 (95% CI: 19.2, 62.6; P < 0.001)
- Safety:
- The most common adverse events in the tirzepatide group were gastrointestinal, primarily mild to moderate in severity.
Conclusion: Tirzepatide significantly enhanced weight loss in adults with overweight or obesity who had previously achieved at least a 5% weight reduction through intensive lifestyle intervention. The treatment was generally well-tolerated, with manageable side effects. These findings suggest that tirzepatide could be an effective adjunct therapy for sustained weight management in this population.
Reference: Wadden, T. A., et al. (2023). Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine, 29, 2909–2918.