Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.

Summary

In a 72-week, open-label, randomized trial (n=751), tirzepatide achieved greater weight loss (−20.2% vs −13.7%) and waist reduction (−18.4 cm vs −13.0 cm) than semaglutide in adults with obesity without diabetes. Gastrointestinal adverse events were most common and mostly mild-to-moderate during dose escalation.

Key Findings

• At 72 weeks, mean weight change was −20.2% with tirzepatide vs −13.7% with semaglutide (P<0.001).
• Waist circumference decreased more with tirzepatide (−18.4 cm) than semaglutide (−13.0 cm) (P<0.001).
• Higher proportions achieved ≥10%, ≥15%, ≥20%, and ≥25% weight loss with tirzepatide; GI adverse events were common and mostly mild–moderate during dose escalation.

Clinical Implications

For adults with obesity without diabetes, tirzepatide may be preferred when maximizing weight and waist reduction is prioritized, with counseling on gastrointestinal tolerability during uptitration.

Limitations

• Open-label design may introduce expectation bias.
• Industry-sponsored trial; long-term safety beyond 72 weeks was not assessed.

Future Directions

Evaluate comparative cardiometabolic outcomes, quality of life, maintenance strategies, and long-term safety beyond 72 weeks, including cost-effectiveness analyses.