Semaglutide vs tirzepatide: which is more effective for weight loss?

What SURMOUNT-5 measured A phase 3b, open-label, controlled trial. 751 adults with obesity but without type 2 diabetes. Random 1:1 assignment to the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or the maximum tolerated dose of semaglutide (1.7 mg or 2.4 mg), subcutaneously once weekly for 72 weeks.

The primary result, in the trial''s own words "Among participants with obesity but without diabetes, treatment with tirzepatide was superior to treatment with semaglutide with respect to reduction in body weight and waist circumference at week 72."

The numbers - Weight loss: −20.2% (tirzepatide) vs −13.7% (semaglutide) - Waist circumference: −18.4 cm vs −13.0 cm - Weight reductions of at least 10%, 15%, 20%, and 25% were all more likely in the tirzepatide arm. - Adverse events: most common were gastrointestinal, mostly mild-to-moderate in severity, mostly during dose escalation, in both arms.

What the trial does not tell you SURMOUNT-5 does not compare cost, insurance coverage, or long-term durability past 72 weeks. It does not cover people with type 2 diabetes — the SURPASS trials do.

Source Aronne LJ et al., "Tirzepatide as Compared with Semaglutide for the Treatment of Obesity" (SURMOUNT-5, NCT05822830), New England Journal of Medicine, 2025. Indexed by the U.S. National Library of Medicine at pubmed.ncbi.nlm.nih.gov/40353578/