Lilly's Zepbound beats Wegovy HD in indirect obesity study

Eli Lilly announced results on September 29, 2026, from an indirect treatment comparison showing that Zepbound (tirzepatide) at 10 mg and 15 mg delivered greater weight loss than Wegovy HD (semaglutide injection 7.2 mg) in adults with obesity. The analysis drew data from the SURMOUNT-1 and STEP UP trials and was presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes in Milan, Italy.

Using the treatment-regimen estimand at 72 weeks, patients on Zepbound 15 mg achieved an average of 4.5% greater weight reduction than those on Wegovy HD, while the 10 mg dose achieved 3.2% more reduction. Under the efficacy estimand, Zepbound 15 mg and 10 mg delivered 1.8% and 0.7% greater mean weight reduction respectively, though those differences did not reach statistical significance.

Participants taking the 15 mg dose were more than three times as likely to reach at least 20% body weight loss under the treatment-regimen estimand, and four times as likely under the efficacy estimand, compared with Wegovy HD. Discontinuation rates caused by adverse events were comparable between both doses of Zepbound and Wegovy HD across both estimands.

The findings build on Lilly's previous SURMOUNT-5 head-to-head trial, in which Zepbound delivered an average weight loss of 20.2% (50.3 pounds) against 13.7% (33.1 pounds) for lower-dose Wegovy at 72 weeks.