Indianapolis – September 29, 2026 -- Eli Lilly and Company said a new indirect treatment comparison shows Zepbound (tirzepatide) 15 mg produced 4.5% greater body-weight loss than Novo Nordisk's Wegovy HD (semaglutide 7.2 mg) in adults with obesity, intensifying the competitive battle in the obesity-drug market. The 10 mg dose of Zepbound delivered 3.2% greater weight reduction than Wegovy HD, according to data presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan.
Indirect analysis draws on SURMOUNT-1 and STEP UP trial data
The comparison, covariate-adjusted for gender, age, baseline weight and baseline A1C, used 72-week outcomes from the SURMOUNT-1 and STEP UP studies. Using the treatment-regimen estimand, Zepbound 15 mg and 10 mg showed weight-loss advantages of 4.5% (95.0% CrI: -6.3, -2.8) and 3.2% (95.0% CrI: -5.0, -1.4), respectively, over Wegovy HD. Under the efficacy estimand, the gaps narrowed to 1.8% and 0.7% and did not reach statistical significance.
Zepbound users showed higher odds of major weight-loss milestones
Participants on Zepbound 15 mg were 3.54 times more likely to achieve at least 20% body-weight reduction than those on Wegovy HD using the treatment-regimen estimand, and 4.15 times more likely under the efficacy estimand. Zepbound 10 mg users had roughly 2.5 to 2.8 times the odds of hitting that threshold, though these results were not statistically significant. Rates of treatment discontinuation due to adverse events were comparable between Zepbound and Wegovy HD across both estimands.
Findings build on head-to-head SURMOUNT-5 trial results
The indirect comparison adds to SURMOUNT-5, a randomized Phase 3b trial in which Zepbound 10 mg and 15 mg produced 20.2% average weight loss versus 13.7% for Wegovy 1.7 mg and 2.4 mg over 72 weeks -- a 47% greater relative reduction. Zepbound patients lost an average of 50.3 lbs (22.8 kg) compared with 33.1 lbs (15.0 kg) for Wegovy patients in that 751-participant trial across the U.S. and Puerto Rico.
John Wilding, professor of medicine at the University of Liverpool, said the new data give physicians additional evidence in the absence of a direct trial pitting tirzepatide 15 mg against semaglutide 7.2 mg. Thomas Seck, Lilly's senior vice president of product development for cardiometabolic health, said the analysis complements SURMOUNT-5 findings as prescribers weigh treatment options in a market now including several high-dose GLP-1 therapies.