Lilly says Zepbound 10 mg and 15 mg beat Wegovy HD in indirect comparison presented at EASD

Eli Lilly said on September 29, 2026 that an indirect comparison of trial data links Zepbound (tirzepatide) 10 mg and 15 mg to greater weight loss than Wegovy HD, the 7.2 mg dose of semaglutide injection. The analysis was presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy ^[1].

The study is not a head-to-head trial. Researchers pooled results from two separate studies — SURMOUNT-1, which tested tirzepatide against placebo, and STEP UP, which tested semaglutide 7.2 mg — and used a statistical model to estimate how the drugs would compare if they had been tested against each other. The comparison was adjusted for gender, age, baseline weight and baseline A1C ^[1].

What the numbers show

Results differed depending on which analysis method was used. Under the treatment-regimen estimand, which estimates the average effect regardless of whether people stopped treatment, Zepbound 15 mg was associated with 4.5% more body weight lost at 72 weeks (95% credible interval: -6.3 to -2.8), and 10 mg with 3.2% more (95% CrI: -5.0 to -1.4) ^[1].

Under the efficacy estimand, which looks at results before people discontinued the study drug, the gaps narrowed sharply and were no longer statistically significant: 1.8% (95% CrI: -3.8 to 0.1) for 15 mg and 0.7% (95% CrI: -2.6 to 1.3) for 10 mg ^[1].

For the share of people reaching at least 20% body weight reduction, participants on Zepbound 15 mg had about four times the odds versus Wegovy HD using the efficacy estimand (odds ratio 4.15; 95% CrI: 1.02 to 15.64) and more than three times the odds using the treatment-regimen estimand (odds ratio 3.54; 95% CrI: 1.05 to 11.05). The 10 mg comparisons — odds ratios of 2.8 and 2.46 — were not statistically significant, with credible intervals crossing 1 ^[1].

Discontinuation due to adverse events was comparable between Zepbound 10 mg and 15 mg and Wegovy HD across both analyses ^[1].

The context around the comparison

The two drugs have been compared directly once, at lower semaglutide doses. SURMOUNT-5 was a 72-week, randomized, open-label Phase 3b trial in 751 adults in the U.S. and Puerto Rico with obesity, or overweight plus a related condition, and without diabetes. Participants on Zepbound lost an average of 20.2% of body weight versus 13.7% with Wegovy at 72 weeks using the treatment-regimen estimand — a 47% greater relative weight loss, or about 50.3 pounds versus 33.1 pounds ^[1].

Wegovy HD is newer. The FDA approved the 7.2 mg dose on March 19, 2026, for weight reduction and long-term maintenance in adults with obesity, or overweight with at least one weight-related condition. It was the fourth approval under the agency's Commissioner's National Priority Voucher pilot program and came 54 days after filing ^[2]. The FDA noted that altered skin sensation — described as sensitivity, pain or burning — was common, occurred more often at the higher dose than at lower doses, and generally resolved on its own or with a dose reduction. The agency said it is conducting further investigation of that reaction ^[2].

Why it matters for patients

Indirect comparisons carry more uncertainty than randomized head-to-head trials because the two groups being compared never appeared in the same study, and differences in enrolled patients, sites and trial conduct can influence results even after statistical adjustment. Here, the size of the advantage depended heavily on the analysis method, and the efficacy-estimand differences did not reach statistical significance ^[1].

The analysis was announced by Lilly, which makes Zepbound, and one of the quoted investigators, John Wilding of the University of Liverpool, is listed as an author on the presentation ^[1]. Wilding said that in the absence of a head-to-head trial comparing tirzepatide 15 mg with semaglutide 7.2 mg, the indirect comparison "offers useful evidence for physicians as they make treatment decisions" ^[1].

What happens next

Whether a randomized trial will directly compare Zepbound with Wegovy HD has not been reported. Cost, insurance coverage and supply — which often shape which drug a person can actually get — were not addressed in the analysis. The FDA said it would hold a public hearing in June to gather feedback on the voucher program used for Wegovy HD's review ^[2].