In this new analysis, Zepbound 15 mg showed 4.5% greater weight loss than Wegovy HD in adults with obesity

Participants receiving Zepbound 15 mg had more than three times the odds of achieving at least 20% body-weight reduction compared with Wegovy HD

INDIANAPOLIS, Sept. 29, 2026 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY), the maker of Foundayo (orforglipron), today announced results from a new analysis showing that Zepbound (tirzepatide) 10 mg and 15 mg, a dual GIP and GLP-1 receptor agonist, delivered greater weight loss than Wegovy HD (semaglutide injection 7.2 mg) in adults with obesity. The findings come from an indirect treatment comparison of Zepbound and Wegovy HD, drawing on data from the SURMOUNT-1 and STEP UP trials.1,2,3 These results, presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD) in Milan, Italy, add to the growing body of evidence comparing Zepbound and Wegovy, including SURMOUNT-5, a randomized controlled Phase 3b trial in which Zepbound 10 mg and 15 mg demonstrated superior weight loss compared with Wegovy 1.7 mg and 2.4 mg.

"For people living with obesity, the choice of treatment matters, and clinicians increasingly want evidence on how the available options compare," said John Wilding, DM, professor of medicine at the University of Liverpool. "Tirzepatide 10 mg and 15 mg and semaglutide 1.7 mg and 2.4 mg were compared directly in SURMOUNT-5, where tirzepatide helped people with obesity lose more weight. In the absence of a head-to-head trial comparing tirzepatide 15 mg against semaglutide 7.2 mg, this indirect comparison offers useful evidence for physicians as they make treatment decisions."

In the indirect treatment comparison, which was covariate-adjusted for gender, age, baseline weight and baseline A1C, Zepbound 10 mg and 15 mg were associated with greater reductions in body weight than Wegovy HD at 72 weeks using the treatment-regimen estimand.4,5 Participants taking Zepbound 15 mg lost 4.5% more of their body weight (95.0% CrI: -6.3, -2.8) on average, and those taking 10 mg lost 3.2% more of their body weight (95.0% CrI: -5.0, -1.4). Using the efficacy estimand, Zepbound 15 mg and 10 mg were associated with 1.8% (95.0% CrI: -3.8, 0.1) and 0.7% (95.0% CrI: -2.6, 1.3) greater mean weight reduction than Wegovy HD, respectively, though these differences did not reach statistical significance.6

"People with obesity have more treatment options than ever before, and their healthcare providers deserve as much information as possible to help guide their decisions," said Thomas Seck, M.D., senior vice president of product development, Lilly Cardiometabolic Health. "In a head-to-head Phase 3 clinical trial, Zepbound 10 mg and 15 mg delivered greater weight loss than Wegovy 1.7 mg and 2.4 mg, and a new indirect treatment comparison suggests the same doses of Zepbound may outperform Wegovy HD, as well. Together, these results offer physicians more information as they choose a treatment path."

In addition to achieving greater weight loss, participants taking Zepbound 15 mg were four times more likely to achieve 20% or greater body weight reduction compared with Wegovy HD using the efficacy estimand (odds ratio 4.15; 95.0% CrI: 1.02, 15.64), and more than three times more likely using the treatment-regimen estimand (odds ratio 3.54; 95.0% CrI: 1.05, 11.05). While not statistically significant, participants taking Zepbound 10 mg had more than two times the odds of achieving at least 20% body-weight reduction compared with Wegovy HD using the efficacy (odds ratio 2.8; 95.0% CrI: 0.7, 10.8) and treatment-regimen estimands (odds ratio 2.46; 95.0% CrI: 0.7, 7.8).

Zepbound 10 mg and 15 mg showed comparable rates of treatment discontinuation due to adverse events versus Wegovy HD across both estimands.

About SURMOUNT-1 and the SURMOUNT clinical trial program  

SURMOUNT-1 (NCT04184622) is a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. The trial randomized 2,539 participants across the U.S., Argentina, Brazil, China, India, Japan, Mexico, Russia and Taiwan in a 1:1:1:1 ratio to receive either tirzepatide 5 mg, 10 mg or 15 mg or placebo. The co-primary objectives of the study were to demonstrate that tirzepatide 10 mg and/or 15 mg is superior in percentage of body weight reductions from baseline and percentage of participants achieving ≥5% body weight reduction at 72 weeks compared to placebo.

The SURMOUNT phase 3 global clinical development program for tirzepatide in chronic weight management began in late 2019 and has enrolled more than 5,000 people with obesity or overweight across six registration studies, four of which are global studies.

About SURMOUNT-5

SURMOUNT-5 (NCT05822830) was a 72-week, multi-center, randomized, open-label, Phase 3b trial evaluating the efficacy and safety of Zepbound (tirzepatide) compared with Wegovy (semaglutide) in adults with obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea (OSA) or cardiovascular disease, who did not have diabetes. Participants in both treatment groups received counseling on a reduced-calorie diet and increased physical activity. The trial randomized 751 participants across the U.S. and Puerto Rico in a 1:1 ratio to receive maximum tolerated dose of Zepbound (10 mg or 15 mg) or Wegovy (1.7 mg or 2.4 mg). With tirzepatide, 89.3% received at least one dose of the 15 mg dose and with semaglutide 92.8% received at least one dose of the 2.4 mg dose. The primary objective of the study was to demonstrate Zepbound's superiority in percent change from baseline in body weight at 72 weeks compared to Wegovy.

For the primary endpoint, participants treated with Zepbound achieved an average weight reduction of 20.2% compared to 13.7% with Wegovy at 72 weeks using the treatment-regimen estimand, a 47% greater relative weight loss. Participants using Zepbound lost an average of 50.3 lbs (22.8 kg) and participants on Wegovy lost an average of 33.1 lbs (15.0 kg).

About Zepbound (tirzepatide) injection

Zepbound (tirzepatide) is the first and only dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist obesity medication. Zepbound tackles an underlying cause of excess weight. It reduces appetite and how much you eat. Zepbound is indicated for adults with obesity, or some adults who are overweight and also have at least one weight-related medical problem, to lose weight and keep it off. Additionally, Zepbound is FDA-approved to treat adults with moderate-to-severe obstructive sleep apnea and obesity. Zepbound should be used with a reduced calorie diet and increased physical activity.

Endnotes and References

- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038.

- Wharton S, Freitas P, Hjelmesæth J, et al. Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. The Lancet Diabetes & Endocrinology, 2025; 13, 949-963. https://doi.org/10.1016/S2213-8587(25)00226-8

- Wilding J, Postma MJ, Jacobi D, et al. Tirzepatide 10 and 15 mg (SURMOUNT-1) vs semaglutide 7.2 mg (STEP UP) in adults with obesity without type 2 diabetes: an indirect treatment comparison. Presented at the 62nd Annual Meeting of the European Association for the Study of Diabetes (EASD).

- Weight loss data represent an ML-NMR analysis.

- Treatment-regimen estimand represents the estimated average treatment effect regardless of treatment discontinuation.

- Efficacy estimand represents efficacy prior to discontinuation of study drug.

U.S. ZEPBOUND INDICATIONS AND SAFETY SUMMARY WITH WARNINGS

Zepbound® (ZEHP-bownd) is an injectable prescription medicine used with a reduced-calorie diet and increased physical activity to help adults with:

- obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off.

- moderate-to-severe obstructive sleep apnea (OSA) and obesity to improve their OSA.

- Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective for use in children.

Warnings - Zepbound may cause tumors in the thyroid, including thyroid cancer. Watch for possible symptoms, such as a lump or swelling in the neck, hoarseness, trouble swallowing, or shortness of breath. If you have any of these symptoms, tell your healthcare provider.

- Do not use Zepbound if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC).

- Do not use Zepbound if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

- Do not use Zepbound if you have had a serious allergic reaction to tirzepatide or any of the ingredients in Zepbound.

KwikPen®: Do not share your KwikPen with other people, even if the pen needle has been changed. You may give other people a serious infection or get a serious infection from them.

Zepbound may cause serious side effects, including:

Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use Zepbound. Tell your healthcare provider if you have stomach problems that are severe or will not go away.

Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems.