Eli Lilly and Company - Zepbound showed superior weight loss over Wegovy in complete SURMOUNT-5 results published in The New England Journal of Medicine

Published: 2025-05-12 11:14:15 ET LLY

Published on 05/12/2025 at 11:14

INDIANAPOLIS - Eli Lilly and Company (NYSE: LLY) announced detailed results from SURMOUNT-5, a Phase 3b open-label clinical trial, evaluating the safety and efficacy of Zepbound (tirzepatide), a dual GIP and GLP-1 receptor agonist, compared to Wegovy (semaglutide), a mono GLP-1 receptor agonist, in adults living with obesity, or overweight with at least one weight-related medical problem and without diabetes.

At 72 weeks, Zepbound met the primary endpoint and all five key secondary endpoints, demonstrating superiority compared to Wegovy across the trial. The detailed results were presented at the 32nd European Congress on Obesity (ECO) and simultaneously published in The New England Journal of Medicine.

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,1 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).2

In key secondary endpoints, Zepbound was superior across all weight reduction targets with 64.6% of participants treated with Zepbound achieving at least 15.0% weight loss compared to 40.1% on Wegovy. Additionally, participants treated with Zepbound achieved a superior average waist circumference reduction of 7.2 in (18.4 cm), while those treated with Wegovy saw an average reduction of 5.1 in (13.0 cm).

'Thanks to the latest advancements in obesity management medications, more physicians and patients are witnessing significant weight reduction beyond what they have seen before,' said Louis J. Aronne, MD, FACP, DABOM, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, an internist specializing in diabetes and obesity at New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of SURMOUNT-5. 'The SURMOUNT-5 head-to-head results demonstrated tirzepatide led to greater weight reduction compared to semaglutide, providing further evidence to support tirzepatide as an effective option for obesity management.'

Primary and Key Secondary Endpoints: 'In the SURMOUNT-5 trial, Zepbound demonstrated a significantly higher magnitude of weight reduction compared to Wegovy across all comparisons,' said Leonard Glass, MD, FACE, senior vice president, global medical affairs, Lilly. 'These data confirm Zepbound as a leading treatment option for people living with obesity and equip healthcare providers with critical insights to make well-informed treatment decisions as part of a comprehensive obesity care plan.'

The safety profile of Zepbound in SURMOUNT-5 was consistent with previous SURMOUNT trials. Adverse events reported during the trial were primarily gastrointestinal-related and were generally mild to moderate in severity. During the trial, 6.1% of participants taking Zepbound discontinued treatment due to adverse events, compared to 8.0% of participants taking Wegovy. However, the study was not powered to compare the safety and tolerability of Zepbound and the safety and tolerability of Wegovy.

Tirzepatide is commercialized for adults with obesity or with overweight who also have weight-related medical problems as Zepbound in the U.S. and Mounjaro in some countries outside of the U.S. Tirzepatide is also commercialized as Mounjaro for adults with type 2 diabetes in the U.S. and in some countries outside of the U.S. Semaglutide is commercialized as Wegovy for people living with obesity or for adults with overweight who also have weight-related medical problems and Ozempic for people with type 2 diabetes.

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.

About tirzepatide

Tirzepatide is a once-weekly dual GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide decreases calorie intake, and the effects are likely mediated by affecting appetite. Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are ongoing.

Tirzepatide has been approved by the U.S. FDA as Mounjaro for adults with type 2 diabetes to improve glycemic control, and as Zepbound 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. Tirzepatide is also approved as Mounjaro in some countries outside the U.S. for adults with type 2 diabetes, obesity or those who are overweight who also have a weight-related comorbid condition. Both Mounjaro and Zepbound should be used in combination with diet and exercise.

About Lilly

Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable.

The treatment-regimen estimand represents efficacy regardless of adherence to randomized treatment and regardless of initiation of other anti-obesity medication (except for switching to non-study tirzepatide or semaglutide). This estimand assumes that participants who had weight loss procedures during the study did not get any benefit from their randomized study treatment.

Not controlled for family-wise type 1 error rate.

Disclosure: Dr. Aronne is a paid consultant and advisory board member for Lilly, the study sponsor and the manufacturer of Zepbound (tirzepatide). Dr. Aronne also serves as a paid advisory board member for Novo Nordisk, the manufacturer of Wegovy (semaglutide).

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Cautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995), including statements about the efficacy and safety of Zepbound (tirzepatide) as a treatment for adults with obesity or overweight and reflects Lilly's current belief and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date, that Zepbound will receive additional regulatory approvals, or that Lilly will execute its strategy as planned.

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