Survodutide Once Weekly for the Treatment of Adults with Obesity

Survodutide Once Weekly for the Treatment of Adults with Obesity Published June 7, 2026 N Engl J Med 2026;395:776-787 DOI: 10.1056/NEJMoa2600751 Abstract Background Although medications with glucagon-like peptide-1 (GLP-1) receptor agonist activity have transformed the management of obesity and shown substantial cardiometabolic benefits, unmet needs remain. Survodutide, an investigational glucagon receptor–GLP-1 receptor dual agonist, led to substantial weight reduction in a phase 2 trial involving adults with obesity without diabetes. Methods In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously at a dose adjusted up to 3.6 mg or 6.0 mg or placebo, in addition to counseling for lifestyle modification. The two primary end points were the percent change in body weight and a reduction in body weight of at least 5% from baseline to week 76. The primary efficacy analysis was conducted according to the treatment-regimen estimand, which incorporates the effects of any early discontinuation of survodutide or placebo, the use of protocol-prohibited obesity medications, and a prolonged dose-escalation period. Results Among 725 participants (241 in the 3.6-mg survodutide group, 242 in the 6.0-mg survodutide group, and 242 in the placebo group), the mean age was 47.1 years; 294 participants (40.6%) were men. At baseline, the mean BMI was 37.9, and the mean body weight was 108.8 kg. At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was –12.2% (95% confidence interval [CI], −13.6 to −10.8) in the 3.6-mg group, –13.0% (95% CI, −14.4 to −11.6) in the 6.0-mg group, and –5.4% (95% CI, −6.9 to −4.0) in the placebo group; 72.6%, 71.9% and 46.3% of the participants, respectively, had weight reduction of at least 5% (P<0.001 for all comparisons with placebo). The most common adverse events were gastrointestinal symptoms (typically mild to moderate), which occurred in 80.9% of the participants in the 3.6-mg group, in 89.7% of those in the 6.0-mg group, and in 47.9% of those in the placebo group. No deaths were reported. Conclusions Survodutide led to significantly greater reductions in body weight than placebo in adults with obesity without diabetes. (Funded by Boehringer Ingelheim; SYNCHRONIZE-1 ClinicalTrials.gov number, NCT06066515.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes This article was published on June 7, 2026, and updated on July 23, 2026, at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by Boehringer Ingelheim. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the participants, site staff, and the members of the Boehringer Ingelheim trial team who were involved in the conduct of this trial; Ahmad Alhussein, Pharm.D., for critical review of an earlier version of the manuscript; and Giles Brooke, Ph.D. (of Envision Ignite, an Envision Medical Communications agency, a part of Envision Pharma Group), for medical writing and editorial assistance with an earlier version of the manuscript. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: June 7, 2026 Published in issue: August 20, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. Cited by - Synchronizing obesity management with survodutide, Exploration of Drug Science, 4, (2026).https://doi.org/10.37349/eds.2026.1008175 - Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline Characteristics (SYNCHRONIZE™-CN), Diabetes Therapy, (2026).https://doi.org/10.1007/s13300-026-01908-x - Anti-Obesity Medications in Longevity and Aesthetic Medicine, Journal of Clinical Medicine, 15, 15, (6026), (2026).https://doi.org/10.3390/jcm15156026 - CagriSema: a novel dual-pathway approach to target obesity and its complications, Metabolism and Target Organ Damage, 6, 3, (2026).https://doi.org/10.20517/mtod.2026.101 - Medical treatments for obesity: what does the future have in store?, The Journal of Clinical Endocrinology & Metabolism, (2026).https://doi.org/10.1210/clinem/dgag274 Loading...