A new analysis of the SELECT trial – the largest and longest clinical trial to date examining the cardiovascular benefits of semaglutide (a medication used to support weight loss and diabetes management) – confirms it also lowers the risk of major heart problems in people who are overweight or obese and already have heart disease, even if they don’t have diabetes. Importantly, this heart protection happens regardless of how much weight a person loses or their baseline body weight, according to the new study, published in The Lancet.
The SELECT trial originally studied over 17,000 adults with heart disease and a body mass index (BMI) of 27 or higher, comparing semaglutide to a placebo. This new analysis looked closely at how patients’ weight and waist size changed during the trial and how those changes related to cardiovascular events such as heart attacks and strokes. Researchers found that while semaglutide helped people lose weight and reduce waist size, the amount of weight lost early on didn’t predict who would have fewer heart problems. However, shrinking waist size—a sign of less belly fat—was linked to better heart outcomes and accounted for about one-third of semaglutide’s overall benefit.
The authors say that these findings indicate that semaglutide can offer important heart benefits that go beyond weight loss, opening the door to new ways of treating and preventing serious heart problems in people with obesity and cardiovascular disease.
Journal
The Lancet
Method of Research
Observational study
Subject of Research
People
Article Title
Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial
Article Publication Date
22-Oct-2025
COI Statement
JD declares having received consulting honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; and research grants from Aegerion, Alzheimer’s Research UK, British Heart Foundation, Colgate, Medical Research Council (UK), MSD, National Institute for Health and Care Research, Pfizer, Public Health England, and Roche. AML declares having received consulting honoraria from Akebia, Alnylam, Amgen, Ardelyx, Becton Dickson, Brainstorm Cell, Eli Lilly, Endologix, Fibrogen, GlaxoSmithKline, Intarcia, Medtronic, Neovasc, Novo Nordisk, Provention Bio, and ReCor; and research funding to his institution from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion, and Novartis. SEK declares having received consulting honoraria from Anji Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Oramed; and holds stock options from Altpep. SSE declares having received consulting honoraria from 89 Bio, Amylyx, Avillion, Ayala, Bayer, BeiGene, Boehringer Ingelheim, BridgeBio, GlaxoSmithKline, Inovio, Insmed, Ipsen, Karuna, Lilly, Lundbeck, Mirati, Moderna, Novartis, Novavax, Novo Nordisk, NSABP, Pfizer, Principia, Reata, Rebiotx, Roche, Sanofi, SOLVD, Sutro Biopharma, and TG Therapeutics; and participation on a data monitoring or advisory board for 89 Bio, AstraZeneca, Bayer, BioAtla, Bristol Myers Squibb, Daiichi Sankyo, Denovo, Fore Therapeutics, and Immunome. IL declares having received research funding to their institution from Boehringer Ingelheim, Mylan, Novo Nordisk, and Sanofi; and advisory or consulting fees or other support from Altimmune, AstraZeneca, Bayer, Biomea, Boehringer Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen and J&J, MannKind, Mediflix, Merck, Metsera, Novo Nordisk, Pfizer, PharmaVentures, Regeneron, Sanofi, Shionogi, Structure Therapeutics, Target RWE, Terns Pharma, The Comm Group, Valeritas, WebMD, and Zealand Pharma. BMS declares having received institutional research grants to Brigham and Women’s Hospital from Amgen, Better Therapeutics, Merck, Milestone Therapeutics, Novo Nordisk, and Pfizer; consulting fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Better Therapeutics, Elsevier PracticeUpdate Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and equity in health at Scale, Arboretum LifeSciences, and AIwithCare. JP declares having received consulting honoraria from Altimmune, Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; speakers’ honoraria from Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; meeting and travel support from Amgen, Boehringer Ingelheim, Corcept, Esperion Therapeutics, Merck, New Amsterdam, and Novo Nordisk; grants from Boehringer Ingelheim and Novartis; and leadership or fiduciary roles in World Congress Insulin Resistance and Diabetes, Sarnoff Foundation, and cardiometabolic Alliance. RFK declares having received consulting honoraria from Altimmune, Antag, AstraZeneca, Boehringer Ingelheim, Currax, Eli Lilly, Novo Nordisk, Regeneron, Structure, and Weight Watchers. HMC declares serving on advisory panels for Bayer and Novo Nordisk; receiving research grants from Chief Scientist Office, Diabetes UK, European Commission, IQVIA, Juvenile Diabetes Research Foundation, and Medical Research Council; and holding stock options in Roche Pharmaceuticals. GKH, SS, PEW, OKJ, and RB are employees and stockholders of Novo Nordisk. C-CW declares institutional research grants from Amgen, Daiichi Sankyo, Gi Tai, MAC, MSD, Novo Nordisk, and Sanofi; speakers’ honoraria from AstraZeneca, Chen-Hua, Daiichi Sankyo, Gi Tai, MAC, MSD, Novartis, Novo Nordisk, Pfizer, Sanofi, and Tanabe; and consulting honoraria from Daiichi Sankyo, MAC, Power- Biotech, Sanofi, and Tanabe. IK declares research grants from Daiichi Sankyo, Kowa Pharmaceutical, and Tanabe Mitsubishi Pharma Corporation; speakers’ honoraria from AstraZeneca, Bayer, Kowa Pharmaceutical, Nippon Boehringer Ingelheim, Novo Nordisk, Ono Pharmaceutical, and Tanabe Mitsubishi Pharma Corporation; and affiliation with endowed Chairs from BioStream, Idorsia Pharmaceuticals Japan, Nippon Boehringer Ingelheim, Novo Nordisk, Takara Bio, and Toa Eiyo. FS has worked as a consultant, participated in studies, or received travel funds from the following companies that are involved with obesity, lipodystrophy, and diabetes: Aegerion (Amryt), BioItalia, Boehringer Ingelheim, Bruno Pharma, Lilly, Novo Nordisk, and Pfizer. JH declares having received consulting honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, and Vivus. MU-T declares having received consulting and research honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Frosst Laboratories, Johnson & Johnson, Menarini, Novartis, Novo Nordisk, Pfizer, Procaps, Sanofi-Aventis, Servier, and Tecnofarma. SB declares having received advisory or consulting honoraria from Boehringer Ingelheim, Dompè, Eli Lilly, Novo Nordisk, and Pfizer. DHR declares having received consulting honoraria from AbbVie, Altimmune, Amgen, AstraZeneca, Biohaven, Boehringer Ingelheim, Calibrate, Carmot Therapeutics (Roche), CinRx, Eli Lilly, eMedd, Epitomee, Gila Therapeutics, Ifa Celtic, Novo Nordisk, Pfizer, Regeneron, Rhythm, Scientific Intake, Source Bio, Structure Therapeutics, Tenvie, Wondr Health, and Zealand Pharma; and stock options from Calibrate, Epitomee, Scientific Intake, and Xeno Bioscience.