• A Michael Lincoff, Kirstine Brown-Frandsen, Helen M Colhoun, John Deanfield, Scott S Emerson, Sille Esbjerg, Søren Hardt-Lindberg, G Kees Hovingh, Steven E Kahn, Robert F Kushner, Ildiko Lingvay, Tugce K Oral, Marie M Michelsen, Jorge Plutzky, Christoffer W Tornøe, Donna H Ryan, and SELECT Trial Investigators.
• From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Søborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.).
• N. Engl. J. Med. 2023 Dec 14; 389 (24): 222122322221-2232.

BackgroundSemaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown.MethodsIn a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed.ResultsA total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001).ConclusionsIn patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.).Copyright © 2023 Massachusetts Medical Society.

41 keywords...

hide…