• Deepak L Bhatt, Michael Szarek, Bertram Pitt, Christopher P Cannon, Lawrence A Leiter, Darren K McGuire, Julia B Lewis, Matthew C Riddle, Silvio E Inzucchi, Mikhail N Kosiborod, CherneyDavid Z IDZIFrom Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C., B.M.S.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, Unive, Jamie P Dwyer, Benjamin M Scirica, Clifford J Bailey, Rafael Díaz, Kausik K Ray, Jacob A Udell, Renato D Lopes, Pablo Lapuerta, P Gabriel Steg, and SCORED Investigators.
• From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B., C.P.C., B.M.S.); Colorado Prevention Center Clinical Research and Department of Medicine, Division of Cardiovascular Medicine, University of Colorado Anschutz Medical Campus, Aurora (M.S.); the State University of New York Downstate School of Public Health, Brooklyn (M.S.); the University of Michigan, Ann Arbor (B.P.); Li Ka Shing Knowledge Institute and the Division of Endocrinology and Metabolism, St. Michael's Hospital, and the Departments of Medicine and Nutritional Sciences, University of Toronto (L.A.L.), and the Division of Nephrology (D.Z.I.C.) and the Cardiovascular Division, Department of Medicine, Women's College Hospital and Peter Munk Cardiac Centre (J.A.U.), University Health Network, University of Toronto - all in Toronto; the University of Texas Southwestern Medical Center and Parkland Health and Hospital System, Dallas (D.K.M.), and Lexicon Pharmaceuticals, The Woodlands (P.L.) - both in Texas; Vanderbilt University Medical Center, Nashville (J.B.L., J.P.D.); the Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland (M.C.R.); the Section of Endocrinology, Yale School of Medicine, New Haven, CT (S.E.I.); Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City (M.N.K.); the School of Life and Health Sciences, Aston University, Birmingham (C.J.B.), and the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.) - both in the United Kingdom; the Department of Medicine, Estudios Clínicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L.); and Université de Paris, French Alliance for Cardiovascular Trials, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148, Paris (P.G.S.).
• N. Engl. J. Med. 2021 Jan 14; 384 (2): 129-139.

BackgroundThe efficacy and safety of sodium-glucose cotransporter 2 inhibitors such as sotagliflozin in preventing cardiovascular events in patients with diabetes with chronic kidney disease with or without albuminuria have not been well studied.MethodsWe conducted a multicenter, double-blind trial in which patients with type 2 diabetes mellitus (glycated hemoglobin level, ≥7%), chronic kidney disease (estimated glomerular filtration rate, 25 to 60 ml per minute per 1.73 m2 of body-surface area), and risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or placebo. The primary end point was changed during the trial to the composite of the total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure. The trial ended early owing to loss of funding.ResultsOf 19,188 patients screened, 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292 assigned to the placebo group, and followed for a median of 16 months. The rate of primary end-point events was 5.6 events per 100 patient-years in the sotagliflozin group and 7.5 events per 100 patient-years in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.63 to 0.88; P<0.001). The rate of deaths from cardiovascular causes per 100 patient-years was 2.2 with sotagliflozin and 2.4 with placebo (hazard ratio, 0.90; 95% CI, 0.73 to 1.12; P = 0.35). For the original coprimary end point of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the hazard ratio was 0.84 (95% CI, 0.72 to 0.99); for the original coprimary end point of the first occurrence of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.77 (95% CI, 0.66 to 0.91). Diarrhea, genital mycotic infections, volume depletion, and diabetic ketoacidosis were more common with sotagliflozin than with placebo.ConclusionsIn patients with diabetes and chronic kidney disease, with or without albuminuria, sotagliflozin resulted in a lower risk of the composite of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure than placebo but was associated with adverse events. (Funded by Sanofi and Lexicon Pharmaceuticals; SCORED ClinicalTrials.gov number, NCT03315143.).Copyright © 2020 Massachusetts Medical Society.

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