• Vlado Perkovic, Katherine R Tuttle, Peter Rossing, Kenneth W Mahaffey, MannJohannes F EJFEFrom the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washi, George Bakris, BaeresFlorian M MFMMFrom the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Wash, Thomas Idorn, Heidrun Bosch-Traberg, Nanna Leonora Lausvig, Richard Pratley, and FLOW Trial Committees and Investigators.
• From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Søborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.).
• N. Engl. J. Med. 2024 Jul 11; 391 (2): 109121109-121.

BackgroundPatients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown.MethodsWe randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically.ResultsAmong the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).ConclusionsSemaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.).Copyright © 2024 Massachusetts Medical Society.

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