Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

作者：Vlado Perkovic, Meg Jardine, Bruce Neal, Séverine Bompoint, Hiddo J.L. Heerspink, David M. Charytan, Robert Edwards, Rajiv Agarwal, George L. Bakris, Scott Bull, Christopher P. Cannon, George Capuano, Pei-Ling Chu, Dick de Zeeuw, Tom Greene, Adeera Levin, Carol A. Pollock, David C. Wheeler, Yshai Yavin, Hong Zhang, Bernard Zinman, Gary Meininger, Barry M. Brenner, Kenneth W. Mahaffey · 发表于：New England Journal of Medicine · 年份：2019 · DOI：10.1056/nejmoa1811744 · 被引用次数：6164 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Potassium and Related Disorders

BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: ), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS: The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P = 0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization fo...