Perkovic, Vlado, Jardine, Meg J., Neal, Bruce, Bompoint, Severine, Heerspink, Hiddo J.l., Charytan, David M., Edwards, Robert, Agarwal, Rajiv, Bakris, George, Bull, Scott, Cannon, Christopher P., Capuano, George, Chu, Pei-ling, De Zeeuw, Dick, Greene, Tom, Levin, Adeera, Pollock, Carol, Wheeler, David C., Yavin, Yshai, Zhang, Hong, Zinman, Bernard, Meininger, Gary, Brenner, Barry M., Mahaffey, Kenneth W. and Bellary, Srikanth (2019). Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine, 380 (24), pp. 2295-2306.
Abstract
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 In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m 2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), 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 for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
Publication DOI: | https://doi.org/10.1056/NEJMoa1811744 |
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Divisions: | College of Health & Life Sciences > School of Biosciences College of Health & Life Sciences College of Health & Life Sciences > Chronic and Communicable Conditions Aston University (General) |
Uncontrolled Keywords: | General Medicine |
Publication ISSN: | 1533-4406 |
Last Modified: | 05 Dec 2024 08:16 |
Date Deposited: | 19 Aug 2019 09:30 |
Full Text Link: | |
Related URLs: |
http://www.nejm ... 6/NEJMoa1811744
(Publisher URL) http://www.scop ... tnerID=8YFLogxK (Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2019-06-13 |
Accepted Date: | 2019-06-01 |
Authors: |
Perkovic, Vlado
Jardine, Meg J. Neal, Bruce Bompoint, Severine Heerspink, Hiddo J.l. Charytan, David M. Edwards, Robert Agarwal, Rajiv Bakris, George Bull, Scott Cannon, Christopher P. Capuano, George Chu, Pei-ling De Zeeuw, Dick Greene, Tom Levin, Adeera Pollock, Carol Wheeler, David C. Yavin, Yshai Zhang, Hong Zinman, Bernard Meininger, Gary Brenner, Barry M. Mahaffey, Kenneth W. Bellary, Srikanth ( 0000-0002-5924-5278) |