Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Perkovic, V. and Jardine, M. J. and Neal, B. and Bompoint, S. and Heerspink, H. J. L. and Charytan, D. M. and Edwards, R. and Agarwal, R. and Bakris, G. and Bull, S. and Cannon, C.P. and Capuano, G. and Chu, P.-L. and de Zeeuw, D. and Greene, T. and Levin, A. and Pollock, C. and Wheeler, D.C. and Yavin, Y. and Zhang, H. and Zinman, B. and Meininger, G. and Brenner, B.M. and Mahaffey, K.W. and Ukraine: and Kolesnyk, Mykola and Barna, Olga and Bilyk, Svitlana D. and Botsyurko, Volodymyr and Dudar, Iryna and Fushtey, Ivan and Godlevska, Olga and Golovchenko, Oleksandr and Gyrina, Olga and Kazmirchuk, Anatoliy and Komisarenko, Iuliia and Korzh, Oleksii and Kravchun, Nonna and Legun, Oleg and Mankovskyy, Borys and Martynyuk, Liliya and Mostovoy, Yuriy and Pashkovska, Nataliia and Pererva, Larysa and Pertseva, Tetyana and Samoylov, Oleksandr and Smirnov, Ivan and Svyshchenko, Yevgeniya and Tomashkevych, Halyna and Topchii, Ivan and Tryshchuk, Nadiya and Tseluyko, Vira and Vizir, Vadym and Vlasenko, Maryna and Zlova, Tetiana and Zub, Liliia (2019) Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. The New England Journal of Medicine = N Engl J Med, 380 (24). pp. 2295-2306. ISSN 0028-4793 (print); 1533-4406 (online)

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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 m2 of bodysurface 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 m2 ), 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 endstage 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. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.)

Item Type:	Article
Additional Information:	N Engl J Med 2019; 380:2295-2306 DOI: 10.1056/NEJMoa1811744
Uncontrolled Keywords:	cardiovascular outcomes; kidney-disease; empagliflozin
Subjects:	Internal Medicine Endocrinology
Divisions:	Departments > Department of Internal Medicine 1 (formerly - Faculty Therapy and Endocrinology)
Depositing User:	Елена Шрамко
Date Deposited:	25 May 2021 13:16
Last Modified:	25 May 2021 13:19
URI:	http://repo.dma.dp.ua/id/eprint/6496

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