Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

Neal, Bruce and Perkovic, Vlado and Mahaffey, Kenneth W. and de Zeeuw, Dick and Fulcher, Greg and Erondu, Ngozi and Shaw, Wayne and Law, Gordon and Desai, Mehul and Matthews, David R. and Ukraine, : and Larin, Oleksandr and Panina, Svetlana and Kovalenko, Svitlana and Voloshyna, Olena and Tseluyko, Vera and Gyrina, Olga and Vizir, Vadim and Barna, Olga and Dolzhenko, Maryna and Mostovoy, Yuriy and Korpachev, Vadim and Mankovskiy, Boris and Vatutin, Mykola (2017) Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New England Journal of Medicine = N Engl J Med, 377 (7). pp. 644-657. ISSN 0028-4793 (print); 1533-4406 (online)

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Abstract

BACKGROUND Canagliflozin is a sodium–glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. METHODS The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. RESULTS The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. CONCLUSIONS In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754, respectively.)

Item Type:	Article
Additional Information:	N Engl J Med 2017;377:644-57. DOI: 10.1056/NEJMoa1611925
Subjects:	Internal Medicine Cardiology Endocrinology
Divisions:	Departments > Department of Internal Medicine 3 (formerly - hospital therapy 2)
Depositing User:	Елена Шрамко
Date Deposited:	01 Dec 2020 11:08
Last Modified:	01 Dec 2020 11:08
URI:	http://repo.dma.dp.ua/id/eprint/6028

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