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Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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Title: Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
Authors: Perkovic, V
Jardine, MJ
Neal, B
Bompoint, S
Heerspink, HJL
Charytan, DM
Edwards, R
Agarwal, R
Bakris, G
Bull, S
Cannon, CP
Capuano, G
Chu, P-L
De Zeeuw, D
Greene, T
Levin, A
Pollock, C
Wheeler, DC
Yavin, Y
Zhang, H
Zinman, B
Meininger, G
Brenner, BM
Mahaffey, KW
CREDENCE Trial Investigators
Item Type: Journal Article
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 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 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 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. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).
Issue Date: 14-Apr-2019
Date of Acceptance: 1-Apr-2019
URI: http://hdl.handle.net/10044/1/69122
DOI: 10.1056/NEJMoa1811744
ISSN: 0028-4793
Publisher: Massachusetts Medical Society
Start Page: 2295
End Page: 2306
Journal / Book Title: New England Journal of Medicine
Volume: 380
Issue: 24
Copyright Statement: © 2019 Massachusetts Medical Society.
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
KIDNEY-DISEASE
EMPAGLIFLOZIN
Aged
Canagliflozin
Cardiovascular Diseases
Creatinine
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Double-Blind Method
Female
Follow-Up Studies
Glomerular Filtration Rate
Humans
Kidney Failure, Chronic
Male
Middle Aged
Sodium-Glucose Transporter 2 Inhibitors
CREDENCE Trial Investigators
Humans
Diabetic Nephropathies
Kidney Failure, Chronic
Cardiovascular Diseases
Diabetes Mellitus, Type 2
Creatinine
Glomerular Filtration Rate
Follow-Up Studies
Double-Blind Method
Aged
Middle Aged
Female
Male
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
11 Medical and Health Sciences
General & Internal Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-04-14
Appears in Collections:School of Public Health