Canagliflozin and renal outcomes in type 2 diabetes and nephropathy
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Author(s)
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.).
Date Issued
2019-04-14
Date Acceptance
2019-04-01
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.
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30990260
Subjects
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
Coverage Spatial
United States
Date Publish Online
2019-04-14