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Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

By June 10, 2019September 24th, 2020No Comments


The New England Journal of Medicine

Vlado Perkovic 1 ,
Meg J Jardine 1 ,
Bruce Neal 1 ,
Severine Bompoint 1 ,
Hiddo J L Heerspink 1 ,
David M Charytan 1 ,
Robert Edwards 1 ,
Rajiv Agarwal 1 ,
George Bakris 1 ,
Scott Bull 1 ,
Christopher P Cannon 1 ,
George Capuano 1 ,
Pei-Ling Chu 1 ,
Dick de Zeeuw 1 ,
Tom Greene 1 ,
Adeera Levin 1 ,
Carol Pollock 1 ,
David C Wheeler 1 ,
Yshai Yavin 1 ,
Hong Zhang 1 ,
Bernard Zinman 1 ,
Gary Meininger 1 ,
Barry M Brenner 1 ,
Kenneth W Mahaffey 1 ,
CREDENCE Trial Investigators

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.).


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