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CREDENCE - Primary renal outcome benefit demonstrated with Canagliflozin 100mg . Published in NEJM April 14th 2019

Author: 
Peter Winocour (Chairman ABCD, 2008-2011)
Date of the announcement: 
Tuesday, 23 April, 2019

Abstract of published paper:

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 reninangiotensin 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.

 

 

Peter Winocour MD FRCP

Consultant Physician and Clinical Director for Diabetes and Endocrine Services