By Colin Kenny, Editor – Diabetes Distilled
In this trial, investigators randomised patients with type 2 diabetes and kidney disease who had full renin–angiotensin–aldosterone system blockade to receive canagliflozin 100mg or placebo. Patients who took canagliflozin were 30% less likely than the placebo group to develop renal failure or die from either renal failure or cardiovascular disease. Their risk of renal failure or death fromrenal causes was reduced by 34%, and the risk of hospitalisation forheart failure or death due to cardiac causes decreased by 31%. Absolute risk reduction was 4.5%, translating into a number needed to treat of 22 over 2.5 years.
In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, 4401 patients with type 2 diabetes and albuminuric chronic kidney disease were randomised to 100 mg canagliflozin or placebo in addition to renin–angiotensin–aldosterone blockade and baseline diabetes therapy. All participants had an estimated glomerular filtration rate (eGFR) of 30–90 ml/minute/1.73 m2 and a urinary albumin:creatinine ratio of >34 mg/mmol. Of these, 60% had an eGFR of 30–60 ml/min/1.73 m2, with a mean eGFR of 56.2 ml/min and median urinary albumin:creatinine ratio of 11.84 mg/mmol.
The trial was stopped early after a planned interim analysis. The canagliflozin group had a 30% lower relative risk of the primary outcome than the placebo group. Event rates per 1,000 patient years were 43.2 in the canagliflozin group and 61.2 in the placebo group (P=0.00001). Canagliflozin resulted in a 34% reduction in relative risk of the renal-specific composite outcome (end-stage kidney disease, doubling of creatinine level or death from renal causes) and a 32% reduction in the risk of developing end-stage kidney disease. It also lowered the risk of cardiovascular death, stroke, myocardial infarction and hospitalisation for heart failure. There were no significant differences in amputation or fracture rates, although the trial protocol was amended to increase vigilance for foot complications in May 2016.
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