In patients with T2DM and nephropathy, canagliflozin reduces likelihood of end-stage kidney disease and adverse CV outcomes

Reference

Perkovic V, Jardine MJ, Neal B, et al, for the CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380(24):2295-2306.

Synopsis

Patients with T2DM and a GFR of 30 to 89 mL/min/1.73m2 were randomized to receive the SGLT-2 inhibitor canagliflozin 100 mg orally once daily or placebo. The mean age of the 4401 participants was 63 years, 34% were women, half had known vascular disease, and the mean GFR was 56.2 mL/min/1.73m2. Groups were balanced at the start of the study and analysis was by intention to treat. The trial was stopped early after an interim analysis with a median follow-up of 2.6 years. The authors report a composite outcome of ESKD, renal or cardiovascular death, or doubling of serum creatinine. Because doubling of serum creatinine is so different in seriousness from the other outcomes, it is important to focus on the individual endpoints. The risk of ESKD (GFR < 15 or initiation of dialysis) was reduced with canagliflozin (20.4 vs 29.4 events per 1000 person-years; P < .002; NNT = 111 per year). There was no difference in renal deaths, which were rare, and there was a small borderline statistically significant reduction in cardiovascular deaths (19.0 vs 24.4 events per 1000 person-years; P = .05; NNT = 185 per year). There was a reduction in the composite of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in the intervention group (38.7 vs 48.7 events per 1000 person-years; P = .01; NNT = 100 per year), which is consistent with the results of other studies of canagliflozin in high-risk T2DM patients. Safety was good, with no increase in serious adverse events.