In this double-blind, randomized trial, 'abstract of published paper' 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.
Peter Winocour MD FRCP
Consultant Physician and Clinical Director for Diabetes and Endocrine Services
