CANVAS data support renoprotective effect of canagliflozin in type 2 diabetes
medwireNews: Canagliflozin reduces the risk for loss of kidney function, estimated glomerular filtration rate (eGFR) decline, and albuminuria versus placebo in people with type 2 diabetes at high risk for cardiovascular events, CANVAS Program data show.
“These analyses show consistent results on a broad range of renal outcomes, including those used by regulators, guidelines, and clinicians to define renoprotection, and therefore provide strong support for the hypothesis that canagliflozin has clinically relevant renal benefits for patients,” write Vlado Perkovic (The George Institute for Global Health, Sydney, New South Wales, Australia) and co-authors in The Lancet Diabetes and Endocrinology.
They add: “The robustness of these exploratory renal protection findings is further supported by the magnitude of the differences between the canagliflozin and placebo groups, and the consistency of the protection across several prespecified, sustained, and adjudicated renal endpoints.”
Perkovic and team found that the risk for the composite outcome of sustained doubling of serum creatinine, end-stage kidney disease, and death from renal causes was a significant 47% lower among the 5795 patients who received canagliflozin 100 or 300 mg compared with the 4347 who received placebo, at rates of 1.5 versus 2.8 cases per 1000 patient–years.
They note, however, that the study participants were generally at low risk for renal events and that the rate of sustained end-stage kidney disease or death from renal causes did not differ significantly between the canagliflozin and placebo groups (0.4 vs 0.8 cases per 1000 patient–years).
The mean decline in eGFR from baseline to week 338 was significantly smaller with canagliflozin (1.8 mL/min per 1.73 m2) than with placebo (3.9 mL/min per 1.73 m2). Following an acute decline in eGFR during the first 13 weeks, the annual eGFR decline was slower with canagliflozin than with placebo (slope difference between groups 1.2 mL/min per 1.73 m2 per year).
Albuminuria increased over time in both groups, but the mean urinary albumin-to-creatinine ratio was 18% lower among the participants treated with canagliflozin than among those who received placebo.
The researchers also report that there was no significant difference in the rate of serious renal-related adverse events were between the canagliflozin and placebo groups, at 2.5 versus 3.3 cases per 1000 patient–years.
Perkovic et al say their findings indicate that “canagliflozin could have an important role in reducing the burden of kidney disease in people with type 2 diabetes.”
However, in an accompanying comment, Marcel Muskiet and colleagues from VU University Medical Center in Amsterdam, the Netherlands, “caution against premature conclusions” as the CANVAS Program was not specifically designed to assess renal outcomes.
They say that dedicated renal outcome trials with longer follow-up to assess the “clinically important renal outcomes of end-stage kidney disease or renal death” are needed.
Muskiet and co-authors conclude: “For now, we suggest keeping calm and carrying on with testing this promising drug class, until definite renal outcome data provide a clearer answer to the important questions regarding the renoprotective effects of [sodium-glucose cotransporter 2] inhibitors in type 2 diabetes, and perhaps beyond.”
By Laura Cowen
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