medwireNews: Findings from the CREDENCE trial indicate that the sodium-glucose cotransporter (SGLT)2 inhibitor canagliflozin reduces the risk for renal failure and cardiovascular disease among individuals with type 2 diabetes and albuminuric chronic kidney disease (CKD).
As reported at the ISN World Congress of Nephrology 2019 in Melbourne, Victoria, Australia, and published simultaneously in The New England Journal of Medicine, the relative risk for the primary outcome of end-stage kidney disease, doubling of serum creatinine levels, or death from renal or cardiovascular causes was a significant 30% lower among participants treated with canagliflozin versus placebo.
Specifically, 11.1% of 2202 patients with an estimated glomerular filtration rate (GFR) of 30 to less than 90 mL/min per 1.73 m2 and albuminuria who were randomly assigned to receive canagliflozin 100 mg/day experienced the primary outcome over a median follow-up of 2.62 years. By comparison, 15.5% of the 2199 participants given placebo experienced the primary endpoint, translating into event rates of 43.2 and 61.2 per 1000 person–years, respectively. All patients received background treatment with renin–angiotensin system blockade.
Vlado Perkovic (George Institute for Global Health, Sydney, New South Wales, Australia) and co-authors estimate that among 1000 patients treated for 2.5 years, 21.2 individuals would need to be treated to prevent the composite primary outcome.
They note that the trial was stopped early in July 2018 when the data and safety monitoring committee advised that the prespecified efficacy criteria had been met.
The CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) investigators also found that participants treated with canagliflozin had a significant 34% reduced risk for the renal-specific composite outcome of end-stage kidney disease, doubling of creatinine level, or death from renal causes relative to those in the placebo group, as well as a significant 20% reduced risk for cardiovascular death, myocardial infarction, or stroke.
Perkovic told delegates at the ISN World Congress of Nephrology that “these results were consistent across a broad range of prespecified subgroups,” including when patients were categorized by baseline estimated GFR and urine albumin-to-creatinine ratio.
The researchers report that overall rates of adverse events and serious adverse events were “similar” in the canagliflozin and placebo groups, with no significant difference in the rates of lower limb amputation (12.3 vs 11.2 per 1000 person–years) and fracture (11.8 vs 12.1 per 1000 person–years). The rates of diabetic ketoacidosis were “low,” they say, but were higher in the canagliflozin- than the placebo-treated group (2.2 vs 0.2 per 1000 patient–years).
The comparable rates of amputation and fracture “are reassuring and consistent with trials of other SGLT2 inhibitors but differ from the CANVAS Program findings,” write the investigators.
Taken together, the CREDENCE results “indicate that canagliflozin may be an effective treatment option for renal and cardiovascular protection in patients with type 2 diabetes with chronic kidney disease,” they conclude.
Writing in an accompanying editorial, Julie Ingelfinger (Massachusetts General Hospital, Boston, USA) and Clifford Rosen (Maine Medical Center Research Institute, Scarborough, USA) say that “the importance of CREDENCE, a well done and large clinical trial, cannot be overstated.”
The “data are certain to be welcomed by patients with diabetes and chronic kidney disease and by the clinicians who treat them,” they add.
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