Type 2 diabetes (T2D) patients with chronic kidney disease (CKD) may find improved cardiovascular and renal outcomes with canagliflozin, an oral, sodium-glucose co-transporter-2 (SGLT2) inhibitor, according to findings from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial. The study’s results were presented at the American Diabetes Association’s (ADA’s) 79th Scientific Sessions at the Moscone Convention Center in San Francisco.
CREDENCE, a randomized, double-blind controlled trial, was brought to an early end after significant benefit was observed during a planned interim analysis. At the study’s end, 4,401 patients (mean age, 63 years) had been enrolled and had an average 2.62 years of follow-up. Average T2D duration was 15.8 years. Patients were randomized to receive a daily dose of either 100 mg of oral canagliflozin or placebo. HbA1c levels among the patients ranged between 6.5% and 12%, and estimated glomerular filtration rate (eGFR) was between 30-90 mL/minute/1.73 m2.
The canagliflozin cohort, compared to the placebo group, had a reduced risk of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR], 0.80; 95% CI, 0.67 to 0.95; P=0.01), as well as a significantly lower risk of CV death or hospitalization for heart failure (HR, 0.61; 95% CI, 0.47 to 0.80; P<0.001). The canagliflozin group had a 34% lower relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatine level, or renal-related mortality (HR, 0.66; 95% CI, 0.53 to 0.81; P<0.001), as well as 32% lower relative risk of end-stage kidney disease (HR, 0.68; 95% CI, 0.54 to 0.86; P=0.002).
“Considering type 2 diabetes is a leading cause of kidney failure, our study of canagliflozin in this patient group achieved the positive outcomes we had hoped for,” said co-investigator, Meg Jardine, MBBS, PhD, conjoint associate professor of medicine at the University of New South Wales in Australia, and program head at the George Institute for Global Health, in a press release. “Patients with type 2 diabetes are already at a high risk for serious kidney or cardiac events. This risk is even higher in those who have chronic kidney disease, and canagliflozin reduces the chance of these events safely and effectively without increasing negative side effects.”