Canagliflozin decreases the risk of kidney failure and cardiovascular events in patients with chronic kidney disease and type 2 diabetes, according to a new study.
The finding is from the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, which was discontinued early following a planned interim analysis on the recommendation of the study’s data and safety monitoring committee. At the time the trial was stopped, 4401 patients with type 2 diabetes and CKD had been randomly assigned to receive canagliflozin, which is an inhibitor of sodium-glucose cotransporter 2 (SGLT2), or placebo.
After a median follow-up duration of 2.62 years, canagliflozin-treated patients had a statistically significant 30% lower risk of the trial’s primary composite outcome of end-stage renal disease (ESRD), doubling of serum creatinine level, or death from renal or cardiovascular causes compared with placebo recipients, Vlado Perkovic, MBBS, PhD, of the George Institute for Global Health, University of New South Wales, Sydney, Australia, and colleagues reported at the 2019 World Congress of Nephrology in Melbourne, Australia. Results were published simultaneously in The New England Journal of Medicine.
In addition, the treatment group had a statistically significant 32% decreased risk of ESRD (need for dialysis or a kidney transplant or a sustained estimated glomerular filtration rate (eGFR) below 15 mL/min/1.73 m2), 20% decreased risk of cardiovascular death, myocardial infarction (MI), or stroke, and 39% decreased risk of hospitalization for heart failure.
“These 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,” the investigators concluded in their journal article.
In a press release issued by Janssen Pharmaceutical Companies of Johnson & Johnson, the maker of canagliflozin, Dr Perkovic stated: “Canagliflozin is the first medical breakthrough in nearly twenty years proven to slow the progression of chronic kidney disease in patients with diabetes at high risk of developing kidney failure. These impressive results from the CREDENCE study have significant clinical implications for preventing kidney failure and improving health for millions of people living with chronic kidney disease and type 2 diabetes.”
In March, Janssen included CREDENCE data in the submission of a supplemental New Drug Application asking the FDA to approve a new indication for canagliflozin for use in decreasing the risk of ESRD, doubling of serum creatinine, and renal or cardiovascular death among adults with type 2 diabetes and CKD. According to Janssen, if the new indication is approved, canagliflozin would be the first and only therapy in nearly 20 years indicated to reduce the risk of ESRD when added to current standard of care.
Based on the trial data, Dr Perkovic’s team estimated that among 1000 study patients treated for 2.5 years, the primary composite outcome would occur in 47 fewer patients in the canagliflozin group than in the placebo group, including 36 fewer composite renal outcomes of ESRD, doubling of serum creatinine, or renal death and 24 fewer ESRD events. In addition, canagliflozin also would prevent 22 hospitalizations for heart failure and 25 composite events of cardiovascular death, MI, or stroke.
The canagliflozin and placebo groups had 2202 and 2199 patients, respectively. Patients had a mean age of 63 years. About two-thirds of both groups were men and white.
Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019; published online ahead of print.