The Food and Drug Administration (FDA) has approved a new indication for Invokana (canagliflozin; Janssen) to reduce the risk of end-stage renal disease (ESRD), doubling of serum creatinine, cardiovascular (CV) death, and hospitalization for heart failure (HF) in adults with type 2 diabetes (T2D) and diabetic nephropathy with albuminuria >300mg/day.
The approval was based on results from the phase 3 event-driven, placebo-controlled, parallel-group, 2-arm CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial (N=4401). The study enrolled patients with T2D, stage 2 or 3 chronic kidney disease (CKD) (eGFR ≥30 to <90mL/min/1.73m2), and albuminuria, who were receiving standard of care including a maximum tolerated daily dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB); patients were randomized to receive canagliflozin 100mg daily or placebo.
Results showed that after a median follow-up duration of 2.62 years, canagliflozin-treated patients had a statistically significant 30% lower risk of the primary composite outcome of ESRD, doubling of serum creatinine level, or death from renal or CV causes compared with those who received placebo (HR: 0.70; 95% CI, 0.59 to 0.82; P <.0001). Findings also revealed canagliflozin-treated patients had a statistically significant lower risk of the secondary composite outcome of CV death, myocardial infarction, or stroke (HR: 0.80; 95% CI, 0.67 to 0.95; P =.02) along with a 39% reduction in hospitalization for HF (HR: 0.61; 95% CI, 0.47 to 0.80; P <.001).
With regard to safety, canagliflozin had an overall similar adverse event and serious adverse event profile compared with placebo; higher rates of diabetic ketoacidosis and genital mycotic infections were observed with canagliflozin.
“Millions of T2D patients around the world have DKD [Diabetic Kidney Disease] and almost half of them aren’t even aware of it. By the time they are referred to a nephrologist, it is often too late because their disease has progressed to the point where dialysis is inevitable,” said CREDENCE study investigator George Bakris, MD, Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago. “With the approval for this new indication for Invokana, physicians will not only be able to help reduce the risks associated with diabetic kidney disease, but also reduce the risk of hospitalization for heart failure in patients with T2D and DKD.”
Invokana, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is currently approved as an adjunct to diet and exercise to improve glycemic control in adults with T2D, as well as to reduce the risk of major CV events (eg, CV death, nonfatal MI and stroke) in adults with T2D and established CV disease.
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