SGLT2i approved for treatment of DKD and reduction of HHF in T2DM patients with DKD

Based on the CREDENCE renal outcomes trial, the FDA granted the approval of canagliflozin to treat diabetic kidney disease (DKD) and reduction of HF hospitalization in patients with T2DM and DKD.

The US Food and Drug Administration (FDA) approved a new indication for the SGLT2 inhibitor canagliflozin to reduce the risk of end-stage kidney disease (ESKD), worsening of kidney function, CV death, and hospitalization for heart failure (HF) in patients with type 2 diabetes (T2DM) and diabetic kidney disease (DKD). This new indication is based on results from the phase 3 CREDENCE trial, that enrolled patients with T2DM and DKD.

The CREDENCE trial showed that canagliflozin treatment resulted in 30% reduction in risk of the primary end point, a composite of end-stage kidney disease (ESKD), doubling of serum creatinine and renal or CV death. Canagliflozin use also reduced the risk of the secondary end point of risk of hospitalization for HF; a 39% reduction. Adverse events and serious adverse events were similar in the canagliflozin group compared to the placebo group.

CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) was a renal outcomes study evaluating the SGLT2 inhibitor canagliflozin in patients with T2DM and DKD in addition to standard of care. The study was a randomized, double-blind, event-driven, placebo-controlled, parallel-group, 2-arm, multicenter study, which enrolled 4,401 patients with T2DM, Stage 2 or 3 DKD (defined as an estimated glomerular filtration rate [eGFR] of ≥30 to <90 mL/min/1.73 m2) and macroalbuminuria (defined as urinary albumin-to-creatinine ratio [ACR] >300 to ≤5,000 mg/g) who were receiving standard of care, including a maximum tolerated labeled daily dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB).

"Millions of T2D patients around the world have DKD 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, M.D., Professor of Medicine and Director, Comprehensive Hypertension Center, University of Chicago.‡ "For nearly two decades, we've been searching for a treatment that can help us intervene earlier to slow kidney disease progression. With the approval for this new indication for canagliflozin, 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."

Source: press release Janssen, September 30, 2019 Read our summary of the CREDENCE trial