Canagliflozin Benefits Consistent across Levels of Kidney Function

Washington, DC—Canagliflozin is US FDA approved for treatment of patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2. Researchers, led by Meg J. Jardine, MB, BS, PhD, conducted a secondary analysis of data from the CREDENCE trial to examine the efficacy and safety of canagliflozin according to strata based on eGFR, including patients with eGFR 30 to <45 mL/min/1.73 m2. Results of the analysis were reported during an oral session at Kidney Week 2019; the session was titled Renal, Cardiovascular, and Safety Outcomes of Canagliflozin (CANA) According to Baseline Kidney Function: A CREDENCE Secondary Analysis.

A total of 4401 participants were enrolled in the CREDENCE study. Eligible participants had eGFR 30 to <90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio <300 to 5000 mg/g. Study participants were randomized within eGFR-based strata to receive canagliflozin 100 mg daily or placebo. Cox proportional hazards regression models were used to analyze primary and prespecified secondary composites and safety outcomes within each screening eGFR stratum: 30 to <45 mL/min/1.73 m2, 45 to <60 mL/min/1.73 m2, and 60 to <90 mL/min/1.73 m2.

At screening, 29.8% (n=1313) of participants had an eGFR 30 to <45 mL/min/1.73 m2, 29.1% (n=1279) had eGFR 45 to <60 mL/min/1.73 m2, and 41.1% (n=1809) had eGFR 60 to <90 mL/min/1.73 m2. Overall, treatment with canagliflozin resulted in reduction of the primary outcome, the renal composite of end-stage renal disease, sustained doubling serum creatinine, or renal death; as well as a range of cardiovascular outcomes and serious adverse events. There were no associations between treatment with canagliflozin and fractures or amputations.

There was no difference in the impact of canagliflozin between eGFR subgroups (all P for interaction >.11). For the primary composite, renal composite, and composite of cardiovascular death or hospitalization for heart failure, the benefits of canagliflozin were individually significant in participants with a screening eGFR of 30 to <45 mL/min/1.73 m2.

“Canagliflozin safely reduces the risk of renal and cardiovascular events in people with type 2 diabetes and substantial albuminuria, and these benefits are preserved across a spectrum of eGFR 30 to <90 mL/min/1.73 m2, including eGFR 30 to <45 mL/min/1.73 m2,” the researchers said.

Source: Jardine MJ, Mahaffey KW, Agarwal R, et al. Renal, cardiovascular, and safety outcomes of canagliflozin (CANA) according to baseline kidney function: A CREDENCE secondary analysis. Abstract of a presentation at the American Society of Nephrology Kidney Week 2019 (Abstract SA-OR078), November 9, 2019, Washington, DC.

Funding provided by The Janssen Pharmaceutical Companies of Johnson & Johnson.