Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial

RATIONALE AND OBJECTIVE: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs).

STUDY DESIGN: A randomized, double-blind, placebo-controlled, multicenter, international trial.

SETTING AND PARTICIPANTS: 4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g.

INTERVENTIONS: Participants were randomly assigned to receive canagliflozin 100mg/day or placebo.

OUTCOMES: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73m2).

RESULTS: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR]: 0.71 [95% confidence interval (CI): 0.61, 0.82]; P<0.001), with consistent results for serious kidney-related AEs (HR: 0.72 [95% CI: 0.51, 1.00]; P=0.05) and acute kidney injury (AKI; HR: 0.85 [95% CI: 0.64, 1.13]; P=0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73m2, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04).

LIMITATIONS: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants.

CONCLUSION: Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.