Canagliflozin Safe and Effective in Patients with Reduced and Preserved Kidney Function

Austin, Texas—Glucose lowering in patients with type 2 diabetes can be achieved with sodium glucose co-transporter 2 inhibitors; the agents may confer renal benefits but because the glycemic efficacy is dependent on glomerular filtration rate (GFR), they are not approved for use in people with significantly reduced kidney function.

Researchers recently performed a prespecified analysis of CANVAS (Canagliflozin Cardiovascular Assessment Study) data by baseline kidney function. The study randomized patients with type 2 diabetes with or at high risk of cardiovascular disease to either canagliflozin or placebo. Brendon L. Neuen, MBBS, reported results of the analysis during a poster session at the NKF 2018 Spring Clinical Meetings in a poster titled Canagliflozin and Renal Outcomes in Patients with Chronic Kidney Disease.

Prespecified renal outcomes were urinary albumin to creatinine ratio (UACR), and composites of end-stage renal disease (ESRD), renal death, and either 40% decline in estimated GFR (eGFR) or doubling of serum creatinine. The analysis was conducted according to kidney function: eGFR <60 mL/min/1.73 m2 (reduced eGFR) versus ≥60 mL/min/1.73 m2 (preserved eGFR).

Of 10,142 participants, 20.1% (n=2039) had baseline eGFR <60 mL/min/1.73 m2. Patients with reduced eGFR had at least as large a placebo-adjusted reduction in UACR as did those with preserved eGFR (–23% vs –17%, P-heterogeneity=.01).

For the composite outcome of 40% decline in eGFR, ESRD, or renal death, the effect of canagliflozin was similar in patients with reduced and preserved eGFR (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.49-1.17 vs 0.53, 95% CI, 0.39-0.73, respectively; P-heterogeneity=.28). When doubling of serum creatinine was used rather than 40% decline in eGFR in the renal composite outcome, findings were similar (HR, 0.81; 95% CI, 0.37-1.77 vs 0.42; 95% CI, 0.23-0.75, respectively; P-heterogeneity=.21).

The risk of serious adverse events with canagliflozin was similar in patients with reduced or preserved eGFR (HR, 0.91; 95% CI, 0.47-1.74 vs 0.70; 95% CI, 0.38-1.26, respectively; P-heterogeneity=.69).

In summary, the researchers said, “The effect of canagliflozin on the composite renal outcomes was large, particularly in people with preserved kidney function, with evidence of benefit for the eGFR ≥60 mL/min/1.73 m2 and <60 mL/min/.1.73 m2 subgroups. Results for major safety outcomes were consistent across eGFR ≥60 mL/min/1.73 m2 and <60 mL/min/.1.73 m2 subgroups. The effects in people with reduced kidney function will be more clearly defined in the ongoing Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE; clinicaltrials.gov identifier: NCT02065791.”

Source: Neuen BL, Ohkuma T, Neal B, et al. Canagliflozin and renal outcomes in patients with chronic kidney disease. Poster presented at the National Kidney Foundation 2018 Spring Clinical Meetings, April 19014, 2018, Austin, Texas.

Support for the study was provided by Janssen Research & Development, LLC.