Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study in Japan

Abstract

Aims/introduction: The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial has shown the effects of canagliflozin on preventing clinically important kidney outcomes in patients with type 2 diabetes mellitus and chronic kidney disease; however, not many Japanese patients were included in the trial. The present study evaluated the efficacy and safety of canagliflozin in Japanese chronic kidney disease patients with type 2 diabetes mellitus.

Materials and methods: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase III study, chronic kidney disease patients with type 2 diabetes mellitus were randomly assigned to receive either 100 mg canagliflozin or a matching placebo once daily for 104 weeks. The primary efficacy end-point was the incidence of a 30% decline in estimated glomerular filtration rate.

Results: Overall, 308 patients were randomized to the canagliflozin (n = 154) and placebo (n = 154) groups. The incidence of a 30% decline in estimated glomerular filtration rate at week 104 was 18.2% and 29.5%, respectively, and the point estimate of the intergroup difference (placebo - canagliflozin) was 11.3% (95% confidence interval 1.2-21.5, P = 0.029), which was significant. The overall incidence of adverse events was similar in the two groups.

Conclusions: This study suggests that canagliflozin safely reduces the risk of end-stage renal disease in Japanese chronic kidney disease patients with type 2 diabetes mellitus.

Keywords: Canagliflozin; Chronic kidney disease; Type 2 diabetes mellitus.

Figure 1

Effects of canagliflozin on renal‐related outcomes over time in Japanese chronic kidney disease patients with type 2 diabetes mellitus. (a) Changes in estimated glomerular filtration rate from the mean of the values at the first days of the run‐in and treatment period, and (b) urinary albumin (mg)‐to‐creatinine (g) ratio (UACR) from the first day of the treatment period. Data are presented as least square (LS) mean ± standard error (SE) in (a), and as the geometric mean with 95% confidence interval (CI) in (b).