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.

Comparative efficacy of sodium‐glucose co‐transporter‐2 inhibitors, glucagon‐like peptide‐1 receptor agonists and non‐steroidal mineralocorticoid receptor antagonists in chronic kidney disease and type 2 diabetes: A systematic review and network meta‐analysis

“…All studies compared SGLT‐2is, GLP‐1RAs or nsMRAs with placebo (Figure S1). There were 18 studies assessing SGLT‐2is, 11‐14,20‐33 nine studies assessing GLP‐1RAs 15,34‐41 and two studies assessing nsMRAs 42,43 (Table S1). This network meta‐analysis covered 50 938 participants for MACE and 49 965 for CRO (Figure S1).…”

“…All studies compared SGLT-2is, GLP-1RAs or nsMRAs with placebo (Figure S1). There were 18 studies assessing SGLT-2is, [11][12][13][14][20][21][22][23][24][25][26][27][28][29][30][31][32][33] nine studies assessing GLP-1RAs 15,[34][35][36][37][38][39][40][41] and two studies assessing nsMRAs 42,43 (Table S1).…”

“…While previous network meta-analyses have compared the relative efficacy of SGLT-2is, GLP-1RAs and finerenone in improving CV and renal outcomes, [7][8][9][10] our study makes several important contributions. First, it includes recent large clinical trials of SGLT-2is [11][12][13][14] and GLP-1RAs 15 among patients with CKD and T2D that were not included in previous meta-analyses. 7,8 In particular, it covers trials of new SGLT-2is, such as bexagliflozin 14 and luseogliflozin.…”

Comparative safety of different recommended doses of sodium–glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials

“…Four RCTs involving 5,393 patients reported bone fracture (23,25,32,43). Both the direct comparison and the synthesized results from the NMA did not show any treatments significantly associated with a higher risk of bone fracture compared to placebo or other active treatments (Table S4).…”

“…Two RCTs involving 4,705 patients reported DKA (23,25). The synthesized results showed no significant difference between canagliflozin 100mg/d and placebo in terms of the risk of DKA (OR 3.45, 95%CrI 0.41 to 29.41) (Table S4).…”