Renal protective effect and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease and type 2 diabetes mellitus: a network meta-analysis and systematic review

Abstract

Purpose: A network meta-analysis was conducted to evaluate the renal protective effect and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease and type 2 diabetes mellitus.

Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched by two authors using the Cochrane Collaboration risk of bias tool.

Results: Compared with controls, luseogliflozin 2.5 mg (MD = - 3.50, 95% CI - 6.65 to - 0.35), bexagliflozin 20 mg (MD = - 3.48, 95% CI - 6.57 to - 0.39), and dapagliflozin 10 mg (MD = - 3.08, 95% CI - 5.09 to - 1.06) reduced the estimated glomerular filtration rate (eGFR). Empagliflozin 25 mg (MD = - 240.43, 95% CI - 414.13 to - 66.73), dapagliflozin 10 mg (MD = - 94.15, 95% CI - 111.72 to - 76.59), and canagliflozin 100 mg (MD = - 193.25, 95% CI - 279.16 to - 107.34) reduced urine albumin-creatinine ratio levels compared with controls. Empagliflozin 25 mg, canagliflozin 100 mg and dapagliflozin 10 mg induced a significant decline in urine albumin-creatinine ratio compared to dapagliflozin 5 mg. In terms of safety, ertugliflozin 5 mg reduced the risk of urinary tract infection. Compared with controls, empagliflozin 10 mg and 25 mg, and canagliflozin 100 mg reduced the risk of any adverse events while canagliflozin 100 mg reduced the risk of serious adverse events. Dapagliflozin 10 mg had a lower risk of treatment discontinuation.

Conclusions: Sodium-glucose cotransporter-2 inhibitors have favourable renal protective effect and safety; however, additional randomised clinical trials are needed to validate these findings.

Keywords: Chronic kidney disease; Network meta-analysis; Sodium-glucose cotransporter-2 inhibitors.