Sodium-glucose cotransporter 2 (SGLT2) inhibitors for the prevention and treatment of diabetic kidney disease: A network meta-analysis of randomized controlled trials

Abstract Objectives To evaluate and compare the effectiveness and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors for the prevention and treatment of diabetic kidney disease (DKD). Methods We searched articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials, which are published from 2010 to 2021, to identify randomized controlled trials (RCTs) by comparing SGLT2 inhibitors with placebo. A network meta-analysis (NMA) was conducted within a frequency framework using a random-effects model. Results We included 16 studies involving 51,925 patients in the analysis. Only empagliflozin significantly lowered urine albumin-to-creatinine ratio (UACR) than a placebo (mean differences [MD]: −83.01, 95% confidence intervals [CI]: −117.74 to −48.27). With regard to the composite kidney outcomes, canagliflozin (relative risk [RR] = 0.74, 95% CI: 0.69–0.80), dapagliflozin (RR = 0.76, 95% CI: 0.68–0.85), empagliflozin (RR = 0.69, 95% CI: 0.63–0.76), and ertugliflozin (RR = 0.82, 95% CI: 0.68–0.99) were significantly associated with a lower risk than placebo. Conclusions The UACR-lowering effects of empagliflozin were greater than most other SGLT2 inhibitors. There were few clinically significant differences in the renal protective effects among these drugs.