Effects of sodium-glucose cotransporter 2 inhibitors on renal outcomes in patients with type 2 diabetes: a systematic review and meta-analysis

초록

Background and aims: To investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal outcomes in patients with type 2 diabetes mellitus (T2D). Materials and methods: We searched Medline, Embase, and the Cochrane Central Registration of Controlled Trials to identify randomized controlled trials (RCTs) of SGLT2 inhibitors up to Sep 18, 2017. RCTs comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs and reporting at least one kidney-related variable including changes in urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR), and development of microalbuminuria, macroalbuminuria, or end-stage renal disease in patients with T2D were selected. We performed a meta-analysis using fixed-effects model and random-effects model to calculate mean differences and relative risk for renal outcomes. Results: A total of 45 eligible RCTs involving 45,654 patients with T2D were included in the analysis. Compared with placebo or other oral antidiabetic drugs, SGLT2 inhibitors significantly decreased urine albumin-to-creatinine ratio (mean difference −7.84 mg/g, 95% confidence interval [CI] −12.84 to −2.84, P = 0.0021). In addition, SGLT2 inhibitors were associated with the lower risk of developing microalbuminuria (relative risk [RR] 0.73, 95% CI 0.54 to 1.00, P = 0.0505) and macroalbuminuria (RR 0.68, 95% CI 0.60 to 0.77, P < 0.0001) compared with controls. The overall change in eGFR was comparable between SGLT2 inhibitors and controls (mean difference −0.08 mL/min/1.73 m², 95% CI –0.66 to 0.49, P = 0.7833). However, in subgroup analyses according to study duration and baseline eGFR, SGLT2 inhibitors decreased eGFR in T2D patients with the study duration of <26 weeks and baseline eGFR of <45 mL/min/1.73 m² compared with controls. The risk of developing ESRD tended to be reduced in SGLT2 inhibitors compared with controls (RR 0.78, 95% CI 0.43 to 1.41, P = 0.4114). Conclusion: SGLT2 inhibitors were associated with the lower risk of development or progression of albuminuria, although the overall changes in renal function were comparable to placebo or other oral antidiabetic drugs in patients with T2D.