Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

This study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2017 to identify randomized controlled trials comparing SGLT2 inhibitors with placebo or antidiabetic drugs and reporting any renal outcomes in patients with type 2 diabetes. Additionally, we identified 4 articles which were published after the predefined period to include relevant data. A meta-analysis was performed to calculate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) for each renal outcome. We included 48 studies involving 58,165 patients in the analysis. SGLT2 inhibitors significantly lowered urine albumin-to-creatinine ratio (UACR) (WMD, -14.64 mg/g; 95% CI, -25.15 to -4.12; P = 0.006) compared with controls. The UACR-lowering effects of SGLT2 inhibitors were greater with a higher baseline UACR. Overall changes in estimated glomerular filtration rate (eGFR) were comparable between two groups (WMD, 0.19 mL/min/1.73 m²; 95% CI, -0.44 to 0.82; P = 0.552). However, SGLT2 inhibitors significantly slowed eGFR decline in patients with a higher baseline eGFR and a longer duration of treatment. Compared with controls, SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97; P = 0.032), macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73; P < 0.001), and worsening nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93; P = 0.012). In addition, the risk of end-stage renal disease was significantly lower in SGLT2 inhibitors than in controls (RR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). In conclusion, SGLT2 inhibitors had beneficial renal effects by lowering the risk of albuminuria development or progression and reducing the risk of end-stage renal disease compared with placebo or other antidiabetic drugs.

Figure 1

Study screening and selection process.

Figure 2

Weighted mean differences in changes in urine albumin-to-creatinine ratio from baseline (mg/g) for sodium-glucose cotransporter 2 inhibitors versus placebo or other antidiabetic drugs. CI, confidence interval; MD, mean difference; SD, standard deviation; W, weight.

Figure 3

Meta-regression of changes in urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) for sodium-glucose cotransporter 2 inhibitors versus placebo or other antidiabetic drugs. (A) Changes in UACR according to baseline UACR. (B) Changes in eGFR according to baseline eGFR. (C) Changes in eGFR according to treatment duration.

Figure 4

Weighted mean differences in estimated glomerular filtration rate from baseline (mL/min/1.73 m²) for sodium-glucose cotransporter 2 inhibitors versus placebo or other antidiabetic drugs. (A) According to baseline estimated glomerular filtration rate. (B) According to treatment duration. CI, confidence interval; MD, mean difference; SD, standard deviation; W, weight.

Figure 5

Relative risks of microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage renal disease for sodium-glucose cotransporter 2 inhibitors versus placebo or other antidiabetic drugs. (A) Microalbuminuria. (B) Macroalbuminuria. (C) Worsening nephropathy. (D) End-stage renal disease. CI, confidence interval; RR, relative risk; W, weight.