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.
Highlights
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
SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% confidence intervals (CIs), 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)
This systematic review and meta-analysis found that SGLT2 inhibitors were associated with a significantly lower risk of development or progression of albuminuria compared with placebo or other antidiabetic drugs in patients with type 2 diabetes
Summary
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. Dapagliflozin reduced the composite renal outcome of 40% decrease in estimated glomerular filtration rate (eGFR), end-stage renal disease (ESRD), or renal death compared with placebo[11]. These studies were performed in patients with an established cardiovascular disease or high cardiovascular risk[9,11,12]. In the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, canagliflozin significantly reduced the risk of new-onset microalbuminuria and 40% decrease in eGFR with no difference in the need for RRT9,13 In both studies[6,9], renal outcomes were secondary endpoints and the number of events indicating ESRD was not sufficient to provide conclusive information. Canagliflozin and dapagliflozin have increased the risk of acute kidney injury in patients who have predisposing factors including hypoglycemia, chronic kidney disease (CKD), heart failure, and potentially nephrotoxic drugs[14,17,18]
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