Sodium-glucose co-transporter 2 inhibitors (SGLT2i); as a preventive factor of kidney failure in patients with type 2 diabetes; a meta-analysis of randomized controlled trials

Abstract

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs. SGLT2 inhibitors lower blood glucose levels by decreasing glucose reabsorption in the proximal renal tubule, resulting in increased urinary glucose and sodium excretion. Objective: This study was conducted to investigate the effects of SGLT2i on individual renal outcomes in diabetic patients. Methods: This study was a systematic review and meta-analysis of clinical trials. A comprehensive search of Cochrane Central Register of Controlled Trials was conducted in the Cochrane Library and PubMed, to identify relevant articles focusing on SGLT2i and chronic kidney disease (CKD) in diabetic patients. The most recent article search was conducted on July 12, 2021. Results: Seven randomized controlled trials (RCTs) were included in the meta-analysis. Two trials were comparing dapagliflozin, two comparing empagliflozin, one comparing ertugliflozin, one comparing canagliflozin, and one comparing sotagliflozin. Composite renal outcome and acute kidney injury (AKI) was found in seven and four studies, respectively. Data on end-stage kidney disease (ESKD) and albuminuria or initiation of renal replacement therapy were reported in the two studies. The pooled risk ratio (RR) 95% confidence interval (CI) for the composite renal outcome was 0.54 (0.50–0.59), with 92 % heterogeneity. The pooled RR for AKI was 0.77 (0.66–0.89), with no heterogeneity. A significant lower incidence of albuminuria (RR: 0.69; 95% CI: 0.59–0.81), initiation of renal replacement therapy (RR: 0.71; 95% CI: 0.58–0.87), was observed following the use of SGLT2 inhibitors. Conclusion: Our findings confirm that the SGLT2 inhibitors can reduce the risk of albuminuria, AKI and renal replacement therapy in ESKD patients with T2D (type 2 diabetes). These meta-analyses provide substantial evidence supporting the beneficial effect of SGLT2 inhibitors on reducing CKD events in individuals with T2D.