Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Nephropathy: A Systematic Review and Meta-Analysis

One of the most common causes of end-stage renal disease, which still inflicts a significant clinical and economic burden, is diabetic nephropathy. Even though glycemic and blood pressure management have improved, a considerable proportion of patients progressing to renal failure develop progressive renal dysfunction. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have also proven to be agents with far-reaching renoprotective effects beyond glucose lowering. The present systematic review and meta-analysis synthesizes the existing evidence on the effectiveness and safety of SGLT2 inhibitors in diabetic nephropathy. The review of randomized controlled trials was conducted in line with PRISMA requirements. Twenty studies comprising 131,011 participants were included. SGLT2 inhibitor therapy significantly reduced the risk of composite renal outcomes by 30% (pooled relative risk, 0.70; 95% confidence interval, 0.67 to 0.73; p < 0.001), with minimal heterogeneity across studies (I² = 8.3%). The benefit was consistent across all SGLT2 inhibitor classes (p-value for between-group difference = 0.682), across all stages of chronic kidney disease (CKD) from early to advanced (p = 0.658), and regardless of background renin-angiotensin system (RAS) inhibitor use (p = 0.795). This meta-analysis provides robust evidence that SGLT2 inhibitors confer significant renal protection in patients with diabetic nephropathy, with consistent benefits observed across all drug classes, across all stages of CKD, and irrespective of background RAS inhibitor use. These findings support the incorporation of SGLT2 inhibitors as foundational organ-protective therapy in contemporary clinical practice guidelines for diabetic kidney disease management.