Renoprotective effects and safety of sodium–glucose cotransporter 2 inhibitors in diabetic chronic kidney disease

Background: Chronic kidney disease (CKD) is a major global health burden characterized by progressive loss of renal function and high cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed as glucose-lowering agents, have demonstrated pleiotropic metabolic and cardiorenal benefits. However, previous evidence syntheses have not fully clarified the magnitude of metabolic, hemodynamic, renal surrogate, and safety effects specifically in patients with diabetic CKD. Methods: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to December 2025. Randomized controlled trials (RCTs) evaluating SGLT2 inhibitors in patients with diabetic CKD were included. Outcomes were prespecified and grouped as primary renal surrogate marker outcomes (eGFR and UACR), secondary metabolic and hemodynamic outcomes (glycated hemoglobin, body weight, and blood pressure indicators), and safety outcomes (urinary tract infection and volume depletion-related adverse events). Meta-analyses were performed using RevMan 5.3 and R version 4.4.2 software. Results: A total of 17 randomized controlled trials involving 29,192 participants were included. For secondary metabolic and hemodynamic outcomes, SGLT2 inhibitors significantly reduced glycated hemoglobin levels (MD = −0.40%, 95% CI: −0.44 to −0.36), body weight (MD = −1.36 kg, 95% CI: −1.55 to −1.18), and systolic blood pressure (MD = −2.98 mm Hg, 95% CI: −3.44 to −2.52). For primary renal surrogate marker outcomes, no statistically significant differences were observed in eGFR (MD = 0.25 mL/min/1.73 m 2 , 95% CI: −0.08 to 0.57) or UACR (MD = −31.55 mg/g, 95% CI: −137.21 to 74.12). Regarding safety outcomes, SGLT2 inhibitors did not significantly increase the risk of urinary tract infections (RR = 1.20, 95% CI: 0.94 to 1.54) but were associated with a significantly higher risk of volume depletion-related adverse events (RR = 1.36, 95% CI: 1.16–1.59). Conclusion: In patients with diabetic CKD, SGLT2 inhibitors significantly improve glycemic control, reduce body weight, and lower systolic blood pressure, while showing neutral short- to medium-term effects on eGFR and albuminuria. These neutral surrogate-marker findings should be interpreted alongside large outcome trials showing long-term cardiorenal protection. Although SGLT2 inhibitors increase the risk of volume depletion-related adverse events, their overall safety profile remains acceptable with appropriate clinical monitoring.