Comparative Effectiveness of Sodium-glucose Cotransporter 2 Inhibitors Versus Renin-Angiotensin System Inhibitors in Chronic Kidney Disease.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated cardiorenal benefits in patients with chronic kidney disease (CKD) receiving background renin-angiotensin system inhibitor (RASi) therapy. We compared the effectiveness of SGLT2is versus RASis on the risks of heart failure (HF) development, kidney disease progression, and mortality in patients with CKD. We conducted a retrospective, active-comparator, new-user cohort study using the global electronic health record database. Adults with CKD (estimated glomerular filtration rate [eGFR] 15 to <60 mL/min/1.73 m²), without prior HF, who initiated SGLT2is or either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers between 2020 and 2023 were included. The primary outcome was a composite of all-cause death, new-onset HF, hemodialysis, or decline in eGFR to <15 mL/min/1.73 m² within two years. Propensity score (PS) matching was used to balance baseline characteristics. After PS matching, 18,075 matched pairs were analyzed. SGLT2i initiation was associated with a lower incidence of the primary composite outcome compared with RASi initiation (15.6% vs. 19.9%; hazard ratio 0.76, 95% confidence interval 0.72-0.80, P <0.001). SGLT2i was also associated with lower risks of the composite of all-cause death or new-onset HF and the composite of all-cause death, hemodialysis, or eGFR decline to <15 mL/min/1.73 m². In subgroup analyses of the PS-matched cohorts, these findings were consistent across diabetes status, CKD severity, urine albumin-to-creatinine ratio, SGLT2i type, and RASi class. In conclusion, initiation of SGLT2i was associated with lower risks of HF and kidney disease progression compared with RASi in patients with CKD.