Cardiorenal Outcomes of Dapagliflozin vs. Empagliflozin in Advanced Chronic Kidney Disease and Diabetes

Although sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiorenal benefits, direct comparisons between dapagliflozin and empagliflozin-the two most commonly used and studied agents in this class-remain limited, particularly in patients with advanced chronic kidney disease (CKD). In the current study, we aimed to compare the cardiorenal effectiveness and safety of dapagliflozin versus empagliflozin in adults with type 2 diabetes (T2D) and stage 3B-5 CKD. We used the TriNetX network and identified adults with T2D and stage 3B-5 CKD newly initiating dapagliflozin or empagliflozin. Following a target trial emulation framework, we applied 1:1 propensity score matching and Cox proportional hazards models to estimate hazard ratios (HRs) for major adverse kidney events (MAKE), major adverse cardiovascular events (MACE), all-cause mortality, and adverse events. After matching, 4,361 participants were included per group. The mean age was 67.6-67.9 years and men comprised 45.3-45.9% with a median follow-up duration of 780-790 days. Dapagliflozin users showed comparable HRs for MAKE (1.04; 95% CI: 0.94-1.16), MACE (1.02; 95% CI: 0.95-1.09), all-cause mortality (0.86; 95% CI: 0.74-1.00), and adverse events (1.03; 95% CI: 0.92-1.14). However, the risk of end-stage kidney disease (ESKD) was higher with dapagliflozin (1.28; 95% CI: 1.11-1.48). We concluded that in adults with T2D and advanced CKD, dapagliflozin and empagliflozin demonstrated comparable cardiorenal effectiveness and safety. Dapagliflozin was associated with a modestly higher ESKD risk, but this finding warrants cautious interpretation and further study given the observational design and potential residual confounding.