Head-to-head comparative effectiveness of empagliflozin versus dapagliflozin and DPP-4 inhibitors on clinical and metabolic outcomes: a nationwide propensity-matched study

This retrospective study compared the clinical and metabolic effectiveness of empagliflozin (EMPA) versus dapagliflozin (DAPA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) using real-world data from the Korean National Health Insurance Service (2013–2024). Adults with type 2 diabetes who initiated treatment and maintained it for > 365 days were evaluated. Clinical and metabolic outcomes were analyzed using Cox models and linear mixed models, respectively, following 1:1 propensity score matching ( n = 17,050 per group for EMPA vs. DAPA and EMPA vs. DPP-4i). Compared with DAPA, EMPA was associated with lower risks of hypoglycemia (adjusted hazard ratio [aHR] 0.60, 95% CI 0.44–0.82) and all-cause hospitalization (aHR 0.96, 95% CI 0.92–0.99). Compared with DPP-4i, EMPA was associated with lower risks of all-cause hospitalization (aHR 0.83, 95% CI 0.80–0.87) and kidney events (aHR 0.76, 95% CI 0.66–0.88). Acute safety outcomes, including hypoglycemia and diabetic ketoacidosis, were evaluated exploratorily because the sustained-exposure design may underrepresent early events. In conclusion, EMPA and DAPA showed broadly similar outcomes consistent with a class effect; however, EMPA was associated with lower risks of all-cause hospitalization and kidney events compared with DPP-4i. These associations should be interpreted cautiously given the observational study design.