Sodium–glucose cotransporter-2 inhibitor therapy and risk of mortality and morbidity following hospitalization for pneumonia in type 2 diabetes mellitus: An international propensity score-matched cohort study

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM). Objectives: This study investigated the association between SGLT2 inhibitor therapy and mortality and morbidity after hospitalization for pneumonia among adults with T2DM. Design: International retrospective propensity score-matched cohort study. Methods: We conducted a cohort study using the TriNetX database, including adults with T2DM who were hospitalized for pneumonia between January 1, 2013, and March 31, 2025. Patients were categorized based on whether they had received a prescription for SGLT2 inhibitors within 90 days before the index admission. The primary outcome was all-cause mortality within 30 days. Secondary outcomes included major adverse respiratory events (MAREs, comprising respiratory failure, acute respiratory distress syndrome, pleural effusion or empyema, sepsis, mechanical ventilation, and intensive care unit admission), acute kidney injury (AKI), and diabetic ketoacidosis (DKA). Results: Among the 6505 matched patients, SGLT2 inhibitor users had significantly lower 30-day mortality (8.72% vs 12.27%; relative risk (RR): 0.71, 95% confidence interval (CI): 0.64–0.79, p < 0.0001), MAREs (RR: 0.87, 95% CI: 0.84–0.91, p < 0.0001), AKI (RR: 0.89, 95% CI: 0.84–0.94, p < 0.0001). Diabetic ketoacidosis (DKA) events were rare in both groups (0.25% vs 0.46%) but occurred less frequently among SGLT2 inhibitor users (RR: 0.53, 95% CI: 0.29–0.98, p = 0.0387). These findings were consistent across multiple follow-up periods and sensitivity analyses. Additionally, a dose–response relationship was observed between the duration of SGLT2 inhibitor use and reduced rates of all-cause mortality, MAREs, and AKI. Conclusion: Patients with T2DM who used SGLT2 inhibitors had significantly lower risks of mortality and morbidity following hospitalization for pneumonia, including a notable reduction in DKA, contrary to prior concerns. Randomized controlled trials are warranted to validate these findings.