Association Between Sodium–Glucose Cotransporter‐2 Inhibitors and Sepsis Risk in Patients With Type 2 Diabetes Mellitus

Aims: This retrospective study is aimed at evaluating the effect of SGLT2 inhibitors (SGLT2i) on the risk of sepsis among patients with Type 2 diabetes mellitus (T2DM). Materials and Methods: An active-comparator new user design was utilized based on Taiwan's National Health Insurance Research Database. Adult patients diagnosed with T2DM between 2017 and 2020 who initiated either SGLT2i or DPP-4 inhibitors (DPP-4i) were included. After 1:2 matching by age, sex, and Charlson Comorbidity Index, the study enrolled 34,672 SGLT2i users and 69,344 DPP-4i users. The primary outcome was sepsis, with secondary outcomes including septic shock, organ dysfunction, and mortality. Hazard ratios (HRs) were estimated using Cox proportional hazards regression. Results: SGLT2i users had a significantly lower risk of sepsis than DPP-4i users (10.1% vs. 15.5%; adjusted HR [aHR]: 0.77; 95% CI: 0.74-0.81). The risk of septic shock and mortality in SGLT2i users was also reduced by 30% (aHR: 0.70; 95% CI: 0.57-0.87) and 40% (aHR: 0.60; 95% CI: 0.54-0.66), respectively, compared with that of DPP-4i users. Conclusions: The findings suggest that SGLT2i is associated with a significantly lower risk of sepsis, septic shock, and mortality compared with that of DPP-4i in patients with T2DM.