S1037 Association Between SGLT2 Inhibitor Use and the Risk of Eosinophilic Esophagitis in Patients With Type 2 Diabetes Mellitus: A Retrospective Cohort Study

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are widely used to treat type 2 diabetes mellitus (T2DM) and recent interest has emerged in their potential immune-modulating effects. SGLT2is have shown to have anti-inflammatory effects which are related to their cardiovascular and renal outcomes in patients with T2DM. Therefore, the protective association between eosinophilic eosophagitis (EoE) and SGLT2is may be biologically possible given that EoE pathogenesis is driven by type 2 cytokine-mediated inflammation, promoting eosinophil infiltration. This retrospective cohort study explores the association between SGLT2 inhibitor use and the risk of developing EoE in patients with T2DM. Methods: We performed a retrospective cohort study using the TriNetX Global Collaborative Network. Adults aged 18-65 years with T2DM were included and divided into 2 cohorts: those prescribed SGLT2is and those treated with other antidiabetic medications. Patients with type 1 diabetes mellitus, prior EoE, inflammatory bowel disease, connective tissue disease, malignancy, or history of bariatric or esophageal surgeries were excluded. Propensity score matching was performed. The primary outcome was a new diagnosis of EoE after cohort entry. Risk analysis and Kaplan-Meier survival analysis were conducted. Results: After matching, 37,948 patients were included in each group. Baseline characteristics were balanced. Three hundred fifty-eight patients in SGLT2i users and 536 patients in non-SGLT2i users were excluded from the results because they had the outcome prior to starting them on antidiabetic medications. Incident EoE occurred in 269 (0.072%) SGT2i users and 371 (0.099%) in non SGLT2i users. SGLT2i use was associated with 38% relative reduction in EoE risk (relative risk 1.38; 95% confidence interval [CI] 1.179-1.614; P < 0.001). Survival analysis showed no significant difference in time to diagnosis (hazard ratio 1.093; 95% CI 0.931-1.282; P = 0.14). Conclusion: SGLTis were associated with a significantly reduced risk of EoE incidence in patients with T2DM. The lack of significance in time-to-diagnosis analysis may reflect the low incidence of EoE, diagnostic delays, or uniform endoscopic surveillance across cohorts. Limitations of this study include reliance on International Classification of Diseases coding for the outcome without histologic confirmation and unmeasured confounding related to healthcare utilization patterns (e.g. frequency of esophagogastroduodenoscopy). These findings suggest a possible immune-modulating role for SGLT2is and may guide future research into inflammation-targeted therapies in EoE.