S243 Comparative Risk of Acute Pancreatitis in Hypertriglyceridemia Patients Treated With SGLT2 Inhibitors vs GLP-1 Receptor Agonists: A Propensity-Score Matched Analysis

Introduction: Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used antidiabetic agents with demonstrated cardiovascular and renal benefits. However, their comparative safety profiles regarding pancreatitis and lipid disorders remain underexplored. This study aimed to evaluate and compare the 1-year risk of acute pancreatitis and hypertriglyceridemia among users of SGLT2 inhibitors and GLP-1 receptor agonists. Methods: We performed a retrospective cohort analysis using data from the TriNetX Research Network. Adults who initiated either an SGLT2 inhibitor or a GLP-1 receptor agonist were identified and followed for 1 year. After 1:1 propensity-score matching for baseline demographics and comorbidities, 22,042 patients were included in each cohort. Primary outcomes were the incidence of acute pancreatitis and hypertriglyceridemia, defined by ICD-10 codes. Risk comparisons were assessed using odds ratios, risk differences, and Cox proportional hazards models adjusted for medication type. Results: In propensity-score–matched cohorts of 22,042 patients per arm, the incidence of acute pancreatitis was higher in patients treated with SGLT2 inhibitors compared to GLP-1 receptor agonists, acute pancreatitis occurred in 0.349% of the SGLT2 users vs 0.263% of the GLP-1 RA (odds ratio 1.33, 95% CI 0.95–1.87; P = 0.10). In a multivariable Cox regression analysis adjusting for individual medications, For SGLT2 inhibitors, the adjusted hazard ratios were: canagliflozin (aHR <0.0001, 95% CI 0–0; P = 0.9844), dapagliflozin (aHR 1.22, 95% CI 0.45–3.28; P = 0.6982), empagliflozin (aHR 0.77, 95% CI 0.34–1.73; P = 0.5249), and ertugliflozin (aHR <0.0001, 95% CI 0–0; P = 0.9954). For GLP-1 receptor agonists, results included: albiglutide (aHR <0.0001, 95% CI 0–0; P = 0.9962), dulaglutide (aHR 1.19, 95% CI 0.63–2.25; P = 0.5968), semaglutide (aHR 1.58, 95% CI 0.81–3.10; P = 0.1808), liraglutide (aHR 0.59, 95% CI 0.24–1.45; P = 0.2501), and exenatide (aHR 0.30, 95% CI 0.04–2.17; P = 0.2348). Conclusion: In this large real-world matched cohort study, the risk of acute pancreatitis and hypertriglyceridemia did not differ significantly between SGLT2 inhibitor and GLP-1 receptor agonist users. While male sex and older age were independently associated with pancreatitis risk, no individual agent demonstrated a statistically significant association. These findings support the pancreatic safety of both classes in routine practice.