S242 SGLT2 Inhibitors and Chronic Pancreatitis: A Protective Twist in Pancreatic Outcomes

Introduction: Chronic pancreatitis (CP) is a progressive inflammatory disease associated with complications such as exocrine pancreatic insufficiency, pseudocysts, malignancy, and increased mortality. SGLT2 inhibitors have demonstrated anti-inflammatory and antifibrotic properties in preclinical models, but their effect on pancreatic outcomes in CP remains unclear. This study aimed to evaluate whether SGLT2 inhibitor use is associated with improved pancreatic outcomes in patients with CP. Methods: A validated, multicenter research platform database encompassing more than 70 healthcare systems and over 130 million patients across the United States was utilized to construct this study. Cohort 1 included patients aged 18–65 years with chronic pancreatitis on SGLT2 inhibitors (N = 7,906), while Cohort 2 included patients with chronic pancreatitis not on SGLT2 inhibitors (N = 131,909). Propensity score matching (1:1) was performed, adjusting for demographics and comorbidities. Outcomes assessed included exocrine pancreatic insufficiency, pancreatic stones, pancreatic pseudocysts, pancreatic cancer, and mortality. Results: After matching, 7,446 patients remained in each group. SGLT2 inhibitor use was associated with reduced risks of exocrine pancreatic insufficiency (5.3% vs 7.3%; odds ratio [OR] 0.71; P < 0.001), pancreatic pseudocysts (2.7% vs 4.6%; OR 0.58; P < 0.001), pancreatic cancer (1.3% vs 2.3%; OR 0.58; P < 0.001), and mortality (7.0% vs 12.7%; OR 0.52; P < 0.001). There was no significant difference in the risk of pancreatic stones (0.3% vs 0.4%; OR 0.84; P = 0.51). Kaplan–Meier analysis confirmed higher survival probabilities for SGLT2 users across all outcomes except stone formation. Conclusion: SGLT2 inhibitor use was associated with significantly improved pancreatic outcomes and reduced all-cause mortality in patients with chronic pancreatitis. These findings suggest a potential protective role and raise important questions about the broader therapeutic applications of SGLT2 inhibitors in this population. Further studies are warranted to confirm these associations and evaluate their potential as disease-modifying agents.