Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study.

BACKGROUND: Acute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. OBJECTIVES: Our objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. METHODS: We conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. RESULTS: GLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). CONCLUSIONS: GLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans.