Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in subjects with type 2 diabetes (T2D) and obesity. However, concerns over their association with acute pancreatitis (AP) have emerged. Our aim was to evaluate the risk of recurrence of AP in subjects on GLP-1RAs with a history of AP.

This retrospective study deployed the TriNetX platform. We identified adult cohorts of subjects with a history of AP and analyzed the impact of individual medications (GLP-1RAs, SGLT2i, or DPP4i) on the risk of recurrence of AP. To adjust for baseline differences, propensity score matching was done in cohorts with and without risk factors for AP.

Our analysis of 672,069 patients with a history of AP and T2D revealed significant risk reductions associated with GLP-1RAs compared to other treatments. Over one to five years, GLP-1RAs consistently showed a lower risk of AP recurrence compared to SGLT2i and DPP-4i. Specifically, over a one-year period, GLP-1RAs users had a risk reduction of -0.071 (95 % CI:0.085 to -0.057) (p < 0.001) compared to SGLT2i, and -0.064 (95 % CI:0.080 to -0.048) (p< 0.001) compared to DPP-4i. These trends persisted, with the risk differences further widening by the fifth year to -0.086 and -0.094, respectively.

Based on our findings, we conclude that GLP-1RAs may be safely used in subjects with a history of acute pancreatitis. While our analysis showed that there was a significantly lower risk of AP recurrence in subjects on GLP-1compared to DPP-IV inhibitors and SGLT2 inhibitors, as this is a retrospective analysis we suggest that these findings need to be confirmed in prospective studies.