Clinical outcomes associated with GLP-1 receptor agonist exposure in non-diabetic patients with chronic pancreatitis: a retrospective cohort study

Background: GLP-1 receptor agonists (GLP-1 RAs) are increasingly used for obesity and metabolic disease, but their use in people with chronic pancreatitis is not a chronic pancreatitis-directed indication and direct evidence is limited. We described recorded outcomes among non-diabetic adults carrying a chronic pancreatitis diagnosis who did or did not have recorded GLP-1 RA exposure.

Methods: We performed a retrospective propensity score-matched cohort study using the TriNetX Collaborative Network. Chronic pancreatitis was identified from a recorded diagnosis; supporting imaging, histological, functional, or specialist-confirmation criteria were unavailable. The exposed cohort included patients receiving dulaglutide, semaglutide, or tirzepatide (n = 1441 before matching), and the comparator cohort included patients without recorded GLP-1 RA exposure (n = 142,047 before matching). One-to-one propensity score matching generated 1422 patients in each cohort. Outcomes were assessed from 1 to 1095 days after the index date using risk comparisons and time-to-event analyses.

Results: Mean follow-up after matching was 458.8 days in the exposed cohort and 664.4 days in the comparator cohort. Recurrent acute pancreatitis was recorded in 19/799 (2.4%) versus 76/704 (10.8%) patients (HR 0.247, 95% CI 0.149–0.409), pancreatic cancer in 10/1373 (0.7%) versus 40/1345 (3.0%) (HR 0.255, 95% CI 0.128–0.511), and all-cause mortality in 21/1419 (1.5%) versus 157/1416 (11.1%) (HR 0.167, 95% CI 0.105–0.263). A similar direction was observed across several coded outcomes. Vitamin D deficiency showed a higher hazard (HR 1.556, 95% CI 1.129–2.145), although its risk comparison was not significant.

Conclusions: These estimates describe outcomes in a selected treatment-exposed phenotype of chronic pancreatitis. The findings are hypothesis-generating and should not guide prescribing decisions. Further prospective studies are required to confirm this hypothesis.