Glucagon-like peptide-1 receptor agonists and pancreatic outcomes in chronic pancreatitis: a real-world cohort study

Goal To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy and pancreatic, gastrointestinal, and mortality outcomes in chronic pancreatitis (CP) using the TriNetX US Collaborative Network. Background CP patients face heightened risks of pancreatic insufficiency, cancer, and mortality. There are concerns regarding GLP-1 RA use and adverse pancreatic outcomes. Methods In this retrospective cohort study, adults (age ≥ 18 years) with CP (ICD-10-CM K86.0 or K86.1) were stratified into Cohort 1 (CP + GLP-1 RA, n = 10,978) and Cohort 2 (CP without GLP-1 RA, n = 245,024. After propensity score matching on age, sex, race, and comorbidities, 10,625 patients remained in each cohort. Primary and secondary outcomes were assessed over 3 years via risk analyses and Kaplan-Meier survival analyses. Results GLP-1 RA users had significantly lower incidence of exocrine insufficiency (3.1% vs. 6.3%; RR 0.491, 95%CI 0.429–0.562, p < 0.001), endocrine insufficiency (6.0% vs. 8.2%; RR 0.742, 95%CI 0.664–0.829, p < 0.001), recurrent acute pancreatitis (5.8% vs. 10.5%; RR 0.554, 95%CI 0.487–0.631, p < 0.001), pancreatic cancer (2.0% vs. 3.9%; RR 0.498, 95%CI 0.421–0.590, p < 0.001), ED visits (17.4% vs. 22.4%; RR 0.778, p < 0.001), hospitalizations (18.0% vs. 26.3%; RR 0.684, p < 0.001), and gastroparesis (2.3% vs. 3.0%; RR 0.771, p = 0.003). Critically, all-cause mortality was 6.9% in GLP-1 RA users versus 16.4% in non-users (RR 0.423, 95%CI 0.390–0.459, p < 0.001), with 3-year survival of 88.6% versus 79.1%. Conclusions GLP-1 RA use was associated with substantially lower risks of pancreatic and gastrointestinal outcomes, along with improved overall survival, providing observational evidence supporting safety signals.