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.