Calvarysky_2026_Diabetes.Metab.Res.Rev_42_e70116

AIMS: The use of glucagon-like peptide-1 (GLP1) analogues has increased due to benefits in glycaemic control, weight loss, and cardiorenal protection. However, concerns persist regarding their potential link to pancreatitis. We assessed this link in high-risk patients with a history of pancreatitis or elevated lipase enzyme. METHODS: Retrospective data from a large health maintenance organisation (> 4.5 million insured members) were extracted using the MDClone data-sharing platform, with complete de-identification. We included adults with diabetes who experienced pancreatitis or had elevated lipase (> 1.5 times the upper reference limit), defining an index date for start of follow-up. GLP1 analogues were initiated in a portion of the cohort during the follow-up period. Patients who had used GLP1 analogues prior to or within 1 month of the index date were excluded. The primary outcome was recurrent pancreatitis. Survival and multivariate analyses, including time-varying models, were performed to assess the impact of GLP1 analogues on recurrent pancreatitis risk. RESULTS: The cohort included 46,186 patients (10,933 for pancreatitis, and 35,253 for elevated lipase, 55% men, median age 70.9 years). GLP1 analogue use was an independent risk factor for recurrent pancreatitis in a time-varying analysis (HR 1.252, 95% CI 1.178-1.332). This remained significant after adjusting for factors like gender, alcohol use, and medications associated with pancreatitis. CONCLUSIONS: An increased risk of recurrent pancreatitis was observed in high-risk patients receiving GLP1 analogue therapy. These findings align with pharmacovigilance data and support caution when prescribing GLP1 analogues in this population. Prospective studies are warranted to further evaluate this association.