Impact of GLP-1 receptor agonists on patients with intraductal papillary mucinous neoplasms: Study protocol for a multicentric cohort study

Aim of the study Intraductal papillary mucinous neoplasms (IPMNs) are among the most common cystic pancreatic neoplasms, with a potential to progress to malignancy. The increasing prevalence of IPMNs, coupled with the widespread use of GLP-1 receptor agonists (GLP-1 RAs) for diabetes and obesity management, raises concerns about the safety of these medications in patients with preexisting pancreatic conditions. Despite their proven metabolic benefits, questions remain about their impact on pancreatic pathology. This study investigates the association between GLP-1 RA use and IPMN progression to address this critical gap in the current literature. Methods This retrospective multicentric cohort study will analyse data from January 2010 to July 2026 across three Swiss tertiary institutions. Patients with a radiological diagnosis of IPMN and/or treated with GLP-1 RAs will be included. Patients will be stratified into four groups according to a 2 × 2 design based on GLP-1 RAs exposure and IPMN status. The primary objective is to evaluate the impact of GLP-1 RAs on IPMN progression using radiological criteria from the Kyoto 2023 Consensus. Secondary objectives include assessing changes in tumour markers (CA19−9, CEA), the incidence of acute pancreatitis, the progression of IPMNs to high-grade dysplasia or invasive carcinoma, and the need for surgical intervention or altered surveillance protocols associated with GLP1 RAs use. Discussion This study aims to explore potential associations between GLP-1 RA use and changes in IPMN characteristics, tumour markers, and disease progression. Given the retrospective design and expected small sample size (estimated at 30–60 patients in total), the study may not be powered to establish definitive correlations. Nonetheless, it will generate preliminary data to help inform hypotheses and guide future research. Any observed trends could provide valuable insights into the safety of GLP-1 RAs in patients with IPMNs and contribute to more informed clinical decision-making regarding the use of these agents in a population at risk for pancreatic disease progression. Trial registration ClinicalTrials.gov NCT07014709