Impact of GLP-1 Receptor Agonists on Patients With Intraductal Papillary Mucinous Neoplasms: A Retrospective Multicentric Cohort Study

This is a retrospective, multicentric cohort study designed to investigate the impact of GLP-1 receptor agonists (GLP-1 RAs) on patients with intraductal papillary mucinous neoplasms (IPMNs), a subtype of pancreatic cystic neoplasms with variable but potentially significant malignant potential. IPMNs are increasingly diagnosed due to advancements in cross-sectional imaging techniques, and their management often includes long-term radiological and clinical surveillance.

Concurrently, the prescription of GLP-1 RAs for type 2 diabetes mellitus and obesity has grown substantially. While GLP-1 RAs have shown excellent efficacy in glycemic control and weight reduction, concerns persist regarding their potential effects on the exocrine pancreas, particularly in patients with preexisting pancreatic abnormalities. Preclinical data in rodent models have been inconsistent, showing both pro-inflammatory and anti-inflammatory effects on the pancreas. Moreover, changes in pancreatic ductal morphology, including ductal gland proliferation, have been reported in animal studies, but with limited translation to human models. Meta-analyses of human clinical trials have not established a conclusive association between GLP-1 RAs and acute pancreatitis or pancreatic cancer; however, these studies typically exclude patients with underlying pancreatic lesions, such as IPMNs.

To address this gap, this study aims to assess the real-world effects of GLP-1 RA therapy on patients diagnosed with IPMNs. The hypothesis driving this research is that GLP-1 RA use may influence IPMN characteristics or related outcomes, which could affect management decisions including surveillance intervals, imaging modality choice, and surgical indications.

Study Setting and Data Sources The study is being conducted across 3 major Swiss medical centers: Hôpital Fribourgeois (HFR), Hôpitaux Universitaires de Genève (HUG), and the Inselspital in Bern. Data will be extracted from electronic medical records and include radiological images, laboratory test results, medication history, and clinical notes. The retrospective inclusion period ranges from January 2010 to May 2025.

Study Population Eligible participants are adult patients (aged ≥18 years) with a radiological diagnosis of IPMN who have been treated with any GLP-1 RA (e.g., exenatide, liraglutide, dulaglutide, semaglutide) during the study period. IPMN diagnoses will be validated based on radiologic criteria, with reference to the Kyoto 2023 Consensus. Patients must have complete medical records including at least one cross-sectional imaging (MRI or CT), serum tumor markers (CA19-9, CEA), and documented use of a GLP-1 RA.