Intraductal papillary mucinous neoplasms (IPMNs) are common cystic pancreatic lesions with potential progression to malignancy, particularly in main-duct subtypes. Improved imaging has increased IPMN detection. Concurrently, GLP-1 receptor agonists (GLP-1 RAs) have become widely used for type 2 diabetes and obesity management. Although GLP-1 RAs confer metabolic benefits, safety concerns remain about possible links to acute pancreatitis and pancreatic neoplasia. Existing meta-analyses have not established a definitive association with pancreatitis or pancreatic cancer, and pharmacovigilance reports provide a potential signal without proven causality. No prior study has specifically evaluated GLP-1 RA safety in patients with preexisting IPMNs. This retrospective multicentric cohort protocol was developed to explore potential associations between GLP-1 RA exposure and changes in IPMN radiological features, tumour markers, acute pancreatitis incidence and progression to high-grade dysplasia or invasive carcinoma.
Primary objective: To evaluate the impact of GLP-1 RA therapy on IPMN progression as determined by radiological criteria specified in the Kyoto 2023 Consensus. The primary outcome is radiological progression of IPMN characteristics.
Secondary objectives/outcomes: 1) Variation in serum tumour markers, specifically CA19-9 and CEA; 2) incidence of acute pancreatitis (AP) in patients exposed to GLP-1 RAs; 3) progression of IPMNs to high-grade dysplasia or invasive carcinoma; 4) need for surgical intervention or modification of surveillance protocols potentially associated with GLP-1 RA use.
This study is a retrospective multicentric cohort review conducted at three Swiss tertiary hospitals: Cantonal Hospital of Fribourg (HFR), University Hospital of Geneva (HUG) and Inselspital, University Hospital of Bern. Medical records, laboratory results and imaging studies dated between 1 January 2010 and 31 July 2026 will be reviewed. The design uses a 2 × 2 stratification based on presence or absence of IPMN and exposure or non-exposure to GLP-1 RAs to assess comparative outcomes.
Eligible participants are patients with a radiological diagnosis of IPMN and/or patients treated with GLP-1 RAs for diabetes or obesity during the study period at one of the participating centres. Patients will be stratified into four groups according to IPMN status and GLP-1 RA exposure in the planned 2 × 2 design. Specific inclusion and exclusion criteria beyond radiological diagnosis and medication exposure were not detailed in the source.
The study will extract data from existing institutional medical records, laboratory databases and imaging archives. Key variables include demographic and clinical characteristics, details of GLP-1 RA exposure (agent, duration — note: specific exposure definitions were not reported in the source), radiological features of IPMNs documented on MRI or other imaging modalities, serial tumour marker values (CA19-9, CEA), and recorded episodes of acute pancreatitis. Outcomes such as pathology-confirmed high-grade dysplasia or invasive carcinoma and records of pancreatic surgery or changes to surveillance protocols will also be collected when available.
Radiological progression will be assessed using criteria from the Kyoto 2023 Consensus, as stated in the protocol. Surveillance modalities favouring MRI are acknowledged in the literature and will form the primary imaging basis for assessing IPMN changes. Serial serum tumour markers (CA19-9, CEA) will be compared over time to evaluate potential biochemical changes during or after GLP-1 RA exposure. The protocol references case reports and animal studies highlighting potential marker perturbations and structural effects but does not add new experimental assays.
The investigators anticipate a small sample size and report an estimated total of 30–60 patients; this retrospective design may therefore limit statistical power. The protocol frames the study as exploratory and hypothesis-generating rather than definitive. Specific statistical methods, power calculations beyond the sample size estimate, and planned covariate adjustments were not reported in the source text.
The protocol acknowledges several limitations: its retrospective nature, expected small sample size, and the potential for confounding inherent to observational data. These constraints may preclude establishing causal relationships between GLP-1 RA exposure and IPMN progression. The study does not report any specific funding and states there are no competing interests. Data availability is noted: no datasets were generated or analysed at the time of protocol publication, and relevant data will be shared upon study completion. Ethical approvals and committee identifiers were referenced in abbreviations (for example, CER-VD) but full ethical approval details were not provided in the source extract.
This study is registered on ClinicalTrials.gov under identifier NCT07014709. The authors report that data will be made available after the study is completed. The protocol was published in PLOS One with open access and authorship across the three participating Swiss centres. The investigators present the study as an initial effort to inform future research and clinical decision-making regarding the safety of GLP-1 RAs in patients with preexisting IPMNs.