# Glucagon-like Peptide-1 Receptor Agonist Use and Pancreatic Cancer Risk in Patients with Chronic Pancreatitis

## TL;DR

This study finds that using GLP-1 receptor agonists may reduce the risk of pancreatic cancer in patients with chronic pancreatitis.

## Contribution

The study is the first to show a potential protective effect of GLP-1 RAs against pancreatic cancer in patients with chronic pancreatitis.

## Key findings

- GLP-1 RA use was associated with a 51% reduced 5-year pancreatic cancer risk in patients with chronic pancreatitis.
- The protective effect was also observed in patients with both chronic pancreatitis and type 2 diabetes.
- Propensity score matching confirmed the association after adjusting for multiple confounding factors.

## Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being prescribed for treatment of type 2 diabetes mellitus (T2DM) and obesity. However, the risk of developing pancreatic cancer with the administration of GLP-1 RAs is currently unclear. In this study, using large healthcare database, we evaluate the association between incidence of pancreatic cancer in 89,596 patients with chronic pancreatitis and intake of GLP1 RAs. GLP-1 RA use was associated with a significantly reduced 5-year incidence of pancreatic cancer in all patients with chronic pancreatitis (HR 0.49, 95% CI 0.30–0.80), as well as the subpopulation with both chronic pancreatitis and T2DM (HR 0.53, 95% CI 0.31–0.91). Future larger studies with longer follow up are needed to confirm the potential beneficial effect of GLP-1 RA on incidence of pancreatic cancer.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have advanced the treatment of type 2 diabetes mellitus (T2DM), yet their association with cancer risk remains subject of ongoing research. Chronic pancreatitis (CP) is a well-established risk factor for pancreatic cancer, yet the impact of GLP-1 RA therapy in this high-risk population is unknown. In this study, we aimed to evaluate the association between GLP-1 RA use and pancreatic cancer incidence among patients with CP, and among those with CP and T2DM. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. In the first analysis, adult patients with pre-existing CP were identified and stratified by use of a GLP-1 RA (semaglutide, dulaglutide, tirzepatide, exenatide, liraglutide, lixisenatide, and albiglutide). Propensity score matching (PSM) was conducted between GLP1-RA users and non-users, matching for age, sex, race, tobacco use, alcohol use, hypertension, hyperlipidemia, obesity, and pancreatic cysts. Five-year incidence of pancreatic cancer was compared between GLP-1 RA users and non-users in the matched cohort between 2015 and 2025. We then restricted the cohort to patients with CP and T2DM and repeated this analysis. Results: We identified 89,596 patients with CP, including 3183 GLP-1 RA users and 86,413 non-users. After PSM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.30–0.80, p < 0.005). Similarly, amongst patients with CP and T2DM, GLP-1 RA use was associated with a lower 5-year incidence of pancreatic cancer (HR 0.53, 95% CI 0.31–0.91, p < 0.05). Conclusions: GLP-1 RA use was associated with a significantly reduced incidence of pancreatic cancer in all patients with CP, as well as the subpopulation with both CP and T2DM. Given the elevated cancer risk in CP, these findings suggest a potential beneficial effect of GLP-1RA use in this high-risk population. Prospective studies will be important to further analyze and confirm this potential benefit.