Survival in patients with hepatobiliary and pancreatic cancers taking GLP-1 receptor agonist therapy.

Abstract

e16276 Background: Metabolic syndrome has been identified as an independent risk factor for hepatobiliary and pancreatic cancers. Although it is linked as a causative factor, the impact of treatment directed towards risk-reduction and the result on oncologic outcomes remain limited. Since the introduction of glucagon-like peptide-1 receptor agonists (GLP1), emerging evidence has shown associations with reducing the incidence of several cancers, including endometrial, ovarian and meningioma. To our knowledge, this is the first large-scale study to specifically address survival outcomes in patients with hepatobiliary and pancreatic cancers taking GLP1. Methods: A retrospective cohort study using the TriNetX Research Network from 158 healthcare organizations (HCO) from the Global Collaborative Network was carried out. We identified patients who were diagnosed with hepatocellular carcinoma (HCC), fibrolamellar HCC, cholangiocarcinoma, gallbladder and pancreatic cancer using the ICD-10 code and either received GLP1 treatment or not. Cohorts were balanced using propensity score matching for age at diagnosis, female, Black race, body mass index, comorbidities, and concomitant medications. Kaplan-Meier survival curves were used to assess overall survival (OS). Results: From 01/01/2010-12/31/2025, a total of 337,275 patients who had a hepatobiliary or pancreatic cancer were identified from 38 HCO, of these 4,404 patients started GLP1 after the diagnosis and 332,871 were not on GLP1. After balancing, each cohort had a total of 3,607 patients. Patients using GLP1 were noted to be younger and with more diverse ethnical and racial background. A higher body mass index was reported in those patients taking GLP1. Statistically significant differences were noted in laboratory values showing a lower creatinine, ALT and AST in those taking GLP1. Patients who were diagnosed with a hepatobiliary or pancreatic cancer who were taking GLP1 were noted to have better OS than those who did not [p-value < 0.001]. At 10 years, the median survival for those who received GLP1 was not reached vs 1,133 days for those who didn’t. Survival probabilities for patients using GLP1 vs. not at 6, 12, and 24 months were 92% vs. 77%, 86% vs. 67%, and 80% vs. 56%, respectively. Conclusions: Patients with hepatobiliary and pancreatic malignancies receiving GLP1 therapy demonstrated superior survival outcomes. This survival benefit may be driven by the anti-inflammatory properties of GLP1, mediated through both immunomodulatory pathways and the direct attenuation of oncogenic signaling and proliferation. Beyond gastrointestinal malignancies, emerging evidence suggests that GLP1 exert an effect against various metabolically driven malignancies. Given the expanding clinical indications for GLP1 therapy, further investigation into its broader oncologic effect is warranted.