Glucagon-like peptide 1 receptor agonists: More than just weight loss medications.

520 Background: Emerging evidence suggest a protective effect for Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RA) with obesity associated malignancies. This study was designed with the aim to assess the risk of gallbladder and biliary malignancies in patients taking GLP-1 RAs regardless of obesity status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, a federated, de-identified EMR database from 72 U.S. healthcare organizations. Adult patients (≥18 years) with type 2 diabetes initiating GLP-1 RA (without prior insulin) were compared to those initiating insulin (without GLP-1 RA), excluding individuals with prior gallbladder cancer, biliary resection, or related malignancies. Propensity score matching (1:1) balanced baseline covariates, and outcomes were assessed beginning 181 days post-index using risk and Kaplan-Meier survival analyses, excluding those with events before the outcome window. Results: Over a median follow-up of ~600–757 days, the GLP-1 RA cohort had fewer biliary cancer events (14 vs. 167), corresponding to a significantly lower risk (RR ≈ 0.084; p < 0.001). Survival probability at end of follow-up was slightly higher in GLP-1 RA users (99.96% vs. 99.84%), with a hazard ratio of ~0.116 (p = 0.002), indicating markedly reduced risk compared to insulin. Conclusions: In this matched cohort study of adults with T2DM, GLP-1 RA use was associated with significantly lower incidence of gallbladder and biliary tract cancers compared to insulin therapy. These findings concur with previously published evidence regarding the potential protective benefit of GLP-1 RA, which warrant further investigation into their long-term protective outcome.