Clinical impact of GLP-1 receptor agonist use on lung cancer incidence in high-risk patients: A real-world analysis.

10559 Background: Lung cancer (LC) is the leading cause of cancer-related mortality in the United States. Lifetime risk is ~7% in the general population but substantially higher among high-risk groups with tobacco use, environmental exposures, or family/genetic predisposition. Despite screening recommendations for select high-risk populations, no pharmacologic prevention is established. Emerging evidence suggests that Glucagon-like peptide-1 receptor agonists (GLP-1RA) may influence cancer risk through antiproliferative, anti-inflammatory, and immunomodulatory effects, but data on LC remain limited. This study evaluated the association between GLP-1RA use and LC incidence in high-risk patients. Methods: This multicenter retrospective study used de-identified electronic health data from TriNetX, a global federated research network. Adults ≥18 with high-risk features of tobacco use, environmental or occupational exposure, chronic lung disease, personal/family cancer history, or radiation were included. Participants were stratified by GLP-1RA use. Propensity score matching (1:1) adjusted for demographics, comorbidities, and medications. The primary endpoint was LC incidence. Participants with LC before the study entry were excluded. Multivariate logistic regression and Cox models assessed associations; results reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Before matching, 2,715,963 participants were identified. After matching, 68,374 were analyzed (34,187 per cohort) with similar demographics (mean age 58, 54% female, 46% male; 75% White, 17% Black, 1.5% Asian). Median follow-up was 2,324 days. LC incidence was 2% (688/33,784) in the GLP-1RA cohort vs 2.4% (797/33,369) in controls, yielding an absolute risk reduction of 0.4% and a number needed to treat (NNT) of 250. GLP-1RA use was associated with a 31% reduction in LC incidence [HR 0.687 (0.621–0.761)]. Conclusions: In this large retrospective cohort of high-risk individuals, GLP-1RA use was associated with lower LC incidence compared with matched controls. Despite modest absolute risk reduction, relative risk reduction and favorable number needed to treat suggest potential population-level impact in a disease with limited preventive options. Findings are biologically plausible given the anti-inflammatory, metabolic, and immunomodulatory effects of GLP-1RAs. While causal inference is limited by observational design, this study supports further prospective investigation of GLP-1RAs as a pharmacologic strategy for LC prevention in high-risk populations.