Abstract
BACKGROUND: To determine whether initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA) within 3 months of type 2 diabetes (T2DM) diagnosis alters the subsequent risk of overall and site-specific cancer and whether this association differs by baseline body-mass index (BMI). METHODS: This retrospective cohort study used electronic health records from the TriNetX U.S. research network. Adults aged 20 years or older diagnosed with T2DM between 2016 and 2024 were included if they received any hypoglycemic agents within 3 months before and after diagnosis. Following 1:1 propensity score matching, both the GLP-1 RA user and non-user groups included 183,264 patients. The study outcome was defined as a diagnosis of malignant neoplasms. Hazard ratios (HRs) for overall and site-specific cancer risk were estimated using Cox proportional hazards models. Kaplan-Meier analysis and stratified analysis by BMI were performed. RESULTS: Early GLP-1 RA use demonstrated a modest but significant association with reduced overall cancer risk (HR 0.93; 95% CI: 0.90-0.96). Reduced risks were noted for cancers of the digestive (HR 0.81), respiratory (HR 0.66), and female genital (HR 0.87) systems. In stratified analysis, benefits were more pronounced in patients with BMI ≥ 30, particularly for pancreatic and colorectal cancers. CONCLUSION: Early initiation of GLP-1 receptor agonists in patients with diagnosed T2DM was associated with a modest reduction in overall cancer risk, particularly among individuals with obesity. These findings highlight the dual metabolic and oncologic value of prompt GLP-1 RA therapy.