Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors.

3143 Background: GLP-1 receptor agonists (GLP-1RAs) are pleiotropic medications, initially developed for diabetes, yet with beneficial effects on obesity and cardiovascular disease. Given the rapidly expanding therapeutic use of these agents and emerging preclinical data suggesting immunomodulatory effects, we examined whether GLP-1RA exposure following cancer diagnosis was associated with altered risk of progression to metastatic disease. Methods: Utilizing the TriNetX Global Health Research Network, we identified 10,225 patients with stage I-III cancer who initiated GLP-1RA therapy after diagnosis. GLP-1RA-exposed patients were propensity-matched 1:1 to DPP-4 inhibitor controls across seven cancers: breast adenocarcinoma, prostate adenocarcinoma, NSCLC, colorectal adenocarcinoma (CRC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and pancreatic adenocarcinoma. Matching included demographics, BMI, glycemic factors, smoking, comorbidities, screening frequency, oncologic treatments, and concurrent medications. Primary outcome was progression to stage IV disease. Additionally, we used The Cancer Genome Atlas (TCGA) data to assess whether GLP-1R expression correlated with overall survival. Results: GLP-1RA exposure demonstrated reduced metastatic progression across 6/7 malignancies, with statistically significant reductions in four cancer types: NSCLC, breast, CRC, and HCC (Table 1). No significant safety signals or increased adverse events were observed in GLP-1RA-exposed patients compared to controls. Additionally, high tumor GLP-1R expression correlated with improved survival across the seven tumors (HR=0.67, 95% CI 0.54-0.83, p