Do glucagon-like peptide 1 receptor agonists offer protective effect on colon cancer risk?

91 Background: Previous evidence have evaluated the impact of GLP-1 receptor agonists (GLP-1 RA) on colon cancer risk in patients with obesity. We aim to provide updated population-based data, analyzing the potential effect of GLP-1RA on the risk of colon cancer in patients with or without obesity. Methods: This retrospective observational study leveraged the TriNetX database, forming two propensity-score–matched cohorts of type 2 diabetes (T2DM) patients without prior colon cancer. One cohort consisted of insulin-treated individuals not using GLP-1 agonists, and the other included new users of GLP-1 agonists. Both groups excluded patients with inflammatory bowel disease, personal or family history of colon cancer or polyps, or hereditary colon cancer syndromes. Matching accounted for age, sex, ethnicity, and race, resulting in 965,333 comparable patients. The main outcome was the incidence of new colon cancer diagnoses identified via ICD-10 codes. Analyses included odds ratios (ORs), risk ratios (RRs), Kaplan–Meier survival curves with hazard ratios (HRs), and statistical significance was set at p < 0.05. Results: Patients not treated with GLP-1 agonists had significantly higher colon cancer risk across all metrics: RR = 3.06 (95% CI: 2.921–3.207), OR = 3.08 (95% CI: 2.935–3.223), and HR = 2.702 (95% CI: 2.578–2.833), all with p < 0.0001. The absolute risk difference was 0.498% (95% CI: 0.478–0.517%). Additionally, the GLP-1 agonist cohort demonstrated superior overall survival regarding colon cancer. Conclusions: GLP-1 RA use was associated with significantly lower colon cancer risk and improved survival compared with insulin therapy. These findings align with previously published data showing the potential protective role of GLP-1 RA in reducing malignancy risk, supporting the need for further studies to evaluate their long-term beneficial profile.