Obesity is a well-established risk factor for numerous cancers, with body habitus, especially central adiposity, contributing to increased cancer incidence and worse prognosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed to treat Type 2 diabetes, have rapidly gained prominence as powerful anti-obesity agents due to their ability to induce significant weight loss and potential to improve metabolic health. These medications act by reducing appetite, enhancing insulin sensitivity, lowering systemic inflammation, and preferentially targeting fat mass for reduction. This review explores the growing body of evidence linking GLP-1 RA therapy to potential changes in cancer risk among individuals with obesity. To date, data suggest that GLP-1 RAs do not increase overall cancer risk and may reduce the risk of certain obesity-related cancers, likely by interrupting obesity-driven metabolic dysregulation. Still, questions remain about the beneficial effects of weight loss and the sustainability of health benefits if weight is regained after stopping treatment. We examine how GLP-1 RAs' anti-inflammatory and metabolic effects might mediate reductions in cancer risk, review emerging data regarding both protective signals and specific safety concerns (e.g., increased risk of medullary thyroid carcinoma), and emphasize the critical role of combining pharmacotherapy with lifestyle interventions to maintain muscle mass and long-term weight loss. Ultimately, given the strong link between obesity and cancer, GLP-1 RAs represent a promising new class of agents that may not only help to manage obesity but also serve as effective chemopreventive tools against obesity-associated cancers.
