Metabolic Modulation in Cancer Care: The Potential Role of Glucagon-Like Peptide-1 Receptor Agonists

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the management of type 2 diabetes and obesity by providing sustained improvements in glycemic control, weight loss, and cardiovascular outcomes. These benefits have led to increasing interest in their potential role in cancer treatment. Obesity and metabolic dysfunction are well-known factors that promote the development, progression, and resistance to therapy in various cancers, suggesting that drugs targeting these pathways may have anticancer effects. Emerging epidemiologic and clinical evidence shows that GLP-1RA therapy is linked to a lower risk of several obesity-related cancers, including GI, breast, endometrial, ovarian, prostate, and hematologic malignancies. Mechanistic studies also reveal effects on insulin signaling, long-term inflammation, angiogenesis, and immune system modulation. This comprehensive review integrates current knowledge of GLP-1RAs in cancer care, covering drug action, epidemiology, underlying mechanisms, and clinical application. We evaluate evidence for cancer prevention, their use as complementary treatments, and outcomes in patients with existing cancer. Overall, the evidence suggests that GLP-1RAs could become a novel class of agents linking metabolic health and cancer therapy, with potential applications in neoadjuvant treatment strategies, particularly in settings where prolonged neoadjuvant intervals allow for metabolic optimization before definitive surgical intervention.