Examining the Molecular Mechanisms of Glucagon-like Peptide-1 Receptor Agonists in Cancer Cell Biology

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are synthetic analogs of glucagon-like peptide-1 (GLP-1) used to treat obesity and diabetes by reducing blood glucose levels and appetite. While early rodent studies suggested a link between GLP-1RAs and thyroid cancer pathogenesis, evidence in humans remains inconclusive, with randomized controlled trials not supporting that link. Due to the rapid, widespread use of these drugs, concerns have expanded to other obesity-associated cancers, with conflicting findings on their role in cancer progression. With this contradictory evidence in a novel intersection of obesity medicine and oncology, this literature review aims to summarize current understandings between GLP-1-RAs and cancers to address these worries. Recent studies indicate that GLP-1RAs may regulate signaling pathways associated with cancer, including cAMP-mediated, PI3K/Akt/mTOR, AMPK, and NF-κB signaling, with pro- and anti-cancer effects depending on the cancer type. Preclinical and retrospective clinical studies have suggested that GLP-1RA treatment may alleviate liver, colorectal, and pancreatic cancer. However, research on thyroid, breast, and kidney cancers remains inconclusive, with some studies indicating cancer-promoting effects while others suggest no effect or even anti-cancer effects. Patients currently being treated should follow their physician’s recommendations; yet more research is needed to fully understand the molecular mechanisms of GLP-1RAs in cancer to provide clear guidance.