Advances in GLP-1 receptor agonists for pain treatment and their future potential

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) show substantial efficacy in regulating blood glucose levels and lipid metabolism, initially as an effective treatment for diabetes mellitus. In recent years, GLP-1RAs have become a focal point in the medical community due to their innovative treatment mechanisms, robust therapeutic efficacy, and expansive development prospects. Notably, GLP-1RAs benefit pain management through their neuroprotective and metabolic regulatory properties, such as inhibiting inflammation responses and oxidative stress, promoting β-endorphin release and modulating several other crucial biological pathways. Hence GLP-1RAs hold promise for repurposing as treatments for pain disorders. In this narrative review, we thoroughly trace the current preclinical and clinical evidence of seven pain modalities, including inflammatory pain, osteoarthritis, visceral pain, neuropathic pain, diabetic neuropathy, cancer pain and headache, to support the efficacy and underlying biological mechanisms of GLP-1RAs as therapeutic agents for pain suffering. Despite these promising findings, further research is necessary to establish their long-term efficacy, optimal dosing strategies, and potential synergistic interactions of GLP-1RAs with existing pain management therapies. Future clinical trials should aim to distinguish the direct analgesic effects of GLP-1RAs from their metabolic benefits and explore their broader applications in pain conditions. The ongoing exploration of new indications for GLP-1RAs further highlights their transformative potential in advancing medical treatments across diverse clinical fields.