The therapeutic potential of GLP-1 receptor agonists in central nervous system diseases: immune cell modulation and neuroinflammation

INTRODUCTION: Central nervous system (CNS) diseases impose a substantial global burden; however, effective treatments remain limited. Neuroinflammation contributes to the development and progression of various CNS diseases. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may alleviate neuroinflammation by modulating immune cell-related processes, showing therapeutic potential in CNS diseases. AREAS COVERED: We searched PubMed/MEDLINE, Embase, and Web of Science for literature published between 2016 and 2026. We summarize preclinical evidence that various GLP-1RAs alleviate neuroinflammation across different CNS diseases through modulation of peripheral and central immune cells, focusing on neutrophils, monocytes/macrophages, T lymphocytes, microglia, astrocytes, and their crosstalk, and discuss related clinical translation and challenges. EXPERT OPINION: Repurposing GLP-1RAs, including exenatide, liraglutide, semaglutide, and dulaglutide, may provide a therapeutic option for CNS diseases. However, most mechanistic evidence remains preclinical, and clinical efficacy has not been established. Future studies should integrate neuroimmune biomarkers with clinical outcomes to determine whether immunomodulatory effects translate into clinical benefit. Future research should also distinguish direct CNS effects from peripheral metabolic effects across different GLP-1RAs and identify appropriate patient populations. The effects of age, sex, comorbidities, and concomitant medications on efficacy and safety, as well as potential adverse effects of long-term use, also warrant attention.