Narrative Review Synthesizes Evidence on GLP-1 Receptor Agonists' Safety, Efficacy, and Neuroprotective Potential in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease often accompanied by comorbidities like type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for T2DM and obesity, have shown anti-inflammatory and neuroprotective properties in preclinical models. Given the increasing use of GLP-1RAs in patients with MS for metabolic comorbidities, and the lack of a formal synthesis of evidence, there's a growing need to understand their broader impact on MS disease course.

This topical narrative review synthesized research on GLP-1RAs in Multiple Sclerosis (MS) patients. Researchers conducted a comprehensive search across PubMed.gov and Google Scholar for articles published between January 1, 2005, and September 17, 2026. The search strategy combined terms like glucagon‐like peptide‐1 receptor agonist, exenatide, semaglutide, and liraglutide with MS-related keywords. Article selection, though not systematic, adhered to PRISMA guidelines for identifying relevant studies in English.

The review synthesized existing literature regarding GLP-1RAs' safety, tolerability, and efficacy for approved indications in Multiple Sclerosis (MS) patients, alongside their potential to attenuate MS disease progression. It highlighted preclinical evidence suggesting GLP-1RAs possess anti-inflammatory and neuroprotective properties, which could translate into therapeutic benefits for MS.

The review aimed to update clinicians on the current knowledge and research regarding GLP-1RAs in pwMS, addressing both comorbidity management and potential disease-modifying effects. The synthesis covered various GLP-1RAs, including semaglutide and liraglutide, examining their impact on MS-related metabolic comorbidities and exploring their direct effects on neuroinflammation and demyelination pathways.