Reported effects of glucagon-like peptide-1 receptor agonists in multiple sclerosis: a scoping review of preclinical and clinical studies

Abstract Background Multiple sclerosis (MS) is a neuroinflammatory and neurodegenerative disease whose available therapies target peripheral immunity, leaving neurodegeneration unaddressed. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown neuroprotective and anti-inflammatory effects in preclinical models of neurodegeneration, although phase 3 trials in Alzheimer’s and Parkinson’s disease were negative. This scoping review aimed to map the extent and nature of available evidence on GLP-1 RAs in MS. Methods This study was guided by the Joanna Briggs Institute methodology and the PRISMA-ScR checklist. PubMed/MEDLINE, Embase, Scopus, Web of Science, and LILACS were last searched in October 2026, without time or language restrictions. Eligibility followed a Population-Concept-Context framework: humans with MS or preclinical/in vitro demyelination models, any GLP-1 RA, any setting. Screening was performed blindly and independently by three reviewers, with a fourth resolving existing conflicts. Data were charted and summarized narratively. Results Of 396 unique records screened, 14 studies were included: ten preclinical and four clinical. Preclinical studies, although heterogeneous in models, agents, doses, and outcomes, reported beneficial effects (reduced disease severity or delayed onset, with anti-inflammatory and neuroprotective effects) in nine of ten studies. Clinical evidence was centered on safety, tolerability, and metabolic outcomes; the single randomized trial (n = 28) showed no detectable effect on neurodegeneration biomarkers or imaging. Conclusions GLP-1 RAs are promising candidates for further investigation in MS, but their disease-modifying role in humans remains unproven. Blood–brain barrier penetrance, dose translation, and control of food intake are relevant considerations for adequately powered, biomarker-guided trials.