GLP-1 receptor agonists in multiple sclerosis: a systematic review of preclinical and clinical evidence

This systematic review of 15 studies found that GLP-1 receptor agonists reduce clinical severity in animal models of multiple sclerosis through several anti-inflammatory mechanisms. Human evidence, from two small cohorts and pharmacovigilance data, shows metabolic benefits without worsening neurologic disability, but no randomised trials have been done.

Systematic review. Population: Patients with MS, EAE/cuprizone animal models, and case reports. Sample size: 15 studies. Interventions: GLP-1 receptor agonists; Semaglutide; Dulaglutide; Liraglutide.

Fifteen studies met inclusion criteria: eight preclinical (six EAE, two cuprizone), four human observational, and three narrative-context. GLP-1RAs reduced clinical severity in EAE via AMPK/SIRT1 activation, NLRP3 suppression, Th1/Th17 modulation, and microglial deactivation. In two human cohorts (n=109), use was associated with BMI reduction and vitamin D augmentation without changes in EDSS or relapse rate. Pharmacovigilance reporting odds ratios were inverse for semaglutide (0.238), dulaglutide (0.165), and liraglutide (0.161). Mendelian randomization found no causal association between GLP-1R activation and MS susceptibility.

Researchers working on liraglutide will find this the first registered, PRISMA-compliant synthesis summarising its effects in MS models and human observational data. Liraglutide showed an inverse reporting odds ratio (0.161), suggesting a potential signal worth investigating. This paper does not establish causal clinical benefit in MS, and its human results are observational with moderate-to-high risk of bias.

Key findings

• GLP-1 receptor agonists consistently reduced clinical severity in EAE models.
• In two human cohorts (n=109), GLP-1RA use was associated with BMI reduction and vitamin D augmentation without change in EDSS or relapse rate.
• A NARCOMS survey (n=4181) documented 7.4% ever-use of GLP-1RAs.
• Pharmacovigilance showed inverse reporting odds ratios: semaglutide 0.238, dulaglutide 0.165, liraglutide 0.161.
• Mendelian randomization found no causal association between GLP-1R activation and MS susceptibility.
• Most preclinical studies were high risk of bias; human studies were moderate to high risk.

Limitations

• Most preclinical studies were high risk of bias.
• Human studies were moderate to high risk of bias.
• Human evidence is limited to observational cohorts and surveys, with no randomised controlled trials.
• The review is restricted by the small number of studies and heterogeneity across animal models and human designs.

The record

• Journal: Multiple sclerosis and related disorders 113: 107388
• Published: 2026-07-10
• PMID: 42470876 — DOI: 10.1016/j.msard.2026.107388
• MeSH terms: Animals, Humans, Multiple Sclerosis, Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide
• Author countries: Pakistan, USA

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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