The Role of Glucagon-Like Peptide-1 Agonists in the Treatment of Multiple Sclerosis: A Narrative Review

Abstract

Multiple sclerosis (MS) is a chronic, progressive autoimmune disease modulated by autoantibodies that inflame and destroy the myelin sheath encasing neuronal axons, impairing proper axonal conduction and function. Glucagon-like peptide-1 (GLP-1) receptor agonists have been demonstrated to exert anti-inflammatory and neuroprotective effects, making these drugs particularly exciting prospects in the treatment of MS. While the exact mechanism remains unclear, GLP-1 receptor agonists may modulate inflammatory responses by targeting GLP-1 receptors present on immune cells such as macrophages, monocytes, and lymphocytes. In animal models, GLP-1 agonists have been shown to significantly delay the onset and severity of experimental autoimmune encephalopathy symptoms, as well as to increase nerve myelination and brain weight. In further experiments using animal models of nerve crush injury, specimens given GLP-1 agonists reported a significant increase in the rate and density of nerve regeneration compared to controls. Thus, GLP-1 agonists show promise as both prophylactic and symptomatic treatment for MS and may provide further utility in the treatment of other autoimmune, inflammatory, and neurodegenerative conditions.

Keywords: alzheimer’s; diabetes mellitus; glucagon-like peptide-1 agonists; liraglutide; metformin; multiple sclerosis; neurodegenerative disease; obesity; ozempic.

Figure 1. Summary of mechanisms by which GLP-1 agonists offer promising treatment potential in the disease pathogenesis and progression of multiple sclerosis.

GLP-1: Glucagon-like peptide-1; PI3K/AKT: Phosphatidylinositol 3-kinase/protein kinase B; NF-kB: Nuclear factor-kB. Image credits: Kelly R. Sala and Alexandra N. Dicke.