GLP-1 Receptor Agonists Linked to Improved Physical Activity in Multiple Sclerosis

Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in people with multiple sclerosis (MS) was associated with significantly greater physical activity and improvements across several patient-reported symptom domains, according to new data presented at the 2026 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting in Charlotte, North Carolina.¹

The retrospective single-center cohort study adds to a growing body of evidence examining whether GLP-1 therapies, commonly prescribed for obesity and type 2 diabetes, may also influence neurologic symptoms, inflammation, and functional outcomes in MS.^2,3 Investigators from the University of Washington noted that GLP-1 receptor agonists have biologically plausible effects on neuroinflammation, fatigue, balance, mood, and energy regulation, all of which may contribute to disease burden in MS.

“GLP-1 RA initiation in [people with MS] was associated with greater physical activity and improvements in several [patient-reported outcome] domains, further supporting the association of metabolic health with MS outcomes and the need for prospective studies to validate these findings,” study authors, including Shuvro Roy, MD, an MS neurologist, University of Washington, wrote.¹

In the analysis, investigators evaluated 70 patients with MS who initiated GLP-1 therapy and had available clinical and patient-reported outcome (PRO) data both before treatment initiation and at least 6 months afterward. Participants had a mean age of 51.3 years, 87% were women, and the median Expanded Disability Status Scale (EDSS) score was 2.5 (IQR, 1.0-4.5). Mean follow-up occurred approximately 7.2 months after treatment initiation.

Researchers assessed self-reported moderate-to-vigorous physical activity, as well as SymptoMScreen PRO scores spanning 13 neurologic symptom domains. Physical activity increased substantially after initiation of GLP-1 therapy, rising from 52.3 minutes per week at baseline to 115.7 minutes per week following treatment, representing a mean increase of 65.8 minutes weekly (95% CI, 48.5-83.0; P <.001).

Several symptom domains also showed statistically significant improvements after treatment initiation. Anxiety scores improved by 0.65 points, while bowel dysfunction, bladder dysfunction, and sensory symptoms improved by 0.52, 0.64, and 0.54 points, respectively (all P <.001). Smaller but statistically significant improvements were additionally observed for body pain, spasticity, dizziness, and vision-related symptoms.

Investigators did not observe statistically significant changes in walking ability, hand function, fatigue, cognition, or depression. Still, the findings continue to build momentum around the potential neurologic relevance of GLP-1 therapies in MS care, particularly as obesity and metabolic dysfunction become increasingly recognized contributors to disability progression and inflammatory burden in the disease.²

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Interest in GLP-1 therapies in MS has grown considerably over the past year. At the 2025 American Academy of Neurology (AAN) Annual Meeting, a separate retrospective TriNetX analysis comparing 7046 adults with MS treated with GLP-1 agonists against a propensity-matched untreated cohort found lower rates of disease progression across multiple Expanded Disability Status Scale functional domains among patients receiving GLP-1 therapies. That analysis showed lower risks of brainstem dysfunction, cerebellar dysfunction, and bowel/bladder impairment over a 5-year follow-up period in the GLP-1-treated cohort.³

The expanding interest in GLP-1 therapies also follows broader research exploring metabolic interventions in MS. Prior studies have demonstrated that bariatric surgery in people with MS can lead to significant weight reduction without worsening neurologic disability or ambulation outcomes, while also improving vitamin D levels, a factor previously associated with lower relapse risk and reduced MRI lesion activity.^2,4,5

Although the CMSC analysis provides encouraging early signals, investigators acknowledged several important limitations, including its retrospective design, relatively small sample size, and lack of a comparator control group.1 Additional subgroup analyses examining body mass index changes, indications for GLP-1 use, and adjusted PRO outcomes were expected to be presented separately during the meeting.¹

Prospective controlled studies will likely be needed to determine whether GLP-1 receptor agonists exert direct neuroprotective or immunomodulatory effects in MS, or whether observed benefits are primarily mediated through improvements in metabolic health, weight reduction, and increased physical activity.

Click here for more CMSC 2026 coverage.

REFERENCES
1. Heward KD, Hou G, Simmons SB, et al. Glucagon-Like Peptide-1 Receptor Agonists Use Associated With Greater Physical Activity and Improved Patient-Reported Outcomes in Multiple Sclerosis: A Single-Site Retrospective Cohort Study. Presented at: 2026 CMSC Annual Meeting; May 27-30, 2026; Charlotte, NC. Abstract QOL25.
2. Balshi A, Bove R, von Geldern G, et al. Glucagon-like peptide-1 receptor agonist safety and efficacy in multiple sclerosis: a review of emerging evidence. Mult Scler Relat Disord. 2025;91:105864. doi:10.1016/j.msard.2025.105864
3. The Impact of GLP-1 Agonists on Multiple Sclerosis Disease Progression. Presented at: 2025 American Academy of Neurology Annual Meeting; April 5-9, 2025; San Diego, CA. Accessed May 27, 2026. AAN Abstract Listing
4. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
5. Mowry EM, Krupp LB, Milazzo M, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67(5):618-624. doi:10.1002/ana.21972