To evaluate the impact of GLP-1 agonists on multiple sclerosis (MS) disease progression.

Multiple sclerosis is characterized by immune-mediated demyelination and axonal loss, leading to neurological dysfunction including sensory, motor, and autonomic impairment. An increasing number of adults with multiple sclerosis receive GLP-1 agonists such as semaglutide to treat comorbid diabetes and/or obesity. We hypothesized that GLP-1 agonists would provide neuroprotective and immunomodulatory effects, potentially mitigating MS disease progression.

This retrospective cohort study with used the TriNetX electronic health registry and propensity score matching to compare 7,046 adults with MS receiving oral and injectable GLP-1 agonists (Cohort B) to 7,046 MS patients not receiving the treatment (Cohort A). We analyzed the outcomes over five years, assessing neurological function based upon the Kurtzke Functional Systems Scores (FSS) subscales that comprise the Expanded Disability Status Scale (EDSS): pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral function, and ambulation. We used ChatGPT to produce graphical elements.

Patients not treated with GLP-1 agonists (Cohort A) demonstrated significantly more MS disease progression across all functional categories compared to those receiving GLP-1 treatment (Cohort B). Notably, Cohort A had a higher risk of brainstem dysfunction (4.36% risk difference, p < 0.0001), cerebellar dysfunction (4.54% risk difference, p < 0.0001), and bowel/bladder dysfunction (4.98% risk difference, p < 0.0001).

In this preliminary study, use of GLP-1 agonists correlated with reduced risk of MS disease progression as measured by Kurtzke Functional Systems Scores (FSS). Future research can further explore the potential role of GLP-1 agonists as a therapeutic option to delay disease progression in adults living with MS.