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Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions
Shirani A, Stuve O.. Expert opinion on investigational drugs, 2025-11-10
Topic: Brain proteins, microglia and lab models
Introduction This review evaluates the potential of glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs) - first developed for type 2 diabetes and later approved for chronic weight management and additional indications - to be repurposed as neuroprotective and remyelinating therapies in multiple sclerosis (MS). We synthesize emerging pre‑clinical and early clinical evidence, highlight practical barriers to translation, and outline directions for future research. Areas covered In experimental autoimmune encephalomyelitis and toxin-induced demyelination mouse models, GLP-1RAs have been shown to reduce oxidative stress, preserve axonal integrity, suppress microglial and astrocytic activation, and, in some cases, promote remyelination. Early observational data in people with MS suggest GLP-1RAs are well tolerated, provide expected metabolic benefits, and do not exacerbate disease activity. Moreover, signals of reduced neurological impairment and lower dementia incidence in broader diabetic cohorts further support their translational promise. However, to date, there are no published randomized controlled trials of GLP-1RAs in MS. Expert opinion Pre‑clinical and early clinical signals support GLP‑1RAs as promising candidates for neuroprotection in MS, yet definitive evidence of disease‑modifying efficacy is lacking. Practical barriers, such as drug availability and cost, together with unresolved mechanistic questions underscore the need for biomarker‑rich mechanistic trials. Rigorous prospective studies are essential to establish whether GLP‑1RAs can meaningfully alter the trajectory of MS.
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APA 7th
Shirani, A., & Stuve, O. (2025). Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions. Expert opinion on investigational drugs. https://doi.org/10.1080/13543784.2025.2587277
Vancouver
Shirani A, Stuve O. Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions. Expert opinion on investigational drugs. 2025. doi:10.1080/13543784.2025.2587277. PMID: 41196232.
BibTeX
@article{shirani2025-41196232,
author = {Shirani, A. and Stuve, O.},
title = {{Glucagon‑like peptide‑1 receptor agonists in multiple sclerosis: therapeutic promise, challenges, and future directions}},
journal = {Expert opinion on investigational drugs},
year = {2025},
doi = {10.1080/13543784.2025.2587277},
pmid = {41196232},
url = {https://doi.org/10.1080/13543784.2025.2587277}
}
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Key findings
- Moreover, signals of reduced neurological impairment and lower dementia incidence in broader diabetic cohorts further support their translational promise.
- However, to date, there are no published randomized controlled trials of GLP-1RAs in MS.
- Expert opinion Pre‑clinical and early clinical signals support GLP‑1RAs as promising candidates for neuroprotection in MS, yet definitive evidence of disease‑modifying efficacy is lacking.
- Practical barriers, such as drug availability and cost, together with unresolved mechanistic questions underscore the need for biomarker‑rich mechanistic trials.
- Rigorous prospective studies are essential to establish whether GLP‑1RAs can meaningfully alter the trajectory of MS.
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Study details
- Evidence strengthHigh
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Expert opinion on investigational drugs) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41196232) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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2 studies in the library carry the topic tag “multiple-sclerosis”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 2 tagged studies.