GLP-1 receptor agonists and neuroprotection: prevent or modify neurodegenerative diseases?
DOI:
https://doi.org/10.66476/mf.v3n2.7537Keywords:
Glucagon-Like Peptide-1 Receptor, Neurodegenerative Diseases, Dementia, Parkinson Disease, Primary Health CareAbstract
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show neuroprotective effects in preclinical models and are associated with less dementia in observational studies. It is unknown whether they prevent or modify neurodegenerative diseases.
Methods: Narrative review of the literature since 2020, searching MEDLINE and Europe PMC (August and October 2026), with title and abstract screening.
Results: Sixty-one sources were identified. Prevention data come mainly from people with type 2 diabetes. Observational studies associated GLP-1 RAs with lower dementia risk, with HRs of 0.30 without an active comparator and confidence intervals including 1 with an active comparator. Among trials, not designed to assess cognition, a meta-analysis of 23 studies found less dementia or cognitive impairment with GLP-1 RAs (OR 0.55); REWIND and GRADE showed no clear differences. In Parkinson's disease, most studies showed lower risk (HR 0.68 to 0.81), but two cohorts found no difference. For disease modification, evoke and evoke+ did not slow Alzheimer's disease; in Parkinson's disease, two phase 2 trials were positive, but the phase 3 exenatide trial and NLY01 were negative, and the phase 3 trial carries an unresolved expression of concern. For tirzepatide (dual GIP/GLP-1 agonist) only observational studies exist.
Conclusions: GLP-1 RAs are supported for their metabolic indications. Evidence for preventing neurodegenerative diseases is insufficient and inconclusive; for modifying Alzheimer's disease it is negative, and in Parkinson's disease, discordant. In family medicine they should be prescribed for their indication, without promising brain protection.
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