Revista de Medicina Familiar y Comunidad · Oct 30, 2026
GLP-1 receptor agonists and neuroprotection: prevent or modify neurodegenerative diseases?
By Marmori AIM, Dos Reis YLE, Miranda LR et al.
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (AR-GLP-1) show neuroprotective effects in preclinical models and are associated with less dementia in observational studies. Whether they prevent or modify neurodegenerative diseases is unknown. METHODS: Narrative review of the literature since 2020, with searches in MEDLINE and Europe PMC (August and October 2026), with title and abstract screening. RESULTS: A total of 61 sources were identified. Prevention data come mainly from people with type 2 diabetes. Observational studies associated AR-GLP-1 with a lower risk of dementia, with an HR of 0.30 without an active comparator and intervals that included 1 with an active comparator. Among trials, which were not designed to assess cognition, a meta-analysis of 23 studies found less dementia or cognitive impairment with AR-GLP-1 (OR 0.55); REWIND and GRADE showed no clear differences. In Parkinson's disease, most studies showed a lower risk (HR 0.68 to 0.81), but two cohorts found no difference. Regarding 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 has an unresolved expression of concern. For tirzepatide (a dual GIP/GLP-1 agonist), there are only observational studies. CONCLUSIONS: AR-GLP-1 have supporting evidence for their metabolic indications. For preventing neurodegenerative diseases, the evidence is insufficient and inconclusive; for modifying Alzheimer's disease, it is negative, and in Parkinson's disease, it is discordant. In family medicine, they should be prescribed for an indication without promising brain protection.