Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and MetabolismSep 21, 2020

Glucagon-like peptide-1 receptor agonists as brain protectors after stroke: a broad review

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

A total of 35 pre-clinical studies support the potential neuroprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in acute ischemic stroke.

GLP-1RAs may reduce infarct volume, apoptosis, oxidative stress, and inflammation in normoglycemic models when administered up to 24 hours after stroke onset.
Increased neurogenesis, angiogenesis, and cerebral blood flow were observed following GLP-1RA treatment.
Improved neurological function and a trend towards increased survival were noted in pre-clinical studies.
Cardiovascular outcome trials indicated a significant reduction in stroke incidence with semaglutide and dulaglutide.
Retrospective studies showed a trend towards neuroprotection associated with GLP-1RAs.
Ongoing prospective clinical trials have initial indicators of favorable safety and tolerability.

Simplified

Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.

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Competing interests

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CH is a named inventor on several patent applications that cover the use of GLP-1RAs for the treatment of neurodegenerative disorders. WDS has received speaker honoraria, conference sponsorship by Astra-Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Colgate Palmolive, Eli Lilly, GlaxoSmithKline, Lundbeck, Menarini, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, and Takeda. He holds research grants from Astra-Zeneca, Novo Nordisk and Novartis.

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Glucagon-like peptide-1 receptor agonists as brain protectors after stroke: a broad review

Abstract

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