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Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Maskery, MP; Holscher, C; Jones, SP; Price, CI; Strain, WD; Watkins, CL; Werring, DJ; (2020) Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review. Journal of Cerebral Blood Flow & Metabolism 10.1177/0271678X20952011. (In press). Green open access

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Abstract

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.

Type: Article
Title: Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/0271678X20952011
Publisher version: https://doi.org/10.1177/0271678X20952011
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Acute stroke, animal models, clinical trials, neuroprotection, reperfusion
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10111514
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