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

Maskery, M.P. and Holscher, C. and Jones, S.P. and Price, C.I. and Strain, W.D. and Watkins, C.L. and Werring, D.J. and Emsley, H.C.A. (2020) Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke:a systematic scoping review. Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X

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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.

Item Type:
Journal Article
Journal or Publication Title:
Journal of Cerebral Blood Flow and Metabolism
Additional Information:
The final, definitive version of this article has been published in the Journal, Journal of Cerebral Blood Flow and Metabolism, ? (?), 2020, © SAGE Publications Ltd, 2020 by SAGE Publications Ltd at the Journal of Cerebral Blood Flow and Metabolism page: https://journals.sagepub.com/home/jcb on SAGE Journals Online: http://journals.sagepub.com/
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2800/2808
Subjects:
ID Code:
148281
Deposited By:
Deposited On:
16 Oct 2020 13:20
Refereed?:
Yes
Published?:
Published
Last Modified:
31 Oct 2020 07:21