Rights statement: The final, definitive version of this article has been published in the Journal, Journal of Cerebral Blood Flow and Metabolism, 41 (1), 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/
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Glucagon like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke
T2 - a systematic scoping review
AU - Maskery, M.P.
AU - Holscher, C.
AU - Jones, S.P.
AU - Price, C.I.
AU - Strain, W.D.
AU - Watkins, C.L.
AU - Werring, D.J.
AU - Emsley, H.C.A.
N1 - The final, definitive version of this article has been published in the Journal, Journal of Cerebral Blood Flow and Metabolism, 41 (1), 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/
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 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.
AB - 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.
KW - Acute stroke
KW - animal models
KW - clinical trials
KW - neuroprotection
KW - reperfusion
U2 - 10.1177/0271678X20952011
DO - 10.1177/0271678X20952011
M3 - Journal article
VL - 41
SP - 14
EP - 30
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 1
ER -