{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:00:40Z","timestamp":1792299640370,"version":"4.4.0"},"reference-count":96,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Reperfusion therapies for ischemic stroke are a cornerstone of acute treatment, though only available for a subset of patients due to a narrow time window. Other supplementary treatment is warranted, as only half of the patients reach functional independence. GLP-1 RA (glucagon-like peptide-1 receptor agonists) are associated with decreased cardiovascular disease, mainly driven by reduced stroke risk, and have gained interest as therapeutic agents for stroke recovery in experimental stroke models. This review aims to evaluate the current data on the effect and safety of GLP-1 RA in nondiabetic patients with ischemic stroke and in animal models of cerebral ischemia. We will describe its potential neuroprotective mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>On June 20, 2024, keyword-based literature searches were conducted in PubMed and Embase and repeated on March 6, 2025. Records evaluating GLP-1-based therapies in animals and patients with ischemic stroke who did not have diabetes were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>In total, 35 studies, 31 preclinical and 4 clinical, applying 9 different GLP-1 therapies were reviewed. GLP-1 RA improved functional outcome and induced a marked infarct volume reduction compared with vehicle (placebo) in preclinical animal stroke models. The proposed mechanisms include reduced oxidative stress, hypoxia-triggered cell death, and inflammatory response following acute ischemic stroke. Despite these neuroprotective effects observed in stroke models, evidence for improved clinical outcomes in humans remains limited. Recent randomized trials have not shown a significant effect on stroke incidence or neurological recovery in patients without diabetes who are treated with GLP-1 RA. GLP-1 RA appears safe and well-tolerated in both acute and chronic settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>GLP-1 RA improves functional outcome and reduces infarct volume in preclinical animal stroke models without diabetes. Translating these promising preclinical findings into clinical benefits remains a key challenge and a critical opportunity for future research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.053075","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:00:15Z","timestamp":1763632815000},"page":"415-437","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["GLP-1 Receptor Agonists as Treatment of Nondiabetic Ischemic Stroke: A Systematic Review and Meta-Analysis"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3333-7680","authenticated-orcid":true,"given":"Michael Knudsen","family":"Michaelsen","sequence":"first","affiliation":[{"name":"Department of Neurology (M.K.M., C.Z.S., R.A.B.), Aarhus University Hospital, Denmark."},{"name":"Department of Clinical Medicine (M.K.M., K.R.D., J.B.L., C.Z.S., R.A.B.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-2741","authenticated-orcid":true,"given":"Kim Ryun","family":"Drasbek","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine (M.K.M., K.R.D., J.B.L., C.Z.S., R.A.B.), Aarhus University, Denmark."},{"name":"Center of Functionally Integrative Neuroscience (K.R.D.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-7179","authenticated-orcid":true,"given":"Jan Brink","family":"Valentin","sequence":"additional","affiliation":[{"name":"Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry (J.B.L.), Aarhus University Hospital, Denmark."},{"name":"Department of Clinical Medicine (M.K.M., K.R.D., J.B.L., C.Z.S., R.A.B.), Aarhus University, Denmark."},{"name":"Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Denmark (J.B.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-0612","authenticated-orcid":true,"given":"Mads","family":"Svart","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center Aarhus (M.S.), Aarhus University Hospital, Denmark."},{"name":"Department of Internal Medicine, Horsens Regional Hospital, Denmark (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie Brogaard","family":"Larsen","sequence":"additional","affiliation":[{"name":"Thrombosis and Haemostasis Research Unit, Department of Clinical Biochemistry (J.B.L.), Aarhus University Hospital, Denmark."},{"name":"Department of Clinical Medicine (M.K.M., K.R.D., J.B.L., C.Z.S., R.A.B.), Aarhus University, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4210-0523","authenticated-orcid":true,"given":"Christina","family":"Kruuse","sequence":"additional","affiliation":[{"name":"Copenhagen Neuroinjury and Rehabilitation Research Center, Department of Brain and Spinal Cord Injury, Copenhagen University Hospital Rigshospitalet, Denmark (C.K.)."},{"name":"Institute for Clinical Medicine, Copenhagen University (C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1363-0266","authenticated-orcid":true,"given":"Claus Ziegler","family":"Simonsen","sequence":"additional","affiliation":[{"name":"Department of Neurology (M.K.M., C.Z.S., R.A.B.), Aarhus University Hospital, Denmark."},{"name":"Department of Clinical Medicine (M.K.M., K.R.D., J.B.L., C.Z.S., R.A.B.), Aarhus University, 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