GLP-1 receptor agonists lack evidence for routine use as acute neuroprotective therapy in acute ischemic stroke, but should be considered for secondary prevention in established indications.
Does GLP-1RA improve outcomes in acute ischemic stroke and secondary stroke prevention?
While preclinical data suggests neuroprotective effects of GLP-1RAs in acute ischemic stroke, clinical application remains limited to secondary prevention pending dedicated stroke trials.
Background Acute ischemic stroke (AIS) is a leading cause of death and disability. Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce atherosclerotic events in type 2 diabetes and obesity, and meta-analyses of cardiovascular outcome trials (CVOTs) suggest a modest reduction in incident stroke. Their safety and efficacy within acute AIS pathways remain uncertain. Methods We conducted a narrative review by searching MEDLINE (PubMed), Cochrane CENTRAL, and ClinicalTrials.gov for studies through January 2026. We included in vitro and animal stroke models, observational studies, randomized controlled trials, and meta-analyses reporting AIS-related outcomes or stroke prevention endpoints with GLP-1RA. Results Experimental models commonly show reduced infarct volume and improved neurological outcomes, with proposed mechanisms including attenuation of excitotoxicity, apoptosis, oxidative stress, neuroinflammation, and blood-brain barrier disruption, alongside signals of angiogenesis and neurogenesis. Translation is limited by heterogeneity of agents, timing, dosing, and routes, and by uncertainty over direct central nervous system versus systemic mediation. CVOTs and meta-analyses support long-term stroke risk reduction, whereas observational studies and small AIS trials mainly inform feasibility, metabolic control, and safety, with efficacy unproven. Ongoing stroke-dedicated trials should define patient selection, exposure–response relationships, and interactions with thrombolysis or thrombectomy, while prospectively incorporating imaging and biomarker endpoints to test mechanisms. Conclusions Current evidence does not support routine GLP-1RA use as an acute neuroprotective therapy in AIS in humans. At present, GLP-1RA should be considered primarily for secondary prevention in patients with established indications, pending dedicated stroke trials clarifying acute safety, optimal timing/dosing, interactions with reperfusion therapies, and functional endpoints.
Samanidou et al. (Wed,) conducted a review in Acute ischemic stroke. GLP-1 Receptor Agonists was evaluated. GLP-1 receptor agonists lack evidence for routine use as acute neuroprotective therapy in acute ischemic stroke, but should be considered for secondary prevention in established indications.