ABSTRACT NUMBER: ESOC2026A2308 GLP-1 OR DUAL GIP/GLP-1 RECEPTOR AGONIST IN ACUTE ISCHAEMIC STROKE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF PRE-CLINICAL STUDIES

Abstract Background and aims Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GLP-1/ glucose-dependent insulinotropic polypeptide (GIP) agonists are licensed for the management of diabetes and obesity. This review assesses the neuroprotective effects of these agents in experimental acute ischaemic stroke. Methods Studies were identified through searches in EMBASE, Medline, Web of Science, and Scopus. Data were extracted on infarct volume, functional outcome, mechanisms, and study quality. Meta-analyses (random effects models) are expressed as standardised mean difference (SMD) and weighted mean difference (WMD). Results 46 publications (141 studies) were included, 44 involving GLP-1-based therapies, 1 dual GIP/GLP-1RAs, and 1 both. Compared to control, infarct volume 24-48 hours post-stroke improved in diabetic (SMD -2.61; 95% CI -3.35, -1.87; P < 0.00001) and non-diabetic rodents (SMD-1.90; 95% CI -2.33, -1.46; P < 0.00001). GLP-1RAs improved Day 1 functional outcomes: Rotarod, SMD 1.78, 95% CI -0.27, 3.82; p = 0.09; and Modified Neurological Severity Score 0-18 (mNSS), WMD -1.38, 95% CI -3.35, 0.59, p = 0.17. At 14 days, Rotarod test and mNSS significantly improved in the treatment group, SMD 0.79 (95% CI 0.26, 1.33; p = 0.004) and WMD -2.84 (95% CI -5.28, -0.39; p = 0.02), respectively. Heterogeneity was observed and Egger’s test suggested publication bias ( p<0.001). Conclusions GLP-1RAs reduce experimental stroke infarct volume in diabetic and normoglycaemic animals, and improve short- and long-term functional outcomes. However, further studies using dual GIP/GLP-1RAs, larger animals, females, and those with additional comorbidities and drug co-administration (thrombolysis) are needed Conflict of interest Sara Eltirafi, Harry Keevil, Viswesh Anand and Tim England: Nothing to disclose