GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers.
GLP-1 receptor agonists may reduce the risk of stroke in individuals with type 2 diabetes, but the clinical significance of these findings requires further investigation.
Where it sits
this study against the rest of the semaglutide corpusSummary and findings
This narrative review evaluates the cerebrovascular protective effects of GLP-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM). It synthesizes data from cardiovascular outcome trials, meta-analyses, and mechanistic studies, focusing on stroke prevention. The review highlights relative risk reductions for stroke ranging from 15% to 39%, depending on the agent and patient characteristics.
Abstract
Objectives To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. Methods A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. Results GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. Conclusion GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management.