Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms

Cardiovasc Diabetol. 2022 Nov 15;21(1):242. doi: 10.1186/s12933-022-01686-3.

Abstract

Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood-brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.

Keywords: GLP-1; Glucagon-like peptide-1 receptor agonists; Mechanisms; Neuroprotection; Stroke.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / chemically induced
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hyperglycemia* / chemically induced
  • Hypoglycemic Agents / adverse effects
  • Stroke* / chemically induced
  • Stroke* / prevention & control

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents