Glucagon-like peptide-1 receptor agonists reduce cardiovascular risk through multifactorial indirect and direct antiatherogenic mechanisms, including plaque stabilization.
What are the direct and indirect mechanisms underlying the antiatherosclerotic effects of GLP-1 RAs?
GLP-1 RAs reduce cardiovascular risk through a combination of indirect systemic benefits and direct vascular antiatherogenic actions, though human mechanistic data remains limited.
Cardiovascular diseases (CVD) remain the leading cause of global mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce major adverse cardiovascular events in patients with and without Type 2 diabetes, offering benefits that extend beyond glycemic control. This review summarizes proposed multifactorial mechanisms underlying these effects, categorizing them into indirect and direct pathways. Indirect mechanisms include, among others, improvements in lipid metabolism, insulin sensitivity, blood pressure, and renal protection. In addition to the previously described effects, GLP-1 RAs may exert direct vascular actions, including anti-inflammatory actions, suppression of oxidative stress, improved endothelial function, modulation of macrophage polarization, reduction of adhesion molecule expression, and inhibition of vascular smooth muscle cell proliferation and migration, as well as downregulation of matrix metalloproteinases and plasminogen activator inhibitor-1. Collectively, these processes contribute to plaque stabilization and reduced atherothrombotic risk. Although clinical evidence for cardiovascular risk reduction of GLP-1 RAs is robust, mechanistic insights are predominantly derived from preclinical or animal models. Therefore, further functional studies in humans are warranted to clarify the direct antiatherogenic actions of GLP-1 RAs.
Zawadzki et al. (Thu,) conducted a review in Cardiovascular diseases. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was evaluated. Glucagon-like peptide-1 receptor agonists reduce cardiovascular risk through multifactorial indirect and direct antiatherogenic mechanisms, including plaque stabilization.