Role of glucagon-like peptide-1 receptor agonists in type 2 diabetes-associated atherosclerosis: from vascular mechanism to omics-based biomarkers and imaging

Atherosclerosis is a chronic metabolic disorder driven by endothelial dysfunction, inflammation, oxidative stress, and progressive plaque remodeling; processes amplified in type 2 diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), originally developed for glycemic control, have emerged as modulators of vascular biology with potential anti-atherosclerotic effects. This review synthesizes evidence across key mechanistic domains, including endothelial dysfunction, inflammatory signaling, oxidative stress pathways, plaque biology, extracellular matrix remodeling, and immune-cell modulation. GLP-1RAs reduce circulating inflammatory mediators, suppress NLRP3 inflammasome activity, and lower oxidized LDL, thereby limiting the initiation of vascular injury. At the endothelial level, they enhance nitric oxide (NO) availability, decrease NOX-derived oxidative stress, and reduce adhesion molecule expression, collectively improving vascular function. Within plaques, GLP-1RA signaling alters macrophage behavior, promotes cholesterol efflux, and modulates metalloproteinase activity, suggesting potential effects on plaque composition and stability. Emerging biomarker platforms, including microRNA profiling and high-throughput proteomic and lipidomic signatures, together with advanced imaging approaches such as MRI-visible nano-GLP-1RA formulations, provide novel tools to monitor molecular and spatial drug effects <i>in vivo</i>. Collectively, these findings position GLP-1RAs as modulators of atherosclerotic disease beyond glycemic control, with integrated effects spanning systemic immunometabolism and plaque biology. By linking mechanistic insights with emerging imaging and multi-omics technologies, this review highlights a path toward biomarker-driven patient stratification and precision cardiovascular therapeutics, redefining how vascular risk is assessed and treated in metabolic disease.