The Role of Nano-systems in the Delivery of Glucose-lowering Drugs for the Pre-emption and Treatment of Diabetes-associated Atherosclerosis

Diabetes is one of the most prevalent diseases worldwide. In recent decades, type-2 diabetes has become increasingly common, particularly in younger individuals. Diabetes leads to many vascular complications, including atherosclerosis. Atherosclerosis is a cardiovascular disease characterized by lipid-rich plaques within the vasculature. Plaques develop over time, restricting blood flow; and can therefore be the underlying cause of major adverse cardiovascular events, including myocardial infarction and stroke. Diabetes and atherosclerosis are intrinsically linked. Diabetes is a metabolic syndrome which accelerates atherosclerosis and increases the risk of developing other co-morbidities, such as Diabetes-associated Atherosclerosis (DAA). Gold-standard anti-diabetic medications focus on attenuating hyperglycemia. Though recent evidence suggests that glucose-lowering drugs may have broader applications, beyond diabetes-management. This review mainly evaluates the role of glucagon-like peptide-1 receptor agonists (GLP-1 RA), such as Liraglutide and Semaglutide in DAA. These drugs mimic gut hormones (incretins), which inhibit glucagon secretion whilst stimulating insulin secretion, thus improving insulin sensitivity. This facilitates delayed gastric emptying and increased patient satiety; hence they are also indicated for the treatment of obesity. GLP-1 RAs have significant cardioprotective effects, including decreasing low-density lipoprotein (LDL)-cholesterol and triglycerides levels. Liraglutide and Semaglutide have specifically been shown to decrease cardiovascular risk. Liraglutide has displayed a myriad of anti-atherosclerotic properties, with the potential to induce plaque regression. This review aims to address how glucose-lowering medications can be applied to treat diseases other than diabetes. We specifically focus on how nanomedicines can be used for the site-specific delivery of anti-diabetic medicines for the treatment of diabetes-associated atherosclerosis.