Glucagon-like peptide-1 receptor Agonist (GLPI-RA) for plaque buRden improveMent in Diabetic patients with Acute coronary syndrome — ARMYDA-10 randomized study
Progetto 4.1 Abstract Beneficial effects of glucagon-litre peptide-1 receptor agonists (GLP-lRAs)
have been consistently reported in cardiovascular outcome trials on diabetic patients with or at risk of cardiovascular disease. GLP-lRas decrease blood glucose levels and glycated hemoglobin (HbAlc) by stimulating glucose- dependent insulin secretion and reducing glucagon secretion, resulting in decreased gastric emptying, appetite, lipids, blood pressure, and weight. Notably, GLP-lRAs provided cardiovascular protection, regardless of glucose control, by reducing the risk of myocardial infarction and stroke. Such effects might derive from protective effects on atherosclerotic plaques, possibly mediated by reduced oxidative stress, inflammation, endothelial dysfunction, and platelet aggregation.
Based on these assumptions, we hypothesized that using GLP-lRAs decreases progression and improves stabilization of coronary plaques in diabetic patients admitted for acute coronary syndrome (ACS). The overall project aim is to identify the determinants and pathophysiological mechanisms underlying the progression and stabilization of coronary plaques in patients treated with oral administration of semaglutide.
The project will involve 5 Universities in a inultilevel research collaboration, including clinical and in vivo analysis. We will use a clinical trial approach to evaluate the molecular effect of sernaglutide. Patients with diabetes and ACS will be randomized to the use of semaglutide vs placebo on top of optimal medical therapy. Demographic and clinical data will be evaluated and collected in a database, then in vivo experiments will be implemented. In particular, the effect of semaglutide will be investigated, comparing 1) treated- vs control- and 2) baseline- vs after treatment- samples, through clinical endpoints and in vivo experiments (endothelial function, platelet function, thrombin generation, lipid profile, oxidative stress profile, inflammatory and metalloproteases profile, extracellular vesicles (EVs) characterization and omics analysis).
Increasing knowledge on the determinants and pathophysiological
mechanisms underlying the progression and stabilization of coronary plaques in patients treated with semaglutide may lead to 1) identify new markers of coronary plaque progression; 2) examine the protective role of semaglutide, and 3) provide an alternative therapeutic approach to coronary plaque atherosclerosis stabilization and regression.