Endothelial Dysfunction and Platelet Hyperaggregation in Type 2 Diabetes Mellitus: The Era of Novel Anti-diabetic Agents

Background: The incidence of diabetes mellitus (DM) is ever-increasing and along with its microvascular and macrovascular complications, it is associated with a high morbidity and mortality burden globally. Major components of diabetes pathophysiology include glucotoxicity, lipotoxicity and insulin resistance, disturbing the vascular wall integrity and leading to endothelial dysfunction and platelet hyper aggregation. Objective: This review aims to identify and summarize the effect of novel anti-diabetic agents (glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter -2 inhibitors) on endothelial (EF) and platelet function (PF) and evaluate the consistency with the results of cardiovascular outcomes studies. Methods: We performed a structured search of the PubMed database for peer-reviewed research of the literature between 1981 and 2020 regarding the effect of DM and novel antidiabetic agents on EF and PF. Results: We analyzed data regarding the effect of novel anti-diabetic agents on EF and PF as well as the pathophysiological interplay between DM, PF, and EF. The available studies use different methods to evaluate these outcomes and the results of different studies are rather conflicting as a result of different study designs, combinations of drugs tested, small study samples and patient population heterogeneity. Conclusion: The currently available data do not unequivocally support a consistent effect of novel antidiabetic agents on EF and PF. Further study is required ideally for the validation of the results with clinical outcomes.