Raising the Bar When Assessing Cardiovascular Disease Outcome When Studies with Patients with Type 2 Diabetes Mellitus are Constructed: Revisiting ASCEND

Abstract

The emergence of Type 2 Diabetes Mellitus (T2DM) as a clinical syndrome deviating from rudimentary models including “glucose-insulin” disparities to a clinical syndrome impinged upon hyperactivation of inflammatory-mediated signaling pathways, maladaptive pathophysiological changes, and pleiotropic sequelae has not only changed the nature of discussions regarding diabetes in academic circles, but also the treatment of T2DM clinically. The new challenges faced in preventing the advancement of T2DM coupled with the management of associated chronic disease states have impelled avenues for innovative treatments for T2DM sequelae while also ensuring glycemic control. For example, Sodium-Glucose Transport 2 inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA), in addition to passing mandated Food and Drug Administration (FDA) Cardiovascular Outcome Trials (CVOT), have displayed positive outcomes with respect to cardiorenal considerations in patients with T2DM. Such performances have recently elevated these pleiotropic medications to higher tiers of recommendations by medical societies such as the American Diabetes Association and the American College of Cardiology. Moreover, the tandem of the notion that pleiotropic pharmacotherapeutic options with an expanded understanding of T2DM on the epigenetic, molecular, and cellular domains have galvanized researchers to explore pharmacologic mechanisms in the context of our ever-changing model in T2DM. In this communication, we would like to use lessons from the “Effects of aspirin for primary prevention in persons with diabetes mellitus” (ASCEND) trial to implore aspiring researchers and practitioners to explore, or at least consider external factors of the T2DM patient populous when reporting findings of cardiovascular clinical endpoints for proper context.