Clinical application of glucagon-like peptide-1 receptor agonists in cardiovascular disease: lessons from recent clinical cardiovascular outcomes trials

Abstract Recent clinical trials investigating cardiovascular (CV) safety of newer antidiabetic agents have been rapidly and largely changing the landscape of diabetes care and providing highly important clinical information on decision-making regarding the choice of antidiabetic agents. Similar to the sodium-glucose cotransporter 2 (SGLT2) inhibitors, some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have also demonstrated a marked risk reduction in major adverse CV events (MACE) in patients with type 2 diabetes at high risk of CV events. However, the two classes of agents differ largely in their pharmacological modes of action on glucose-lowering and CV parameters. Furthermore, CV benefits on individual components of MACE and other outcomes, including heart failure (HF), appear to differ partly between the two classes. Specifically, improvement of overall CV outcomes was likely driven by reduction in HF-related events in trials investigating SGLT2 inhibitors, and by reduction in atherosclerotic events in those investigating GLP-1RAs. This difference in CV benefit observed in the trials has important clinical implications regarding how to use the two classes of agents and how to identify suitable patients to obtain the best benefit from each class during routine diabetes care, possibly leading to a treatment plan tailored to an individual patient’s CV risk and clinical condition. At this stage, however, we cardiologists may overlook such differences and may be unfamiliar with GLP-1RAs specifically. Herein, we highlight the potential benefits of GLP-1RAs on CV parameters observed in recent CV outcomes trials and further discuss clinical application of GLP-1RAs in CV medicine