The cardiovascular (CV) safety of glucagon-like peptide 1 (GLP-1) receptor agonists has been established in robust cardiovascular outcomes trials (CVOTs) in patients with type 2 diabetes at high CV risk. The GLP-1 receptor agonists liraglutide, dulaglutide, and injectable semaglutide demonstrated a significant CV benefit in these trials and now have indications to reduce the risk of major adverse CV events, including CV death, myocardial infarction, and stroke in adult patients with type 2 diabetes and established cardiovascular disease or high CV risk (dulaglutide). The dipeptidyl peptidase 4 inhibitors have also demonstrated CV safety in dedicated CVOTs but have not been associated with any CV benefit. Guidelines for the treatment of type 2 diabetes have evolved from a glucocentric focus to one that now focuses on reducing overall CV risk by personalizing therapy and using drugs such as GLP-1 receptor agonists with proven CV benefits.