Cardiovascular Outcome Trials with Glucose-Lowering Drugs

Purpose of Review This review summarizes recent cardiovascular outcome trials (CVOTs) with glucose-lowering drugs. Recent Findings The majority of recent CVOTs with glucose-lowering drugs have tested dipeptidyl peptidase-4 inhibitors (DPP4-i), glucagon-like peptide-1 receptors agonists (GLP1-RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), but studies have also been performed with other agents including thiazolidinediones and insulin. All CVOTs with DPP4-I, GLP1-RA, and SGLT2-i have demonstrated the cardiovascular (CV) safety of these agents compared to usual care. However, certain GLP1-RAs (liraglutide, subcutaneous semaglutide, albiglutide, dulaglutide) and SGLT2-i (empagliflozin, canagliflozin) have demonstrated a CV benefit, showing significant reductions in composite cardiovascular outcomes. Furthermore, all SGLT2-i also significantly decreased the risk for hospitalization for heart failure. Results from these studies have altered clinical guidelines worldwide and have resulted in new indications for some glucose-lowering drugs. In patients with T2D and high risk for CVD, GLP-1RA or SGLT2-i with proven cardiovascular benefit are recommended, irrespective of glycemic control.