Advances in Cardiovascular Pharmacotherapy. III. Sodium-Glucose Cotransporter Type 2 Inhibitors, Part 1: Efficacy in...

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of oral hypoglycemic medications used for the treatment of type 2 diabetes mellitus. Cardiovascular safety testing of these drugs unexpectedly revealed that they improve outcomes in patients with heart failure, findings that were subsequently confirmed regardless of diabetes status in randomized clinical trials. The widespread application of SGLT2 inhibitors over the past 5 years is a groundbreaking advance in heart failure pharmacotherapy. This is especially the case in those with heart failure with preserved ejection fraction, whose treatment was previously limited to symptom mitigation and lifestyle modification. Encouraging results from additional clinical trials supporting the use of these drugs in myocardial infarction have also emerged. However, these data are not as robust as those related to heart failure. This two-part article provides an overview of SGLT2 inhibitor cardiovascular pharmacology. The first part briefly describes the physiology of SGLT2, including its role in glucose regulation and the impact of its inhibition in type 2 diabetes; discusses the safety trials indicating that these drugs had previously unrecognized advantages in patients with heart failure and atherosclerotic cardiovascular disease; and reviews the major clinical trials and their substudies demonstrating the efficacy of these medications across heart failure phenotypes and in myocardial infarction.