Sodium-Glucose Cotransporter-2 Inhibition in Type 2 Diabetes Mellitus: A Review of Large-Scale Cardiovascular Outcome Studies and Possible Mechanisms of Benefit.

Cardiovascular (CV) disease remains the leading cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). However, conventional antihyperglycemic medications seem to have minimal effect on lowering CV risk despite achieving excellent reductions in glycated hemoglobin A1c and associated reductions in microvascular risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as noteworthy antihyperglycemic agents with concomitant CV and renal protection in T2DM patients. In this comprehensive review, we present the key CV findings from major large-scale outcome trials of SGLT2 inhibitors to date. We also review the mechanistic studies that might explain the CV benefits of SGLT2 inhibition in patients with T2DM.