Diabetes, Heart Failure and Beyond: Elucidating the Cardioprotective Mechanisms of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors.

Approximately 5 million individuals in the US are living with congestive heart failure (CHF), with 650,000 new cases being diagnosed every year. CHF has a multifactorial etiology, ranging from coronary artery disease, hypertension, valvular abnormalities and diabetes mellitus. Currently, guidelines by the American College of Cardiology advocate the use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, β-blockers, diuretics, aldosterone antagonists, and inotropes for the medical management of heart failure. The sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of drug that have been widely used in the management of type 2 diabetes mellitus that work by inhibiting the reabsorption of glucose in the proximal convoluted tubule. Since the EMPA-REG OUTCOME trial, several studies have demonstrated the benefits of SGLT2 inhibitors in reducing cardiovascular risk related to heart failure. While the cardiovascular benefits could be explained by their ability to reduce weight, improve glycemic index and lower blood pressure, several recent trials have suggested that SGLT2 inhibitors exhibit pleiotropic effects that underlie their cardioprotective properties. These findings have led to an expansion in preclinical and clinical research aiming to understand the mechanisms by which SGLT2 inhibitors improve heart failure outcomes.