Expanding Applications of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) with Attention to Euglycemic Ketoacidosis (Eka) for No Diabetic History

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have their origins in phlorizin, which was discovered in apple bark in 1835. SGLT-2i has been effective in treating type 2 diabetes (T2D), chronic kidney disease (CKD), and cardiovascular disease (CVD). In heart failure, cardiac tissue becomes less able to metabolize glucose and fatty acids, and begins to rely more on ketone bodies. Subjects with heart failure with reduced ejection fraction showed higher cardiac output at rest and lower filling pressures, cardiac volumes, and NT-proBNP levels when treated with ketone esters. As an adverse effect of SGLT-2i, euglycemic ketoacidosis (eKA) has been reported and requires careful attention.