Vasilis Tsimihodimos, Thalia Panagiotopoulou, Elefteria Tzavella, Moses Elisaf
Abstract
SGLT2 inhibitors represent a new class of glucose-lowering drugs that act through the inhibition of glucose reabsorption at the proximal tubular cells of the kidney. There are 3 drugs of this class currently available in Europe andUnited States of America: empagliflozin, dapagliflozin and canagliflozin. These compounds selectively inhibit the reabsorption of glucose in the kidney by almost 30-50% and the resulting glycosuria is translated to meaningful reductions is serum glucose. Apart from their effects on carbohydrate homeostasis these drugs also affect human metabolism in various ways. Thus, they reduce blood pressure, arterial stiffness and body weight, decrease serum concentrations of insulin and increase those of glucagon and shift energy metabolism towards the utilization of ketone bodies. In a recent clinical trial empagliflozin was found to reduce cardiovascular mortality and to preserve renal function in patients with type 2 diabetes and established cardiovascular disease. In this review, we summarize the knowledge on the metabolic effects of SGLT2 inhibitors, discuss the potential mechanisms that underlie the cardioprotective and renoprotective effect of these drugs and present their side effects and the possible contraindications to their use.
Keywords: SGLT2 inhibitors, dapagliflozin, empagliflozin, canagliflozin, ketone bodies, euglycemic ketoacidosis, glycosuria