Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest addition to the class of oral glucose-lowering drugs. They have been rapidly adopted into clinical practice because of therapeutic advantages, including weight loss and reduction in blood pressure, in addition to glycaemic benefits and a low intrinsic risk of hypoglycaemia. Although there are extensive data on the clinical effects of SGLT2 inhibition, the metabolic effects of inhibiting renal glucose reabsorption have not been fully described. Recent studies have identified compensatory metabolic effects, such as an increase in endogenous glucose production, and have also shown an increase in glucagon secretion during SGLT2 inhibition. In addition, there is a discrepancy between the expected and observed weight loss found in clinical studies on SGLT2 inhibitors, probably as a result of changes in energy balance with this treatment approach. SGLT2 inhibition is likely to have intriguing effects on whole body metabolism which have not been fully elucidated, and which, if explained, might help optimize the use of this new class of medicines.