Sodium-glucose Cotransporter 2 Inhibitors: Glucose Lowering Against other Hypoglycemic Agents

Background: The treatment of diabetes remains challenging over the decades, even after the introduction of numerous novel drugs of different classes. Most patients with type 2 diabetes require a combination of multiple agents and eventually the use of insulin. The newest antidiabetic drugs, possibly with the most pleiotropic actions after metformin are the sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT-2i). This class has a unique mechanism inhibiting the glucose reabsorption in the proximal tubule of the kidney. Objective: The purpose of this review is to critically discuss the beneficial effect of SGLT-2i on glycemic control as monotherapy or in combination with other hypoglycemic agents. Methods: A systematic review of randomised clinical trials on SGLT-2i vs placebo, other glucoselowering drugs or insulin was performed, and studies assessing glycemic control, mainly expressed through glycated hemoglobin and fasting plasma glucose levels (FPG) were included in the review. Electronic and manual searches on MEDLINE, EMBASE and Cochrane Library were performed. Results: In our review, we mainly focused on dapagliflozin, empaglifozin and canagliflozin. All agents exhibited a sufficient reduction of HbA1c as well as FPG. Conclusions: SGLT-2i are a reliable second-line therapy of T2DM, since they can be combined safely with metformin, sulfonylures, incretin mimetics, insulin as well as in triple combinations. In many studies, they were prioritised as monotherapy with satisfying effects regarding HbA1c and FPG level reductions.