SGLT2 Inhibitors Therapy in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by chronic hyperglycemia and increased risk of cardiovascular disease (CVD). It results from multiple defects that lead to defective regulation of the blood glucose and requires continuous medical care with multifactorial risk-reduction strategies beyond glycemic control. Multiple groups of drugs have been approved in the past decades that work through different mechanisms. Apart from their limited efficacy in reducing cardiovascular outcome, most of them are neutral, and some may even increase mortality from CVDs such as rosiglitazone. The kidney has an important role in glucose regulation that was only recently targeted for drug development. Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) are a new class of oral antihyperglycemic (OAH) agents that mainly act by preventing the reabsorption of filtered glucose by renal convoluted tubules. By their insulin-independent unique mechanism of action, SGLT2-I result in treating hyperglycemia while avoiding hypoglycemia, promote weight loss, reduce blood pressure, and, more importantly, decrease the risk of major adverse cardiovascular events (MACE). Therefore, SGLT2-I address fundamental aspects of the unmet needs of T2DM management that most of the other OAH failed to resolve. The main side effects of SGLT2-I are slight increase in the incidence of genital mycotic infections (GMI) and euglycemic ketoacidosis (EKA) along with increased risk of lower limb amputations, which has been reported with some but not all agents of this class