Glucose control and cardiovascular outcomes in clinical trials of sodium glucose co-transporter 2 inhibitor treatments in type 2 diabetes

Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycemic control independently of insulin pathways while avoiding hypoglycemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose, and glycated hemoglobin (HbA_1C) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit-risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.