The Clinical Efficacy and Safety of Sodium Glucose Cotransporter-2 Inhibitors in Adults with Type 2 Diabetes Mellitus

The use of currently available antihyperglycemic agents can be limited by contraindications; cost; renal and hepatic dosage adjustments; dosing schedules; and adverse effects such as gastrointestinal upset, weight gain, and hypoglycemia. These limitations have led the pharmaceutical industry to identify and pursue alternative therapies. Sodium glucose cotransporter-2 (SGLT-2) inhibitors belong to a new class of diabetes drugs and have a novel mechanism of action. These agents are unique in that they increase glucose excretion, independent of insulin secretion, by inhibiting the renal reabsorption of glucose, inducing glycosuria. To summarize the current evidence for SGLT-2 inhibitor therapy, we reviewed abstracts and published data from human trials evaluating the efficacy and safety of dapagliflozin, canagliflozin, and empagliflozin through February 2013. Data from these trials suggest that SGLT-2 inhibitors are able to lower hemoglobin A1c and fasting blood glucose when used as either monotherapy or combination therapy. Cardiometabolic benefits included a reduction in systolic blood pressure, reduction in triglycerides, and weight loss of up to 3 kg. Common and serious adverse effects including infections, cancer, and pollakiuria were identified and reviewed. Although these agents have generally demonstrated efficacy, the adverse effects associated with dapagliflozin have caused a delay in its regulatory approval. Continued research in this area will determine the risk: benefit ratio of SGLT-2 inhibitor therapy.