Dapagliflozin combination therapy in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a progressive disease, and most patients ultimately require two or more antidiabetes drugs in addition to lifestyle changes to achieve and maintain glycemic control. Current consensus statements and guidelines recommend metformin as first-line pharmacotherapy for the treatment of T2DM in most patients. When glycemic control cannot be maintained with metformin alone, the sequential, stepwise addition of other agents is recommended. Agents such as thiazolidinediones or sulfonylureas have typically been added to metformin therapy. Although effective in reducing glycated hemoglobin, these drugs are often associated with adverse effects, most notably weight gain, and in the case of sulfonylureas, hypoglycemia. Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, are the newest class of antidiabetes drugs approved for the treatment of T2DM. Dapagliflozin effectively improves glycemic control by increasing the renal excretion of excess glucose. In clinical trials, dapagliflozin has been well tolerated and has additional benefits of weight loss, low risk of hypoglycemia and reduction in blood pressure. This review discusses the clinical evidence and rationale for the use of dapagliflozin as add-on therapy in T2DM. The results suggest that dapagliflozin add-on therapy is a promising new treatment option for a wide range of patients with T2DM. Results from an ongoing cardiovascular outcomes trial are needed to establish the long-term safety of dapagliflozin.