In the last decade, researchers have gained a greater understanding of the pathophysiologic mechanisms of type 2 diabetes as a chronic and progressive disease. One of the more recent treatment targets is the kidney. The kidneys become maladaptive in diabetes by increasing the reabsorption of glucose above the normal physiologic renal threshold. This discovery has led to the development of the sodium/glucose cotransporter 2 inhibitors (SGLT2). These agents readjust the renal threshold for glucose reabsorption to a lower level and decrease glucose reabsorption, while increasing urinary glucose when the glucose is above the renal threshold and subsequently lowering plasma glucose. The mechanism of action of the SGLT2 inhibitors is insulin independent, which makes them a novel treatment of diabetes. At the time of preparation of this manuscript, there were three SGLT2 inhibitors available in the US. This manuscript focuses on empagliflozin, the newest SGLT2 inhibitor, the trials in its development, and the clinical data available to date. Further, the authors propose future applications of empagliflozin, including in the treatment of type 1 diabetes, and its potential role in renoprotection.

The management of type 2 diabetes mellitus (T2DM) by primary care physicians (PCPs) has become increasingly complex due to limitations on consultation time, an increasing array of drug treatment options, and issues of comorbidities and polypharmacy. Diabetes is a progressive condition and treatment with a single glucose-lowering agent can only address limited pathophysiologic targets and does not provide adequate glycemic control in many cases. Consequently, most patients with T2DM will eventually require treatment with multiple glucoselowering medications. Oral combination therapy in T2DM may be given as multiple-pills, or as single-pill, fixed-dose combinations (FDCs), the latter of which offer convenience, ease of administration, and a reduction in the medication burden. Therefore, FDCs can potentially improve patients' treatment adherence and optimize achievement and maintenance of glycemic targets. However, cost factors also need to be considered. An understanding of the issues associated with the use of combination therapy in T2DM will help PCPs to guide patient-centered decision making and promote the effective management of T2DM.

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