Shannon A Miller1, Erin L St Onge2, J Roger Accardi31Pharmacotherapy Faculty, Florida Hospital East Family Practice Residency, Orlando, Florida, USA; 2University of Florida College of Pharmacy, Orlando Campus, Florida, USA; 3Accardi Clinical Pharmacy, Orange City, Florida, USAAbstract: The American Diabetes Association and The European Association for the Study of Diabetes recommend metformin as the initial agent of choice in the treatment of type 2 diabetes mellitus. Unfortunately, most patients require multiple medications to obtain glycemic control. One of the newest additions to the antidiabetic armamentarium is the class of drugs known as dipeptidyl-peptidase IV (DPP-IV) inhibitors. This novel approach focuses on harnessing the beneficial effects of GLP-1, an incretin hormone released from the gut postprandially. The first DPP-IV inhibitor approved in the United States was sitagliptin. It has been studied in both monotherapy and combination therapy. Combination studies with metformin realize a hemoglobin A1c reduction of 0.65%–1.1%. The combination of the two has a modest positive effect on body weight with the convenience of an oral route of administration. It has also been shown to be highly tolerable, efficacious and with little risk of hypoglycemia. This review will focus on combination therapy with sitagliptin with emphasis on combination with metformin. Keywords: DPP-IV inhibitor, sitagliptin, metformin, type 2 diabetes, incretins