Adequate glycemic control in type 2 diabetes remains a difficult but achievable goal. The development of new classes of glucose-lowering medications, including in particular the incretin-based therapies, provides an opportunity to utilize combinations of medications which target multiple physiologic abnormalities in type 2 diabetes. Complementary combination therapy with sitagliptin-metformin lowers glucose via enhancement of insulin secretion, suppression of glucagon secretion, and insulin sensitization. Use of this combination in diabetes management will provide a greater degree of glycosylated hemoglobin-lowering than that seen with the use of either drug as monotherapy, is unlikely to cause significant hypoglycemia, and is generally associated with weight loss. The effectiveness, tolerability, and potential cost savings associated with the use of sitagliptin-metformin combination therapy make this an attractive option in diabetes management. The possible beneficial effects of this therapy on beta cell function, as well as its cardiovascular impact, remain inadequately explored but are of significant interest.