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Rationale for Combination Therapy Combination therapy may provide more glycemic control than the individual monotherapies. Combination therapy may provide more comprehensive coverage of the key pathophysiologies of type 2 diabetes than monotherapies. An appropriately chosen combination therapy may help more patients achieve their HbA1c goal without increasing side effects.1 Reference: 1. Del Prato S, Felton-A-M, Munro et al. Improving glucose management: Ten steps to get more patients with type 2 diabetes to glycaemic goal Int J Clin Pract 2005;59:1345-1355. Clinical Effects of Oral Antidiabetic Therapies Given the multiple pathophysiologic abnormalities in type 2 diabetes, combination therapy with 2 or 3 drugs with distinct mechanisms of action is an approach to managing the disease1. These therapies would target key pathophysiologies of type 2 diabetes2. This approach has been shown to provide improved HbA1c reduction1 and significantly improve fasting, and postprandial glucose control.3 The combination of a DPP-4 inhibitor with metformin would be a combination that would provide coverage of key pathophysiologies of type 2 diabetes.1 In addition, the combination of a DPP-4 inhibitor with metformin has the benefit of not inducing weight gain with a low risk of hypoglycemia.3 References: 1. Charbonnel B, Karasik A, Liu J, et al for the Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care 2006;29:2638–2643. Brazg R, Xu L, Dalla Man C, et al. Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycaemic control and β-cell function in patients with type 2 diabetes. Diabetes Obes Metab 2007;9:186–193. Nauck MA, Meininger G, Sheng D, et al for the Sitagliptin Study 024 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, co