Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM

Inclusion Criteria: * Patients must meet all of the following inclusion criteria to participate in the study. * Patients with screening values/findings outside ranges described in the protocol may have one repeat determination performed and if the repeat value satisfies the criterion, they may continue in the screening process. * If the repeat value does not satisfy the criterion, the principal investigator will review the abnormal laboratory value and decide whether the subject may continue in the screening process. * All screening laboratory measurements are to be performed after an overnight fast ≥10 hours in duration. * Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent. * Patients can be either male or female. * Patients are ≥18 and ≤70 years of age on the day of signing informed consent. * Patients must meet the current American Diabetes Association criteria for the diagnosis of type 2 diabetes mellitus * Patients must be on diet or diet plus exercise therapy. * Patients must have a HbA1c ≥ 7.5% and ≤ 9.5% * Patients must have a BMI of 23-40 kg/m2 * Patients must have the following laboratory values: * Hematocrit Males ≥ 34 vol% * Females ≥ 33vol% * Serum creatinine ≤ 1.5 mg/dL in males and ≤ 1.4 mg/dL in females * AST (SGOT): ≤ 2.5 times upper limit of normal * ALT (SGPT): ≤ 2.5 times upper limit of normal * Alkaline phosphatase ≤ 2.5 times upper limit of normal * If serum creatinine is \> 1.5 mg/dl in males and \> 1.4 mg/dl in females, the Principal Investigator can include the patient if the measured GFR is \>70 ml/min (24 hour creatinine clearance) * Patients must have been on a stable dose of allowed chronic medications for ≥30 days prior to entering the study. * Only patients whose body weight has been stable (±4 pounds) over the three months prior to the study will be included. Exclusion Criteria: * Patients are excluded from participation in the study if they meet any of the following criteria: * Patient has type 1 diabetes. * Patient has received insulin for more than one week within the previous year prior to entry. * Patient has been treated with exenatide or a non-TZD, oral antihyperglycemic agent within the last 2 months or with a TZD (pioglitazone or rosiglitazone) within the last 4 months. * Patient is receiving any medications with known adverse effects on glucose tolerance (e.g., systemic glucocorticoids, psychotropic drugs like clozapine, olanzapine, haloperidol, risperidone). Note: Patients may be taking stable doses of estrogens, other hormonal replacement therapy, or lipid and blood pressure lowering agents if the patient has been on these agents for the prior three months. * Patient has evidence of a significant cardiovascular disorder within 6 months of signing informed consent (e.g. acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder) or has New York Heart Association Classification greater than Class 2; or has significant findings on ECG (other than non-specific ST-T wave changes); or peripheral vascular disease (history of claudication); or has dyspnea on exertion of one flight or less, or abnormal breath sounds on auscultation. * Patient has a history of intolerance or hypersensitivity to a DPP-4 inhibitor or to metformin. * Patient is pregnant or plans to become pregnant within the projected duration of the study.