Inflammatory processes are increasingly being recognized as a critical step in the pathogenesis of both diabetes and heart disease and may constitute a biological link between the two diseases. Inflammatory cytokines increase vascular permeability, change vasoregulatory responses, increase leukocyte adhesion to endothelium, and facilitate thrombus formation by inducing procoagulant activity, inhibiting anticoagulant pathways, and impairing fibrinolysis. Leukocyte adhesion to arterial endothelial cells is thought to be an important step in the development of atherosclerosis, and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and L-selectin, play key roles in this process. Therefore, identifying novel therapeutic approaches that would favorably affect inflammation, endothelial function, and glucose is of significant interest. Investigators have recently demonstrated that, relative to placebo, sitagliptin treatment resulted in a significant reduction in plasma levels of various inflammatory markers and cell adhesion molecules. The results also suggest that the beneficial effects of sitagliptin on both inflammation and endothelial function are most likely mediated by an elevation in plasma GLP-1 levels and global improvement of the glucose-insulin homeostasis. However, the mechanisms underlying the beneficial effects of sitagliptin on these markers remain to be fully elucidated. The proposed study will address this key issue.

Inclusion Criteria:

• Males 18 to 65 years of age.
• Post-menopausal women under age 65 on stable medical therapy for 6 months before the study (the patient should have demonstrated stable lipid panels)
• Women should not be on hormone replacement therapy (no recent starting or stopping)
• Type 2 diabetes as defined by the American Diabetes Association.
• Non-smoker.
• Body mass index between 25.0 and 40.0 kg/m2.
• Baseline glycated hemoglobin A1c (HbA1c) between 6.5 and 8.5%.
• Baseline fasting plasma glucose < 15.0 mmol/L.
• Plasma triglyceride levels between 1.5 and 8.0 mmol/L (135 and 710 mg/dl) at screening and week -4.
• Patients having received stable doses of metformin for at least 3 months before randomization.
• Subjects must be willing to give written informed consent and able to adhere to dosing schedule, visit schedule and phone follow-up assessment.
• Patients should be otherwise generally healthy, without elevations in hepatic transaminases or abnormal renal function or coagulation.
• Patients having normal thyroid stimulating hormone at screening

Exclusion Criteria:

• Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded.
• Patients with type 1 diabetes, secondary form of diabetes or acute metabolic diabetic complications will be excluded.
• Patients having received or being treated with insulin or a thiazolidinedione within the past 6 months will be excluded.
• Patients taking any other hypoglycemic agent, other than metformin.
• Subjects will be excluded if they have cardiovascular disease (coronary heart disease, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents, significant alcohol intake etc.).
• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
• Individuals with a history of mental instability, drug or alcohol abuse or individuals who have been treated or are being treated for severe psychiatric illness that, in the opinion of the investigator, may interfere with optimal participation in the study.
• History of alcohol or drug abuse within the past 2 years. Patients must not take alcohol during the study.
• Disorders of the hematologic, digestive, or central nervous systems, including cerebrovascular disease and degenerative disease, that would limit study evaluation or participation.
• Known impairment of renal function (serum creatinine levels > 1.7 mg/dL for men), dysproteinemia, nephrotic syndrome, or other renal disease (24-hour urinary protein ≥3 ± 1 g).
• Active or chronic hepatobiliary or hepatic disease. In addition, patients with aspartate aminotransferase or alanine aminotransferase >2 x upper limit of the laboratory reference range will be excluded.
• Subjects with coagulopathy (prothrombin time or partial thromboplastin time at Visit 1 >1.5 times control).
• Subjects with hemoglobin >2 x the lower limit of the laboratory reference range will be excluded.
• Patients who are known to have tested positive for human immunodeficiency virus (HIV).
• Patients who are currently enrolled in another clinical study.
• Patients who have used any investigational drug within 30 days of the first clinic visit.
• Congestive heart failure New York Heart Association (NYHA) Class III or IV. Uncontrolled cardiac arrhythmias within 3 months of study entry.
• Uncontrolled diabetes mellitus (HbA1c>8.5%) or other endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid subjects on replacement doses of thyroid hormone are eligible for enrollment.

During 16 weeks