Effectiveness of Sitagliptin for HIV Insulin Resistance and Inflammation

Inclusion Criteria: * 18-65 yr old HIV infected men and women. * Stable (at least the past 6 months) on combined antiretroviral therapy (cART). * Stable immune (\> 300 CD4+ T-cells/µL) and virologic (\< 50 copies HIV RNA/mL) status. * Insulin resistant/impaired glucose tolerance (fasting glucose 100-125mg/dL, or 2-hr glucose 140-200mg/dL or fasting HOMA-IR= 2.5-6.0). * Waist circumference \> 102 cm (men), \> 88 cm (women). * BMI \> 20 kg/m2. * Fasting hypertriglyceridemia \> 150 mg/dL. * Low HDL-cholesterol (\< 40 mg/dL in men or \< 50 mg/dL in women). * Platelet count \> 30,000/mm3. * Absolute neutrophil count \> 750/mm3. * Transaminases \< 2.5x the upper limit of normal. * Long-term non-progressors (not taking anti-HIV medications) are not eligible. Exclusion Criteria: * Diabetes (T2DM, IDDM or diabetic ketoacidosis) or taking any glucose-lowering medication (e.g., insulin, TZDs, metformin, sulfonylurea). * Any agent that might artifactually alter glycemic control (e.g., glucocorticoids, megace, rhGH, GH-secretagogue, testosterone derivatives, creatine monohydrate, chromium picolinate, AA/protein supplements, medium- or long-chain fatty acids) during 6 months prior to or during enrollment. * History of serious CV disease. NYHA Functional Class III or IV (e.g., recent MI, unstable angina, edema, CHF, CAD, CABG, stroke, resting hypertension \> 160/95 mmHg), irregular heart rhythm, resting ST-segment depression \> 1mm). Treatment with medications for CV condition (e.g., α- or ß-blockers). Some BP-lowering medications (Ca++channel blocker, diuretic, or ACE inhibitor) are permitted. * Moderate to severe renal insufficiency. Serum creatinine \> 1.7 mg/dL (men) \> 1.5 mg/dL (women). * Plan or anticipate a change in anti-HIV medications during the study. * Lipid-lowering medications are permitted (fibrate or statin or niacin), but must be stable on that agent for at least 6 months prior to enrollment. Lipid-lowering agents cannot be started during the treatment period. * Chronic hepatitis B (HBV-surface antigen positive). Active hepatitis C (detectable Hep C RNA). * Positive urine drug test for opiates, methamphetamine, heroin, cocaine. Active substance abuse that the MD-scientist believes may compromise safety, compliance, interfere with study drug or data interpretation. * Hematocrit \< 34% in men or \< 25% in women with symptoms (fatigue, "tired-legs", shortness of breath). Hemoglobin \< 10 gm/dL with symptoms. * Pregnant or nursing mothers. Women must agree to use an acceptable form of birth control during the study. If using birth control pills-must be stable on this medication for at least 6 months prior to enrollment. * Active malignancy or treatment with chemotherapeutic agents or radiation therapy or any cytokine or anti-cytokine therapy during 6 months prior to enrollment. * History of pancreatitis * \> 10% unintentional weight loss during the 6 months prior to enrollment. * Reduced cognitive function/unable to provide voluntary informed consent. Prisoners are excluded. * Blinded investigational drugs for 3 months prior to enrollment that will not be unblinded before enrollment. * Nausea, vomiting, diarrhea (\> 4 loose stools/day) that are unresponsive to treatment.