Sitagliptin Versus Placebo in the Treatment of Non-alcoholic Fatty Liver Disease

44 patients with NAFLD will be randomized to either sitagliptin or placebo for 24-weeks. Enrollment of 50 patients is needed to allow for exclusion of some patients after initial evaluation and a dropout of a small number of patients because of intolerance to sitagliptin. Inclusion criteria: 1. Age at entry at least 18 years. 2. Serum alanine (ALT) or aspartate (AST) aminotransferase activities that are above the upper limits of normal. 19 or more in women and 30 or more in men. 3. Evidence of hepatic steatosis or liver fat (≥5%) by MRI. 4. Prediabetic patients and controlled diabetic patients as defined by the ADA position statement on diabetes mellitus. Prediabetics have a HbA1c of 5.7 to 6.4 and controlled diabetic patients have an HbA1c between 6.4 and 8.0. 5. Written informed consent. Exclusion criteria: 1. Uncontrolled diabetes defined as a Hb A1c ≥ 8.0. 2. Evidence of another form of liver disease. * Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg). * Hepatitis C as defined by presence of hepatitis C virus (HCV) RNA in serum. * Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or greater and liver histology consistent with autoimmune hepatitis or previous response to immunosuppressive therapy. * Autoimmune cholestatic liver disorders as defined by elevation of alkaline phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver histology consistent with primary biliary cirrhosis or elevation of alkaline phosphatase and liver histology consistent with sclerosing cholangitis. * Wilson disease as defined by ceruloplasmin below the limits of normal and liver histology consistent with Wilson disease. * Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than normal and liver histology consistent with alpha-1-antitrypsin deficiency. * Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy and homozygosity for C282Y or compound heterozygosity for C282Y/H63D. * Drug-induced liver disease as defined on the basis of typical exposure and history. * Bile duct obstruction as shown by imaging studies. 3. History of excess alcohol ingestion, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year. 4. Advanced liver disease: platelet counts \< 75,000/mm3 or prothrombin time \>16 seconds or history of bleeding disorders 5. Decompensated liver disease, Child-Pugh score greater than or equal to 7 points 6. History of gastrointestinal bypass surgery or ingestion of drugs known to produce hepatic steatosis including corticosteroids, high-dose estrogens, methotrexate, tetracycline or amiodarone in the previous 6 months. 7. Recent initiation or change of anti-diabetic drugs, including insulin, sulfonylureas, or thiazolidinediones in the previous 90 days. 8. Use of sitagliptin or other agents in the same class within the 90 days prior to randomization. 9. Significant systemic or major illnesses other than liver disease, including congestive heart failure, coronary artery disease, cerebrovascular disease, pulmonary disease with hypoxia, renal failure, organ transplantation, serious psychiatric disease, malignancy that, in the opinion of the investigator would preclude treatment with Sitagliptin and adequate follow up. 10. History of acute pancreatitis within the last 5 years with the exception of gallstone pancreatitis. 11. Positive test for anti-HIV. 12. Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year. 13. Pregnancy or inability to practice adequate contraception in women of childbearing potential. 14. Evidence of hepatocellular carcinoma: alpha-fetoprotein levels greater than 200 ng/ml and/or liver mass on imaging study that is suggestive of liver cancer. 15. Any other condition, which, in the opinion of the investigators would impede competence or compliance or possibility hinder completion of the study. 16. Serum creatinine \>1.5 mg/dl. 17. Contraindications to Sitagliptin use : * History of allergic reaction to Sitagliptin * Patients with acute liver injury or unexplained persistent elevations in ALT \> 500 U/L at baseline. * Women who are pregnant or may become pregnant * Nursing mothers 18. Contraindications to MRI: * The subject has any contraindication to MR imaging, such as patients with pacemakers, metallic cardiac valves, magnetic material such as surgical clips, implanted electronic infusion pumps or other conditions that would preclude proximity to a strong magnetic field. * The subject has a history of extreme claustrophobia * The subject cannot fit inside the MR scanner cavity 11\. RECRUITMENT Enrollment of patients may be initiated once IRB approval is acquired and will continue until June 2015. Patients will be recruited from the following populations: * Primary care and internal medicine clinics * Tertiary referral clinics at the Hillcrest Campus and Perlman Clinics: * GI/Liver clinic * Liver transplant clinic * Obesity clinic * Bariatric surgery clinic * Diabetes clinic * Lipid disorders clinic * Physicians taking care of the patients would provide information regarding the study and then either refer the patient to our clinic or ask the patient to directly contact the PI or research assistant. * Patient would be given information regarding possible studies in NAFLD in liver clinic by their providers. We would ask the patient to call or email the PI or research assistant to further discuss the study, if they are interested.