Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease
Condition: Diabetes Complications; Fatty Liver
MeSH terms: Liver Diseases; Fatty Liver; Diabetes Complications
Intervention: exenatide
Intervention description: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24
Intervention MeSH terms: Exenatide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Fatty Liver; Nonalcoholic fatty liver disease; NAFDL; Diabetes; ALT; exenatide

Summary:

      Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common
      complications of type 2 diabetes and leading causes of liver disease in the US and Europe.
      The prevalence of NAFLD and NASH are expected to become a major cause of liver disease
      related deaths and liver transplantation. Currently, there are no specific therapies that
      alter the natural history of NAFLD.Preliminary evidence suggests that exenatide (Byetta®) may
      have several beneficial direct and indirect effects on NAFLD and liver lipid metabolism.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >18 years, < 70 years, inclusive

          -  Type 2 diabetes on stable doses of sulfonylurea and/or metformin

          -  Body mass index > 35 kg/m2

          -  Presumed diagnosis of NAFLD based upon

          -  an ALT > 1.5 times the upper limit of reference range,

          -  no evidence of other causes of liver disease and

          -  ultrasound findings compatible with fatty liver

        Exclusion Criteria:

          -  Clinical signs of cirrhosis as evidenced by any of the following

          -  spider angiomata,

          -  splenomegaly,

          -  ascites

          -  jaundice

          -  encephalopathy

          -  INR > 1.2

          -  Platelet count < 100,000/ml

          -  Serum albumin < 3.0 g/dL

          -  Other liver disease including chronic viral hepatitis (B or C), alcohol abuse,
             hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's
             disease, primary sclerosing cholangitis or primary biliary cirrhosis.

          -  Current use of > 20 g of alcohol per day or unwillingness to avoid alcohol during the
             course of the study

          -  Treatment with a thiazolidinedione or exenatide within 6 months of enrolling in the
             study

          -  AST or ALT > 10 times the upper limit of normal

          -  Treatment with any investigational drug within 4 weeks of enrollment

          -  Pre-menopausal, fertile women unwilling to use contraceptives during the study period.

          -  Pregnancy or lactation

          -  Initiation or change in dose of hypolipidemic drugs (statins, niacin, cholestyramine
             are allowed) within 6 months of enrollment

          -  Use of anticoagulation, bleeding disorders or other contraindications to liver biopsy