Adding Exenatide to Insulin Therapy for Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease
Condition: Nonalcoholic Fatty Liver Disease; Type 2 Diabetes Mellitus
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Exenatide
Intervention description: The participants with T2DM well-controlled on an intensified insulin regimen for the previous 6 months with the combination of a premeal insulin injection of the drug aspart (Novolog) three times a day and a bedtime insulin injection of the drug detemir (Levemir). The dosage of the insulin is determined by the need by the need of the participant. The Exenatide treatment will consist of an injection of the insulin twice daily and will replace the premeal insulin regiment of aspart.
Intervention MeSH terms: Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary aim of the study is to determine the impact on hepatic steatosis of replacing
      premeal rapid-acting insulin for exenatide (Byetta) while maintaining bedtime long-acting
      detemir (Levemir) insulin in well-controlled patients with type 2 diabetes mellitus (T2DM)
      and nonalcoholic fatty liver disease (NAFLD).

      Secondary aims are to learn: 1) the efficacy and safety of such approach and whether it is an
      acceptable treatment strategy compared to intensified insulin therapy alone; 2) mechanisms of
      action (effects on insulin secretion and insulin action); 3) its impact on weight (can it
      prevent insulin-associated weight gain or cause weight loss) and rates of hypoglycemia; 4) if
      it may improve specific plasma biomarkers of disease activity in NAFLD and inflammatory
      markers common to both conditions - T2DM and NAFLD (hsCRP, ICAM, VCAM).
    

Eligibility criteria:

        Inclusion Criteria:

        To enter the study subjects must meet the following criteria:

          1. Have been on intensified insulin therapy with insulin detemir (Levemir) and premeal
             insulin aspart (Novolog®) for the previous 6 months.

          2. Be able to communicate meaningfully with the Investigator and be legally competent to
             provide written informed consent.

          3. Female patients must be non-lactating and must either be at least two years
             post-menopausal, or be using adequate contraceptive precautions (i.e. oral
             contraceptives, approved hormonal implant, intrauterine device, diaphragm with
             spermicide, condom with spermicide), or be surgically sterilized (i.e. bilateral tubal
             ligation, bilateral oophorectomy). Female patients who have undergone a hysterectomy
             are eligible for participation in the study. Female patients (except for those
             patients who have undergone a hysterectomy or a bilateral oophorectomy) are eligible
             only if they have a negative pregnancy test throughout the study period.

          4. Age range of 18 to 70 years (inclusive).

          5. Patients must have been on a stable dose of allowed chronic medications for 6 months
             prior to entering the double-blind treatment period.

          6. All participants must have the following laboratory values:

        Hemoglobin ≥12 g/dl in males or ≥11 g/dl in females Serum creatinine ≤1.5 mg/dl AST (SGOT)
        and ALT (SGPT) ≤2.5 times upper limit of normal Alkaline phosphatase ≤2.5 times upper limit
        of normal

        Exclusion Criteria:

        Patients will be excluded if any of the following criteria are present:

          1. Individuals with type 1 diabetes or type 2 diabetes and a FPG ≥ 300 mg/dl; poor
             compliance with insulin therapy.

          2. Subjects on sulfonylureas, metformin and/or TZDs unless the dose has been stable for
             at least 6 months prior to study entry.

          3. Patients on any of the following medications: thiazide or furosemide diuretics,
             beta-blockers, or other chronic medications with known adverse effects on glucose
             tolerance levels unless the patient has been on stable doses of such agents for the
             past two months before entry into the study. Patients may be taking stable doses of
             estrogens or other hormonal replacement therapy if the patient has been on these
             agents for the prior two months. Patients taking systemic glucocorticoids will be
             excluded.

          4. Past (within 1 year) or current history of alcohol abuse.

          5. Patients will be excluded if there is a history of clinically significant heart
             disease (New York Heart Classification greater than grade II), peripheral vascular
             disease (history of claudication), or pulmonary disease (dyspnea on exertion of one
             flight or less; abnormal breath sounds on auscultation) or chronic renal failure
             (serum creatinine greater than 1.5 mg/dl).