Overview

Adding Exenatide to Insulin Therapy for Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease

Status:
Completed
Trial end date:
2010-02-01
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 4
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Florida
Collaborator:
Amylin Pharmaceuticals, LLC.
Treatments:
Exenatide
Insulin
Insulin, Globin Zinc
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).