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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01006889
Recruitment Status : Completed
First Posted : November 3, 2009
Results First Posted : July 29, 2016
Last Update Posted : September 28, 2016
Amylin Pharmaceuticals, LLC.
Information provided by (Responsible Party):
University of Florida

Brief 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).

Condition or disease Intervention/treatment Phase
Nonalcoholic Fatty Liver Disease Type 2 Diabetes Mellitus Drug: Exenatide Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A New Treatment Strategy of Adding Exenatide to Insulin Therapy for Patients With Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease (NAFLD)
Study Start Date : January 2008
Actual Primary Completion Date : December 2009
Actual Study Completion Date : February 2010

Arm Intervention/treatment
Experimental: Exenatide (twice daily)
Patients with T2DM well-controlled on an intensified insulin regimen for the previous 6 months by the will have their insulin aspart discontinued and replaced for exenatide twice daily while continuing the bedtime detemir insulin. Safety and efficacy parameters will be measured before and after 6 months of treatment.
Drug: Exenatide
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.
Other Name: Byetta

Primary Outcome Measures :
  1. Hepatic Steatosis [ Time Frame: 6 months ]
    Hepatic steatosis was assessed non-invasively by MRS.

Secondary Outcome Measures :
  1. A1c [ Time Frame: 6 months ]
    Patients with controlled T2DM with bedtime insulin alone (n=5) or bedtime insulin and premeal rapid-acting insulin novolog (n=15) had eventide given twice daily for 6 months (if on premeal insulin it was stopped). The goal is to assess if adding SQ exenatide is effective to maintain optimal glycemic control in this population.

  2. Change in Anthropometric Variables (Weight). [ Time Frame: 6 months ]
  3. Number of Severe Hypoglycemic (Glucose ≤40 mg/dL) Events. [ Time Frame: 6 months ]
  4. Insulin Secretion (Hyperglycemic Clamp) [ Time Frame: 6 months ]
    Change in C-peptide levels vs. pretreatment in the first and second phase.

  5. Percent Change From Baseline in Glucose Infusion (M Value) During Hyperglycemic Clamp [ Time Frame: 6 months ]
    M value represents glucose infusion change

  6. Lipid Profiles, Lipoprotein Analysis by NMR (LipoScience). [ Time Frame: 6 months ]
    Change in lipid levels vs. pretreatment.

  7. Change in Anthropometric Variables (BMI). [ Time Frame: 6 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01006889

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United States, Texas
The University of Texas H.S.C. at San Antonio and the San Antonio Audie L. Murphy VA Hospital
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
University of Florida
Amylin Pharmaceuticals, LLC.
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Principal Investigator: Kenneth Cusi, M.D. University of Florida

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Responsible Party: University of Florida Identifier: NCT01006889    
Other Study ID Numbers: HSC20060167-2
First Posted: November 3, 2009    Key Record Dates
Results First Posted: July 29, 2016
Last Update Posted: September 28, 2016
Last Verified: June 2016
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases
Insulin, Globin Zinc
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Hormones, Hormone Substitutes, and Hormone Antagonists