Effect of Exenatide on Abdominal Fat Distribution in Patients With Type 2 Diabetes Pretreated With Metformin

A multicenter, randomized, double-blind, placebo-controlled trial will assess the effects of twice-daily subcutaneous injection with exenatide versus treatment with matching placebo injection on abdominal visceral fat content.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: placebo; Drug: exenatide

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • Research Site
  • Alberta
    • Calgary, Alberta, Canada
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Research Site
    • Victoria, British Columbia, Canada
      • Research Site
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Research Site
  • New Brunswick
    • Saint John, New Brunswick, Canada
      • Research Site
  • Ontario
    • Brampton, Ontario, Canada
      • Research Site
    • London, Ontario, Canada
      • Research Site
    • Ottawa, Ontario, Canada
      • Research Site
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Chicoutimi, Quebec, Canada
      • Research Site
    • Pointe-Claire, Quebec, Canada
      • Research Site
• United States
  • Arizona
    • Temple, Arizona, United States
      • Research Site
  • Colorado
    • Colorado Springs, Colorado, United States
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States
      • Research Site
  • Nebraska
    • Bellevue, Nebraska, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients between 18 and 85 years of age, inclusive.
• Patients with type 2 diabetes
• Patients have been treated with metformin, at a stable dose for at least 3 months prior to Visit 1
• Patients have HbA1c of 7.0% to 8.9%, inclusive.
• Patients have a body mass index >27 kg/m2 and <40 kg/m2 and meet local CT scan body weight requirements. For South Asian, Japanese, and Chinese patients, a body mass index >=25 kg/m2 is acceptable as the lower limit.
• Patients have a history of stable body weight (not varying by >2 kg in the 3 months prior to Visit 1).
• Medications for the treatment of high blood pressure are stable with respect to treatment regimen for 4 weeks prior to Visit 1.
• Stable regimen of lipid-lowering agents for 6 weeks prior to Visit 1.

Exclusion Criteria:

• Have received treatment in the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Have an active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
• Have a history of renal transplantation, or are currently receiving renal dialysis.
• Have had a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year prior to Visit 1, including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure, coronary artery bypass surgery, or angioplasty; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
• Have known hemoglobinopathy or clinically significant, chronic anemia.
• Known or are likely to become transfusion dependent during the study.
• Have active, symptomatic proliferative retinopathy.
• Are receiving chronic treatment for gastrointestinal disease with a drug directly affecting gastrointestinal motility. (i.e. metoclopramide, cisapride, and chronic use of macrolide antibiotics)
• Have severe gastrointestinal disease, including gastroparesis.
• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 months immediately prior to Visit 1.
• Have taken exenatide, liraglutide or any other GLP-1 receptor agonist in the past 6 months, either in a clinical study or as commercially available medication. Patients with known allergy to exenatide should be excluded.
• Have used any prescription or over the counter drug to promote weight loss within 3 months prior to Visit 1, or intend to use such a drug during the study. (Examples: Xenical [orlistat], Meridia [sibutramine], Acutrim [phenylpropanolamine], Acomplia [rimonabant]).
• Have participated in a structured weight loss program within 3 months prior to Visit 1, or intend to participate in such a plan during this study.
• Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to Visit 1: Insulin; Thiazolidinediones; Alpha-glucosidase inhibitors; Sulfonylureas; Oral DPP-IV inhibitors; Meglitinides.
• Are taking warfarin, or a coumarol derivative.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2	Drug: exenatide; subcutaneous injection, twice a day, 10mcg
Placebo Comparator: 1	Drug: placebo; subcutaneous injection, twice a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Abdominal Visceral Fat From Baseline to 6 Months	Percentage change in abdominal visceral fat	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in Total Abdominal Fat From Baseline to 6 Months	Percentage change in total abdominal fat	baseline, 6 months
Percentage Change in Subcutaneous Abdominal Fat From Baseline to 6 Months	Percentage change in subcutaneous abdominal fat	baseline, 6 months
Change in HbA1c From Baseline to 6 Months	Change in HbA1c from baseline to 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated.	baseline, 6 months
Percentage of Patients With HbA1c <=7.0% at 6 Months	Percentage of patients with HbA1c values <= 7.0% measured at 6 months. HbA1c is a measurement of the amount of hemogobin that is glycosylated.	6 months
Change in Fasting Plasma Glucose From Baseline to 6 Months	Change in Fasting plasma glucose	baseline, 6 months
Change in Weight From Baseline to 6 Months	Change in weight	baseline, 6 months
Change in Systolic Blood Pressure From Baseline to 6 Months	Change in Systolic blood pressure	baseline, 6 months
Change in Diastolic Blood Pressure From Baseline to 6 Months	Change in Diastolic blood pressure	baseline, 6 months
Change in Total Cholesterol From Baseline to 6 Months	Change in total cholesterol	baseline, 6 months
Change in Triglycerides From Baseline to 6 Months	Change in triglycerides	baseline, 6 months
Change in High-Density Lipoprotein (HDL) Cholesterol From Baseline to 6 Months	Change in HDL cholesterol	baseline, 6 months
Assessment of Event Rate of Treatment- Emergent Hypoglycemic Event	All hypoglycemia episodes defined as major (results in loss of consciousness, seizure or coma resolving after administration of glucagon or glucose OR needing third-party assistance to resolve due to severe impairment in consciousness and associated with glucose concentration < 2.8 mol/L.) or minor (non-major event with symptoms consistent with hypoglycemia and glucose value < 2.8 mmol/L prior to treating) or symptoms of hypoglycemia (does not meet the criteria for a major or minor event).	baseline, 6 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Chief Medical Officer, MD Eli Lilly and Company, Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: June 17, 2008
• First Submitted That Met QC Criteria: June 18, 2008
• First Posted (Estimate): June 19, 2008

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Lilly; Amylin; diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: H8O-CA-GWCE