Addition Of Exenatide To Insulin Glargine In Type 2 Diabetes Mellitus

A Randomized Trial Comparing Exenatide With Placebo in Subjects With Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications

This study will compare the efficacy and safety of exenatide versus placebo in adults whose diabetes is not fully controlled by insulin glargine with or without metformin and/or pioglitazone.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: placebo; Drug: exenatide

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece
    • Research Site
  • Thessaloniki, Greece
    • Research Site
• Israel
  • Holon, Israel
    • Research Site
  • Kfar Sava, Israel
    • Research Site
  • Tel Hashomer, Israel
    • Research Site
• Mexico
  • Coatzacoalcos, Mexico
    • Research Site
  • Mexico, Mexico
    • Research Site
  • Monterrey, Mexico
    • Research Site
• Puerto Rico
  • Carolina, Puerto Rico
    • Research Site
  • Hato Rey, Puerto Rico
    • Research Site
  • Ponce, Puerto Rico
    • Research Site
  • San Juan, Puerto Rico
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom
    • Research Site
  • Guildford, United Kingdom
    • Research Site
  • Leicester, United Kingdom
    • Research Site
  • Livingston, United Kingdom
    • Research Site
  • Middlesbrough, United Kingdom
    • Research Site
  • Swansea, United Kingdom
    • Research Site
  • Torquay, United Kingdom
    • Research Site
• United States
  • Arizona
    • Peoria, Arizona, United States
      • Research Site
    • Phoenix, Arizona, United States
      • Research Site
  • California
    • Buena Park, California, United States
      • Research Site
    • Concord, California, United States
      • Research Site
    • Fresno, California, United States
      • Research Site
    • Greenbrae, California, United States
      • Research Site
    • La Mesa, California, United States
      • Research Site
    • Lancaster, California, United States
      • Research Site
    • Northridge, California, United States
      • Research Site
    • Palm Springs, California, United States
      • Research Site
    • Salinas, California, United States
      • Research Site
  • Florida
    • Hollywood, Florida, United States
      • Research Site
    • Jacksonville, Florida, United States
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States
      • Research Site
  • Idaho
    • Idaho Falls, Idaho, United States
      • Research Site
  • Iowa
    • Des Moines, Iowa, United States
      • Research Site
  • Kansas
    • Wichita, Kansas, United States
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States
      • Research Site
    • Lafayette, Louisiana, United States
      • Research Site
    • Matairie, Louisiana, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Research Site
  • Missouri
    • Chesterfield, Missouri, United States
      • Research Site
    • St Louis, Missouri, United States
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New Jersey
    • Berkeley Heights, New Jersey, United States
      • Research Site
    • Teaneck, New Jersey, United States
      • Research Site
  • New Mexico
    • Alburquerque, New Mexico, United States
      • Research Site
  • New York
    • New York, New York, United States
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States
      • Research Site
  • Oregon
    • Bend, Oregon, United States
      • Research Site
  • Texas
    • Dallas, Texas, United States
      • Research Site
    • El Paso, Texas, United States
      • Research Site
    • Georgetown, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
  • Virginia
    • Richmond, Virginia, United States
      • Research Site
  • Washington
    • Vancouver, Washington, United States
      • Research Site
  • Wisconsin
    • Kenosha, Wisconsin, United States
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have type 2 diabetes.
• Have been taking insulin glargine at a dose of ≥20 units/day for at least 3 months before entering the study.

Have been taking insulin glargine alone or in combination with one of the following for at least 3 months before entering the study:

1. metformin (stable dose for 6 weeks)
2. pioglitazone (stable dose for 6 weeks)

3. a combination of metformin and pioglitazone (stable dose for 6 weeks)

   • Have HbA1C between 7.1% and 10.5%, inclusive.
   • Have a body mass index (BMI) ≤45 kg/m2.
   • Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).

Exclusion Criteria:

• Have taken medications to lower blood sugar other than insulin glargine, pioglitazone, or metformin in the 3 months before entering the study for more than a 1-week period, or within 1 week of entering the study.
• Have had more than one episode of major (severe) hypoglycemia in the 6 months before entering the study.
• Are pregnant or intend to become pregnant during the study or are sexually active women not actively practicing birth control.
• Women who are breastfeeding.
• Have any significant diseases of the blood, heart, kidney, gastrointestinal system, or other significant diseases such as cancer.
• Have had a kidney transplant or are currently on kidney dialysis.
• Have a cancer that's never been treated, that's currently being treated, or that was diagnosed within the last 5 years.
• Have had a bad reaction to exenatide in the past or have a condition that is not recommended to be exposed to exenatide or any of exenatide's other ingredients.
• Have used a drug for weight loss in the 3 months before entering the study for more than a 1-week period, or within 1 month of entering the study.
• Are currently on a weight-loss program or have been on one within 3 months of entering the study.
• Have had a blood transfusion or severe blood loss within 3 months of entering the study.
• Are taking systemic glucocorticoids or have received systemic glucocorticoids within 8 weeks of entering the study.
• Have an irregular sleep cycle (for example, sleeping during the day and working during the night).
• Have a history of pancreatitis.
• Have received treatment with an experimental drug within 30 days of entering the study.
• If on metformin, have a condition that is not recommended to be exposed to metformin, or any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
• If on metformin, have had a radiologic contrast study performed within 48 hours of entering the study.
• If on pioglitazone, have a condition that is not recommended to be exposed to pioglitazone, including congestive heart failure, or are taking pioglitazone at a dose that is not approved for use with insulin.

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
Change in Glycosylated Hemoglobin (HbA1c)	Change in HbA1c from baseline following 30 weeks of therapy (i.e., HbA1c at week 30 minus HbA1c at baseline). Unit of measure is percent of hemoglobin that is glycosylated.	baseline and 30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Achieving HbA1c <=7%	Percentage of patients in each arm who had HbA1c >7% at baseline and had HbA1c <=7% at week 30 (percentage = [number of subjects with HbA1c <=7% at week 30 divided by number of subjects with HbA1c >7% at baseline] * 100%).	baseline and 30 weeks
Percentage of Patients Achieving HbA1c <=6.5%	Percentage of patients in each arm who had HbA1c >6.5% at baseline and had HbA1c <=6.5% at week 30 (percentage = [number of subjects with HbA1c <=6.5% at week 30 divided by number of subjects with HbA1c >6.5% at baseline] * 100%).	baseline and 30 weeks
Change in Fasting Serum Glucose	Change in fasting serum glucose following 30 weeks of therapy (i.e., fasting serum glucose at week 30 minus fasting serum glucose at baseline)	baseline and 30 weeks
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile	Change in 7-point (pre-breakfast, 2 hour post-breakfast, pre-lunch, 2 hour post-lunch, pre-dinner, 2 hour post-dinner, 0300 hours) SMBG profile from baseline to week 30 (change = blood glucose value at week 30 minus blood glucose value at baseline)	baseline and 30 weeks
Change in Total Cholesterol	Change in total cholesterol following 30 weeks of therapy (i.e., total cholesterol at week 30 minus total cholesterol at baseline)	baseline and 30 weeks
Change in Low Density Lipoprotein (LDL) Cholesterol	Change in LDL cholesterol following 30 weeks of therapy (i.e., LDL cholesterol at week 30 minus LDL cholesterol at baseline)	baseline and 30 weeks
Change in High Density Lipoprotein (HDL) Cholesterol	Change in HDL cholesterol following 30 weeks of therapy (i.e., HDL cholesterol at week 30 minus HDL cholesterol at baseline)	baseline and 30 weeks
Change in Triglycerides	Change in triglycerides following 30 weeks of therapy (i.e., triglycerides at week 30 minus triglycerides at baseline)	baseline and 30 weeks
Change in Body Weight	Change in body weight following 30 weeks of therapy (i.e., body weight at week 30 minus body weight at baseline)	baseline and 30 weeks
Change in Waist Circumference	Change in waist circumference following 30 weeks of therapy (i.e., waist circumference at week 30 minus waist circumference at baseline)	baseline and 30 weeks
Change in Daily Insulin Dose	Change in daily insulin dose following 30 weeks of therapy (i.e., daily insulin dose at week 30 minus daily insulin dose at baseline)	baseline and 30 weeks
Change in Daily Insulin Dose (on a Per Body Weight Basis)	Change in daily insulin dose per kilogram (kg) following 30 weeks of therapy (i.e., daily insulin dose per kg at week 30 minus daily insulin dose per kg at baseline)	baseline and 30 weeks
Change in Systolic Blood Pressure (SBP)	Change in SBP following 30 weeks of therapy (i.e., SBP at week 30 minus SBP at baseline)	baseline and 30 weeks
Change in Diastolic Blood Pressure (DBP)	Change in DBP following 30 weeks of therapy (i.e., DBP at week 30 minus DBP at baseline)	baseline and 30 weeks
Minor Hypoglycemia Rate Per Year	Number of minor hypoglycemia events experienced per subject per year. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL).	baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30
Percentage of Subjects Experiencing Minor Hypoglycemia	Percentage of subjects in each arm experiencing at least one episode of minor hypoglycemia at any point during the study. Minor hypoglycemia was defined as any time a subject felt he or she was experiencing a sign or symptom associated with hypoglycemia that was either self-treated by the subject or resolved on its own and had a concurrent finger stick blood glucose <3.0 mmol/L (54 mg/dL).	baseline and weeks 2, 4, 6, 8, 10, 14, 18, 22, 26, and 30

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Pencek R, Blickensderfer A, Li Y, Brunell SC, Anderson PW. Exenatide twice daily: analysis of effectiveness and safety data stratified by age, sex, race, duration of diabetes, and body mass index. Postgrad Med. 2012 Jul;124(4):21-32. doi: 10.3810/pgm.2012.07.2567.
• Buse JB, Han J, Miller S, MacConell L, Pencek R, Wintle M. Addition of exenatide BID to insulin glargine: a post-hoc analysis of the effect on glycemia and weight across a range of insulin titration. Curr Med Res Opin. 2014 Jul;30(7):1209-18. doi: 10.1185/03007995.2014.896329. Epub 2014 Mar 18.
• Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, Endahl L, Mathieu C; NN1250-3579 (BEGIN Once Long) Trial Investigators. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes: a 1-year, randomized, treat-to-target trial (BEGIN Once Long). Diabetes Care. 2012 Dec;35(12):2464-71. doi: 10.2337/dc12-1205. Epub 2012 Oct 5.
• Rosenstock J, Shenouda SK, Bergenstal RM, Buse JB, Glass LC, Heilmann CR, Kwan AY, MacConell LA, Hoogwerf BJ. Baseline factors associated with glycemic control and weight loss when exenatide twice daily is added to optimized insulin glargine in patients with type 2 diabetes. Diabetes Care. 2012 May;35(5):955-8. doi: 10.2337/dc11-1434. Epub 2012 Mar 19.
• Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, Hoogwerf BJ, Rosenstock J. Use of twice-daily exenatide in Basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011 Jan 18;154(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. Epub 2010 Dec 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: October 1, 2008
• First Submitted That Met QC Criteria: October 1, 2008
• First Posted (Estimate): October 3, 2008

Study Record Updates

• Last Update Posted (Estimate): October 24, 2016
• Last Update Submitted That Met QC Criteria: October 21, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; metformin; pioglitazone; exenatide; Lilly; Amylin; insulin glargine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Exenatide
• Other Study ID Numbers: H8O-US-GWCO