A Study Comparing Exenatide With Basal Insulin in Achieving a Target HbA1c With Minimum Weight Gain in Type 2 Diabetes Patients

An Open Label Study Comparing Exenatide With Basal Insulin in Achieving an HbA1c of ≤ 7.4% With Minimum Weight Gain, in Type 2 Diabetes Patients Who Are Not Achieving Adequate HbA1c Control on Oral Anti Diabetic Therapies Alone

This is a phase 3 trial designed to compare the effects of twice daily exenatide plus oral antidiabetic agents (OADs) and once-daily insulin glargine plus OADs with respect to glycemic control, as measured by hemoglobin A1c, with minimum weight gain, in patients with uncontrolled type 2 diabetes on OADs.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 235
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom
    • Research Site
  • Bath, United Kingdom
    • Research Site
  • Blackburn, United Kingdom
    • Research Site
  • Bolton, United Kingdom
    • Research Site
  • Bournemouth, United Kingdom
    • Research Site
  • Bristol, United Kingdom
    • Research Site
  • Chippenham, United Kingdom
    • Research Site
  • Edinburgh, United Kingdom
    • Research Site
  • Glasgow, United Kingdom
    • Research Site
  • Haywards Heath, United Kingdom
    • Research Site
  • High Wycombe, United Kingdom
    • Research Site
  • Hull, United Kingdom
    • Research Site
  • Ipswich, United Kingdom
    • Research Site
  • Kent, United Kingdom
    • Research Site
  • Leicester, United Kingdom
    • Research Site
  • Liverpool, United Kingdom
    • Research Site
  • Livingstone, United Kingdom
    • Research Site
  • London, United Kingdom
    • Research Site
  • Manchester, United Kingdom
    • Research Site
  • Middlesborough, United Kingdom
    • Research Site
  • Norwich, United Kingdom
    • Research Site
  • Nottingham, United Kingdom
    • Research Site
  • Oldham, United Kingdom
    • Research Site
  • Oxford, United Kingdom
    • Research Site
  • Plymouth, United Kingdom
    • Research Site
  • Rochdale, United Kingdom
    • Research Site
  • Salford, United Kingdom
    • Research Site
  • Swansea, United Kingdom
    • Research Site
  • Torquay, United Kingdom
    • Research Site
  • Wakefield, United Kingdom
    • Research Site
  • Wirral, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosed with type 2 diabetes
• Currently being treated with the following: Dual or triple oral therapy - on a stable combination and dose for at least 3 months.
• HbA1c between 7.5% and 10.0%.
• BMI >27.

Exclusion Criteria:

• Receive chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within 2 weeks immediately prior to study.
• Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which a medical or surgical treatment was given) within 30 days prior to entry into the study.
• Treatment with the following medications: *Insulin as outpatient therapy within last 3 months; *Meglitinides, or acarbose within the last 3 months; *Regular use of any drugs that directly affect gastrointestinal motility; *Any previous (study) therapy with exenatide or glucagon-like peptide-1 (GLP-1) analogue; *Anti-obesity agent use within the last 3 months.
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: exenatide; subcutaneous injection, 5mcg or 10mcg, twice a day; Other Names: Byetta
Active Comparator: 2	Drug: insulin glargine; subcutaneous injection, titrated to target blood glucose level, once a day; Other Names: Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Who Achieved HbA1c ≤ 7.4% With Minimal Weight Gain (≤ 1kg)	Composite endpoint evaluating effect of treatment on glycemic control and weight	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Patients Who Achieved HbA1c ≤ 7.4% and Weight Gain ≤ 0.5kg	Composite endpoint evaluating effect of treatment on glycemic control and weight	26 weeks
Change in Fasting Serum Glucose	Change in fasting serum glucose from baseline (week 0) to endpoint (week 26)	26 weeks
Percent of Patients Achieving HbA1c ≤ 7.4%	Percent of patients achieving specified HbA1c target at endpoint	26 weeks
Percent of Patients Achieving HbA1c < 7%	Percent of patients achieving specified HbA1c target at endpoint	26 weeks
Percent of Patients Achieving HbA1c < 6.5%	Percent of patients achieving specified HbA1c target at endpoint	26 weeks
Change in 7 Point Self Monitored Blood Glucose Profile	Change from baseline to endpoint in self monitored blood glucose levels measured at 7 time points during the day	26 weeks
Change in Body Mass Index (BMI)	Change in BMI from baseline to endpoint	26 weeks
Change in Waist Circumference	Change in waist circumference from baseline to endpoint	26 Weeks
Change in Waist-to-hip Ratio	Change in waist-to-hip ratio from baseline to endpoint	26 weeks
Change in Body Weight	Change in body weight from baseline to endpoint	26 weeks
Percent Change in Body Weight	Percent change in baseline body weight at endpoint	26 Weeks
Percent of Patients Achieving 5% Weight Loss	Percent of patients who lost at least 5% of baseline body weight at endpoint	26 weeks
Percent of Patients Achieving 10% Weight Loss	Percent of patients who lost at least 10% of baseline body weight at endpoint	26 weeks
Change in Systolic Blood Pressure	Change in systolic blood pressure from baseline to endpoint	26 weeks
Change in Diastolic Blood Pressure	Change in diastolic blood pressure from baseline to endpoint	26 weeks
Change in Fasting Serum Total Cholesterol (TC)	Change in TC from baseline to endpoint	26 weeks
Change in High Density Lipoprotein (HDL) Cholesterol	Change in HDL cholesterol from baseline to endpoint	26 weeks
Change in TC to HDL Cholesterol Ratio	Change in TC to HDL cholesterol ratio from baseline to endpoint	26 weeks
Change in Fasting Serum Triglycerides	Change in fasting serum triglycerides from baseline to endpoint	26 weeks
Change in Low Density Lipoprotein (LDL) Cholesterol	Change in LDL cholesterol from baseline to endpoint	26 weeks
Change in Apolipoprotein-B	Change in apolipoprotein-B from baseline to endpoint	26 weeks
Incidence of Hypoglycemic Episodes	Percent of total patients in each arm experiencing hypoglycemia at any point in the 26 week study	26 weeks
Incidence of Nocturnal Hypoglycemic Episodes	Percent of total patients in each arm experiencing nocturnal hypoglycemia at any point in the 26 week study	26 weeks
Incidence of Severe Hypoglycemic Episodes	Percent of total patients in each arm experiencing severe hypoglycemia at any point during the 26 week study	26 weeks
Hypoglycemic Rate Per 30 Days	Number of hypoglycemic episodes per patient adjusted per 30 days	26 weeks
Nocturnal Hypoglycemic Rate Per 30 Days	Number of nocturnal hypoglycemic episodes per patient adjusted per 30 days	26 weeks
Severe Hypoglycemic Rate Per 30 Days	Number of severe hypoglycemic episodes per patient adjusted per 30 days	26 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Mauricio Silva de Lima, MD, 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.
• Davies MJ, Donnelly R, Barnett AH, Jones S, Nicolay C, Kilcoyne A. Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study. Diabetes Obes Metab. 2009 Dec;11(12):1153-62. doi: 10.1111/j.1463-1326.2009.01154.x.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: August 2, 2006
• First Submitted That Met QC Criteria: August 2, 2006
• First Posted (Estimate): August 4, 2006

Study Record Updates

• Last Update Posted (Estimate): April 7, 2015
• Last Update Submitted That Met QC Criteria: March 19, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: diabetes; exenatide; Lilly; Amylin; insulin glargine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Body Weight; Body Weight Changes; Diabetes Mellitus; Diabetes Mellitus, Type 2; Weight Gain; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Insulin Glargine; Exenatide
• Other Study ID Numbers: H8O-BP-GWBG