How Glargine Insulin, Oral Diabetes Medications and Exenatide May Improve Blood Sugar Control and Weight Gain in Type 2 Diabetics

Study Overview
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Brief Summary
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This study is designed to look at how using glargine insulin with oral diabetes medications and exenatide may improve control of blood sugar levels and weight gain in type 2 diabetics. The main study will last 32 weeks. However, all participants completing 32 weeks will be invited to continue for another 24 weeks taking the insulin and oral medication and exenatide treatment. This extension comparing insulin and oral medication with insulin and oral medication and exenatide will look at the long term weight loss/gain and blood sugar level control effects of this new drug regimen. There is also a sub-study in the Clinical Research Center (CRC), which requires two 38-hour inpatient stays during the main study. This study offers the opportunity to study 24-hour blood sugar and metabolic patterns quantitatively.

Official Title
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Metformin, Exenatide, and Glargine Insulin in Combination for Treatment of Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: exenatide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients with type 2 diabetes Taking metformin at least 1000 mg daily plus a secretagogue, an alpha glucosidase inhibitor, a thiazolidinedione, or a single injection of any kind of insulin up to 0.4 units/kg daily for > 3 months Age range 30 to 70 years Body mass index 25-45 kg/m2 HbA1c 7.0 to 10.0% (or 7.0 to 8.5% if the second antihyperglycemic agent is insulin) Less than 50% of randomized participants will have used insulin previously Exclusion Criteria: Use of more than two antihyperglycemic agents within the last 3 months Use of more than one daily injection of any kind of insulin in the last 3 months Positive anti-GAD antibody (test required in screening) Fasting C-peptide <0.5 ng/mL (test required in screening) Pregnancy (test required in screening if able to conceive) or lactation Excessive use of alcohol or evidence of other form of drug dependency Unwillingness or inability to grant informed consent Unwillingness or inability to perform self-monitoring of blood glucose Unwillingness or inability to inject insulin and/or inject exenatide Serum creatinine >1.3 mg/dL in women or 1.4 in men Retinopathy which has required photocoagulation for treatment Major active systemic illness (e.g. neoplastic disorder, symptomatic ischemic heart disease, congestive heart failure) that might interfere with performing the study protocol Clinically significant gastrointestinal disorder including prior gastric or intestinal surgery for weight-control Ongoing use of any drug (e.g. narcotic analgesic, tricyclic antidepressant) that might alter gastric emptying Use prednisone or other systemic glucocorticoid drug in the last 3 months Use of any drug for weight-control (e.g. sibutramine, phentermine, orlistat) in the last 3 months Use of any unproven investigational drug within the last 3 months

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Participants will receive exenatide as part of their diabetes treatment | Drug: exenatide<br>* 5mcg twice a day, increasing to 10mcg twice a day for 24 weeks<br>* Other names: Byetta;|
| Placebo Comparator: 2<br>Participants will receive placebo rather than exenatide as part of their diabetes treatment | Drug: placebo<br>* 5mcg twice a day, increased to 10mcg twice a day for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Intent to Treat Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment |  | After 24 weeks of randomized treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Per Protocol Participants Randomized and Treated in Each Arm Who Had Lab-measured A1c <6.5% at 24 Weeks of Treatment | efficacy criteria, 50% of per protocol participants reached A1c target of <6.5% | After 24 weeks of randomized treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, insulin, byetta, glucose, blood sugar, metformin, A1c