Addition Of Exenatide To Insulin Glargine In Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: placebo
* Drug: exenatide


Participation Criteria
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Eligibility Criteria
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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: metformin (stable dose for 6 weeks) pioglitazone (stable dose for 6 weeks) 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Drug: placebo<br>* subcutaneous injection, twice a day<br>|
| Experimental: 2<br> | Drug: exenatide<br>* subcutaneous injection, twice a day, 10mcg<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, exenatide, Amylin, Lilly, metformin, pioglitazone, insulin glargine