Effects of Exenatide and Insulin Glargine in Subjects With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
This Phase 3, open-label, multicenter study is designed to compare the effects of exenatide and insulin glargine (Lantus® injection) on beta-cell function in patients with type 2 diabetes mellitus using metformin.

Official Title
-----------------
A Phase 3, Randomized, Open Label, Comparator-Controlled, Parallel Group, Multicenter Study to Compare the Effects of Exenatide and Insulin Glargine on Beta Cell Function and Cardiovascular Risk Markers in Subjects With Type 2 Diabetes Treated With Metformin Who Have Not Achieved Target HbA1c

Conditions
-----------------
Type 2 Diabetes Mellitus

Intervention / Treatment
-----------------
* Drug: exenatide
* Drug: Insulin glargine
* Drug: Metformin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of type 2 diabetes, but otherwise healthy HbA1c between 6.6% and 9.5%, inclusive. Body mass index (BMI) of 25 kg/m2 to 40 kg/m2, inclusive. Treated with a stable dose of metformin for at least 2 months prior to screening. Exclusion Criteria: Patients previously in a study using exenatide. Treated with oral anti-diabetic medications other than metformin within 2 months of screening (thiazolidinediones within 5 months of screening). Treated with insulin within 3 months of screening.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide Arm<br>Exenatide and Metformin | Drug: exenatide<br>* subcutaneous injection, titrated up to a maximum of 20mcg three times a day in order to meet defined blood glucose targets<br>* Other names: Byetta;Drug: Metformin<br>* Patients usual dosage<br>|
| Active Comparator: Insulin Glargine Arm<br>Insulin Glargine and Metformin | Drug: Insulin glargine<br>* subcutaneous injection, once a day, titrated as necessary in order to meet defined blood glucose targets<br>* Other names: Lantus;Drug: Metformin<br>* Patients usual dosage<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell Function After 52 Weeks of Therapy | Treatment effect on beta-cell function as measured by the ratio of Week 52 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 52 divided by arginine-stimulated insulin secretion at baseline [week -2]). | Baseline (week -2) and 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell Function 4 Weeks After Cessation of Therapy | Treatment effect on beta-cell function as measured by the ratio of Week 56 arginine-stimulated insulin secretion during a hyperglycemic clamp(specifically, the incremental AUC of insulin with respect to basal value over a 10 min period [i.e., clamp time 290 min to 300 min]) to that at baseline (i.e., the ratio is calculated as arginine-stimulated insulin secretion at week 56 divided by arginine-stimulated insulin secretion at baseline [week -2]). | Baseline (week -2) and 56 weeks | 
| Change in First Phase C-peptide Release | Ratio of first phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to first phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. First phase C-peptide/insulin release is measured during the first ten minutes of glucose infusion during a hyperglycemic clamp procedure. | baseline (week -2), 52 weeks, and 56 weeks | 
| Change in Second Phase C-peptide Release | Ratio of second phase C-peptide response to glucose at 52 weeks (end of on-drug period) and 56 weeks (during off-drug period) compared to second phase C-peptide response to glucose at baseline (i.e., C-peptide response to glucose at week 52 or week 56 divided by C-peptide response to glucose at baseline [week -2]). C-peptide is measured as a surrogate marker of insulin secretion. Second phase C-peptide/insulin release is measured from time=10 minutes to time=80 minutes of glucose infusion during a hyperglycemic clamp procedure. | baseline (-2 weeks), 52 weeks, and 56 weeks | 
| Change in Glycosylated Hemoglobin (HbA1c) | Change in HbA1c from week 0 to week 52 (i.e., HbA1c at week 52 minus HbA1c at week 0). | Week 0 and week 52 | 
| Change in Fasting Plasma Glucose | Change in fasting plasma glucose from week 0 to week 52 (i.e., fasting plasma glucose at week 52 minus fasting plasma glucose at week 0). | 0 weeks and 52 weeks | 
| Seven Point Self Monitored Blood Glucose (SMBG) Measurements | SMBG measured at 7 time points (before and after breakfast, before and after lunch, before and after dinner, at bedtime). | 0 weeks and 52 weeks | 
| Change in Body Weight | Change in body weight from week 0 to week 52 (i.e., body weight at week 52 minus body weight at week 0). | 0 weeks and 52 weeks | 
| M-value at Baseline, Week 52 and Week 56 | M-value at baseline (week -2), week 52 (end of on-drug period), and week 56 (during off-drug period). Insulin sensitivity was assessed during the euglycemic/hyperglycemic clamp test at baseline (week -2), week 52, and week 56. Insulin-mediated glucose uptake (M-value) was calculated as the mean glucose requirement during the 90-120 minute interval of the clamp. | baseline (week -2), 52 weeks, and 56 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
diabetes, exenatide, exendin-4, Amylin, Lilly