The Effect of Exenatide Compared to Lantus Insulin on Vascular Function Before and After a Meal Tolerance Test in Patients With Type 2 Diabetes

The trial is a randomized, controlled, comparator study. Subjects and investigators will not be blinded due to the nature of the treatment. After providing informed consent and meeting the inclusion and exclusion criteria, subjects will undergo baseline studies then be randomized to either treatment with Exenatide or Lantus insulin to achieve comparable improvement in glycemic control, as measured by HbA1c. A computer program (randomization.com) will be utilized to randomize 72 patients to receive either Exenatide or Lantus. The treatment group will receive twice daily injections of Exenatide, initially of 5ug BID, and increased to 10ug BID after 1 month. The control group will receive daily injections of Lantus insulin each evening, which will be titrated to achieve blood glucose targets based on self monitoring of blood glucose (SMBG), as outlined by the American Diabetes Association (ADA) (goal: fasting 90-130, peak postprandial less than180 mg/dl). The subjects on Lantus should achieve this goal by week 6 of the study, so that they have six weeks of maximal therapy. The control group will receive Lantus with the goal of similar glycemic control between the groups, with a goal of HbA1c reduction of 0.5-1.5% after 3 months. Based on recent data, it should be feasible to accomplish similar improvements in glycemia between the groups.

The trial will be preceded by a one-week screening and evaluation period, during which time the patient will be informed about the trial, and qualification will be determined based on the inclusion/exclusion criteria, as noted below. The patient will also be instructed in injection technique and SMBG techniques at the screening visit. Subjects will be asked to perform daily fasting blood glucose monitoring, and in addition on 2 days per week (1 weekday and 1 weekend day) to obtain 6 blood glucose measurements (fasting, 1-2hours post-breakfast, pre-lunch, 1-2 hours post-lunch, pre-dinner, and 1-2 hours post-dinner). Baseline studies will then be performed at week 0, including fasting laboratory studies, FMD, PWA, and Meal Challenge Test. The subject will then be randomized to receive treatment with either Lantus or Exenatide for 12 weeks duration. Repeat studies will then be performed at 12 weeks, including repeat of the baseline laboratory studies, FMD, PWA, and Meal Challenge test.

Schedule/Flow Chart

Visit 1 (week -1): Potential participants will be informed regarding the trial, records will be reviewed, and inclusion/exclusion criteria will be evaluated. Informed consent will be administered, and a history and physical will be performed. They will have baseline labs drawn, including HbA1c, glucose, lipids, CBC, chemistry, renal function, liver function, and urinalysis. If they are female and of reproductive age, they will also have a urine HCG performed. Subjects will be fasting for this visit.

Visit 2 (week 0): Participants will come in fasting. Interval medical history and medications will be reviewed. Vital signs will be obtained. PWA and FMD will be performed. The patient will then have fasting labs drawn which will include glucose, insulin, c-peptide, lipids, free fatty acids (FFA), CRP, TNFA, IL-6, ICAM, VCAM, endothelin 1, PAI-1 protein, PAI-1 activity, and FOX2. The patient will then have a mixed meal (time 0), and labs will again be drawn at 15, 30 minutes, 45 minutes, 60 minutes, 120 minutes, 180 minutes, and 240 minutes after the meal challenge measuring glucose, insulin, c-peptide, lipids, and FFA. At time 120 minutes, FWA and FMD will be performed again along with blood samples for CRP, TNFA, IL-6, ICAM, VCAM, endothelin 1, PAI-1 protein, PAI-1 activity, and FOX2. At 240 minutes, PWA, FMD, and TNG will be performed.