The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes

What this study is testing ClinicalTrials.gov NCT00353834 ↗

Description as written by the study sponsor.

The main goals of the study are to evaluate the effect of Exenatide on endothelial-dependent vasodilation, as measured by flow mediated dilation (FMD), to evaluate the effect on endothelial-independent vasodilation, as measured by nitroglycerin (TNG) response, and to evaluate the effect on arterial stiffness, as measured by pulse wave analysis (PWA). We will also measure the effects on various markers of endothelial function, subclinical inflammation, fibrinolysis, and oxidative stress. The control group for the study will receive Lantus insulin, with a goal of similar glycemic control between the treatment and control groups. Specific Aims We will test the following hypotheses: 1. Treatment of patients with type 2 diabetes who are inadequately controlled by monotherapy with a Sulfonylurea (SU) or Metformin, or on combination therapy of a SU and Metformin with Exenatide (GLP-1 mimetic) will result in improved endothelial dependent vasodilation, as measured by FMD, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 2. Treatment with Exenatide (GLP-1 mimetic) will result in improved arterial stiffness, as measured by AI by PWA, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 3. Endothelial dependent vasodilation, as measured by FMD, and arterial stiffness, as measured by AI, measured in the postprandial state (following a standard test meal) will be improved following treatment with Exenatide as compared to treatment with once daily basal insulin (Lantus). 4. Treatment will result in no improvement in endothelial-independent vasodilation, as measured by a response to TNG, as compared to the control group, who will be treated with Lantus insulin to achieve comparable HbA1c levels. 5. Treatment with Exenatide, compared with treatment with Lantus, will result in a reduction in various plasma markers of inflammation (CRP, TNFA, IL6), endothelial activation (ICAM, VCAM, endothelin 1), fibrinolysis (PAI-1 protein, PAI-1 activity), and oxidative stress (FOX2).

Treatments tested

• Exenatide also known as Byetta Drug

  Exenetide 5ug twice daily for 4 weeks, then 10ug twice daily for 8 weeks

• Glargine Insulin also known as Lantus insulin Drug

  Glargine insulin 10-20 units once daily and subsequently adjusted per protocol to achieve a fasting glucose of 100mg/dl and avoid hypoglycemia.