The Effect of Exenatide Compared to Lantus Insulin on Vascular Function in Type 2 Diabetes
Status:
Completed
Trial end date:
2010-09-01
Target enrollment:
Participant gender:
Summary
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).
Phase:
Phase 4
Details
Lead Sponsor:
Joslin Diabetes Center
Collaborators:
Amylin Pharmaceuticals, LLC. Eli Lilly and Company