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: 0
• Participant gender: All

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
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Joslin Diabetes Center
• Collaborators: Amylin Pharmaceuticals, LLC.; Eli Lilly and Company
• Treatments: Exenatide; Insulin; Insulin Glargine; Insulin, Globin Zinc

Criteria

Inclusion Criteria:

• age 18-75

• Type 2 Diabetes (diagnosed at least 3 months prior to study)

• HbA1c: above 7.0 and less than or equal to 10.0

• At least one HbA1c over preceding 3-6 months, and HbA1c at screening, with less than 1% difference between lowest and highest values

• Stable doses of antidiabetic medications (SU and/or Metformin) for 3 months

• reproductive age females must have negative urine HCG at screening, and be using appropriate contraception during the study or be surgically sterile

• postmenopausal woman

• stable weight for 3 months prior to study (+/- 2kg)

• willingness to participate in the study

Exclusion Criteria:

• Type 1 diabetes

• Type 2 diabetes less than 3 months in duration

• HbA1c less than 7.0 or greater than 10

• age less than 18 or greater than 75

• pregnant or planning to become pregnant during study period

• current insulin therapy or insulin within 6 months prior to study

• current use of Thiazolidinedione or within 6 months prior to study

• current use of Nateglinide or Repaglinide

• current use of an Alpha-glucosidase Inhibitor

• current weight loss program

• active smoker, or quit smoking within preceding 6 months

• creatinine greater than 2.0 mg/dL

• total cholesterol greater than 300 mg/dL

• triglycerides greater than 600 mg/dL

• blood pressure greater than 160/105 mmHg

• ALT/AST greater than twice the upper limit of normal

• any other medical condition that may interfere with trial participation or trial results

• if on Statin: Statin therapy for less than 3 months or dose change within preceding 3 months

• if on ACE Inhibitor: ACE Inhibitor therapy for less than 3 months or dose change within preceding 3 months

• current use of any medication that is known to alter gastric motility