Investigators will be determining whether a once weekly injectable medication Bydureon versus placebo is able to reduce the development of atherosclerosis.

Investigators are testing the overall hypothesis that 18 months of Bydureon treatment will improve cardiovascular risk factors, endothelial function and retard carotid atherosclerosis plaque progression in type 2 diabetes mellitus (T2DM). Investigators anticipate these studies will provide novel information about the temporal relationship between Bydureon induced changes in risk factors, endothelial function and atherosclerosis progression.

148 typical T2DM patients (ages 21-75) will participate in a rolling recruitment over approximately 2.25 years and be randomly allocated for 18 months to Bydureon (2 mg/week) or matching placebo subcutaneous injections 1x/week in a 2:1 ratio. Participants are expected to have a wide range of cardiovascular (CVD) risk and will therefore allow us to explore the importance of disease extent at baseline as a predictor of response. Blocked randomization will be used to ensure equal distribution of gender and CVD history. Carotid plaque MRI assessments will be performed at baseline, 9 and 18 months.

Inclusion Criteria:

• males and females of any race and ethnicity with T2DM, HbA1c of ≥6.5% and ≤10.0% on diet only
• take stable doses of oral antihyperglycemic agents with or without long-acting insulin
• must have a regular primary care provider (PCP) that is amenable to patient study participation and will facilitate (blinded to the treatment) the research team's study protocol efforts

Exclusion Criteria:

• type 1 diabetes mellitus (T1DM)
• current or recent glucagon-like peptide 1 receptor (GLP-1R) agonist use
• contraindications to MRI (e.g., claustrophobia, ferromagnetic materials, body habitus inappropriate for MRI exam)
• screening carotid ultrasound plaque thickness of <0.75 mm, prior or anticipated carotid stenting or endarterectomy
• recent CVD (past 6 months) or other major illness or conditions affecting risk (e.g., pancreatitis, severe renal disease) or personal or family history of medullary thyroid carcinoma
• patients with Multiple Endocrine Neoplasia syndrome type 2
• serious hypersensitivity to exenatide or any product components
• severe gastrointestinal disease, or pregnancy

Subject to VA regulation.