The purpose of this study is to determine whether treatment with ticagrelor + aspirin is more effective than treatment with clopidogrel + aspirin in patients with type-2 diabetes. Both treatments will be given (separately) to all subjects as a one-time loading dose (i.e. higher than a normal daily dose), followed by daily dose for the next 5 to 7 days. Effectiveness of treatment will be measured with specialized blood tests before the loading dose, at two time-points after the loading dose, and once after the last daily dose.

The rising prevalence of diabetes mellitus and its associated cardiovascular complications present a major burden to healthcare providers worldwide. Cardiovascular mortality is much higher among subjects with Type 2 Diabetes Mellitus (T2DM). Increased platelet reactivity is considered a potential link between the two diseases. Thus, given the higher blood thrombogenicity of T2DM with CAD, the availability of more potent antiplatelet drugs should be associated with improvements in the prevention of cardiovascular events in the diabetic populations. Ticagrelor has been shown to possess a faster onset of action and more potency than clopidogrel. Furthermore, the PLATO has shown that these characteristics results in a significant reduction in Cardiovascular events and even death as compared with Clopidogrel.

We plan to compare the antithrombotic activity of ticagrelor versus clopidogrel in T2DM patients using a cross-over study design. Each participant will be randomly assigned to receive ticagrelor/clopidogrel + aspirin as a loading dose followed by 5-7 days of daily maintenance dosing. After a washout period of 1-2 weeks, each participant will receive the second treatment (clopidogrel/ticagrelor + aspirin) again as a loading dose followed by 5-7 days of daily dosing. Platelet function will be tested at pre-treatment baseline, two post-dose time-points on the day of loading dose, and one time-point after the last maintenance dose on day 5-7. Platelet testing will be carried out using the following methodologies:

1. Badimon Perfusion Chamber: an ex-vivo model of thrombosis that has been extensively utilized for evaluation of antithrombotic or prothrombotic effects under various pathological states. The model involves native blood perfusing over a thrombogenic substrate, triggering thrombus formation that can be measured by planimetry.
2. Platelet Aggregation - Multiplate Analyzer.
3. Platelet Aggregation - VerifyNow P2Y12 assay.
4. Vasodilator-Stimulated Phosphoprotein (VASP).

Inclusion Criteria:

• Diagnosed with type-2 diabetes being treated with oral or parenteral hypoglycemic therapy or both.
• Have not had thienopyridine therapy for at least 30 days before the study.
• Are of legal age (at least 18 years of age but less than 75 years of age) and competent mental condition to provide written informed consent.
• For women of child-bearing potential only test negative for pregnancy at the time of enrollment.

Exclusion Criteria:

• Have a defined need for thienopyridine therapy.
• Subjects within ≤30 days of coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI).
• Known glycosylated hemoglobin (HbA1c) ≥10 mg/dL within last 3 months prior to study entry.
• Have received fibrinolytic therapy <48 hours prior to randomization.
• Have active internal bleeding or history of bleeding diathesis.
• Have clinical findings that are, in the judgment of the investigator, associated with an increased risk of bleeding.
• Have history of ischemic or hemorrhagic stroke, transient ischemic attack (TIA) or intracranial neoplasm, arteriovenous malformation, or aneurysm.
• Have an International Normalized Ratio (INR) known to be >1.5 within 1 week of study entry.
• Have a known platelet count of <100,000/mm3 within 1 week of study entry.
• Have known anemia (hemoglobin [Hgb] <10 gm/dL) within 1 week of study entry.
• Are receiving or will receive oral anticoagulation or other antiplatelet therapy (other than ASA) that cannot be safely discontinued for the duration of the trial.
• Are receiving daily treatment with non-steroidal anti-inflammatory drugs (NSAIDS) that cannot be discontinued.
• Have a concomitant medical illness that in the opinion of the investigator may interfere with or prevent completion in this study.
• Have known severe hepatic dysfunction (e.g., cirrhosis or portal hypertension).
• Have a history of intolerance or allergy to ASA or approved thienopyridines (ticlopidine or clopidogrel).

there were no adverse events.