Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL): A Trial To Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly In Patients With Type 2 Diabetes Mellitus

• The primary efficacy outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: No ]
• The primary safety outcome variable is defined as the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke. [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: Yes ]

• All-cause mortality [ Time Frame: Time to event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: No ]
• Components of the primary composite endpoint (cardiovascular death, fatal or nonfatal MI, fatal or nonfatal stroke). [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: No ]
• Hospitalization for acute coronary syndrome [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: No ]
• Hospitalization for heart failure [ Time Frame: Time to first event. Information collected during study period (anticipated to be up to 7.5 years). ] [ Designated as safety issue: No ]

• Time to all-cause mortality [ Time Frame: 5.5 years (average) ] [ Designated as safety issue: No ]
• Time to first confirmed cardiovascular event for each component of the primary composite endpoint [ Time Frame: 5.5 years (average) ] [ Designated as safety issue: No ]
• Time to hospitalization for acute coronary syndrome [ Time Frame: 5.5 years (average) ] [ Designated as safety issue: No ]
• Time to hospitalization for heart failure [ Time Frame: 5.5 years (average) ] [ Designated as safety issue: No ]

This study will compare the impact of including exenatide once weekly in addition to usual care vs. usual care without exenatide on major cardiovascular outcomes as measured by the primary composite endpoint of cardiovascular-related death, nonfatal myocardial infarction (MI), or nonfatal stroke.

• Drug: Exenatide Once Weekly
  Subcutaneous injection, 2 mg, administered once weekly.
• Drug: Placebo
  Subcutaneous injection, matching volume of placebo, administered once weekly.

• Experimental: Exenatide Once Weekly
  Intervention: Drug: Exenatide Once Weekly
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Patient has type 2 diabetes mellitus
• Patient has an HbA1c of ≥ 6.5 % and ≤ 10.0% and is currently using one of the following treatment regimens: A) Treatment with 0-3 oral antihyperglycemic agents B) Insulin therapy, either alone or in combination with up to two oral agents
• Female patients must not be breast feeding and agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant.

Exclusion Criteria:

• Patient has a diagnosis of type 1 diabetes mellitus, or a history of ketoacidosis.
• Patient has ever been treated with an approved or investigational GLP-1 receptor agonist.
• Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.
• Patient has a planned or anticipated revascularization procedure.
• Pregnancy or planned pregnancy during the trial period.
• Patient has end-stage renal disease or an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m2.
• Patient has a history of gastroparesis or pancreatitis.
• Personal or family history of medullary thyroid cancer or MEN2 (Multiple EndocrineNeoplasia Type 2) or calcitonin level of >40 ng/L at baseline.