BACKGROUND
The cardiovascular effects of adding once-weekly treatment with exenatide to usual
care in patients with type 2 diabetes are unknown.
METHODS
We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide
at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to
safety and superior to placebo with respect to efficacy.
RESULTS
In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular
disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4).
A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7
events per 100 person-years) in the exenatide group and in 905 of 7396 patients
(12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91;
95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis
indicating that exenatide, administered once weekly, was noninferior to placebo with
respect to safety (P<0.001 for noninferiority) but was not superior to placebo
with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke,
hospitalization for heart failure, and hospitalization for acute coronary syndrome,
and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid
carcinoma, and serious adverse events did not differ significantly between the two
groups.
CONCLUSIONS
Among patients with type 2 diabetes with or without previous cardiovascular
disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number,
NCT01144338.