Adding a weekly exenatide injection to usual care did not affect the rate of major adverse cardiovascular events in patients with type 2 diabetes, according to a recent industry-funded trial.
Patients with type 2 diabetes (with or without previous cardiovascular disease) were randomized to receive 2 mg of exenatide or matching placebo injection once a week. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
Researchers followed more than 14,700 patients for a median of 3.2 years. Results of the study, which was funded by Amylin Pharmaceuticals, were published online on Sept. 28 by The New England Journal of Medicine.
Overall, the primary composite outcome occurred in 839 of 7,356 patients (11.4%) in the exenatide group compared to 905 of 7,396 patients (12.2%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.83 to 1.00). Once-weekly exenatide was noninferior to placebo in terms of safety (P<0.001 for noninferiority) but was not superior to placebo in terms of efficacy (P=0.06 for superiority), an intention-to-treat analysis determined.
The risk of all-cause mortality was 6.9% in the exenatide group and 7.9% in the placebo group (hazard ratio, 0.86; 95% CI, 0.77 to 0.97), a difference that was not considered statistically significant. The groups also had similar rates of serious adverse events (e.g., acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma).
The authors noted limitations of the study, such as the high rate of early discontinuation of the trial regimen (3,164 [43.0%] patients in the exenatide group and 3,343 [45.2%] patients in the placebo group), which was most often the decision of the patient. “We speculate that probable factors for discontinuation were the complexity of the first-generation injection device that was used and the fact that our trial had no run-in period,” they wrote.
They added that other limitations of the trial include the fact that usual-care regimens were not standardized and that there was a modest between-group difference in glycated hemoglobin levels.