Effects of Once-Weekly Exenatide on Cardiovascular Outcomes

Summary and Comment |
October 5, 2017

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes

  1. Allan S. Brett, MD

Compared with placebo, this diabetes drug demonstrated neither harm nor significant benefit.

  1. Allan S. Brett, MD

To satisfy regulatory requirements about showing cardiovascular (CV) safety of new diabetes medications, industry-sponsored researchers have conducted this randomized trial of once-weekly injected exenatide (Bydureon), a glucagon-like peptide-1 (GLP-1)-receptor agonist. Nearly 15,000 patients (mean age, 62) with longstanding type 2 diabetes received exenatide or placebo. During the trial, patients were permitted to use other diabetes drugs (oral agents and insulin). At baseline, about 70% of patients had experienced previous adverse CV events, and glycosylated hemoglobin (HbA1c) level averaged 8%.

During average follow-up of about 3 years, mean HbA1c levels changed little in the placebo group and dropped by roughly 0.5% in the exenatide group. The incidence of the primary CV outcome (CV-related death, myocardial infarction, or stroke) was 11.4% in the exenatide group and 12.2% in the placebo group. This difference met statistical criteria for exenatide's noninferiority (for safety) but not superiority (for efficacy).

Comment

In this study, exenatide did not demonstrate CV harm, but it fell short of showing a statistically significant CV benefit. In contrast, another FDA-approved GLP-1 analogue (liraglutide) was associated with a significant 2 percentage-point reduction in adverse CV events during 4 years (NEJM JW Gen Med Jul 15 2016 and N Engl J Med 2016; 375:311). This apparent inconsistency might reflect intrinsically different CV effects of the two drugs or just differences in various aspects of the two trials.

Editor Disclosures at Time of Publication

  • Disclosures for Allan S. Brett, MD at time of publication Nothing to disclose

Citation(s):

Your Comment

(will not be published)

Filtered HTML

  • Allowed HTML tags: <a> <em> <strong> <cite> <blockquote> <code> <ul> <ol> <li> <dl> <dt> <dd>
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Do you have any conflict of interest to disclose?
CAPTCHA
This question is for testing whether you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

* Required

Reader comments are intended to encourage lively discussion of clinical topics with your peers in the medical community. We ask that you keep your remarks to a reasonable length, and we reserve the right to withhold publication of remarks that do not meet this standard.

PRIVACY: We will not use your email address, submitted for a comment, for any other purpose nor sell, rent, or share your e-mail address with any third parties. Please see our Privacy Policy.