Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes

  1. Richard E. Scranton, MD, MPH1,2,3,4
  1. 1Massachusetts Veterans Epidemiology Research and Information Center/VA Cooperative Studies Programs, VA Boston Healthcare System, Boston, Massachusetts;
  2. 2Brigham and Women's Hospital, Division of Aging, Boston, Massachusetts;
  3. 3Harvard Medical School, Boston, Massachusetts;
  4. 4VeroScience, LLC, Tiverton, Rhode Island;
  5. 5Duke Clinical Research Institute, Durham, North Carolina;
  6. 6Everest Clinical Research Services, Inc., Ontario, Canada;
  7. 7Department of Statistics, Columbia University, New York, New York.
  1. Corresponding author: J. Michael Gaziano, jmgaziano{at}partners.org.

Abstract

OBJECTIVE Quick-release bromocriptine (bromocriptine-QR), a D2 dopamine receptor agonist, is indicated as a treatment for type 2 diabetes. The Cycloset Safety Trial, a 52-week, randomized, double-blind, multicenter trial, evaluated the overall safety and cardiovascular safety of this novel therapy for type 2 diabetes.

RESEARCH DESIGN AND METHODS A total of 3,095 patients with type 2 diabetes were randomized 2:1 to bromocriptine-QR or placebo in conjunction with the patient's usual diabetes therapy (diet controlled only or up to two antidiabetes medications, including insulin). The all-cause–safety end point was the occurrence of any serious adverse event (SAE), with a hazard ratio (HR) noninferiority margin of 1.5. In a prespecified analysis, the frequency of cardiovascular disease (CVD) events defined as a composite of myocardial infarction, stroke, coronary revascularization, and hospitalization for angina or congestive heart failure was evaluated using modified intent-to-treat analysis (clinicaltrials.gov, NCT00377676).

RESULTS In the bromocriptine-QR group, 176 (8.6%) people reported SAEs compared with 98 (9.6%) in the placebo group (HR 1.02 [96% one-sided CI 1.27]). Fewer people reported a CVD end point in the bromocriptine-QR group versus the placebo group (37 [1.8%] vs. 32 [3.2%], respecively) (HR 0.60 [95% two-sided CI 0.35–0.96]). Nausea was the most commonly reported adverse event in the bromocriptine-QR group.

CONCLUSIONS The frequency of SAEs was comparable between the treatment arms. Compared with patients in the placebo arm, fewer patients taking bromocriptine-QR experienced a cardiovascular end point.

Footnotes

  • Clinical trial reg. no. NCT00377676, clinicaltrials.gov

  • A complete list of site investigators and coordinators is available in an online appendix at http://care.diabetesjournals.org/cgi/content/full/dc09-2009/DC1.

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • Received October 29, 2009.
  • Accepted March 16, 2010.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

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  1. Diabetes Care vol. 33 no. 7 1503-1508
  1. Online Appendix
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