Randomized Clinical Trial of Quick-Release Bromocriptine Among Patients With Type 2 Diabetes on Overall Safety and Cardiovascular Outcomes
- J. Michael Gaziano, MD, MPH1,2,3,
- Anthony H. Cincotta, PHD4,
- Christopher M. O'Connor, MD5,
- Michael Ezrokhi, PHD4,
- Dean Rutty, MSC6,
- Z.J. Ma, PHD7 and
- Richard E. Scranton, MD, MPH1,2,3,4
- 1Massachusetts Veterans Epidemiology Research and Information Center/VA Cooperative Studies Programs, VA Boston Healthcare System, Boston, Massachusetts;
- 2Brigham and Women's Hospital, Division of Aging, Boston, Massachusetts;
- 3Harvard Medical School, Boston, Massachusetts;
- 4VeroScience, LLC, Tiverton, Rhode Island;
- 5Duke Clinical Research Institute, Durham, North Carolina;
- 6Everest Clinical Research Services, Inc., Ontario, Canada;
- 7Department of Statistics, Columbia University, New York, New York.
- Corresponding author: J. Michael Gaziano, .
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.
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.
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- Received October 29, 2009.
- Accepted March 16, 2010.
- © 2010 by the American Diabetes Association.
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