Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes

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.

Figure 1

Kaplan-Meier curve of the occurrence of the prespecified composite cardiovascular end point among patients randomized to bromocriptine-QR or placebo. The composite cardiovascular end point consisted of the time to first myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina, or hospitalization for congestive heart failure that occurred after randomization. All cardiovascular events were independently adjudicated. The hazard ratio of bromocriptine-QR versus placebo for the occurrence of the composite cardiovascular end point was 0.60 (95% CI 0.37–0.96). The effect of treatment was estimated from the unadjusted Cox proportional-hazard model that used all the available data.