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

Abstract

OBJECTIVEQuick-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 METHODSA 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).RESULTSIn 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.CONCLUSIONSThe 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.

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

“…60 In very preliminary reports, therapy with GLP-1 receptor agonists and DPP-4 inhibitors has been associated with improvement in either cardiovascular risk or risk factors, but there are no long-term data regarding clinical outcomes. 113 There are very limited data suggesting that AGIs 114 and bromocriptine 115 may reduce cardiovascular events. Heart failure.…”

Bromocriptine-QR therapy for the management of type 2 diabetes mellitus: developmental basis and therapeutic profile summary

“…The CST was designed to investigate the influence of bromocriptine-QR therapy upon overall and cardiovascular safety across a wide spectrum of T2DM subjects. The CST was a large (3070 subject), randomized, double blind, placebo controlled 1-year study of T2DM subjects across a wide range of glycemic control, and anti-diabetes therapy regimens [186]. Inclusion criteria were the diagnosis of type 2 diabetes, age between 30 and 80 years, body mass index <43 kg/ m 2 , stable anti-diabetes regimen consisting of either diet, oral hypoglycemic agents (no more than two), or insulin (alone or with no more than one oral hypoglycemic agent) for at least 30 days prior to randomization.…”

Different Effects of Cabergoline and Bromocriptine on Metabolic and Cardiovascular Risk Factors in Patients with Elevated Prolactin Levels

“…In addition to reducing fasting and postprandial glucose levels, its administration resulted in a small decrease in glycated haemoglobin, free fatty acid (FFA) and triglyceride levels [14,15]. In a 52-week, randomized, doubleblind, multi-centre trial, quick-release bromocriptine, in addition to their usual diabetes therapy, led to a reduction in the composite cardiovascular end-point by 42% [16]. The favourable changes in glucose and lipid metabolism as well as a beneficial cardiovascular risk profile suggest that bromocriptine (and possible also other dopamine agonists) may be particularly useful in the treatment of patients with type 2 diabetes suffering from cardiovascular disease or of patients with the presence of cardiovascular risk factors [17].…”