Dopamine Receptor Agonist

Bromocriptine Mesylate (Cycloset)

The ergot derivative, bromocriptine mesylate (Cycloset) is approved by the Food and Drug Administration (FDA) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D).

Mechanism of Action

The mechanism by which bromocriptine mesylate improves glycemic control is not well understood. However, morning administration of bromocriptine mesylate has been shown to improve glycemic control in patients with T2D without increasing plasma insulin concentrations. This may be related to the circadian peak in central dopaminergic tone in the brain areas that regulate peripheral fuel metabolism (including glucose, lipid metabolism and protein metabolism) provided by morning administration of the quick-release bromocriptine formulation. This circadian peak in central dopaminergic tone that normally occurs at this time of day in healthy individuals has been linked to preservation and/or induction of normal insulin sensitivity and glucose metabolism in preclinical studies.

Clinical Efficacy

The approval of bromocriptine mesylate for the treatment of patients with T2D was based on the results of four randomized, double-blind, placebo-controlled clinical trials that enrolled 3,723 patients; a 24-week monotherapy trial, two 24-week trials in which bromocriptine mesylate was added to an sulfonylurea (SFU), and a 52-week safety trial in which patients also received various oral antidiabetic agents. In all four clinical trials, patients assigned to treatment with bromocriptine mesylate received an initial dose of 0.8 mg once daily, which was increased by 0.8 mg each week for 6 weeks (4.8 mg/day final dose) if no intolerance occurred or until the maximum tolerated dose ≥1.6 mg/day was reached. In these trials, treatment with bromocriptine mesylate resulted in clinically and statistically significant improvements in glycosylated hemoglobin (A1C).

In the monotherapy trial, the mean changes from baseline A1C were -0.1% and -0.3% in the bromocriptine mesylate and placebo groups, respectively. In one of the add-on to SFU trials, the mean changes in A1C were -0.4% and +0.3% with bromocriptine mesylate and placebo, respectively. In the second add-on to SFU trial, the changes in A1C were -0.1% and +0.4% in the bromocriptine mesylate and placebo groups, respectively. In these trials, treatment with bromocriptine mesylate also resulted in significant mean reductions in fasting plasma glucose (FPG) compared with placebo. In these trials, there were small increases in body weight with both bromocriptine mesylate and placebo that were not significantly different (eg, +0.2 kg and 0.5 kg, respectively, in the monotherapy trial).

Adverse Events (AEs)

In the pooled phase 3 clinical trials (bromocriptine mesylate n = 2,298; placebo n = 1,266), the most commonly reported AEs (nausea, fatigue, vomiting, headache, dizziness) lasted a median of 14 days and were more likely to occur during the initial titration. AEs leading to discontinuation of study drug occurred among 24% of the bromocriptine mesylate-treated patients and 15% of the placebo-treated patients. This between-group difference was driven mostly by gastrointestinal (GI) AEs, particularly nausea. The incidence of hypoglycemia was slightly higher in bromocriptine mesylate-treated patients than in those who received placebo. In the monotherapy trial, hypoglycemia was reported in 2 (3.7%) and 1 (1.3% in the bromocriptine mesylate and placebo groups, respectively. In the two add-on to SFU trials, the incidence of hypoglycemia was 8.6% and 5.2% with bromocriptine mesylate and placebo, respectively. In the 52-week safety trial, the incidence of hypoglycemia was 6.9% and 5.3%, respectively. Bromocriptine mesylate can cause hypotension, including orthostatic hypotension and syncope, particularly when administered with antihypertensive medications.

The Cycloset Safety Trial studied the risk of adverse cardiovascular (CV) events with this drug. The 52-week study randomized 3,095 patients with T2D 2:1 to bromocriptine-QR or placebo in conjunction with the patient’s usual diabetes therapy. The use of this quick-release formulation of bromocriptine was associated with a 42% relative risk reduction in the composite cardiovascular disease (CVD) end point of time to first event following randomization of myocardial infarction (MI), stroke, coronary revascularization, hospitalization for unstable angina, or hospitalization for congestive heart failure (CHF).

Prescribing Bromocriptine Mesylate

The administration of bromocriptine mesylate is time-sensitive. It should be taken once daily with food within 2 hours after waking in the morning. The initial dose is 1 tablet (0.8 mg) daily increased weekly by 1 tablet until maximal tolerated daily dose of 1.6 to 4.8 mg is achieved. Bromocriptine mesylate is contraindicated in patients with hypersensitivity to ergot-related drugs and in those with syncopal migraines. It should not be given to nursing women since it may inhibit lactation.

This article was last updated: October 26, 2022