Late phase completed clinical trials investigating bromocriptine mesylate quick release as treatment of type 2 diabetes mellitus

ABSTRACT

Introduction

Bromocriptine mesylate quick release (QR) is a dopamine D2 receptor agonist and is the only oral, primarily centrally acting drug that can be used for the treatment of adults with type 2 diabetes.

Areas covered

The authors describe current recommendations on the use of bromocriptine mesylate QR. Major efficacy and safety parameters of the late phase trials, including The Cycloset Safety Trial, have been identified and presented.

Expert opinion

Efficacy of bromocriptine mesylate QR monotherapy appears to be low but is compensated by favorable safety profile: low risk of hypoglycemia and no weight gain. The latter makes the drug an acceptable choice for obese individuals with type 2 diabetes. As a valuable additional benefit, bromocriptine is associated with significant cardiovascular risk reduction. Current recommendations include bromocriptine mesylate QR as part of dual or triple antihyperglycemic therapy especially in individuals with type 2 diabetes who are hesitant to add injectable treatment options and/or have cardiovascular disease.

KEYWORDS:

• Bromocriptine
• glycemia
• diabetes
• HbA1c
• Cycloset®

Article highlights

• Bromocriptine mesylate and the form (quick release (QR)) specifically formulated for type 2 diabetes is a sympatholytic dopamine D2 receptor agonist believed to increase dopaminergic activity, resynchronize circadian rhythm, improve insulin sensitivity and reduce body weight.

• The recommended starting dose is 0.8 mg once daily in the morning within 2 hours of awakening, which can be increased at weekly intervals to a maximum dose of 4.8 mg/day.

• Up to 95% of the dose is absorbed, 7% reaches systemic circulation and the maximum plasma concentration is achieved in about 60 minutes in fasting and 2 hours after high fat meal.

• Bromocriptine QR monotherapy has been demonstrated to improve glycosylated hemoglobin (HbA1c) by about 0.5% with the highest effect in individuals with poor glycemic control.

• The favorable safety profile of the drug includes low risk of hypoglycemia and no weight gain.

• Frequent adverse effects of bromocriptine QR are: nausea, dizziness, postural hypotension, headache and somnolence.

• Significant cardiovascular risk reduction (with improved insulin resistance, decreased triglycerides, suppressed inflammation and oxidative stress) has been associated with the drug.

• Bromocriptine QR is typically prescribed as part of the combination therapy for individuals with type 2 diabetes who do not desire to start injectable medications especially if they also have a cardiovascular disease.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer declares that they are on a speaker’s bureau for Salix Pharmaceuticals Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.