Bromocriptine: old drug, new formulation and new indication

• Published in: Diabetes, obesity & metabolism Vol. 12; no. 12; pp. 1048 - 1057
• Main Authors: Holt, R.I.G, Barnett, A.H, Bailey, C.J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2010; Wiley Subscription Services, Inc
• Subjects: Alkaloids; antidiabetes drug; Basal ganglia; Bromocriptine; Bromocriptine - administration & dosage; Bromocriptine - pharmacokinetics; Central nervous system diseases; Chemistry, Pharmaceutical; Circadian rhythm; Circadian rhythms; clinical trials; Controlled Clinical Trials as Topic; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Dopamine; Dopamine Agonists - administration & dosage; Dopamine Agonists - pharmacokinetics; Dopamine D2 receptors; drug mechanism; Drugs; Ergot; Fibrosis; glycaemic control; Glycated Hemoglobin A - drug effects; Hemoglobin; Humans; Hyperglycemia; Hypothalamus; Insulin; Insulin resistance; Movement disorders; Nausea; Neurodegenerative diseases; Obesity; Parkinson's disease; Rheumatic heart disease; Serotonin; treatment; Treatment Outcome; United States
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01304.x

Bromocriptine is an ergot alkaloid dopamine D₂ receptor agonist that has been used extensively in the past to treat hyperprolactinaemia, galactorrhoea and Parkinsonism. It is known that hypothalamic hypodopaminergic states and disturbed circadian rhythm are associated with the development of insulin resistance, obesity and diabetes in animals and humans. When administered in the early morning at the start of the light phase, a new quick release (QR) formulation of bromocriptine appears to act centrally to reset circadian rhythms of hypothalamic dopamine and serotonin and improve insulin resistance and other metabolic abnormalities. Phase II and III clinical studies show that QR‐bromocriptine lowers glycated haemoglobin by 0.6-1.2% (7-13 mmol/mol) either as monotherapy or in combination with other antidiabetes medications. Apart from nausea, the drug is well tolerated. The doses used to treat diabetes (up to 4.8 mg daily) are much lower than those used to treat Parkinson's disease and have not been associated with retroperitoneal fibrosis or heart valve abnormalities. QR‐bromocriptine (Cycloset™) has recently been approved in the USA for the treatment of type 2 diabetes mellitus (T2DM). Thus, a QR formulation of bromocriptine timed for peak delivery in the early morning may provide a novel neurally mediated approach to the control of hyperglycaemia in T2DM.