Bromocriptine: A Sympatholytic, D2-dopamine Agonist for the Treatment of Type 2 Diabetes

Ralph A. DeFronzo, MD

Disclosures

Diabetes Care. 2011;34(4):789-794. 

In This Article

Abstract and Introduction

Abstract

Bromocriptine is a sympatholytic D2-dopamine agonist that has been approved for the treatment of type 2 diabetes. Based on animal and human studies, timed bromocriptine administration within 2 h of awakening is believed to augment low hypothalamic dopamine levels and inhibit excessive sympathetic tone within the central nervous system (CNS), resulting in a reduction in postmeal plasma glucose levels due to enhanced suppression of hepatic glucose production. Bromocriptine has not been shown to augment insulin secretion or enhance insulin sensitivity in peripheral tissues (muscle). Addition of bromocriptine to poorly controlled type 2 diabetic patients treated with diet alone, metformin, sulfonylureas, or thiazolidinediones produces a 0.5–0.7 decrement in HbA1c. Bromocriptine also reduces fasting and postmeal plasma free fatty acid (FFA) and triglyceride levels. In a 52 double-blind, placebo-controlled study in type 2 diabetic patients, bromocriptine reduced the composite cardiovascular end point by 40%. The mechanism of the drug's beneficial effect on cardiovascular disease remains to be determined.

Introduction

Type 2 diabetes is a chronic metabolic disorder characterized by insulin resistance, impaired β-cell function, and multiple other metabolic/endocrine abnormalities.[1] Because of its multifactorial pathogenesis, restoration of normoglycemia is difficult to achieve and requires multiple antidiabetic medications that have different mechanisms of action and can be used in combination to produce an additive effect.[1,2] Therefore, the development of antidiabetic agents that have novel mechanisms of action and can be used in combination with currently approved medications for the treatment of type 2 diabetes is highly desirable.

Type 2 diabetic patients are at high risk for atherosclerotic cardiovascular complications.[3] Although hyperglycemia is a risk factor for coronary artery disease and stroke, it is a relatively weak risk factor compared with other more established risk factors such as dyslipidemia, hypertension, obesity, and the insulin resistance (metabolic) syndrome.[4,5] However, even after correction of dyslipidemia, hypertension, and dysglycemia, type 2 diabetic patients still remain at high risk for atherosclerotic cardiovascular complications.[6] Therefore, antidiabetic agents that not only improve glycemia but also reduce cardiovascular risk are desirable.

Recently, timed-release bromocriptine (Cycloset), a sympatholytic dopamine D2 receptor agonist, has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of type 2 diabetes. This centrally acting antidiabetic agent has a novel mechanism of action; reduces plasma glucose, triglyceride, and FFA levels; and in a prospective 1-year study reduced cardiovascular events. In this review, we will examine the mechanism of action, pharmacokinetic properties, glucose-lowering efficacy, potential antiatherogenic benefits, and safety of Cycloset.

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