Mechanism of Action

How does Cycloset work?

Mechanism of Action

Cycloset contains bromocriptine mesylate, a sympatholytic, dopamine D2 receptor agonist. In patients with type 2 diabetes, timed morning administration of Cycloset is associated with increased insulin sensitivity and glucose disposal and reduced fasting and postprandial hyperglycemia throughout the meals of the day without raising plasma insulin levels.

Pharmacodynamics

Postprandial Glucose and Insulin Response to a Meal

Patients with type 2 diabetes and inadequate glycemic control on diet alone were randomized to Cycloset or placebo in a 24-week monotherapy clinical trial. At baseline and study end, plasma samples for insulin and glucose were obtained before and 1 hour, and 2 hours after standardized meals for breakfast, lunch, and dinner. In this trial, once-daily (8 a.m.) Cycloset improved postprandial glucose without increasing plasma insulin concentrations.

Insulin-Mediated Glucose Disposal

Patients with type 2 diabetes and inadequate glycemic control on sulfonylurea therapy were randomized to Cycloset or placebo in a 16-week clinical trial. In this trial Cycloset therapy improved insulin-mediated glucose disposal and glucose tolerance and resulted in lower plasma glucose and HbA1c levels.

Dopamine-Clock Interactions in the Regulation of Peripheral Fuel Metabolism

The circadian peak of brain dopamine activity (upon daily waking) is abnormally diminished in insulin resistant states such as type 2 diabetes and results in a chronic increase in sympathetic nervous system activity which in turn causes fasting and (especially) post-meal hyperglycemia. Morning dopamine agonist administration at the time of daily waking counters this abnormally diminished dopamine activity and thus reduces elevated sympathetic nervous system activity thereby improving insulin resistance and post-meal hyperglycemia without raising plasma insulin levels.