Cycloset -a new antidiabetic

The U.S. FDA approved Cycloset, a new quick-release oral formulation of bromocriptine mesylateis, which is the first therapy directly targeting the body’s dopamine activity to improve glycemic control. It is also the only drug to be approved subsequent to the FDA's guidelines that require studies demonstrating that diabetes drugs do not increase cardiovascular risk.

Preclinical studies indicate that while an increase in dopamine activity leads to improvements in diabetes, the time of day of the increased dopamine activity is also important. Studies in diabetic animals have shown that increased dopaminergic activity at a particular time of day is most effective in “resetting” the biological clock neurochemistry to a physiology that improves diabetic dysmetabolism. Taken orally, once-a-day, in the morning, Cycloset provides a single brief pulse of dopamine agonist activity shortly after its administration. Morning Cycloset improves post-prandial (after-meal) glucose without increasing plasma insulin concentrations, and the beneficial effects of Cycloset on post-meal glycemic control in patients with Type 2 diabetes are demonstrable many hours after the drug has been substantially cleared from the circulation, for example at lunch and dinner.

Mechanism: Bromocriptine mesylate, an ergot derivative, is a sympatholytic dopamine D2 agonist that exerts inhibitory effects on serotonin turnover in the central nervous system. It has been proposed that bromocriptine can reverse many of the metabolic alterations associated with obesity by resetting central (hypothalamic) circadian organization of monoamine neuronal activitties. Indeed, bromocriptine, if administered systemically or into the cerebral ventricle during the early hours of the light cycle, prevents or reverses seasonal fattening, insulin resistance, and decreased endogenous (hepatic) glucose production in mammals. Moreover, timed bromocriptine treatment decreased body weight and improved glucose tolerance in obese individuals who were instructed to follow a hypocaloric diet . Bromocriptine has also been shown to reduce mean daylong plasma glucose, triglyceride, and free fatty acid (FFA) levels in the absence of a change in body weight in obese nondiabetic women.