Anthony Cincotta, Ph.D. looked at a migrating bird and let his imagination fly. The result, after decades of research, is a FDA-approved drug for type 2 diabetes called Cycloset. It’s a new version of bromocriptine, which has long been prescribed at higher doses for Parkinson’s disease and other disorders. Unlike its parent drug, however, Cycloset is a quick-release pill taken within two hours of waking.
It works in a completely different way than other diabetes drugs. A morning dose triggers a surge of a brain chemical called dopamine. That appears to reset a biological clock that influences metabolism and blood sugar levels, says Cincotta, president and chief scientific officer of VeroScience, the Tiverton, Rhode Island maker of Cycloset. “It turns out that the master control of metabolism is the brain.”
A year-long clinical study of 3,070 diabetics found that 39 percent of those taking Cycloset met the recommended blood sugar goal, compared with 11 percent of patients taking a placebo, the manufacturer reports. What’s more, the Cycloset users had a 42 percent drop in heart attack and stroke risk. The drug is the first to be approved under new FDA rules requiring better proof that diabetes therapies are heart-safe.
The “aha moment” that sparked the drug occurred 30 years ago when Cincotta was part of a Louisiana State University team of scientists studying the metabolism of the white-throated sparrow. They discovered that sparrows aren’t such birdbrains after all. To fatten up for migration, birds go into a pre-diabetic state—and rapidly double or even quadruple their body fat.
“That means birds have a biological clock that predicts seasons when food will be scarce,” says Cincotta. “They become obese and insulin resistant—a hallmark of diabetes—at precisely the right time to survive the stress of annual migration, then reverse the process in the spring so they become lean and non-diabetic when food is plentiful.”
Many other species, from certain fish to hibernating bears, have evolved similar biological clocks, prompting Cincotta to wonder if humans might have them too. While it’s common for people to develop obesity and diabetes, our bodies aren’t very good at reversing these conditions, which have hit epidemic levels.
The researchers mapped seasonal changes in the birds’ brain chemicals and learned that dopamine was the main driver of the seasonal clock. “If we pumped up dopamine, we could change a pre-diabetic winter animal into a non-diabetic spring animal, regardless of the time of year,” says Cincotta. By developing Cycloset—named because it seems to help set a daily metabolic cycle–he adds, “we were trying to copy Mother Nature’s well-crafted timing mechanism.”
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