Impotence drug boosts insulin in some with diabetes

A drug initially developed to treat erectile dysfunction helps a subset of people with type 2 diabetes. Called yohimbine, the drug is effective in people with a variant of a gene called ADRA2A, researchers report October 8 in Science Translational Medicine. 

Such a treatment would provide a new therapeutic option to a substantial group of people. Approximately 40 percent of people with type 2 diabetes have a version of the ADRA2A gene that makes insulin-releasing cells in the pancreas more sensitive to the stress hormone adrenaline. When adrenaline binds to proteins on the cell surface called receptors, less insulin is secreted. People with the gene variant have more adrenaline receptors.

“It’s like driving a car with the brakes constantly on,” says Anders Rosengren, an author of the new study and diabetologist at Lund University in Malmö, Sweden.

Yohimbine can bind to the same receptors, blocking the effects of adrenaline and allowing more insulin to be released. The treatment “is analogous to releasing the brake and being able to drive with normal speed,” Rosengren says.

Stephen Liggett, a geneticist at the University of South Florida Morsani College of Medicine in Tampa, says the approach might benefit patients. Right now, “we really don’t have anything that targets that receptor,” he says. “Secondly, it provides for more individualization of the treatment regimen for diabetics.”

In type 2 diabetes, patients have trouble producing and efficiently using insulin, which helps ferry glucose from the blood so that the sugar can be used by cells for energy. In the United States, an estimated 29.1 million people — 9.1 percent of the population — have diabetes.

In the study, Rosengren and his colleagues recruited 49 people with type 2 diabetes, 28 of whom had the insulin-reducing version of ADRA2A. The team treated patients with yohimbine, a drug that has been available since the 1940s as a treatment for erectile dysfunction. The chemical is also an ingredient in the herbal supplement yohimbe bark. The researchers knew that yohimbine has been documented to block adrenaline receptors. Because it has been on the market for decades, it had already been tested for safe use in humans.

Patients took various amounts of yohimbine and drank a high-glucose solution. Researchers then measured patients’ insulin levels. Those with the insulin-suppressing version of ADRA2A secreted 29 percent more insulin when given the highest dose of yohimbine than when they received a placebo.

Yohimbine did not boost insulin secretion in patients without the ADRA2A variant.

A side effect of using yohimbine in this trial was a minor increase in blood pressure, which worries Jose Florez, a diabetologist at Massachusetts General Hospital in Boston. Because diabetes patients often have coronary artery disease, he says, yohimbine’s beneficial effect on blood glucose levels might not outweigh the risks it presents.

Another caveat was that researchers looked only at the drug’s short-term effect, less than 2 hours, on insulin levels. “They looked at a very brief snapshot in time of the status of these diabetics,” says Liggett.

Rosengren agrees that more needs to be done. “This is not a pill that will be out tomorrow,” he says. “We’ll try now to modify it to reduce the side effects, and then we will test it in larger patient samples over a longer time.”

If yohimbine clears these tests, he says, “it will be a new strategy to personalize drug treatment — to make drug treatment more effective compared to the one-size-fits-all treatments available today.” 

Editor’s Note: This article was updated October 29, 2014, to correct how much more insulin was secreted by people given the highest dose of yohimbine than by people receiving a placebo.