February 24, 2006

New drug may aid both diabetes, weight loss

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Stephen Davis, M.D.

New drug may aid both diabetes, weight loss

Vanderbilt University Medical Center researchers will soon be testing rimonabant, a new drug which in earlier clinical trials has proven to reduce weight and improve HDL cholesterol and triglyceride levels.

“Rimonabant has been shown in a series of studies in people with diabetes, and without, to cause weight loss of about 20 pounds,” said Stephen Davis, M.D., chief of the Division of Diabetes, Endocrinology and Metabolism.

“At the same time the drug has also exhibited the ability to increase HDL cholesterol (good cholesterol) over 20 percent, and reduce triglycerides by about 20 percent. This drug has also been shown to improve glucose control in patients with diabetes.”

In clinical trials, rimonabant has shown potential to become a significant tool to treat a constellation of health concerns facing many Americans, and according to Davis is the first in a new class of drugs being developed to simultaneously combat a group of cardio-metabolic risk factors.

“We now understand there is a group of risk factors which can coalesce and increase the risk of heart attack and stroke,” Davis said. “The most common term for this grouping of health problems is metabolic syndrome.”

Davis says metabolic syndrome is characterized by increased waist circumference, high blood pressure, high triglycerides, low levels of HDL and insulin resistance. Metabolic syndrome can occur by itself or in conjunction with carbohydrate intolerance during pre-diabetes or diabetes.

“One of the features of obesity, certainly in the western style of living is central (abdominal) obesity. It is believed that central obesity is a real driving force for these cardio-metabolic risks,” he said. “Adipose (fat) tissue is no longer considered just an inert storage place for fat cells. We now know it secretes hormones, and inflammatory markers. These hormones can, in turn, signal the brain to stop eating, or they can behave just the reverse. Similarly, the inflammatory markers are indicating that an inflammatory process is at work.”

What has been sorely needed to combat metabolic syndrome is not only a drug which can help people lose weight, but one which also can help with its other complications.

According to the Centers for Disease Control and Prevention, over the last 20 years obesity rates in the U.S. have skyrocketed. The National Center for Health Statistics report that 30 percent of U.S. adults age 20 and older are obese. This number represents over 80 million Americans. In fact, 60 percent of Americans are overweight. The increase in obesity is not limited to adults; the number of young people who are overweight has more than tripled since 1980, now totaling over 16 percent of the population ages 6 to 19.

These increasing obesity rates raise serious concerns because of long-term implications for Americans' health.

“There are very high hopes for rimonabant. The way it works is by blocking increased appetite, specifically increased appetite for really palatable foods,” he said. “We believe the process by which the drug works is by inhibiting receptors of the endocannabinoid system, which are found throughout the body, the brain, GI tract, liver and the pancreas. The drug also has the ability to lower insulin resistance and reduce blood pressure.

If successful in clinical trials, Davis says rimonabant could be useful for people with diabetes and those with metabolic syndrome.

Davis plans to launch a clinical trial of rimonabant in late spring.

— Davis is Rudolph Kampmeier professor of Molecular Physiology and Biophysics