by James J. Galligan,  Ph.D., Associate  Chair,World Diabetes Day - November 17
Department of Pharmacology and  Toxicology

The Center for Disease Control (CDC) has recently released the results of a new study that shows that the number of Americans with diabetes will triple by 2050.  Currently, 10% of Americans are diabetic so this means that 30% of Americans will be diabetic in 40 years.

Diabetes is a major cause of a variety of secondary illnesses and this places a tremendous burden on the U.S. health-care system.  There are a number of causes of diabetes and some are out of the control of the patient.  However, the growing rate of obesity in America is one cause of the increased incidence of Type 2 diabetes.

People have been concerned about their weight for many years and at least in some cases this is related to vanity.  However, as body weight increases health risks also increase and obesity rates in the U.S. are alarming.  Diet and exercise are tried and true measures for controlling body weight.  It would be much easier of course if there was a pill available to help us control appetite and body weight.  This apparent need has prompted the pharmaceutical industry to study brain mechanisms that control appetite.  If such a safe and effective drug became available then the drug company would have hit a home run.  Right now there are limited drug choices for this purpose.  So, the recent Food and Drug Administration (FDA) failure to approve the use of a new weight loss drug is news.   Locaserin is a stimulant of 5-HT2C type receptors for the neurotransmitter, 5-hydroxytryptamine (5-HT).  The 5-HT2C receptor is found in the hypothalamus, an area of the brain that is involved in appetite regulation.  Stimulation of this receptor would decrease hunger and the urge to eat and therefore would help with weight loss.

Locanserin fell down in the approval process because the data indicate that it had very modest effects on body weight loss (most subjects lost ~3% or less of their initial body weight) and laboratory tests showed that rats taking high doses of locanserin for two years developed tumors at much higher rates then untreated rats.  The relatively low efficacy (body weight loss) coupled with a cancer risk sounded the death knell for this new drug.  This bodes poorly for future weight loss drugs that target 5-HT receptors.  The weight loss drugs fenfluramine and dexfenfluramine were removed from the market in 1997 because these drugs caused diseases of heart valves.  Fenfluramine and dexfenfluramine acted at 5-HT2B receptors to suppress appetite but unfortunately these receptors are also expressed by cells that make the tissues that compose heart valves.

There is a huge market for safe and effective weight loss drugs and this will catalyze future research and drug development but safe and effective are both difficult to achieve.  A healthy diet and exercise are safe and effective; they just require a little more commitment than simply popping a few pills.