Side effects slow progress in fighting fat

Search is still on for 'clean' drugs that can suppress appetite without affecting other systems in the body

AFTER decades of hunting for the perfect diet pill, scientists thought they might have found a family of chemicals that could become a new generation of powerful weight-loss drugs.

Mice and rats given the drugs, which act on the brain, dramatically reduced their food intake while seeming to suffer no ill effects. Several drug companies were so encouraged that they had begun testing the compounds, called melanocortin 4 receptor agonists, in people.

But researchers conducting those trials began to report an unexpected side effect: Men given the medicines experienced prolonged, unwanted and sometimes uncomfortable erections.

While the experimental drugs may have a future as competitors for Viagra, companies seeking new pills to treat obesity will probably have to look elsewhere.

The setback illustrates how difficult it is for researchers to find 'clean' weight-loss drugs, compounds that can safely suppress appetite without affecting other body systems and that will not lose their effectiveness with prolonged use.

Such problems have frequently occurred with previous treatments, ranging from amphetamines (no longer approved to suppress appetite) to fen/phen, a drug combination that produced heart valve damage in some users.

The body tends to use the same signals over and over for different jobs, said Dr Philip Smith of the National Institute of Diabetes and Digestive and Kidney Diseases.

Melanocortin 4 receptor agonists are a good example. Because they belong to a group of chemicals that can affect production of skin pigment as well as suppress appetite and cause an erection, Dr Smith joked that a single drug from the family might 'make you tan, make you thin and get you ready for sex'.

New and better medicines to aid in weight loss are urgently needed. Obesity rates are soaring in the United States and many other countries. Sixty-five per cent of American adults are overweight, and recent government figures show obesity on the rise in both sexes and in every age group.

In Singapore, a 1998 National Health Survey revealed that 6 per cent of the adult population were obese, and 24.4 per cent overweight.

Meridia and Xenical, the only medicines currently approved in the US for long-term treatment of obesity, are only modestly effective, and both have side effects in some users. Many patients given the drugs stop losing weight after about six months.

'Obesity is harder to cure than cancer,' said Dr Xavier Pi-Sunyer of Columbia University at a recent conference. 'The body defends its latest and highest weight. It tries to return you to the weight you started at.'

Because humans have suffered from periods of starvation or food shortages during most of history, genes that help the body store and use calories efficiently have been evolutionarily favoured.

For that reason, much of the world's population is genetically prone to becoming overweight, especially in a modern environment that offers abundant, high-calorie foods and facilitates an inactive lifestyle.

At least three large drug firms - Pfizer, Eli Lilly and Merck - and a host of smaller ones are working to develop new treatments for obesity.

'It's a very ancient, complex system,' said Dr Matthias Tschoep of the German Institute of Human Nutrition outside Potsdam.

Instead of the one-drug-for-all approach, specific treatments might have to be tailored to different subgroups of overweight people, depending on what genetic factors are contributing to their obesity. --The Washington Post