[Obesity Discussion]

Hundreds of other medicines to treat obesity are being developed. Scientists are researching drugs based on melanocortin, a hormone that regulates the production of leptin, an appetite-suppressing hormone. Researchers recently announced they had immunised rats against ghrelin, an appetite-stimulating hormone - but that approach cannot be applied to people because ghrelin has diverse functions in the human body. Another target is peptide YY, an appetite-control hormone produced in the gut to monitor when sufficient food has been consumed. Human trials of a peptide YY drug in a nasal spray have been conducted.

The barriers to treating weight seriously are cultural as well as financial, Caterson believes. While doctors and the community in general have no problem with the idea of popping a pill to bring blood pressure down or rebalance blood lipids - both consequences of excess body fat - collectively we seem to baulk at treating overweight people with medicine. "There's still that blame" of fat people for their plight, Caterson says, as well as the legacy of failed drugs from the 1970s and '80s that colour some doctors' judgements.

The current generation of obesity drugs - two are available in Australia and others are not yet marketed here - have proved effective compared with placebos, but still have limitations. For a start, they generally sustain only a modest weight loss of about 5 per cent of body weight, when 15 to 20 per cent would have more meaningful effects on patients' health. Drugs do little for the severely obese, nor are they the best option for mildly overweight people who have the most to gain from lifestyle changes.

But for the many people whose body mass index remains around 27 to 35 despite attempts to diet and exercise - heavy enough to make some health consequences almost inevitable - obesity specialists say drugs may be warranted to amplify the benefits of lifestyle changes. And if only 10 per cent of people in that range were medicated - a common estimate of those who may desire and be suitable for such therapy - that could still amount to nearly a million Australians.

If shedding excess weight is difficult, keeping it off presents a much greater challenge. "The natural history of weight loss is weight regain," says Professor Gary Wittert, head of the School of Medicine at the University of Adelaide and a specialist in obesity treatment at Royal Adelaide Hospital. "If a drug is required, by its very nature it's required long-term." The community, including people with weight problems, will have to accept that drug therapy will usually need to be continued in the same way as blood pressure or cholesterol treatment, says Wittert, who supervised about 30 Melbourne patients in international trials of rimonabant sponsored by its manufacturer, Sanofi-Aventis.

Professor Paul Zimmet, the director of the International Diabetes Institute, says "in Western societies there is always going to be a role for pharmacotherapies for obesity" because nothing will rein in their levels of consumption "short of a depression or a war".

Some obesity drugs are listed here, with explanations of how they work and people for whom they are suitable.

> Reductil (sibutramine) increases the activity of the mood chemicals norepinephrine and serotonin in the brain, reducing food cravings by promoting a feeling of fullness after eating. It is only available on prescription for about $120 a month. Caterson says it often works well for women who have been unsuccessful maintaining weight loss after previous attempts with diet and exercise. But many people cannot take it because of other medical conditions or potential interactions with other medicines.

> Xenical (orlistat) allows about 30 per cent of fat in the diet to pass unabsorbed through the gut. This requires major dietary change because it causes diarrhoea in people who still consume high-fat foods. Caterson says it is often helpful to men making their first conscientious attempt to bring their weight down. It is available over the counter from pharmacies and costs about $120 for a month's supply.

> Acomplia (rimonabant) is not available in Australia. Its manufacturer, Sanofi-Aventis, has applied to the Therapeutic Goods Administration to sell it here and a decision is expected by early next year. In Britain and Europe rimonabant costs about the same as other anti-obesity drugs. It is licensed overseas only to treat cardiovascular disease risk factors such as abnormal glucose tolerance and hypertension, without mention of its effect on weight. It works on the brain's endocannabinoid system that regulates appetite. Depression and anxiety are among its side-effects, and it is not recommended for people with mood disorders.

> Byetta (exenatide) is the first of a new class of diabetes drugs called incretin mimetics that boost insulin levels and reduce the urge to eat by making the stomach empty more slowly. It is not available in Australia. The New York Times recently reported it was being used by people without diabetes in the US because of its weight-lowering effects.

Hundreds of other medicines to treat obesity are being developed. Scientists are researching drugs based on melanocortin, a hormone that regulates the production of leptin, an appetite-suppressing hormone. Researchers recently announced they had immunised rats against ghrelin, an appetite-stimulating hormone - but that approach cannot be applied to people because ghrelin has diverse functions in the human body. Another target is peptide YY, an appetite-control hormone produced in the gut to monitor when sufficient food has been consumed. Human trials of a peptide YY drug in a nasal spray have been conducted.

The barriers to treating weight seriously are cultural as well as financial, Caterson believes. While doctors and the community in general have no problem with the idea of popping a pill to bring blood pressure down or rebalance blood lipids - both consequences of excess body fat - collectively we seem to baulk at treating overweight people with medicine. "There's still that blame" of fat people for their plight, Caterson says, as well as the legacy of failed drugs from the 1970s and '80s that colour some doctors' judgements.

The current generation of obesity drugs - two are available in Australia and others are not yet marketed here - have proved effective compared with placebos, but still have limitations. For a start, they generally sustain only a modest weight loss of about 5 per cent of body weight, when 15 to 20 per cent would have more meaningful effects on patients' health. Drugs do little for the severely obese, nor are they the best option for mildly overweight people who have the most to gain from lifestyle changes.

But for the many people whose body mass index remains around 27 to 35 despite attempts to diet and exercise - heavy enough to make some health consequences almost inevitable - obesity specialists say drugs may be warranted to amplify the benefits of lifestyle changes. And if only 10 per cent of people in that range were medicated - a common estimate of those who may desire and be suitable for such therapy - that could still amount to nearly a million Australians.

If shedding excess weight is difficult, keeping it off presents a much greater challenge. "The natural history of weight loss is weight regain," says Professor Gary Wittert, head of the School of Medicine at the University of Adelaide and a specialist in obesity treatment at Royal Adelaide Hospital. "If a drug is required, by its very nature it's required long-term." The community, including people with weight problems, will have to accept that drug therapy will usually need to be continued in the same way as blood pressure or cholesterol treatment, says Wittert, who supervised about 30 Melbourne patients in international trials of rimonabant sponsored by its manufacturer, Sanofi-Aventis.

Professor Paul Zimmet, the director of the International Diabetes Institute, says "in Western societies there is always going to be a role for pharmacotherapies for obesity" because nothing will rein in their levels of consumption "short of a depression or a war".