Sweet Pill to Swallow?

In the next decade a new generation of drugs could be helping overweight people shed their problem, if current research fulfils its promise. For the first time, drugs could offer hope to the estimated three million obese people in Britain who need help, but until now have had only short-term appetite suppressants to turn to.

The pharmaceutical companies involved shrink from any sensational interpretation, and emphasize that the drugs are not “slimming pills”, but are intended for use in conjunction with diet. But they are exciting some experts, including Professor Michael Stock of the department of physiology at St George’s Medical School, London, who helped organize a symposium on the subject in London recently.

“These drugs will hopefully make slimming and weight maintenance easier,” he said. “They are not magic bullets, nor are they a panacea, but they will make dieting more successful, and give people confidence because they’ll lose weight more rapidly and keep to their diet longer.”

Because most of the drugs are in their infancy, they still have to undergo clinical trials before they arrive on the market. Even then they will be available only on prescription, and perhaps only to people whose obesity is serious someone who is 50 per cent over their ideal weight, about 15 stone for a man of 5ft 7in, for example.

Yet the market for “slimming aids” is vast: it is estimated that 25 to 30 per cent of the population of the West need to lose weight, without being grossly obese. Will these lesser mortals have access to the drugs that prove safe? Stock thinks they might at least become available on private prescription: “If a clinician is convinced that the patient needs treatment, fair enough. They could prescribe it in the way they prescribe nicotine chewing gum. There could be an argument for treating people who fall below a conventional threshold of obesity.”

Obesity can be tackled in one of three ways: by preventing food absorption, controlling appetite, or encouraging the body to burn more calories. The latest drugs each use one of these approaches, although it might eventually be possible to launch a triple attack on obesity by using a combination of all three.

One of the newest advances has taken place in Switzerland, where Hoffmann-La Roche has discovered a substance which, for the first time, can control dietary fat absorption. It works by inhibiting the pancreatic enzymes that dissolve fat ready for absorption in the gut. The fat that is not taken up passes harmlessly through the body. The drug, called tetrahydrolipstatin, also seems to lower the levels of fat in the blood, a factor which could be beneficial in treating heart disease.

There are two drawbacks so far: the absorption of fat-soluble vitamins could also be impeded, although vitamin supplements might compensate, and the drug causes some minor flatulence.

It is currently capable of blocking fat worth about 400 calories a day, which might not be sufficient to help in weight loss, according to Dr Roland Jung, consultant endocrinologist at Ninewells Hospital, Dundee. “But it could be used in maintaining weight once it has been lost,” he explains. “It needs more trials to make sure it’s safe on the pancreas and on the large bowel, and it needs more work on humans, which is said to be under way.”

Some of Jung’s patients have already tried one of the appetite suppressing drugs, fluoxetine, which is on the market as an anti-depressant called Prozac, but has been found to reduce the craving for carbohydrates and sweet things and so cause weight loss.

“On some patients it’s efficacious, though it’s too early to say what I think of it,” he says. “But talking to my colleagues who use it, they seem to be interested. It’s not going to help patients disappear overnight, but it will certainly help with depression. If you’re depressed, you won’t keep on a diet because everything seems to be overwhelmingly awful.”

The drug’s American manufacturer, Eli Lilly, has applied to license it as an anti-obesity agent in the US, and hopes to register it in that capacity in Europe soon.

New hormones that affect the appetite have been identified, one of which, NPY, has been shown to stimulate animals to eat voraciously. The search is now on for a way of blocking the hormone in the hope of being able to suppress human appetites. And scientists at Parke Davis’s research center at Addenbrooke’s Hospital in Cambridge are working on the human application of another appetite inhibitor, CCK, which is thought to make animals feel satiated.

Drugs that increase the metabolic rate have been studied for years in experiments using hormones from the thyroid gland. But these can have the damaging side effect of reducing muscle tissue, including that of the heart muscle. Now Beechams, ICI and La Roche are all developing compounds called thermogenic drugs that stimulate the energy-burning qualities of brown fat, the layer around the kidneys in adults which burns off the white fat stores. Jung has carried out trials on the Beechams version, as The Times reported last spring. “We found a 54 per cent greater weight loss in those who took the drug over 18 weeks while on an 800 calories-a-day diet,” he says. “The beauty of these drugs is that they seem to raise the metabolic rate without affecting the heart.

“There’s always a feeling that the body would overheat if there was a very powerful drug. We are wanting a little bit more overheating than we got with the Beecham drug, which only pushed the metabolic rate up 10 per cent we would want it to go up 60 or 70 per cent.

“Many obese people suffer anxiety and emotional disturbances on a diet, and a study found this drug actually reduced anxiety. One side effect caused a problem it was found everyone had a tremor on the drug in the first few weeks, although after that it was less pronounced.”

ICI is said to have found a compound free from tremor, although the company was wary of confirming this. “We do not see this as a drug for cosmetic purposes,” a spokesman said. “But it would be properly prescribed by doctors for people who suffer from obesity who, because of that, are at risk. At the present rate of progress, we would imagine it would be available by the mid-1990s.”

Professor John Garrow of the Human Nutrition Department at St Bartholomew’s Hospital, London, is not convinced drugs are the answer. “To treat obesity you either have to decrease energy intake, or increase its expenditure,” he said. “Drugs that increase metabolic rate won’t be helpful, because the metabolic rates of obese people are already higher than those of non-obese people. Obese people are short of breath, and the reason is that their metabolic rate is up to their total oxygen capacity.

“If they run for a bus they have very little reserve, so they get out of breath. If you increased their metabolic rate, that reserve would be further decreased.

“Appetite suppressants are moderately useful. But the problem is that someone who’s unable to diet without an anorectic drug will, given a drug, eat less and lose weight, and then what? Will they be on it forever? In any case, food intake is affected by so many factors other than hunger, including psychological factors.

There are two problems with drugs that affect food absorption: if these nutrients are not absorbed in the small bowel, then they will pass into the large bowel where, if the native bacteria can’t take over, you’ll soon get a flora that can. A 10 per cent decrease in absorption could cause quite serious problems with flatulence and possible impaired absorption of other nutrients. A 10 per cent decrease in food intake would cause less trouble.

Garrow thinks a psychological approach might be more fruitful. “I don’t believe that there are many obese people who can’t be successfully treated without drugs.”

But Jung says of the developments: “It’s exciting to think that many different approaches are being planned for the treatment of the overweight, and we hope that new drugs will help patients.

“I think this shows the public that the pharmaceutical industry is actively looking for ways of helping those who are overweight, people who have high fat levels or have diabetes, and therefore although we’re still waiting on drugs other than fluoxetine, there might be some on the way in the late 1990s that really help people.

“If you’re five or six stone overweight, you lose hope. Some people would have to diet for years to come down. These drugs could help them lose weight faster. These are exciting new developments that the public have to be patient with, because it’s no use rushing out a drug that’s unsafe. I think we’re on the right lines.”

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