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A temporary help
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A temporary help

Drugs are not the first-line treatment for obesity.
They are just a temporary help, a tool just like surgery for instance, but in no case a long-term solution. Because of the lack of an efficient first-line treatment, new areas of research are constantly being explored, such as genetics.

Treatments of obesity complications
Drugs used to treat complications of obesity include anti-diabetics, anticholesterol, antihypertensive drugs… They are, however, not specific to obesity. There are currently few approved drugs for medical treatment of severe obesity. Some of them used to be largely prescribed, but are now forbidden or strongly advised against in this particular indication, because of their potential danger, or at least their ineffectiveness. These are the diuretics, laxatives and thyroid hormones.

Current drugs regarded as effective are
- Amphetamins
They are powerful anorexigens or hunger-cutters. They have a strong effect on the central nervous system, and may cause excitability and dependence, or cardiac disorders.
That is the reason why they are contra-indicated in patients with former psychiatric or cardiac disorders.

- Orlistat
It is an inhibitor of digestive enzymes called lipases, which ensure the digestion of fat.
Fat particles will be less absorbed by the small bowel in a proportion of 30%.
Available results show a weight-loss of 10% in one year of treatment.
Unexpected effects are: diarrhoea or abundant stool (10%), fat or smooth stool (20%), anal discharge.

* Outcomes of the survey published in The Lancet 1998 (Sjöström):
In this study, 743 obese people (with a Body Mass Index between 28 and kg/m2) have been included in European centres. They had a slightly low-calorie diet, that is their estimated energy expenditure less 600 calories a day. Patients were separated in two groups: one was treated with Orlistat, the other one with a placebo (that is a sham drug). Treated patients lost an average of 10.3 kg , the others 6.1 kg. 39% of the treated patients lost more than 10% of their weight, 18% in the other group.

Other surveys have shown a significant decrease of diseases related to obesity, and for example a lower cholesterol rate or improvement in hypertension.

- Sibutramine
This drug is now available in the United States, and has been approved by the Food and Drug Administration.
It is not yet authorized in Europe.

- Fenfluramines
These agents act on the central nervous system. They are effective on obesity, but they are presently prohibited because of there potential harmful effects: pulmonary hypertension valvular cardiopathies.

Treatments for the future: research in genetics
>> Genetic basis of obesity

Except some rare diseases (as the Prader-Willi syndrom), obesity never has a unique genetic cause, whatever its type. Rather, it is often a result of interaction of environmental factors and genes that are hereditarily transmitted. These hereditary factors are obvious, as shown in studies based on zygotic obese twins, who had the same food-intake, even when brought up separately. Hereditary factors can affect entire ethnic groups such as the Pimas indians of Arizona, of which 80% are obese.

The genes facilitating obesity are frequent (and even preponderant in Western countries) , because they have been selected by evolution. That is to say that at one moment in the evolution of mankind, they provided an advantage in terms of survival. One can mark this phenomenon from the passage of hunting and gathering to an era of farming and settling. Food-shortages then appeared, where people who were able to store calories and fat inside their organism turned out to be stronger and more likely to survive. Nowadays, this advantage has turned into a drawback, because shortages are rare, and little physical effort is required in daily life.

>> The role of leptin

Leptin is a protein produced by the human organism, precisely by adipose tissue, and now forms part of an important field in research. We know that leptin plays a role in controlling satiety. Hypothalamic receptors (see the chapter on generalities, causes of obesity) may react to the signal resulting from the degree of filling of adipose cells. There is an increased level of plasmatic leptin in obese patients. The gene that is coding for the production of leptin has been identified, as well as the gene coding for its receptor. Experimental data have demonstrated that an injection of leptin can reduce the food-intake in animals in certain conditions. However, a clinical application in man is still out of reach.

>> Therapeutic paths
There are three main directions:

- To develop drugs related to the mechanisms of obesity based on genetic research. This is the case for leptin.
- To classify the different types of obesity according to their causes, which will make it possible to act on specific targets. For example, to be able to determine in a person or a family which genes are more likely to cause obesity, because of insufficient energy expenditure or excess storing, or which genes predispose to a type of obesity, such as the android type (type III) - the most serious one. Therapy could then be more effective, by finding out the proper drugs, and prevention could act in an efficient way on specific topics.
- To develop a pattern of ' nutrigenetics ', that is to say to identify a food-intake behaviour adapted to the specific genes of a patient and then to determine his/her food requirements, the cycle of the meals etc.

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