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Xenical in the treatment of obesity - a modern approach to the problem

Obesity has become a global epidemic, which is accompanied by a significant increase in health risks in connection with the development of clinically significant and associated diseases, as announced by WHO in 1997. In November 2006, European health ministers signed in Istanbul on the European Charter on Counteracting Obesity. It is also called the obesity epidemic.

Adipose tissue can accumulate in various areas of limited body, such as under the skin, in the abdominal cavity in a capsule or parenchymal organ (e.g., liver steatosis formation) between muscle fibers and elsewhere. Simultaneous accumulation of this tissue in different parts of the body leads to the development of general obesity, accompanied by an increase in body mass index (BMI).

Throughout the day people repeatedly change his occupation - from active to passive recreation movement. And regardless of the type of activity it loses energy. In moments of relaxation the energy is spent on digestion, brain function, etc. Obesity, regardless of the presence of predisposing factors, always realized due to excess calorie intake in the body (with food) over caloric consumption, that is the result of maintaining a positive energy balance for a long time, often formed due to dietary habits. Share this mechanism in the development of obesity is 75%, and all together predisposing factors - only 25%. Daily positive energy balance of 100 calories leads to weight gain of 3-5 kg ​​/ year.

Patients with obesity always underestimate the calorie content of food intake, and overestimate their motor load.

When logging, self-control, they underestimate the caloric intake in half or more. Such nutrition and psychological motivation lead to the development of this disease.

Correction of body weight is a key objective aimed at reducing the risks associated with obesity, increase the quality and duration of life for patients with obesity and type 2 diabetes.

The main objectives to achieve this goal are:

- Prevention of further weight gain;

- Body weight reduction of 10-15% (from baseline) for 6 months;

- The maintenance of achieved weight values ​​for a long time, at least 5 years.

In marked obesity should not try to achieve an ideal body weight, as most patients never reach these values, regardless of their wishes. In addition, such failure often leads to lower self-esteem with the rapid recovery of body weight and / or to refuse further treatment.

Maintaining body weight achieved values ​​is more difficult than the actual weight loss. It requires a lifelong lifestyle interventions, behavioral and dietary management. Therefore, body weight correction programs should emphasize continuity of such therapy throughout their lives.

The mainstay of treatment for obesity is to limit caloric intake and increased physical activity to achieve energy balance is included in the concept of lifestyle.

Today it is the most effective and relatively inexpensive approach available to arming physicians. Reducing caloric intake and increase energy expenditure allows not only to prevent a further increase in body weight, but also to reduce it. For the majority of obese patients, the target body weight loss should be up to 10-15% from baseline and weekly body weight loss - about 0.5 kg. Fast weight loss is associated with an increased risk and will necessarily lead to the return of weight. For any active program of treatment of excess weight loss of body weight less than 5% is not satisfactory, and the result - ineffective. The ideal result is to bring the treatment of body weight to the normal range (BMI 25 kg / m2 or less) without increasing it. It is not feasible for most patients.

In the first weeks of treatment, patients should see a doctor twice a week to measure the body weight. In the future, treatment monitoring should be carried out on a monthly basis. The doctor is obliged to analyze the diet causes an excess of body weight, physical activity, discuss the risk factors of obesity complications, require the patient's diary of self-control. Most of the patients are obese behavioral defects (alcohol abuse, eating in the evening or at night, and others.). Therefore, such patients should fix his daily diet, exercise in a special register in which is recorded and body weight 1-2 times a week.

Treatment of overweight and obesity is a multistep process involving lifestyle changes and medication, in some instances, surgical treatment.

Nevertheless, there is much evidence that lifestyle modification is not very effective for long-term treatment of obesity in most patients. Despite the low effectiveness of conservative treatment, many doctors have abandoned the use of invasive methods of treatment of this disease. Currently, drug therapy for obesity is the standard treatment for most other chronic diseases, but with great caution. We should not forget that obesity drug therapy is recommended as an adjunct to lifestyle modifications.

Lifestyle changes

Modifying lifestyle involves a change of attitude to his diet and his character, physical activity and body weight. In addition to the patients themselves in the treatment process should definitely include spouses. Lack of interest in reducing body weight in the family increases the probability of failure of patient weight loss programs. Patients should maintain a self-Journal daily, conduct weighing foods and evaluate their caloric content. Patients can participate in sessions closed support groups (10-20 people), which should create positive emotions, to promote self-affirmation, visually demonstrate the success of other patients.

Regular visits to the doctor are necessary to achieve sustained, controlled weight loss in patients.

OBESITY DIET THERAPY

The word "diet" has arisen from the Latin diaeta - «way of life», which stresses the importance of the use not just of those or other food products, but also compliance with proper diet throughout life.

Restricting caloric nutrition

The restriction in the diet in obese patients may be mild or significant, depending on the potential health risks. There are two levels of caloric restriction - low-calorie diet (food ranges from 800 to 1800 kcal / day), which is acceptable for the majority of obese patients, as well as specialized sverhnizkokaloriynaya diet (food is 250-799 kcal / day), given to patients with high levels of obesity health risks.

Successful weight loss depends on compliance with a low calorie diet, when power consumption per day more than the number of calories obtained when consuming food. The use of a low-calorie diet to reduce body weight by 10% for 6 months. However, only 15% of obese patients comply with such a diet.

Any diet should contain adequate amounts of fruits, vegetables, foods high in fiber and displace power from high-calorie foods. As a result of the set of studies it was concluded that the loss of body mass to a greater extent independent of the set of products and of caloric intake.

Low-calorie diet is appropriate for all patients with excess weight (BMI 25-35 kg / m2) who have decided for the first time to reduce body weight. The recommended caloric intake with a diet is about 1200 kcal / day for women and 1500 kcal / day for men. All patients selected individually powered dietitian.

With the same nutrition patients with different baseline body weight lose different amounts of weight. A BMI of 35 kg / m2 women lose 1-1.5 kg per week, and at a BMI of 25 kg / m2, the loss will be about 0.5 kg per week. Therefore vrachspetsialist vrachdietolog and must work together to determine the caloric intake and daily energy consumption and an average weight loss of 0,5 kg per week during the first month of treatment.

For different patients diet should take into account the peculiarities of the national food culture, season of the year, the personal characteristics of patients, medications, presence of comorbidities. The patient should drink daily at least 1.5-2 liters of water (in the absence of cardiac or renal failure). If you have kidney disease or other metabolic diseases physician should be taken into account in calculating the amount of protein in the diet.

International Organization for the Study of Obesity (NHLBI and NAASO) recommend to take over the standard low-calorie diet, component 1000-1200 kcal / day for women and 1,200-1,600 kcal / day for men and for women, regular exercise, or having a body weight of less than 75 kg.

In the presence of comorbidities (diabetes, hyperlipidemia, hypertension, and others.), In addition to a nutritionist in making menu doctors must take part in related disciplines. Making diet without vrachadietologa unacceptable. When caloric intake below 1200 calories recommended daily intake of multivitamin and additional polimikroelementnyh complexes. WHO experts recommend to reduce body weight at a rate of 6-12 kg for 20-24 weeks of treatment. These studies show that the majority of patients in the US who participate in weight loss programs do not restore the lost weight within 5 years. However, there are a number of studies demonstrating a return to baseline body weight within 5 years after the abolition of the diet.

PHYSICAL EXERCISE

Physical activity is an important part of weight loss program. Scientific studies have shown that people on a diet and applying additional exercise, body weight decreased significantly faster than those who kept only one diet. In particular, the recommended physical activity should include 30 minutes of brisk walking (speed of 4.5 km / h) at least 3 times a week. However, some studies recommend daily pay of up to 60 minutes of physical activity. Patients are encouraged to perform more exercise: use the stairs instead of the elevator, to engage in a brisk walk instead of using transport to spend hiking 10-15minutnye walk after meals.

In accordance with the recommendations of the American College of Sports Medicine to combat the obesity program should include exercises that cause energy consumption for adults of 300-500 calories per session or 1-2 thousand. Kcal per week. However, this is rarely a realistic goal for obese patients. According to recommendations of the NHLBI, obese patients should start weight loss program of moderate physical activity (such as brisk walking) for 30-45 minutes, 3-5 days a week. At the same time the energy consumption should be about 150-225 calories per session. Greetings and housework, such as vacuuming, 3 times a week, which may be more important than 30minutnye walk 6 days a week.

In patients with type 2 diabetes exercise contribute to lowering blood glucose levels, improve insulin sensitivity, reduce the cardiovascular risk, lower blood pressure and dyslipidemia.

By working with patients who have physical limitations, such as myocardial infarction, stroke, trauma, it is recommended to involve specialists in physical therapy for the preparation and holding of specialized rehabilitation programs.

In addition to diet and exercise to reduce body weight for thousands of years used a wide variety of tools and techniques, such as herbal remedies, homeopathy, hypnosis, psychotherapy, reflexology, and others. The abundance of approaches suggests primarily that no one method alone It may not be preferred or effective enough to treat most patients. Therefore, for each patient has to individually select one or the other method of therapy. One reason for failure of many physicians in the treatment of obesity is that in their arsenal are no sufficiently effective and safe means of reducing body weight.

Modern conventional medicine prefers drug, the clinical efficacy of which has repeatedly been proved many a multicenter, placebo-controlled and randomized studies with the use of evidence-based medicine principles. So far in the pharmacopoeia of Europe and North America it has entered only a few drugs with proven efficacy in the treatment of obesity.

Medications recommended for patients with obesity only as part of a comprehensive treatment program, which should include diet therapy, physical activity, behavior modification and diet that can increase the effectiveness of weight loss. It is carried out under the supervision of experienced doctors (endocrinologist, nutritionist, therapist, family doctor).

ADA and the American Association for the fight against obesity (Aase) does not recommend the use of medicated drugs for the treatment of obesity with cosmetic purpose or in cases where the achievement of weight loss is possible without the use of these drugs. Drug treatment is contraindicated in pregnant and lactating women, patients with decompensation of cardiovascular disease, uncontrolled hypertension, mental disorders and several other conditions. In addition, the number of patients body weight loss can be temporarily contraindicated. Therefore criteria exclude patients from weight loss programs have been developed.

Currently, only one drug approved in Europe for long-term use - orlistat. It is recommended for extended use, and its security is estimated at XENDOS study. The drug is approved for use for more than 4 years.

Watching obese patients who received drug treatment, showed that a third of these patients, the use of any drug was ineffective, and the tendency to weight loss is maintained in the majority of patients during the first 6-8 months of therapy. Then there is a plateau effect for no apparent reason. During the first month of combined treatment with the use of drugs in the body weight is reduced by an average of 2 kg. In some studies, reduction of body weight for the same period is equal to 1% of the original weight. In placebo-controlled studies, treatment response minimal doses of drugs is estimated at 89% versus 61% in patients who received placebo.

Sufficient efficacy of placebo demonstrates the importance of lifestyle changes to increase the pharmacological potency.

Medications used to reduce body weight, divided into two main groups - drugs to reduce appetite and medications that reduce the absorption of nutrients (fats, carbohydrates, etc.) From the gut - Diet correctors. Also secrete a number of other drugs, including trace elements, vitamins, amino acids, peptides, hormones, and others. In particular, the ADA and Aase recommend the use of products that have passed full clinical trials and approved by FDA.

Not all medications have the same security. Centrally acting agents (noradrenergic agents), such as, for example, phentermine, approved by FDA, however, are recommended only for short-term treatment in addition to the main treatment for obesity. At reception of preparations on the basis of phendimetrazine benzphetamine or there is a high risk of abuse of these drugs. All this gave rise to the formation of a list of safe drugs.

Effective drugs for weight loss are those that reduce the original weight by at least 5% per year.

During the initial appointment of drugs for weight loss it is recommended to resort to month trial treatment of obesity. During this period, we can estimate the sensitivity of the patient to the treatment regimen used. If the patient is not lost during this period, further treatment with this drug seems to be ineffective even in the appointment of the maximum dose.

After some piece time after the cessation of treatment, patients are prone to weight restoration, but with a repeated course of treatment not only reduces weight, but there is an additional weight loss. Do not plan a weight loss of more than 15% from baseline. As monotherapy any drug can reduce weight by no more than 8-10,6% per year from initial values. However, in order to minimize the risk of obesity and diabetes, weight loss should not be less than 12%. This is a goal that can only be achieved through the use of medication alone.

Since July 1998, when Europe was approved orlistat for use, it got 80 million patients. The drug is approved for use in 140 countries. In the US, the drug is approved for the treatment of obesity April 26, 1999.

Orlistat (Xenical) - stable synthetic substance (tetrahydrolipstatin), which is similar to the waste products of the bacteria Streptomyces toxytricini ( «lipstatin"). The drug has a high lipophilicity, good soluble in fats, but its solubility in water is very low. There is no systemic exposure to the drug, it is practically not absorbed from the intestine. Orlistat is mixed with the fat droplets in the stomach, blocking the active site of lipase molecule, not allowing the enzyme to break down fats (triglycerides). Due to the structural similarity with triglycerides orlistat drug interacts with the active site of enzymes - lipases covalently binding to its serine residue. Binding is slowly reversible, but under physiological conditions, the suppressive effect of the drug during passage through the gastrointestinal tract unchanged. Consequently, about 30% triglycerides of food are not digested and absorbed, enabling a supplementary caloric deficit compared with only diet of approximately 150-180 kcal / day.

Unsplit glycerides may not penetrate the bloodstream and excreted in the feces, creating an energy deficit and reduces body weight. Orlistat has no effect on the hydrolysis and absorption of carbohydrates, proteins and phospholipids. Orally accepted dose of orlistat is almost full (about 97%) is excreted in the faeces, and 83% is eliminated as unchanged drug.

More than three quarters of patients taking Xenical and follow a diet at 1 year achieved a clinically significant reduction in body weight (more than 5% of initial body weight). While taking orlistat and dieting after 1 or 2 years treatment thinned more than 10% of initial body weight twice the number of patients than with a diet and placebo. It can be predicted that patients, strictly complying with the recommendations received (as judged by a reduction in body weight of more than 5% in 3 months), the end of the first year of treatment, significantly reduce body weight (14%). After an initial decrease in body weight, patients treated with placebo and diet again added twice as much patients on diet and orlistat.

Preferably, orlistat appoint to all patients who are overweight and obese who have a taste for fatty foods. In the analysis of fat content in the diet of the patient should be evaluated not only animals but also vegetable oils, not only overt (visible), but hidden fats.

In addition to the actions mediated decrease in body weight, orlistat exerts additional positive effects on levels of total cholesterol and LDL cholesterol.

Orlistat reduces the amount of free fatty acids and monoglycerides in the intestinal lumen, solubility and subsequent absorption of cholesterol help reduce hypercholesterolemia. The ratio of LDL cholesterol / HDL cholesterol levels, a well-known predictor of cardiovascular risk, at 1 and 2 years of treatment with orlistat was significantly improved (p <0.001 and p <0.001, respectively, compared with the placebo group). Significant improvement over 2 years of treatment with orlistat and it was noted by the apolipoproteinaV - a well-known cardiovascular risk factors.

While taking orlistat high blood pressure is reduced significantly.

Weight loss after 1 and 2 years of its receipt accompanied by a reduction in both systolic (BPs) and diastolic (ADD) blood pressure. In high-risk patients (baseline add 90 mm Hg), treatment with orlistat reduced it by 7.9 mm Hg the end of the first year, whereas the placebo add reduction equaled 5.5 mmHg (P = 0.06). Similar results were obtained in respect of BPs in patients at high risk (Td initial 140 mm Hg). At the same time in patients treated with placebo, it decreased by 5.1 mm Hg, and patients receiving orlistat - more than 10.9 mm Hg (P <0.05). Thus, these results show that orlistat in conjunction with a diet strongly reduces blood pressure in patients with obesity and hypertension than diet therapy alone.

Lowering blood pressure reduces the degree of cardiovascular risk.

Orlistat is taken with each meal, washing down with water. The presence of lipases in the gastrointestinal tract is necessary for the manifestation of the effect of orlistat. Since the secretion of lipase is stimulated by the presence of food in the gastrointestinal tract, orlistat should be taken with food. Its effectiveness is optimal while taking the drug during or within up to 1 hour after a meal containing less than 30% calories from fat. Xenical recommended effective dose of the drug is 120 mg three times a day (360 mg / day). Higher doses were not significantly increase the beneficial effects while lower are not accompanied by a notable improvement of portability.

Tolerability orlistat inversely correlated with the amount of fat in food. Side effects are frequent loose stools, which intensified after the consumption of foods rich in fats. In applying the drug observed common negative effects in the form of increased frequency of stool and steatorrhea, as noted in the three-year study among patients receiving different combinations of orlistat with antidiabetic drugs and moderate diet that contains about 30% fat.

Thus, Xenical can be used not only as a remedy but also as a diagnostic. The patient explained the mechanism of action of the drug Xenical and are asked to follow the changes in stool. If he becomes fat and oily, therefore, the patient overeat fats. It is essential that the patient himself is convinced of overeating fat, which is often initially denied - not because of a conscious desire to enter medical misleading, but simply out of ignorance. As a rule, patients take into account only the visible animal fat and completely ignore the hidden fats. In addition, some go to the vegetable diet, start to abuse vegetable oils, forgetting about their very high calorie. This means that the appearance of fatty stools while taking orlistat (Xenical) serves as a marker of excessive fat consumption and requires correction of dietary intake.

In conclusion, the treatment of obesity must necessarily be comprehensive and include both pharmacological and non-pharmacological therapies. The main task of the doctor is to develop a new long-term patient skills proper eating and physical activity, which should remain with him for life. All the means employed - both pharmacological and non-pharmacological - aimed at addressing the primary problem: the formation of a correct way of life of the patient with obesity, as only this can be the key to the absence of relapses.