Treatment of obesity: modern aspects

Modern approaches to the treatment of obesity

Over the past few decades, the prevalence of obesity has been growing rapidly in most countries of the world. The danger of obesity is associated with an increased risk of life-threatening complications of this disease - type 2 diabetes mellitus (DM), arterial hypertension (AH), coronary heart disease (CHD), other manifestations of atherosclerosis, and sleep apnea syndrome (SNA). Obese patients also have an increased risk of malignant cancer. In this regard, all developed countries of the world are actively searching for new highly effective methods of treating obesity. The new methods of treating this disease that have been created to date organically complement the previously developed strategy for the treatment of obesity.

The generally accepted strategy is to apply a non-drug therapy program to all patients, which, if necessary, can be supplemented by medical and (or) surgical treatment of obesity.

When choosing a treatment strategy for obesity, complications of this disease and anamnestic data that increase the risk of death must be taken into account. They are usually referred to as “risk factors for obesity.” Such risk factors include hyperglycemia syndrome (type 2 diabetes, impaired glucose tolerance, high fasting glucose), hypertension, coronary artery disease, atherosclerosis of any vessels, SNA, dyslipidemia, early menopause, smoking, early onset of myocardial infarction or ventricular fibrillation in parents, age over 44 years for men and over 54 years for women.

The non-drug treatment program for obesity includes diet therapy, dosed exercise and behavioral therapy. This treatment is carried out in all obese patients, as well as in some patients with overweight (BMI). BMI is indicated by an increase in body mass index, i.e. Quetelet index (QI), from 24 kg/m² in women and 25 kg/m² in men to 29.9 kg/m². Higher IC values ​​indicate the presence of obesity. For BMI, a full non-drug obesity treatment program is prescribed to patients who have at least two risk factors or a high waist circumference. Waist circumference is regarded as high if its value in women exceeds 88 cm, and in men - 102 cm. For other patients with BMI, it is enough to simply follow a healthy lifestyle. Drug treatment of obesity is performed in case of insufficient effectiveness of non-drug therapy in all obese patients, as well as in those patients with a BMI in whom the IC is at least 27 kg/m² and there are at least two risk factors or a high waist circumference. Surgical treatment of obesity is used in patients with IR equal to or exceeding 40 kg/mI (in case of ineffectiveness of non-invasive treatment), as well as in patients with IR not less than 35 kg/mI, if they have serious concomitant pathology - hypertension, coronary artery disease, insufficiency blood circulation, severe hyperlipidemia, type 2 diabetes, SNA. Surgical treatment is permitted only in adult patients with a history of obesity of at least 5 years - in the absence of alcoholism and mental illness.

When carrying out non-drug treatment, in most cases, a method of moderate gradual weight loss is used, within which three main stages are distinguished. At the first stage, which lasts from 1 to 6 months of treatment, weight loss is achieved by approximately 10% of the initial value. From 7 to 12 months (second stage of treatment), weight is maintained at such a level that it is 5–10% lower than the original. At this stage, you should not strive for further weight loss due to the decrease in basal metabolism, which occurs 6 months after the start of obesity treatment. An attempt to force weight loss at this stage causes such a significant decrease in basal metabolism that patients develop a relapse of obesity. The basal metabolism stabilizes at a new level only after 1 year from the start of treatment. From this time on, the third stage of weight loss begins, in which further reduction in body weight is achieved.

The method of moderate gradual weight loss involves following a low-calorie diet (LCD), in which the daily calorie intake for women is 1200-1400 kcal, and for men - 1400-1600 kcal. In patients observing the NDC, the amount of fat consumed with food should not exceed 29% of the daily caloric intake of food. Consumed fats should consist of 30–50% polyunsaturated fatty acids. The amount of saturated fatty acids is limited - their energy value should not exceed 10% of daily calories. The source of animal fats can be lean fish, poultry (without skin), and occasionally lean beef tenderloin can be consumed. The cholesterol content in food should not exceed 300 mg per day. The energy value of protein in NCD is about 15% of the daily caloric intake of food. It is recommended to consume 1/3 of the daily amount of protein in the form of soy products. Carbohydrates account for 50–60% of the calories consumed daily. Carbohydrates should be represented mainly by fiber (vegetables, fruits, unsweetened berries) and soluble dietary fiber (wholemeal bread, bran, whole oats and barley, legumes). Limited consumption of pasta made from durum wheat is allowed. To enrich food with calcium, milk or kefir with 0.5–1% fat content and completely low-fat cottage cheese are introduced into the diet. Table salt is limited to 4.5 g per day. The amount of fluid consumed daily is 1.5–2 liters. It is recommended to use green tea, which contains a significant amount of catechins, which increase the level of basal metabolism and stimulate postprandial thermogenesis. Drinking three servings of green tea per day before main meals can increase energy expenditure by 80 kcal per day. Alcohol consumption should be limited if possible. It is advisable to take a multivitamin daily. The NCD must be followed for life.

There is also a method of rapid weight loss, in which within 3 months of treatment a reduction in body weight of 15–20% is achieved. Rapid weight loss is carried out only according to strict indications - in patients with IR not lower than 40 kg/mI, if they simultaneously have a treatment-refractory course of diseases such as hypertension, coronary artery disease, circulatory failure, type 2 diabetes, SNA or severe hyperlipidemia, which cannot be compensated without rapid reduction in body weight. This technique uses a very low calorie diet (VLCD). It should be borne in mind that ONCD is contraindicated for kidney disease, liver disease, cholecystitis, cholelithiasis, bronchial asthma, cancer, type 1 diabetes, heart rhythm disturbances, during the recovery period of a stroke or myocardial infarction, infectious diseases, alcoholism, drug addiction. It should not be prescribed to children and patients over 65 years of age. The duration of compliance with the ONKD should not exceed 16 weeks. The daily caloric intake of food for ONCD does not exceed 800 kcal. The proportion of the total amount of fats, proteins and carbohydrates in patients observing ONCD and NKD is the same. However, with ONCD, the energy value of saturated fatty acids should not exceed 7% of daily calories, and cholesterol intake is limited to 200 mg per day. In this regard, only cold-water sea fish fillets, skinless white poultry meat, egg whites, 0.5% milk or kefir, and zero-fat cottage cheese are allowed to be used as products of animal origin. To prevent cachexia of complete protein in ONCD, you should consume at least 1 g per 1 kg of body weight per day. Carbohydrates should be at least 100 g per day to avoid the development of ketoacidosis. The diet for patients with ONCD is enriched not only with calcium, but also with potassium and magnesium. Taking a quality multivitamin daily is a must. The use of ONCD leads to a rapid and pronounced decrease in basal metabolism, which can lead to a relapse of obesity. To prevent relapse of weight gain, patients who have stopped following the ONCD are recommended to take sibutramine for 2–3 months. In some cases, depressive disorders, called “dietary” depression, appear against the background of ONCD. Such patients may be prescribed fluoxetine instead of sibutramine.

Both NCD and ONCD have demonstrated their effectiveness in the treatment of obesity in multicenter clinical trials.

There are also other recommendations for dietary therapy for obesity: the Atkins diet, the protein diet (Zone), the Ornish vegetarian diet, and even a diet that provides nutrition for the patient depending on his blood type. The disadvantages of all these types of dietary therapies are that they have not been tested in multicenter clinical trials, and when followed, significant side effects have been observed. The effectiveness of various types of diet therapy for obesity was assessed by specialists compiling the National Registry of Body Weight Correction (USA). 3,000 cases of successful non-drug treatment of obesity were analyzed. It turned out that in 98.1% of cases, success in the treatment of obesity was achieved in patients who followed the NDC, in 0.9% - in patients who adhered to the Atkins diet, and in 1% - with other types of dietary treatment.

The optimal type of physical activity used to treat obesity is dynamic aerobic exercise. In patients with IR up to 40 kg/m², it is recommended to begin physical training with walking at an average pace - 100 steps per minute. The duration of such training is 30 minutes, and their frequency is 3-4 times a week. Gradually, the intensity of the load is increased: the pace of walking is increased to high (160 steps per minute), duration - up to 45–60 minutes, frequency - up to 1 time per day. This amount of physical activity allows you to increase energy expenditure by 200–300 kcal per day.

In patients with IR of 40 kg/m² or more, physical training begins with walking at a slow pace (65 steps per minute) for 10 minutes 3 times a week. Gradually, the intensity of the load is increased to an average level - 100 steps per minute for 30-45 minutes 4-7 times a week.

Non-pharmacological treatment of obesity cannot be successful without adequate behavioral therapy. The latter involves creating motivation for the patient to lose weight, orienting the patient to a lifelong program to combat obesity, self-control by keeping a diary of weight, nutrition and physical activity, limiting the use of drugs that contribute to weight gain, treatment of sexual dysfunction and depressive disorders, and combating stress. , a “sedimentary” lifestyle, compliance with food intake rules and other activities.

Drug therapy for obesity can achieve good results in almost all patients resistant to non-drug treatment (with the exception of patients with morbid obesity). There are a large number of medications that can reduce body weight, but today only three drugs are officially recommended for the treatment of obesity as the treatment of choice - sibutramine, orlistat and phentermine. Sibutramine and orlistat are first-line drugs, and phentermine is a second-line drug. The advantages of sibutramine and orlistat are that they are more effective in weight loss, reduce the severity of some complications of obesity, can be prescribed for a long time (up to 2 years) and do not cause serious adverse events. Only these two drugs have been proven in multicenter clinical studies that they do not lead to the development of such severe side effects as pulmonary hypertension and valvular heart disease.

Sibutramine (Meridia) is a centrally acting drug. It suppresses appetite by enhancing the action of neurotransmitters (norepinephrine, dopamine and serotonin) on the satiety centers in the ventromedial hypothalamus. This drug also increases basal metabolism by an average of 100 kcal per day and stimulates thermogenesis, which increases the ability of sibutramine to lose weight. The effectiveness and safety of sibutramine have been confirmed in a large number of multicenter studies, which in total involved more than 3 million patients (including patients with type 2 diabetes). The longest of these is the STORM study, in which continuous use of sibutramine continued for 2 years. Sibutramine reduced body weight by more than 10% in 70% of patients. It reduced weight and reduced waist size, respectively, 3 and 1.9 times more effective than placebo. The drug significantly reduced weight even in patients who violated their diet. Under the influence of meridia, the amount of visceral fat decreased by 22%, which was proven by magnetic resonance imaging. Sibutramine can effectively treat obesity in patients with depressive disorders associated with compulsive eating behavior, which is characterized by episodes of severe bulimia. Treatment with sibutramine begins with 10 mg per day, taking the entire dose of the drug before breakfast. After 4 weeks, the effect of the drug is assessed: if the weight loss is less than 2 kg, the dose of Meridia is increased to 15 mg.

The STORM study was able to prove that the effect of sibutramine persists even after its withdrawal. The same study showed that this drug improves metabolic parameters: the level of triglycerides, total cholesterol, low-density lipoproteins significantly decreased, the amount of anti-atherogenic high-density lipoproteins increased, the content of uric acid in the blood plasma decreased, and glycated hemoglobin decreased. Sibutramine, like other centrally acting anorectic drugs, can cause insomnia, dry mouth, constipation, increased heart rate by 4-5 beats per minute, a slight increase in blood pressure (BP) - systolic blood pressure increased by an average of 1.6 mm Hg. Art., diastolic blood pressure - by 1.8 mm Hg. Art. The drug is contraindicated in refractory hypertension, severe ischemic heart disease, clinically significant arrhythmias, congestive circulatory failure, chronic renal failure, severe liver failure, epilepsy.

The mechanism of action of orlistat (Xenical) is based on its ability to inhibit gastric and pancreatic lipases, which disrupts the hydrolysis of dietary fats and reduces their absorption by one third. In 60% of obese patients, orlistat reduced weight by more than 10% and significantly reduced waist size. A significant reduction in body weight was achieved both in patients with a normal state of carbohydrate metabolism and in patients with type 2 diabetes. Orlistat has confirmed its high efficacy and safety in a large number of randomized, placebo-controlled studies, the longest of which was the XENDOS study (4 years of continuous treatment with Xenical). The drug is prescribed 120 mg 3 times a day with meals or within 1 hour after meals. During the 3rd phase of clinical trials of orlistat, it was found that it reduces the level of triglycerides, total cholesterol, low-density lipoproteins, glycated hemoglobin, and lowers blood pressure. Side effects of this drug have been described, such as abdominal pain, profuse bowel movements, fatty feces, oxalaturia, and some patients have had fecal incontinence. Orlistat is contraindicated in case of malabsorption syndrome and urolithiasis with oxalate stones.

Phentermine (ionamine, adipex, fastin) reduced weight by more than 5% in 60% of patients, which was confirmed in randomized placebo-controlled studies. When treating with this drug, no reliable data have been obtained on the possibility of its beneficial effect on the severity of dyslipidemia, hyperglycemia and other complications of obesity. Short-acting forms of phentermine are prescribed 3 times a day 30 minutes before meals. Retard forms of phentermine are taken once a day before breakfast. Phentermine is a centrally acting drug. For this reason, its use may be accompanied by the same side effects as taking sibutramine. In addition, long-term use of phentermine can lead to the development of drug dependence, increased pressure in the pulmonary artery system, and enhance sympathoadrenal manifestations during “panic attacks” in patients with anxiety disorders. Phentermine (unlike sibutramine and orlistat) belongs to the group of potent drugs, is available only with a doctor's prescription, and the duration of its prescription should not exceed 3 months.

For the treatment of obesity, it is allowed to use centrally acting drugs such as mazindol, diethylpropion, benzphetamine, and phendimetrazine. However, these medications are not included in the list of drugs of choice for obesity. Their disadvantages are lack of effectiveness and the ability to cause drug dependence. The effect of these drugs was not assessed in multicenter clinical studies, and therefore their anorexigenic effect is considered unproven.

There are two weight-loss drugs that can be used to treat obesity only for special indications. One of them is the antidepressant bupropion (Wellbutrin), which reduces nicotine addiction in smokers. This drug, at a daily dose of 100 to 300 mg, caused small weight loss (about 5%) in some observational studies. Indications for taking bupropion include depression due to obesity and a situation where a long-term obese patient who smokes intends to quit smoking. Another drug - fluoxetine (Prozac, Profluzac) - also belongs to the group of antidepressants. At a daily dose of 20–40 mg, it reduced weight in short observational, placebo-controlled studies (average 5%). Indications for its use are bulimia neurotic, dietetic depression and the presence of depressive or anxiety-depressive disorders in obese patients.

Currently, seven multicenter clinical studies have been conducted abroad to study the effects of the drug rimonobant, which blocks endocannabinoid receptors. These receptors are located in the hypothalamic hunger centers, the acumba nucleus and on the surface of adipocytes. They are activated under the influence of arachidonylglycerol, anandamide and other arachidonic acid derivatives, which is accompanied by increased appetite, increased triglyceride synthesis and decreased adiponectin synthesis in adipocytes. Stimulation of endocannabinoid receptors in the subtentorial nucleus acumbia leads to the formation of nicotine dependence in long-term smokers. Rimonobant was used in a daily dose of 5 to 20 mg per day. Over 1 year of treatment, this drug reduced weight by an average of 6.6 kg (RIO-Europa), reduced waist circumference by 8.5 cm (RIO-North America), and significantly reduced the level of triglycerides and low-density lipoproteins in plasma (RIO-Lipid ), made it possible to overcome nicotine addiction and stop smoking without rebound weight gain (STRATUS-US). By stimulating the synthesis of adiponectin, rimonobant reduced the insulin resistance index by 41% and led to normalization of carbohydrate metabolism in patients with high fasting glycemia and impaired glucose tolerance (RIO-Diabetes). Taking into account the above results of clinical studies of rimonobant, it can be assumed that this drug will soon be included in the list of drugs recommended for the treatment of obesity.

A new direction in the drug treatment of obesity is the use of topiromate (Topamax), used in the USA as an antiepileptic drug. Multicenter clinical trials of this drug were conducted in obese patients (without epilepsy), during which it was proven that it significantly reduces weight and blood pressure levels. The drug was especially effective in patients with pathological types of eating behavior: compulsive eating behavior, emotional eating behavior, night eating syndrome and panic attacks. Officially, this drug is currently intended only for the treatment of epilepsy. A special indication for the use of topiromate may be a combination of epilepsy and obesity, given the fact that other antiepileptic drugs can increase weight in 50% of patients.

It is not recommended to use medicinal plant herbs and nutritional supplements for obesity. Many medicinal mixtures used for weight loss contain nephrotoxic plants (stephania, magnolia), hepatotoxic herb germander, as well as ephedra, which has a toxic effect on the kidneys, liver and overstimulates the cardiovascular and nervous systems. When using preparations containing ephedra, cases of acute myocardial infarction, stroke, acute liver and kidney failure have been reported. Components such as caffeine, chromium picolinate, chitosan, fiber, and soluble dietary fiber are used in medicinal preparations and in the form of dietary supplements for weight loss. Their ability to influence the severity of obesity has been assessed in various studies. It turned out that of all the remedies listed above, only soluble fiber (guar gum) significantly reduced body weight, but this reduction was only 5%. When using guar gum, some patients developed intestinal obstruction and esophageal obstruction.

Gastroplasty (vertical and bandage), gastric bypass and biliopancreatic bypass are currently used as surgical methods for treating obesity. Gastroplasty allows you to lose from 50 to 70% of excess adipose tissue, with gastric bypass it is possible to get rid of 65–75% of excess fat, and with biliopancreatic bypass - from 70–75%. Gastroplasty is the most common bariatric surgery in Western Europe, as it is less likely than other types of surgery to lead to chronic metabolic complications and gastrointestinal disorders. In the United States, for severe obesity, they prefer to perform gastric bypass surgery, since in this case there is no decrease in effectiveness even many years after its implementation. However, gastric bypass is accompanied by a much greater number of complications. The most severe complications occur in patients undergoing biliopancreatic bypass. The National Institutes of Health (USA) does not recommend the use of this operation due to the frequent development of severe hypoproteinemia and chronic painful diarrhea. To prevent chronic metabolic complications, all patients undergoing bariatric surgery receive high-quality multivitamins, a diet containing at least 60 g of high-quality animal protein per day, and, if necessary, calcium, iron and vitamin B12 supplements are prescribed.

Thus, although over the past few decades obesity has become a pandemic that has engulfed the population of most countries on our planet, it can nevertheless be argued that in the arsenal of modern medicine there are effective methods of treating this disease, which can not only improve the quality of life of patients, but also significantly reduce mortality from complications of obesity.

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A. Yu. Runikhin, Candidate of Medical Sciences, Russian State Medical University, Moscow

Treatment of obesity: modern aspects

over 60 years old (0.0491 x weight in kg + 2.4587) x 240
With minimal physical activity, the result obtained remains unchanged. With an average level of physical activity, it is multiplied by a factor of 1.3, with a high level - by 1.5.

To create a negative energy balance, the daily calorie content is reduced by 500 kcal, while for women it should be at least 1200 kcal/day, for men - 1500 kcal/day. Such an energy deficit will ensure a decrease in body weight by 0.5-1 kg per week. If the initial daily calorie intake was 3000-5000 kcal, it is gradually reduced (by no more than 20%). After reducing body weight by 10-15%, daily calorie intake is recalculated, which is necessary to subsequently maintain the achieved result for 6-9 months [10].

The consumption of fats and easily digestible carbohydrates is limited. Fat

is the most high-calorie component of food: 1 g of fat contains 9 kcal. Fats contribute to overeating because they give food a pleasant taste and cause a low feeling of fullness. Research has shown a direct relationship between the amount of fat consumed and body weight. Therefore, limiting fat helps reduce the intake of calories in the body and, thereby, reduce body weight. The proportion of fat in the diet should be 25-30%. The consumption of saturated fats is also reduced to 8-10% of total fat. Sources of saturated fats are products of animal origin - butter and ghee, lard, meat, poultry, fish, sausages, dairy products. Vegetable fats (with the exception of tropical ones - coconut and palm) contain predominantly unsaturated fatty acids and do not contain cholesterol. The consumption of foods high in fat (mayonnaise, cream, nuts, seeds, fatty cheeses, canned fish in oil, cakes, pastries, homemade pastries, ham, brisket, chips, etc.) is excluded or minimized and low-fat foods are used. (milk 0.5% and 1.5%, kefir 1% and 1.8%, cottage cheese 0% and 9%, milk yoghurts, sour cream 10-15%, lean meats and fish). It is very important to teach patients not only to choose correctly, but also to process and prepare foods: try not to fry food, but to stew it; Dress salads with low-calorie seasonings (salad sauce, ketchup), rather than mayonnaise.

carbohydrates are the basis of nutrition

- wholemeal bread, cereals, pasta, vegetables, legumes, fruits, berries. They should account for 55-60% of daily calories. It is recommended to include vegetables in the diet 3-4 times a day, raw or cooked, and fruits at least 2-3 times a day. Products containing easily digestible carbohydrates are not recommended: sugar, jam, confectionery, sweet drinks, fruits - melon, grapes, bananas, dates [3,5,10].

protein requirement

averages 1.5 g per kilogram of body weight. With a balanced diet, food proteins should provide 15% of the body's energy needs. The daily protein requirement is fully met by 400 g of low-fat product - cottage cheese, fish or meat. Protein products of animal origin often contain fat, and therefore their energy value is higher than protein products of plant origin. But plant protein products (soybeans, beans, peas, mushrooms) contain fiber. Therefore, it is useful to replace a certain amount of animal proteins (about 1/3) with plant proteins. This will reduce the calorie content of food and increase the supply of ballast substances that help fill the stomach and improve intestinal function. Of foods rich in proteins, it is preferable to: lean meats and fish; white poultry meat; low-fat varieties of milk, kefir, cottage cheese, cheeses (Ossetian, Adyghe and other varieties with less than 30% fat); legumes, mushrooms.

The diet should be varied, so it is necessary to teach patients to replace some dishes with others. For example, for breakfast, a sandwich with doctor's sausage can be replaced with 100 g of low-fat cottage cheese, or an omelet of 3 proteins, or 100 g of low-fat boiled fish.

Regularity of nutrition (having 3 main meals and 2 intermediate meals) is an important component of a weight loss program. Calorie content during the day is distributed: for breakfast - 25%, 2nd breakfast - 10%, lunch - 35%, afternoon snack - 10%, dinner - 20%.

For rapid weight loss in the presence of severe concomitant diseases, for medical reasons, special low-calorie diets

(less than 800 kcal/day) for 8-16 weeks. The daily diet includes high-quality proteins (0.8-1.5 g per 1 kg of weight), carbohydrates (10-80 g), dietary fiber (20-30 g), fats (1-20 g), minerals and vitamins. In this case, weight loss is 1.5-2.5 kg per week. Such treatment is carried out only in a hospital setting, since the patient requires constant monitoring. The lowest calorie diets are not recommended for BMI<25-30, pregnancy and lactation, mental illness, eating disorders, type 1 diabetes mellitus, coronary artery disease, arrhythmias, cerebrovascular diseases, severe liver and kidney diseases, cholelithiasis, gout, as well as over 65 and under 16 years of age. Very low-calorie diets are necessarily combined with behavioral therapy [14].

Fasting, as a method of treating obesity, is currently not used due to the fact that there is a high risk of complications (arrhythmias, mental disorders, hypovitaminosis with symptoms of polyneuritis, skin and hair lesions). Long-term observations of patients have shown that upon resumption of nutrition, as a rule, there is an intensive increase in weight.

Particular attention is paid to expanding aerobic physical activity

to increase energy consumption. The most effective ways to reduce body weight are running, swimming, cycling, aerobics, and skiing. The simplest, most accessible and effective form of physical activity is walking. During short-term physical activity, the body uses glycogen to cover energy needs. And only with prolonged physical activity does the burning of fat reserves occur. Start at least 10 minutes a day, with a gradual increase in the duration of physical activity to 30-40 minutes 4-5 times a week and most importantly - regularly. There is a decrease in the amount of the most dangerous, in terms of the development of concomitant diseases, abdominal-visceral fat, which helps improve tissue sensitivity to insulin [5,10].

Since the success of therapy for any chronic disease depends primarily on the participation of the patient himself in the treatment process, an important place is given to training obese patients using specially developed structured programs

.

The training is aimed at creating conscious motivation for long-term treatment and self-control, a gradual transition to proper nutrition, increasing physical activity in combination with lifestyle changes. During the training process, such motivation should be formed that will help the patient accept the concept of moderate, gradual and step-by-step weight loss, lifelong changes in eating habits and lifestyle. The first school in Russia for therapeutic training of patients with obesity, organized at the Scientific Research Center of the Russian Academy of Medical Sciences, confirms the need and importance of training patients to improve the effectiveness of treatment. Analysis of the dynamics of body weight showed that patients who completed a structured training program more effectively reduce body weight and maintain it for a long time compared to untrained patients. The most difficult part of an obesity treatment program is maintaining the body weight achieved during weight loss. At this stage, patients often need psychological support. Experience shows that doctor-patient contact is easier to maintain among trained patients, which allows long-term monitoring of patients’ health while maintaining an individual approach to each.

However, using only non-drug treatment methods often fails to achieve the desired results. According to the US National Institutes of Health, 30-60% of patients who lose weight through diet and exercise return to their original body weight within 1 year, and after 5 years, almost all of them [6,13].

Drug therapy

obesity is needed in the same way as for any other chronic disease. It is designed to significantly increase the effectiveness of non-drug treatment methods, help effectively reduce body weight, prevent relapses, improve metabolic parameters, and increase patient adherence to treatment [2,3].

First of all, pharmacotherapy is indicated when non-drug methods are ineffective - a decrease in body weight of less than 5% within 3 months of treatment (Fig. 4).

Rice. 4. Treatment algorithm for obese patients

In cases where the patient has a long history of obesity with a large number of unsuccessful attempts to lose weight and maintain it and/or a hereditary predisposition to type 2 diabetes, cardiovascular diseases with a BMI>30 kg/m2, drug treatment may be recommended in start of treatment. And in case of abdominal obesity with associated diseases and/or risk factors (dyslipidemia, hyperinsulinemia, type 2 diabetes, arterial hypertension, etc.), pharmacotherapy can also be prescribed for BMI>27 kg/m2 [5,10].

Drug therapy is not recommended for children, during pregnancy and lactation, as well as for persons over 65 years of age, since the effectiveness and safety of drugs for the treatment of obesity have not been studied in these groups. The simultaneous use of several drugs with a similar mechanism of action is not recommended.

The use of diuretics, thyroid hormones, and “extracts” from the pituitary gland is a thing of the distant past [13]. Drugs for the treatment of obesity must have a known mechanism of action, be safe for long-term use and have only mild, transient side effects [4].

Previously, drugs that act on the central nervous system by enhancing the secretion and/or inhibiting the reuptake of neurotransmitters (norepinephrine and serotonin) in the presynaptic terminals of the hypothalamic nuclei were mainly used to treat obesity.

Phentermine

and
mazindol
belong to the group of adrenergic drugs. Their action is based on increased secretion (phentermine) or partial blockade of reuptake (mazindol) of norepinephrine in the lateral hypothalamus, which leads to an increase in the concentration of norepinephrine in the synaptic cleft and is accompanied by stimulation of adrenergic receptors and inhibition of food consumption. A certain contribution to the increased suppression of hunger is made by the partial blockade of dopamine reuptake by phentermine in the same parts of the central nervous system, but this can lead to the development of addiction. Mazindol does not have a similar effect and therefore practically does not cause addiction. Side effects include insomnia, nervous agitation, dizziness, dry mouth, nausea, constipation and depression. The drugs are not approved for long-term use [7].

Phenylpropanolamine

its mechanism of action is similar to phentermine, but it does not affect the reuptake of dopamine and therefore does not cause addiction. Currently, in many countries (Russia is not one of them) it is used as a treatment for obesity. There have been no long-term studies of its effectiveness. In short-term placebo-controlled trials, mild and transient side effects were noted, and an increase in blood pressure was observed when using the drug at a dose of more than 75 mg/day, especially in combination with caffeine [6,7].

Fenfluramine

and its D-isomer
dexfenfluramine
are serotonergic drugs. Their action is ensured by increasing the secretion of serotonin mainly in the hypothalamus. The drugs have been widely used since 1985 in 65 countries. Side effects included dry mouth, diarrhea, fatigue, polyuria and drowsiness. In September 1997, fenfluramine and dexfenfluramine were withdrawn from the market due to the development of primary pulmonary hypertension and heart valve damage associated with their use [6,7].

Currently fluoxetine

is the drug of choice for the treatment of obesity in patients with depression who require both an antidepressant and a weight loss drug. Fluoxetine is a selective serotonin reuptake inhibitor. The drug is not used for the treatment of obesity, because during long-term follow-up (12 months), doses 2-3 higher than usual antidepressant doses were required to achieve weight loss. The effect was observed only for 6 months, and then a reverse increase in body weight occurred, despite ongoing treatment. A number of side effects have been identified - asthenia, increased sweating, nervous agitation, tremor, sexual dysfunction [6,7].

Currently, two drugs for the treatment of obesity are registered in Russia: sibutramine and orlistat.

Sibutramine

unlike other centrally acting drugs, it does not affect the dopaminergic system and the release of neurotransmitters from nerve endings. Its pharmacological action is to selectively inhibit the reuptake of serotonin and norepinephrine from the synaptic cleft. As a result of this dual action, a feeling of fullness is quickly achieved and the amount of food consumed is reduced, while as a result of increased thermogenesis, energy expenditure increases.

A dose-dependent effect of weight loss was established when studying the effect of sibutramine in doses from 1 to 30 mg/day. The optimal doses that produce clinically significant weight loss with good tolerability and safety are 10 and 15 mg. In large multicenter placebo-controlled studies of the drug's effectiveness within a year, a clinically significant reduction in body weight (i5%) was achieved in 82% of patients. Sibutramine is prescribed once, starting with a dose of 10 mg per day. Currently, the drug is approved for continuous use throughout the year. Studies have shown that the amount of weight loss in 1 and 3 months of sibutramine therapy is a predictor of the further effectiveness of treatment. If during the first month body weight decreases by less than 2 kg, the dose of the drug, if well tolerated, is increased to 15 mg per day. The drug is discontinued if you lose less than 2 kg within a month on the background of 15 mg, as well as if your body weight decreases within 3 months from the start of treatment by 5% of the initial one.

The drug is also effective in patients with complicated obesity, for example, with arterial hypertension. However, given the potential for an increase in blood pressure (by 1-3 mm Hg) and heart rate (by 3-7 beats per minute), careful monitoring of blood pressure and heart rate levels is recommended while taking the drug. Against the background of weight loss, most patients, as a rule, experience a decrease in both systolic and diastolic blood pressure, however, to a lesser extent compared to patients who lost weight on non-drug therapy. If systolic and/or diastolic blood pressure increases by more than 10 mm Hg. or heart rate acceleration by 10 beats/min or more (according to ECG data), sibutramine intake is canceled. In patients with dyslipidemia, placebo-controlled studies revealed a decrease in body weight with a significant improvement in lipid metabolism. An analysis of the research results showed that in obese patients combined with type 2 diabetes mellitus, along with a decrease in body weight, there was a decrease in the level of glycemia and HbA1c. However, in this group of patients, the initial recommended dose of the drug is 15 mg/day. Patients with obesity and type 2 diabetes mellitus find it difficult and slow to reduce body weight, so the result is assessed after 6-9 months. As a rule, in these patients, with a decrease in body weight by 5% from the initial one, positive dynamics are observed in terms of impaired metabolism, which helps reduce the overall risk of developing cardiovascular diseases.

The most common side effects (in < 10% of patients) - dry mouth, constipation, insomnia - are usually mild and can be explained by its pharmacological action. Concomitant use of sibutramine with MAO inhibitors or other drugs with similar effects is not recommended. Its good tolerability and safety have been confirmed through clinical use in more than 3 million patients [2,5,6,7].

The drug orlistat (Xenical)

- a peripherally acting agent aimed at the key factor in obesity - dietary fats. Xenical is a powerful, specific and long-acting inhibitor of gastric and pancreatic lipases, preventing the breakdown and subsequent absorption of food fats. There is a decrease in the amount of free fatty acids and monoglycerides in the intestinal lumen, leading to a decrease in the solubility of cholesterol and its subsequent absorption, which reduces cholesterol levels. The drug has a therapeutic effect within the gastrointestinal tract and does not have a systemic effect. Used at a dose of 120 mg 3 times a day with main meals. If a meal is missed or does not contain fat, then Xenical is skipped. Currently, 2 years of experience in continuous use of the drug have been accumulated. As randomized, placebo-controlled studies have shown, a decrease in body weight of more than 5% from the original was observed in 75% of patients. When using the drug in recommended therapeutic doses, approximately a third of the fats obtained from food are not absorbed, which leads to a noticeable decrease in visceral-abdominal fat mass and a decrease in fasting insulin levels.

With long-term use of orlistat in patients with dyslipidemia, a significant decrease in total cholesterol and low-density lipoproteins was noted, which exceeded the expected values, which is explained by the properties of the drug to reduce the absorption of cholesterol in the intestine. When using Xenical, patients with impaired glucose tolerance developed overt diabetes less often than those on a hypocaloric diet (3.0% and 7.6%, respectively) and normalization of carbohydrate metabolism was more often observed (71.6% and 49. 1% respectively). In patients with obesity and type 2 diabetes mellitus, while taking the drug, there was a decrease in body weight and an improvement in diabetes compensation (decrease in fasting glycemia and HbA1c). The drug does not have a systemic effect and is the drug of choice for the treatment of obesity in patients with arterial hypertension

. It is known that when losing weight, blood pressure decreases, and when taking orlistat, a significant decrease in diastolic pressure was noted.

Undesirable effects include: greasy stools, increased frequency of bowel movements, the urge to defecate, and oily discharge from the anus. Typically, side effects are mild, occur in the first 2-3 weeks of treatment, are associated with the mechanism of action of the drug and, with appropriate nutritional correction (fat intake less than 30% of daily calories), go away on their own [5,6,11,12].

In the presence of diseases associated with obesity, symptomatic treatment is carried out based on general principles. However, when prescribing antihypertensive drugs, their effect on lipid and carbohydrate metabolism is taken into account. The decision on the need for lipid-lowering therapy is made after determining lipid levels while following a lipid-lowering diet for 3-6 months.

Due to the increase in obesity worldwide, there is a high need for effective medications that are safe for long-term use. Therefore, the search for new means for weight loss continues. The possibility of using leptin analogues

(hormone of adipose tissue), drugs that increase thermogenesis and basal metabolism through activation of b3-adrenergic receptors, improving receptor sensitivity to insulin (thiazolidinediones).

Surgical methods

Treatment is carried out only in patients with severe obesity (BMI>=40), provided that other treatment methods have not led to a clinically significant reduction in body weight or there are severe concomitant diseases.
Currently, restrictive operations on the stomach
(vertical and horizontal gastroplasty) and
combined interventions
(gastrojejunal, biliopancreatic bypass) are widely used. As a rule, after surgery, body weight decreases during the first year by 50-70%, with the most intensive reduction in the first 6 months [5,10].

Thus, patients with the most common disease - obesity - cannot be left without medical care. According to WHO recommendations, the effectiveness of treatment is assessed at the stage of weight loss: successful

— reducing it by more than 5 kg with reducing the influence of risk factors;
excellent
- reduction by more than 10 kg;
exclusively
- more than 20 kg.
At the stage of maintaining body weight - an increase in it by less than 3 kg over 2 years of observation, as well as a steady decrease in waist circumference by 4 cm. Literature:
1. https://www.pohudenie.ru/news.shtml

2. Butrova S.A. Sibutramine (Meridia) in the treatment of obesity: experience in Russia, Clinical Pharmacology and Therapy, 2001, 10 (2), pp. 55-58.

3. Mark Bessler Multidisciplinary Management of Obesity, 1999, 85th Clinical Congress of the American College of Surgeons.

4. Butrova S.A. Sibutramine in the treatment of obesity, RMJ, 2001, 9 (9), pp. 348-351.

5. Treatment of obesity, recommendations for doctors, ed. Butrovoy S.A., 2000.

6. Bray GA Clinical evaluation and introduction to treatment of overweight. In: Contemporary Diagnosis and Management of Obesity, 1998, 131-166.

7. Belousov Yu.B. Modern approaches to the treatment of obesity. Quality clinical practice,

8. Colditz GA Nurse's Health Study, Ann Intern Med, 1995, 122, 481-486.

9. https://www.rambler.ru/db/news/

10. Savelyeva L.V. Modern approaches to the treatment of obesity, Doctor, 2000, 12, pp. 12-14.

11. Moiseev S.V. Orlistat (Xenical) in the treatment of obesity. Problems of endocrinology, 2001, No. 10 (2), pp. 80-84.

12. Stephan Rossner et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with Orlistat for Obesity, Obesity research, 2000, 8 (1), 49-61.

13. Melnicheko G..A. Obesity in the practice of an endocrinologist, RMJ, 2001, 9 (2), pp. 82–87.

14. P Mustajoki & T Pekkarinen Very low energy diets in the treatment of obesity, Obesity reviews, 2001, 2 (1), 61 - 72.