Xenical in the treatment of obesity: a modern look at the problem

Obesity has become a global epidemic, which is accompanied by a significant increase in health risks due to the development of clinically important and associated diseases, as announced by WHO back in 1997. In November 2006, European ministers of health signed the European Charter against Obesity in Istanbul. In it, obesity is also called an epidemic.

Adipose tissue can accumulate in limited places in various parts of the body, for example under the skin, in the abdominal cavity, in the capsule or parenchyma of organs (for example, in the liver with the formation of fatty hepatosis), between muscle fibers and in other places to buy Xenical online. The 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).

During the day a person repeatedly changes his type of activity – from active movement to passive rest. And regardless of the type of activity it loses energy. In moments of rest, energy is spent on digestion, brain work, etc. Obesity, regardless of the presence of predisposing factors, is always realized due to the excess of calories in the body (with food) over calorie consumption, that is, it is the result of maintaining a positive energy balance for a long time, often due to formed eating habits. The share of this mechanism in the development of obesity is 75%, and all together predisposing factors – only 25%. A daily positive energy balance of 100 kcal leads to an increase in body weight of 3-5 kg ​​/ year.

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

When maintaining a journal of self-control, they lower the caloric intake by two times or more. Such nutrition and psychological motivation lead to the development of this disease.

Correction of body weight is a key goal aimed at reducing the risks associated with obesity, increasing the quality and life expectancy of patients with obesity and type 2 diabetes.

The main objectives for achieving this goal are:

–   preventing further weight gain;

–   decrease in body weight by 10–15% (from baseline values) for 6 months;

–   maintaining the achieved weight values ​​for a long time, at least 5 years.

In severe obesity, one should not strive to achieve ideal body weight, since most patients never reach these values, regardless of their desires. In addition, this failure often leads to a decrease in self-esteem with a rapid recovery of body weight and / or refusal of further treatment.

Maintaining the achieved body weight values ​​is more difficult than losing weight. It requires lifelong correction of lifestyle, behavioral reactions and diet therapy. Therefore, weight management programs should emphasize the continuity of such therapy throughout life.

The basis of obesity treatment is caloric restriction and an increase in physical activity to achieve energy balance, which is included in the concept of lifestyle.

Today, these are the most effective and relatively inexpensive approaches that doctors use. Reducing caloric intake and increasing energy consumption allows not only to prevent further increase in body weight, but also to reduce it. For most obese patients, the target weight loss should be up to 10–15% of their baseline values, and the weekly weight loss should be around 0.5 kg. Rapid weight loss is associated with increased risks and will necessarily lead to weight regain. For any active treatment program for overweight, weight loss of less than 5% is unsatisfactory, and the result is ineffective. The ideal result of treatment is to bring the body weight to the normal range (BMI 25 kg / m2 or below) without further increasing it. This is not possible for most patients.

In the first weeks of treatment, patients should visit the doctor twice a week, measure body weight. In the future, treatment monitoring should be carried out monthly. The doctor is obliged to analyze the diet, causes of excess body weight, exercise, discuss risk factors, complications of obesity, require the patient to keep a diary of self-control. Most obese patients have behavioral defects (alcohol abuse, eating in the evening or at night, etc.). In this regard, such patients should daily record their diet, exercise in a special journal, in which they also record body weight 1–2 times a week.

The treatment of overweight and obesity is a multi-step process, including lifestyle changes, drug therapy and, in some cases, surgical treatment.

Nevertheless, there are numerous data that lifestyle modification is not very effective for long-term obesity treatment in the majority of patients. Despite the low impact of conservative treatment, many doctors refused to use invasive methods of treatment of this disease. Currently, obesity pharmacotherapy is the standard for the treatment of most other chronic diseases, but with great caution. We should not forget that medical therapy for obesity is recommended as an addition to lifestyle modifications.


Lifestyle modification includes a change in attitude towards your diet and its character, physical activity and body weight. In addition to the patients themselves, it is necessary to include spouses in the treatment process. Lack of interest in weight loss among family members increases the likelihood of a patient refusing weight loss programs. Patients should keep a daily log of self-control, weigh foods and evaluate their calories. Patients can participate in classes of closed support groups (10–20 people each), which should create positive emotions, promote self-affirmation, and visually demonstrate the success of other patients.

Regular visits to the doctor are needed to achieve a stable, controlled weight loss in patients.


The word “diet” originated from the Latin diaeta – “lifestyle”, which emphasizes the importance of eating not just certain foods, but also adherence to proper diet throughout life.

Calorie restriction

Nutritional limitations in obese patients can be moderate or significant, depending on the possible health risks. There are two levels of calorie restriction – a low-calorie diet (meals range from 800 to

1800 kcal / day), which is acceptable for most patients with obesity, as well as a specialized ultra-low-calorie diet (250–799 kcal / day) prescribed to patients with a high level of health risks for obesity.

Successful weight loss is largely dependent on adherence to a low-calorie diet, when energy consumption per day is more than the number of calories obtained from eating. The use of low-calorie diet can reduce body weight by 10% in 6 months. However, only 15% of obese patients follow this diet.

Any diet should contain a sufficient amount of fruits, vegetables, foods high in fiber and force out high-calorie foods from the diet. As a result of many studies, it was concluded that the loss of body weight is more dependent not on the set of products, but on the caloric intake.

Low-calorie diet is acceptable for all patients with excess weight (BMI 25-35 kg / m2), who first decided to reduce body weight. The recommended caloric intake with this type of diet is about 1200 kcal / day for women and 1500 kcal / day for men. All patients nutrition is selected individually by a nutritionist.

With the same diet, patients with different initial body weight lose a different amount of weight. With a BMI of 35 kg / m2, women lose 1–1.5 kg per week, and with a BMI of 25 kg / m2, the loss will be about 0.5 kg per week. Therefore, the medical specialist and the medical doctor should jointly determine the caloric intake, daily energy expenditure and the average weight loss at the rate of 0.5 kg per week during the first month of treatment.

For different patients, diets should take into account the peculiarities of the national diet, culture, season of the year, the patient’s personal characteristics, medication, and the presence of concomitant pathology. The patient should drink at least 1.5-2 liters of water daily (in the absence of heart or kidney failure). In the presence of pathology of the kidneys or other metabolic disorders, the doctor must take into account in the calculation of the amount of proteins in the diet.

International organizations for the study of obesity (NHLBI and NAASO) recommend that the standard of low-calorie diet, which is 1000–1200 kcal / day for women and 1200–1600 kcal / day for men, as well as for women who exercise regularly or have a body weight less than 75 kg.

If there is a concomitant pathology (diabetes, hyperlipidemia, arterial hypertension, etc.), in addition to a nutritionist, physicians of relevant specialties should take part in drawing up the menu. Preparing a diet without a physician is unacceptable. When the caloric intake is below 1200 kcal, daily additional consumption of multivitamin and polymicroelement complexes is recommended. WHO experts recommend reducing body weight at a rate of 6–12 kg in 20–24 weeks of treatment. Research data shows that the majority of patients in the United States who participate in weight loss programs do not regain lost body weight over 5 years. However, there are a number of studies demonstrating a return to the original body weight within 5 years after the abolition of the diet.


Physical activity is an important part of a weight loss program. Scientific studies have shown that people on diets who apply additional physical exertion, body weight decreased much faster than those who followed only one diet. In particular, the recommended physical activity should include 30 minutes of brisk walking (speed 4.5 km / h) at least 3 times a week. However, some studies recommend daily exercise for up to 60 minutes. Patients are encouraged to perform additional physical activity: use the stairs, rather than the elevator, go in for fast walking instead of using the transport, and walk 10-15 minutes on foot after eating.

In accordance with the recommendations of the American College of Sports Medicine, the program to combat obesity should include exercises that cause an energy expenditure for adults of 300–500 kcal per lesson or 1-2 thousand kcal per week. However, this goal is rarely realistic for the obese patient. According to NHLBI recommendations, an obese patient should start a slimming program with moderate physical exertion (for example, fast walking) for 30–45 minutes 3–5 days a week. In this case, the energy consumption should be about 150-225 kcal per lesson. Housework is also welcome, such as vacuuming 3 times a week, which may be more important than 30-minute walks 6 times a week.

In patients with type 2 diabetes, exercise helps to reduce blood glucose levels, improves insulin sensitivity, reduces cardiovascular risks, lowers blood pressure and dyslipidemia.

To work with patients with physical limitations, such as those who have suffered a myocardial infarction, stroke, trauma, it is recommended to engage in physical therapy for the preparation and implementation of specialized rehabilitation programs.

In addition to diet and exercise, over the course of thousands of years, a large variety of different methods and techniques have been used, such as herbal remedies, homeopathy, hypnosis, psychotherapy, reflexology, etc. The abundance of approaches indicates that no single method may not be preferred or sufficiently effective for treating most patients. Therefore, for each patient it is necessary to individually select one or another method of therapy. One of the reasons for the refusal of many doctors to treat obesity is that in their arsenal there are no sufficiently effective and safe means of reducing body weight.

Modern official medicine gives preference to drugs, the clinical efficacy of which has been repeatedly proven by many multicenter, placebo-controlled and randomized studies using the principles of evidence-based medicine. Therefore, to date, only a few drugs with proven efficacy for the treatment of obesity have been included in the pharmacopoeia of Europe and North America.

Medicinal preparations are recommended to be prescribed to patients with obesity only as part of a comprehensive treatment program, which should include diet therapy, exercise, correction of behavior and diet, which improves the effectiveness of weight loss. It is carried out under the supervision of experienced doctors (endocrinologist, nutritionist, general practitioner, family physician).

ADA and the American Association for the Prevention of Obesity (AASE) do not recommend the use of drugs for the treatment of obesity for cosmetic purposes 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 decompensated cardiovascular disease, uncontrolled arterial hypertension, mental disorders and some other conditions. In addition, weight loss may be temporarily contraindicated in a number of patients. In this regard, criteria have been developed for excluding patients from weight loss programs.

Currently, only one drug is approved in Europe for long-term use – orlistat. It is recommended for longer use, and its safety is assessed in the XENDOS study. The drug is approved for use for more than 4 years.

Observation of patients with obesity who received drug treatment showed that in a third of these patients the use of any drugs was ineffective, and the tendency to lose weight in most patients during the first 6-8 months of therapy. Then there is a plateau effect for no apparent reason. During the first month of complex treatment using drugs, the body weight on average decreases by 2 kg. In some studies, weight loss for the same period equates to 1% of the initial weight. In placebo-controlled studies, the response to treatment with minimal doses of drugs is estimated at 89% versus 61% in patients who received placebo.

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

Drugs used to reduce body weight, are divided into two main groups – drugs to reduce appetite and drugs that reduce the absorption of nutrients (fats, carbohydrates, etc.) from the intestine – dietary correctors. They also distinguish a number of other drugs, including trace elements, vitamins, amino acids, peptides, hormones, etc. In particular, ADA and AACE recommend the use of drugs that have undergone complete clinical trials and are approved by the FDA.

Not all medicines have the same safety. Centrally acting drugs (noradrenergic drugs), such as phentermine, are approved by the FDA, but are recommended only for short-term treatment as an adjunct to the main treatment for obesity. When taking drugs based on benzphetamine or phendimetrazine, there is a high risk of abuse of these drugs. All this led to the formation of a list of safe medicines.

Effective drugs for weight loss are those that can reduce the initial weight of not less than 5% per year.

In the initial appointment of drugs for weight loss, it is recommended to resort to a month trial treatment of obesity. During this period, it is possible to assess the patient’s sensitivity to the treatment regimen used. If the patient has not lost weight during this period, further treatment with this drug is likely to be ineffective even with maximum doses.

After some time after stopping treatment, patients are prone to recovery of body weight, however, when conducting a second course of treatment, the weight not only decreases, but there is an additional decrease in body weight. You should not plan weight loss by more than 15% from baseline values. As a monotherapy, any drug can reduce body weight by no more than 8–10.6% per year from baseline values. However, to maximize the risk of obesity and diabetes, weight loss should be at least 12%. This is a goal that cannot be achieved only through the use of drug monotherapy.

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

Orlistat (Xenical) is a synthesized stable substance (tetrahydrolipstatin), which is similar to the vital product of the bacterium Streptomyces toxytricini (“lipstatin”). The drug has a high lipophilicity, is well soluble in fats, but its solubility in water is very small. The drug has no systemic effect, it is practically not absorbed from the intestine. Orlistat mixes with drops of fat in the stomach, blocks the active center of the lipase molecule, not allowing the enzyme to break down fats (triglycerides). Due to the structural similarity of orlistat with triglycerides, the drug interacts with the active site of lipase enzymes, covalently bonding with its serine residue. The binding is slowly reversible, but under physiological conditions, the inhibitory effect of the drug during the passage through the gastrointestinal tract remains unchanged.As a result, about 30% of food triglycerides are not digested or absorbed, which allows you to create an additional calorie deficit compared to using only a diet of approximately 150–180 kcal / day.

Undigested triglycerides can not penetrate into the blood and are excreted with feces, which creates an energy deficit and contributes to weight loss. Orlistat does not affect the hydrolysis and absorption of carbohydrates, proteins and phospholipids. The oral dose of orlistat is almost completely (about 97%) excreted in the feces, with 83% eliminated as an unchanged drug.

More than three quarters of patients who took Xenical and followed a diet, after 1 year, achieved a clinically significant weight loss (more than 5% of the initial body weight). With orlistat and dieting, after 1 or 2 years of treatment, the number of patients who lost more than 10% of their initial body weight was twice as large as with dieting and taking placebo. It can be predicted that patients who strictly follow the recommendations received (which can be judged by a decrease in body weight by more than 5% in 3 months), by the end of the first year of treatment will noticeably decrease body weight (by 14%). After an initial decrease in body weight, patients receiving placebo and diet were re-added twice as much as patients on diet and orlistat.

It is preferable to prescribe orlistat to all overweight and obese patients who are addicted to fatty foods. When analyzing the content of fats in the patient’s diet, it is necessary to evaluate not only animal, but also vegetable fats, not only obvious (visible), but also hidden fats.

In addition to the action mediated by weight loss, orlistat has an additional positive effect on the levels of total cholesterol and LDL cholesterol.

The use of 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 / HDL cholesterol cholesterol, a well-known prognostic factor of cardiovascular risk, improved significantly after 1 and 2 years of treatment with orlistat (p <0.001 and p <0.001, respectively, compared with the placebo group). A significant improvement over the 2 years of treatment with orlistat was also noted by apolipoprotein B, a well-known cardiovascular risk factor.

In patients receiving orlistat, increased arterial pressure is significantly reduced.

A decrease in body mass after 1 and 2 years of its administration was accompanied by a decrease in both systolic (ADS) and diastolic (ADD) blood pressure. In high-risk patients (baseline ADD 90 mm Hg), treatment with orlistato reduced it to 7.9 mm Hg. by the end of the first year, while on placebo, the reduction in ADD was 5.5 mmHg. (p = 0.06). Similar results were obtained for ADS in patients at high risk (baseline BPA 140 mm Hg). At the same time, in patients receiving placebo, it decreased by 5.1 mm Hg, and in those who received orlistat by more than 10.9 mm Hg. (p <0, 05). Thus, the obtained results show that orlistat in combination with a diet reduces arterial pressure in patients with obesity and arterial hypertension more strongly than diet therapy.

Reducing blood pressure reduces the risk of cardiovascular risk.

Orlistat is taken with every meal, washed down with water. The presence of lipases in the gastrointestinal tract is necessary for the manifestation of the effect of orlistat. Since lipase secretion is stimulated by the presence of food in the gastrointestinal tract, orlistat should be taken with food. Its effectiveness is optimal when taking the drug during or within 1 hour after a meal containing less than 30% of calories due to fat. The recommended effective dose of Xenical is 120 mg 3 times a day (360 mg / day). Higher doses do not significantly increase the positive effect, and lower doses are not accompanied by a noticeable improvement in tolerability.

The tolerance of orlistat is inversely correlated with the amount of fat in food. Side effects are frequent loose stools, which are aggravated after eating foods rich in fats. When using the drug, there are common negative phenomena in the form of increased stool and steatorrhea, which was noted in a three-year study among patients receiving various combinations of orlistat with hypoglycemic drugs and a moderate diet containing about 30% fat.

Thus, Xenical can be used not only as a therapeutic agent, but also as a diagnostic one. The patient is explained the mechanism of action of the drug Xenical and asked to monitor changes in the stool. If it becomes fatty and oily, then the patient overeat fats. It is essential that the patient himself is convinced of overeating of fats, which often initially denies – not because of a conscious desire to mislead the doctor, but simply because of ignorance. As a rule, patients take into account only visible animal fat and completely ignore the hidden fats. In addition, some, going to the vegetable food, begin to abuse vegetable oils, forgetting about their very high calorie content. It means, that the appearance of fatty stools when taking orlistat (Xenical) is a kind of marker of excessive fat intake and requires correction of the diet.

In conclusion, we note that the treatment of obesity must be comprehensive and include both pharmacological and non-pharmacological means of therapy. The main task of the doctor is to develop in the patient new long-term skills of correct eating behavior and physical activity, which should stay with him for life. All the means used – both pharmacological and non-drug – are aimed at solving the primary task: the formation of the correct lifestyle of the patient with obesity, since only this can be the key to the absence of recurrence of the disease.

You Might Also Like

Leave a Reply

Your email address will not be published. Required fields are marked *