The time-tested effective and safe treatment of obesity with Xenical.
According to the World Health Organization (WHO), there are more than a quarter of a billion people with obesity in the world, and this figure is steadily increasing. More and more children in the world are obese. For example, in Greece, 11% of adolescents and youths have a body mass index (BMI) of more than 30 kg / m2. However, the high prevalence of overweight is predetermined by evolution itself. In the course of evolution, an economical metabolism has developed, in which the body accumulates fats as a concentrated supply of energy for a long time. In the United States, obesity is considered to be the second potentially smoking cause of death after smoking.
Obesity, being a chronic disease, poses a serious threat to health and is accompanied by the development of such serious diseases as type 2 diabetes, hypertension, coronary heart disease, myocardial infarction, colon and rectal cancer, and in women – cervical, ovarian, mammary gland cancer . Obesity is the main cause of limited mobility and working ability of people. This is due to the increase in the load on the supporting joints, damage to the joints of the spine and lower extremities, varicose veins. Obesity also leads to dysfunction of respiration, because the heavy chest wall limits the amplitude of respiratory movements, and the fat accumulated in the abdominal cavity limits the mobility of the diaphragm, which causes shortness of breath with moderate exercise – the most common complaint of obese people.
In addition to these medical aspects, individual УinconveniencesФ should be mentioned, which drastically reduce the quality of life of people. This is sweating, snoring, constipation, unpleasant appearance, a prejudice about isolation in society, reduced income due to early retirement, restriction of promotion. Obesity is a heavy economic burden for the state, since, on the one hand, in developed countries, obesity accounts for 8Ц10% of annual health care costs in general, and on the other hand, obesity leads to an increase in the cost of treating almost all diseases. The role of obesity as a risk factor in the development of sclerocystic ovary syndrome (CSC) is no longer in doubt. This is particularly evident with excessive accumulation of fat in the anterior abdominal wall and abdominal cavity (visceral fat), since with this distribution of adipose tissue there is a marked decrease in the sensitivity of peripheral tissues to insulin (insulin resistance).
The feature of visceral fat is that it is very active metabolic processes. This is due to the high density of receptors for catecholamines, GH, sex steroids, thyroid hormones and a low content of insulin receptors. The insignificant effect of insulin in the abdominal adipose tissue contributes to increased production of free fatty acids. In this regard, the increased accumulation of abdominal fat is a high risk factor for the development of diabetes mellitus or impaired glucose tolerance, hyperinsulinemia, arterial hypertension, cancer, arthritis, CSC syndrome and many other pathological conditions. In addition, with obesity in women, the production of male sex hormones by the ovaries and the adrenal cortex increases. The consequence of these endocrine-hormonal disorders is the development of hirsutism and menstrual dysfunction in women.
The attention of endocrinologists, gynecologists, cardiologists and other specialists is attracted to the metabolic syndrome, which is due to the discoveries of the fine molecular mechanisms of interaction between insulin and other factors in various target tissues. G.M. Reaven connects the development of the clinical signs of this syndrome with insulin resistance, so many authors propose to call this condition the syndrome of insulin resistance. The clinical sign of insulin resistance is considered to be abdominal type of obesity, in which the waist circumference in men exceeds 94 cm, and in women – 80 cm.
Obesity is the result of an imbalance in energy. The energy balance equation is possible if the amount of food consumed fully covers the body’s need for energy consumption. Obesity develops with an increase in food intake and a decrease in energy consumption. The statement often made by obese people: УI eat little, but I put on weight,Ф does not hold water. If a person eats little, but gains weight, it means: he has reduced energy consumption, therefore, it is necessary to increase physical activity, or he eats very high-calorie foods. Fatty foods are high in calories. Vegetable fat has the same caloric content as animal. Alcohol is a high-calorie product and in this respect is second only to fats. High-calorie foods include carbohydrates, especially easily digestible (sugar, sweets, confectionery).
According to the WHO classification, the normal weight range, expressed in BMI, ranges from 18.5Ц24.9 kg / m2. A BMI in the range of 25Ц29.9 kg / m2 is regarded as overweight (pre-obesity), and more than 30 kg / m2 – as obesity. A BMI of 40 kg / m2 and more indicates the presence of morbid (morbid) obesity. As noted above, the basis of obesity is the interaction of predisposing genes and external factors that should be considered when treating patients. However, the impact on a genetic defect is a matter of the distant future, and now clinicians focus on external factors, which include:
- composition of the diet;
- food consumption;
- level of physical activity.
With a balanced diet, the proportion of proteins in the daily ration of a person should be 15%, fat 30%, carbohydrates 55%. The high content of fats in food contributes to weight gain, since the energy value of fat is 2 times higher than that of proteins and carbohydrates. People tend to overeat fatty foods. Keep in mind that fats have a low ability to suppress appetite, in contrast to carbohydrates and proteins. Even a slight weight loss has beneficial effects for obese people. It is enough to reduce body weight by only 5-10% of the initial weight to reduce the risk of cardiovascular disease, reduce or normalize blood pressure during hypertension, reduce blood glucose levels in the presence of diabetes, reduce the risk of respiratory depression during sleep, normalize indicators blood fats, reduce the symptoms of lesions of the joints, reduce mortality by 20%, normalize the functional state of the female genital organs, increase the sexual potency of men. In the treatment of overweight and obesity, the following main approaches are used:
- selection of an adequate diet;
- promotion of physical activity;
- behavior modification;
- psychological and social support;
The results of experimental work allow us to understand the mechanisms for improving the metabolism of carbohydrates, fats, blood pressure indices while reducing weight by only 5Ц10% of the initial body weight. Suffice it to say that losing weight per kilogram in obese people without diabetes reduces the risk of its development by 30%. Recommendations on lifestyle changes should take into account individual dieting, smoking cessation, limited alcohol consumption, increased physical activity, cultural and national foundations. In any case, the diet should be physiological, but low-calorie. In the diet of patients should be dominated by foods rich in plant fiber, which prevents the rapid rise of glycemia after eating and promotes the normal functioning of the intestine. Easily digestible carbohydrates should be excluded from the diet, fats of both animal and vegetable origin should be limited. Low-fat varieties of fish (zander, hake, cod, pollock, tuna, ice fish, etc.) are useful. Meals should be calorie-deficient in the diet of 500Ц1000 kcal (on average 600 kcal) per day from the initial diet to achieve a weight loss of 0.5Ц1 kg per week. This allows you to reduce the total body weight in 3Ц12 months on average by 8%.
Daily exercise should be mandatory. Reduce the degree of insulin resistance contribute to weight loss, increased physical activity and replenishment of magnesium deficiency in the diet. Often, in order to reduce weight, patients use diuretic drugs or drugs with anti-mineralocorticoid effect, laxatives and psychostimulants, provoke vomiting after eating. Especially dangerous is the phenomenon of a restriction in the intake of fluids. In such situations, weight loss is due to dehydration, but not a true decrease in fat mass. On the contrary, the dehydration of adipocytes complicates the oxidative processes in adipose tissue and the reduction of its mass.
Doubtful suggestions like: Уwe guarantee fast weight lossФ or Уweight loss of 10 kg per weekФ should be avoided. Experience shows that young women with a labile psyche are most often susceptible to such УadvertisingФ on the background of a slight excess of the normal body mass index. Being victims of unfair advertising of УmiraculousФ products and numerous food additives, they do not realize that the effect of these УdrugsФ is primarily based on their laxative and diuretic effects.
Unfortunately, most obese patients cannot keep the result for a long time. Thus, among patients who have reduced their weight through diet and physical exertion, about two thirds regain it during the year and the majority in the next 5 years of life . In cases where diet and physical activity do not provide the desired weight loss and / or do not allow it to remain at the level achieved for a long time, obesity pharmacotherapy is used. Obesity pharmacotherapy is used as an adjunct to non-drug methods . Drug therapy is carried out in patients with a BMI ? 30 kg / m2, as well as those with a BMI ? 27 kg / m2 in the presence of obesity-related pathological conditions and risk factors for cardiovascular diseases [3, 4].
Pharmacotherapy can increase patient adherence to non-drug treatment and achieve a more effective weight loss and maintain it over a long period. Drugs used in the treatment of obesity should not only reduce body weight, but also hinder the development and progression of diseases associated with obesity (IHD, arterial hypertension) [1, 4]. In this regard, the greatest interest is caused by drugs, the pharmacological action of which is aimed not only at reducing body weight, but also at correcting hormonal and metabolic disorders and pathological conditions associated with obesity.
In pharmacotherapy of obesity, buy Xenical online (orlistat) is widely used – a drug of peripheral action that does not have systemic effects [5, 6]. The pharmacological action of Xenical is due to the ability of the drug to covalently bind to the active center of the gastrointestinal lipase tract (GIT), further inactivating it. Lipases of the digestive tract are the main enzymes that control the hydrolysis of dietary triglycerides to monoglycerides and fatty acids. Inhibiting GIT lipase, the drug prevents the breakdown and subsequent absorption of about 30% dietary fat. Such a mechanism causes a chronic energy deficit, which, with long-term use, contributes to weight loss.
Xenical is prescribed 120 mg 3 times a day during or within an hour after a meal, subject to the presence of fats in the diet. It was shown that in combination with a moderately low-calorie diet, Xenical significantly reduces body weight and prevents its re-increase, improves the course of diseases associated with obesity and improves the quality of life [7, 8] (Fig. 1, 2). This allows us to recommend the use of the drug for long-term weight control in obese patients. Contraindications to the use of orlistat are malabsorption syndrome, cholestasis, hypersensitivity to the drug or its components.
A detailed study of the clinical efficacy of Xenical in numerous studies has identified new opportunities in the treatment of patients with obesity [7, 9, 10]. A large XXL study (Xenical ExtraLarge Study) was completed recently in Germany, which included 15 549 obese patients (mean age 48 years) with a number of comorbidities (about half had 2-3, one-third patients had 3 or more comorbid obesity diseases)  . Thus, arterial hypertension occurred in 41%, dyslipidemia in 34% and type 2 diabetes in 16% of patients. The majority of patients (15 201 people) were observed on an outpatient basis by general practitioners, 348 patients – by inpatient doctors. The duration of Xenical therapy averaged 7.1 months. Most patients have previously attempted to reduce body weight, but less than 10% of them were able to achieve a 5% reduction in body weight and were able to maintain it in the future. It turned out that at the end of the study, the average weight loss was 10.7%, BMI – 3.76 kg / m2. 87% of patients lost more than 5%, and 51% of patients lost more than 10% of the initial body weight.
Along with a decrease in body weight, the beneficial effects of Xenical were observed in patients with pathological conditions associated with obesity. First of all, positive dynamics was observed from the side of hemodynamic parameters. Thus, the decrease in systolic / diastolic pressure at the end of the study was 8.7 / 5.1 mmHg. Art. In patients with arterial hypertension, the mean systolic pressure decreased by 12.9 mm Hg. Art., and diastolic – at 7.6 mm Hg. Art. The decrease in body weight while taking Xenical was accompanied by an improvement in metabolic parameters. The study demonstrated the improvement of carbohydrate metabolism in patients with obesity, including the presence of type 2 diabetes. By the end of the study, fasting blood glucose decreased in all patients by 7.5%, and in diabetics, the decrease in glycemia reached 15.0%. From the side of lipid profile, a decrease in the ratio of LDL / HDL ratio was observed, amounting to 15.4%. Among patients with dyslipidemia, there was a significant decrease in the concentration of total cholesterol, LDL (14%) and triglycerides (18%), while the level of HDL cholesterol increased by 13%.
The main conclusion of the study, which has great clinical significance, is the prospect of a new comprehensive strategy for managing obesity. An important practical result of the study was a change in the treatment of obesity-associated conditions, including stopping or reducing the use of certain drugs in obese patients who received Xenical. Thus, 18% of patients with hypertension and 31% of patients with dyslipidemia stopped taking antihypertensive and lipid-lowering drugs, respectively. In addition, in 8% of patients with hypertension and 15% with dyslipidemia, the daily dose of drugs was reduced. Among patients with type 2 diabetes, glucose-lowering therapy was canceled in 16%, and in 18% of patients the daily dose of oral sugar-lowering drugs (PSSP) was reduced. Approximately one of six obese patients with hypertension or type 2 diabetes stopped taking antihypertensive or hypoglycemic drugs, respectively. Among patients with obesity and dyslipidemia, one of the three was discontinued with lipid-lowering therapy.
A number of papers evaluated the clinical efficacy and tolerability of Xenical in patients with metabolic syndrome. M.M. Pinkston et al. (2006) studied the effects of Xenical and lifestyle modifications (in comparison only with lifestyle modifications) in 107 women with MS (age 21Ц65 years) . After a year of observation, in the group of MS patients who received Xenical, the decrease in body weight and BMI was 9.3 ± 7.5 kg and 3.1 ± 3.9 kg / m2, respectively, while in the other group only 0.2 ± 3.1 kg and 0.1 ± 1.2 kg / m2. In another study, the effects of Xenical therapy were studied, assessing the 10-year risk of cardiovascular diseases (CVD) according to the Framingham scale in 181 patients with MS . By the end of the 36th week of therapy with Xenical, BMI decreased from 35.0 ± 4.2 to 32.6 ± 4.5 kg / m2, and the waist volume decreased from 108.1 ± 10.1 cm to 100.5 ± 11.1 see Weight loss of more than 5% was achieved in 64.6% of patients. Among patients with impaired glucose tolerance (NTG), 38 of 53 patients (71.7%) showed an improvement in glucose tolerance. By the end of the study, 49.2% of patients moved to a lower risk category for CVD according to the Framingham scale. This and a number of other studies have shown the possibility of using Xenical in obese patients, including IGT and type 2 diabetes, in order to prevent vascular complications.
Another important point is the positive effect of Xenical on the metabolic rates of compensation for type 2 diabetes in obese patients. In a multicenter, randomized, double-blind study of M. Hanefeld et al. 368 patients with type 2 diabetes (BMI> 28 kg / m2, HbA1c 6.5Ц11%) participated . After 1 year of follow-up, a decrease in body weight of more than 5% was achieved in 51.5% of patients receiving Xenical and PSSP, and in 31.6% of patients receiving PSSP and placebo. In patients treated with Xenical, there was a significant improvement in the compensation targets for type 2 diabetes compared with patients who were only on PSSP therapy: HbA1c (-0.9% versus -0.4%; p <0.001), lean glycemia (-1 , 6 against -0.7 mmol / l; p = 0.004), postprandial glycemia (-1.8 against -0.5 mmol / l; p = 0.003). In prognostic terms, it is extremely important to emphasize the effect of Xenical therapy on indicators of postprandial glycemia – a proven risk factor for vascular complications.
R. Rowe et al. studied the clinical efficacy of Xenical in 100 patients with diabetes (91% with type 2 diabetes) . After 6 months, body weight decreased by 7.1 kg, HbA1c level – by 0.62%. At the beginning of the study, 50 patients with type 2 diabetes received insulin therapy, by the end of the study – 47 patients. Treatment with Xenical allowed to reduce the daily insulin dose in patients from 130 IU to 90 IU. Among 44.4% of patients with type 2 diabetes who received PSSP, the daily dose of drugs was also reduced. It is important that by the end of the study, insulin sensitivity improved (baseline – 1.24 U / kg; after 6 months – 0.90 U / kg; p <0.001). Consequently, a decrease in body weight during Xenical therapy in patients with obesity, including IGT and DM, is accompanied by an improvement in the metabolic profile and hemodynamic parameters with good tolerability of the drug. And finally, the most important thing is that Xenical medication reduces cardiovascular risks and improves the course of comorbid diseases, and is also accompanied by a change in the treatment of concomitant diseases – a decrease in the number of drugs, and in some cases their complete abolition.
Significantly replenished our understanding of the preventive aspects of pharmacotherapy Xenical. It is well known that maintaining normal body weight is the best prevention strategy for type 2 diabetes. In the XENDOC study, 3,304 obese patients were examined who were randomly assigned to Xenical and placebo groups . After 4 years, the relative risk of developing type 2 diabetes in the group of patients taking Xenical was reduced by 37% compared with the placebo group. The data obtained demonstrate the long-term effects of the drug associated with a reduction in the potentially high risk of developing type 2 diabetes in patients with obesity and IGT.
In conclusion, obesity is a widespread chronic disease with serious medical consequences. Obesity pharmacotherapy should be considered as an adjunct to non-drug methods of treating this disease, based on lifestyle changes. Based on a discussion of the metabolic and hemodynamic effects of the drug Xenical, it should be recommended its widespread use in clinical practice, including in obese patients with IGT, type 2 diabetes and arterial hypertension. Treatment with Xenical will not only improve the quality and longevity of patients, but also significantly reduce morbidity and mortality from obesity complications, and in some cases eliminate polyphragmas, which often occur in obese patients.
The presented results of clinical studies concern only the original drug orlistat – Xenical. The original is a drug, previously unknown and first introduced to the market by a developer or patent holder, having completed a full cycle of preclinical and clinical studies, protected by a patent for up to 20 years . Given the low cost of generics, due to the low cost of the manufacturer, for patients, and even doctors, the prescription of generics becomes attractive. However, one should ask: УIs generic an exact copy of the original drug or not?Ф No one denies the fact that a generic is a bioequivalent copy of the original drug, but there is also the notion of therapeutic equivalence – the most important component of the problem. According to A. Schneider, L.A. Wessjohann (2009), the actual task of analytical chemistry is precisely the comparison of the impurity profiles of the original drug and the generic.
The reason for the increased attention to research of this kind is the increasing number of cases where the difference in the composition of the impurities of the original and the generic drug affects the therapeutic properties of the drug. A. Schneider and L.A. Wessjohann  conducted a study of the impurity profiles of the original drug (Xenical, F. Hoffmann-La Roche Ltd., Switzerland) and two generics (CobeseTM, Ranbaxy Laboratories Limited, India and Orsoten, KRKA, Russia – Slovenia) using high performance liquid chromatography in combination with tandem mass spectrometry (HPLC-MS / MS). Removing impurities was performed by dissolving the sample in ethanol. This study showed that the Cobes and Orsoten impurity profiles are close to each other and are very different from Xenical. If only 3 impurities were registered for Xenical, then for Cobes – 14, and for Orsoten – 13 impurities. Even a slight difference from the original drug significantly changes the pharmacokinetics, bioavailability, safety of the drug and can cause allergic reactions and intoxication.
The economic feasibility of using generics is also controversial. The relatively low cost of generics, their main and, rather, the only advantage over the original means, considered in isolation from their quality (including efficacy and safety), can turn into a higher cost of treatment in practice. In addition to the medical consequences associated with taking the drug, there are also financial losses when, in case of deterioration of the patient’s condition, it is necessary to increase the amount of drug and non-drug intervention . In 2003, A. Maetzel et al.  undertook a study whose goal was to determine the economic efficiency of Xenical as an addition to standard glucose-lowering therapy compared with only standard treatment (control group) in patients with type 2 diabetes with overweight and obesity.
The results showed that while receiving Xenical, the doses of anti-hypoglycemic drugs decreased, and in 15% they were canceled, they also managed to reduce the doses of hypolipidemic and antihypertensive drugs, in some patients – with complete cancellation. The study showed high economic feasibility of using Xenical in patients with obesity, type 2 diabetes, in patients with dyslipidemia and hypertension on the background of overweight or obesity. The suggested mechanisms of the 120 mg positive effect on glycemia control, independent of changes in body weight, on the glycemic control can be the following:
- improved insulin sensitivity;
- reduced absorption of fat from food;
- decrease in postprandial plasma NEFA;
- stimulation of GLP-1 secretion.