Obesity: Clinical Guidelines

List of Abbreviations

25(OH)D – 25-hydroxyvitamin D

AH – arterial hypertension

BP – blood pressure

ALT – alanine aminotransferase

AST – aspartate aminotransferase

WHO – World Health Organization

GGT – gamma-glutamyl transferase

GLP-1 – glucagon-like peptide-1

GI – gastrointestinal tract

CHD – coronary heart disease

BMI – body mass index

LH – luteinizing hormone

HDL – high-density lipoproteins

LDL – low-density lipoproteins

MO – morbid obesity

NAFLD – non-alcoholic fatty liver disease

OGTT – oral glucose tolerance test

WC – waist circumference

HC – hip circumference

TC – total cholesterol

PTH – parathyroid hormone

PCR – polymerase chain reaction

OSA – obstructive sleep apnea syndrome

T2D – type 2 diabetes mellitus

CVD – cardiovascular disease

TG – triglycerides

TSH – thyroid-stimulating hormone

US – ultrasound examination

FSH – follicle-stimulating hormone

CHF – chronic heart failure

CVD – cerebrovascular disease

CNS – central nervous system

HR – heart rate

TG – thyroid gland

ECG – electrocardiogram

Terms and Definitions

Body mass index – used to diagnose overweight and obesity, as well as to assess its grade (body weight in kilograms divided by height in meters squared, kg/m²).

Morbid obesity is obesity with a BMI ≥ 35 kg/m² in the presence of severe obesity-related complications; or obesity with a BMI ≥ 40 kg/m² regardless of complications.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Obesity is a chronic disease characterized by excessive accumulation of body fat that poses a health threat and serves as a major risk factor for a number of other chronic conditions, including type 2 diabetes mellitus (T2D) and cardiovascular diseases (CVD) [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Obesity is a multifactorial disease in the development of which, aside from an imbalance between energy intake and expenditure, various neurohumoral mechanisms and environmental factors are involved [1, 2]. High-calorie diets and sedentary lifestyles occupy a primary place among the causes of obesity development [3]. It has been proven that BMI is determined by hereditary factors by 40–70%, and numerous genes encoding various components of body weight and metabolism regulation have been identified [4, 5, 6]. At the same time, the rapid rise in obesity rates over the past 30 years is largely driven by cultural and environmental changes. A high-calorie diet, increased portion sizes, disrupted daily eating rhythms, a sedentary lifestyle, chronic stress, and increasingly diagnosed eating disorders are the main factors contributing to the development of obesity [7], meaning that genetic predisposition to obesity is actualized under the influence of the aforementioned factors.

It has been proven that both hormonal and neurotransmitter disturbances within the gut-brain axis and the intestinal microbiota play an important role in the pathogenesis of obesity, with quantitative and qualitative changes in its composition potentially leading to bacterial endotoxemia [8]. The aforementioned factors promote structural changes in adipose tissue (adipocyte hypertrophy and hyperplasia, development of chronic inflammation) and alterations in its secretory function (e.g., adipokine production) [9]. In turn, chronic adipose tissue inflammation underlies the pathogenesis of insulin resistance [10]. The role of brown adipose tissue thermogenesis and its contribution to energy expenditure are being investigated primarily from the perspective of developing strategies to stimulate the growth and activation of brown adipocytes as a preventive and therapeutic measure for weight control in obesity [11, 12].

Obesity can be an independent disease or a syndrome developing secondary to other conditions. Obesity and its associated metabolic disorders are a pressing issue in modern medicine as they lead to a range of severe diseases [13–15]. The most significant among these are T2D, CVD, oncological diseases, osteoarthritis, etc.

CVDs occupy a leading position among the causes of mortality in developed and many developing countries. It has been shown that abdominal obesity plays a key role in the development of CVD risk factors (dyslipidemia, arterial hypertension (AH), carbohydrate metabolism disorders), acting as an independent risk factor for T2D and CVD [16].

These clinical guidelines are dedicated to primary obesity. The pathogenesis, epidemiology, clinical features, and treatment of secondary obesity, when it manifests as a symptom of another underlying disease, are discussed in the relevant clinical guidelines and literature sources.

1.3 Epidemiology of the Disease or Condition

Obesity is a leading cause of disability and mortality worldwide, affecting not only adults but also children and adolescents. According to WHO data from 2016, more than 1.9 billion adults (aged 18 years and older) were overweight (the same data are cited in the 2020 report), of whom over 650 million suffered from obesity [17]. The prevalence of obesity was 11% among men and 15% among women [17]. According to projections, by 2030, 60% of the global population (i.e., 3.3 billion people) could be overweight (2.2 billion) or obese (1.1 billion) if current obesity trends persist [18]. In the Russian Federation as of 2016, the proportion of individuals with overweight was 62.0%, and with obesity, 26.2% [19].

The Rospotrebnadzor report "On the State of Sanitary and Epidemiological Welfare of the Population in the Russian Federation in 2019" notes that between 2011 and 2018, the prevalence of obesity increased by 27.4% among children and by 66.5% among adolescents [20].

According to data from the Organisation for Economic Co-operation and Development (OECD), an international economic organization of 35 developed countries, 19.6% of Russians face obesity issues [21].

According to the ESSE-RF multicenter observational study (Epidemiology of Cardiovascular Diseases and Their Risk Factors in Regions of the Russian Federation), the prevalence of obesity among the adult population aged 25–64 years across 11 regions of the Russian Federation (18,305 individuals) was 29.7% (30.8% among women and 26.6% among men) [22].

The presence of obesity has significant consequences for morbidity, quality of life, disability, and mortality, entailing a higher risk of developing T2D, CVD, certain forms of cancer, osteoarthritis, and other pathologies [13–15].

1.4 Features of Coding the Disease or Condition

E66.0 Obesity due to excess calorie intake

E66.1 Drug-induced obesity

E66.2 Extreme obesity with alveolar hypoventilation

E66.8 Other forms of obesity

E66.9 Obesity, unspecified

1.5 Classification of the disease or condition

According to the etiological principle, obesity is classified into [20]:

I. Primary (exogenous-constitutional, dietary) obesity

II. Secondary (symptomatic) obesity, which includes:

• obesity with an established genetic defect (including as part of known genetic syndromes with multiorgan involvement)

• cerebral obesity (adiposogenital dystrophy, Froehlich's syndrome) resulting from brain tumors, dissemination of systemic lesions and infectious diseases, or psychiatric disorders

• obesity due to endocrinopathies: disorders of the hypothalamic-pituitary system, adrenal glands, hypothyroidism, or hypogonadism

• iatrogenic obesity resulting from the use of medications that promote weight gain

Table 1. Classification of obesity by BMI, WHO, 1997 [1].

Table 2 Classification of obesity by stage [23].

Comments: the presence or absence of comorbid conditions directly associated with obesity (e.g., type 2 diabetes mellitus, NAFLD, OSA, etc.) and their severity determine the stage of obesity and, accordingly, the choice of therapy. The goal of treatment for overweight and stage 1 obesity is to prevent further weight gain and the development of complications. Therefore, in overweight individuals, the emphasis is on lifestyle modification (healthy eating with daily caloric restriction and increased physical activity). In stage 0 obesity, intensive behavioral therapy may be added to the aforementioned strategies. In stage 1 obesity, to reduce body weight and improve the course of associated diseases, pharmacotherapy may be used in addition to the above recommendations (at a BMI ≥ 27 kg/m²). In stage 2 obesity, to achieve more intensive weight loss and treat existing complications, bariatric surgery is also proposed for consideration.

1.6 Clinical presentation of the disease or condition

The clinical presentation of obesity is determined by the increased body weight itself and the presence of comorbid conditions whose course directly depends on body weight. Symptoms and complaints such as elevated blood pressure, headaches, increased sweating, shortness of breath on exertion and at rest, snoring during sleep, menstrual irregularities in women, decreased potency in men, etc., are caused by obesity-associated diseases.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria: based on physical examination data – BMI ≥ 30 kg/m².

• To diagnose overweight, diagnose obesity, and assess its degree, it is recommended to measure body weight, height, and determine BMI [1, 24-30].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

Comments: BMI is not used to diagnose obesity in elderly individuals, athletes, individuals with excessively developed musculature, pregnant women, amputees, and those with pronounced edema, since this indicator does not reliably reflect body fat content [27-28].

• To diagnose abdominal (visceral) obesity, it is recommended to measure waist circumference: a waist circumference (WC) ≥ 94 cm in men and ≥ 80 cm in women is a diagnostic criterion for abdominal obesity [1, 31-33].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

Comments: The accumulation of intra-abdominal fat is associated with a higher risk of metabolic diseases and cardiovascular diseases. An indirect marker of central obesity (also known as visceral or android) in Caucasians is a WC ≥ 94 cm in men and ≥ 80 cm in non-pregnant women. WC is measured along the mid-axillary line at the midpoint between the iliac crest and the lower margin of the last rib.

• For individuals of Asian descent, to assess the risk of developing obesity-related complications, it is recommended to use the BMI-based obesity classification (WHO, 1997 with amendments): grade 1 obesity at BMI ≥ 27.5 kg/m2, grade 2 obesity at BMI ≥ 32.5 kg/m², and grade 3 obesity at BMI ≥ 37.5 kg/m² [39-44].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5).

• In women of Asian descent, abdominal obesity and the presence of cardiometabolic risk should be established at a WC value of ≥ 80 cm; in men of Asian descent, abdominal obesity and increased risk of cardiovascular events correspond to a WC ≥ 90 cm [39-44].

ER CLE 4Level of recommendation confidence C (level of evidence – 4).

2.1 Complaints and Anamnesis

• For the purpose of diagnosing cardiovascular diseases, it is recommended that all patients with obesity be asked whether they have previously experienced elevated blood pressure (BP), whether they are taking antihypertensive drugs, and whether they have a history of myocardial infarction or stroke [38, 45].

GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)

• For the purpose of diagnosing OSA, it is recommended that all patients with obesity be asked about the presence of clinical manifestations of obstructive sleep apnea (OSA): snoring and breathing pauses during sleep, morning headaches, frequent night awakenings, dry mouth upon awakening, and daytime sleepiness [46, 47].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

• During history taking in all patients with obesity, it is recommended to inquire about the presence of cholelithiasis, pancreatitis, and history of viral hepatitis for the purpose of diagnosing obesity-associated gastrointestinal diseases [48, 49].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• During history taking in all patients with obesity, it is recommended to inquire about the regularity of the menstrual cycle in women and the presence of erectile dysfunction in men for the purpose of diagnosing reproductive system pathology [50].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

2.2 Physical Examination

• During the examination of the skin in patients with obesity, it is recommended to determine the presence of striae, areas of skin hyperpigmentation, and hair growth patterns to identify clinical signs of endocrine disorders [50-53].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• Patients with obesity are recommended to have their blood pressure measured on peripheral arteries using a cuff whose size corresponds to the patient's arm circumference, as well as heart rate measurement, for the purpose of diagnosing cardiovascular diseases associated with obesity [45, 54, 55].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.3 Laboratory Diagnostics

• To rule out endocrine causes of obesity, it is recommended that all patients undergo a blood TSH level test, and rule out hypercortisolism and hyperprolactinemia (blood prolactin level test) in accordance with generally accepted diagnostic guidelines [56-63].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: To rule out hypercortisolism, one of the following tests can be used: measurement of free cortisol in urine (24-hour urine collection), overnight 1 mg #dexamethasone suppression test**, or measurement of late-night salivary free cortisol [51].

• For the diagnosis of carbohydrate metabolism disorders, all patients are recommended to be screened for impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes mellitus in accordance with generally accepted diagnostic guidelines, including blood glucose and glycated hemoglobin (HbA1c) testing, as well as an oral glucose tolerance test (OGTT) if necessary [64].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Diagnosis of prediabetes and type 2 diabetes mellitus is carried out based on the results of the OGTT and/or blood glycated hemoglobin testing. Determining basal and stimulated immunoreactive insulin levels is not advisable due to the high variability and low informativeness of this test.

• All patients with obesity are recommended to undergo a general general-clinical biochemical blood test including levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, free and conjugated bilirubin, total calcium, and albumin for the purpose of diagnosing metabolic disorders [13-16, 65].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

• In the presence of complaints and clinical symptoms of hypogonadism, male patients with obesity are recommended to undergo tests for total testosterone in the blood, free testosterone in the blood, serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and sex hormone-binding globulin in the blood for the differential diagnosis of forms of hypogonadism [50].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

• Patients with a BMI above 40 kg/m² are recommended to have blood PTH and blood 25-OH vitamin D levels measured to assess vitamin D status and diagnose secondary hyperparathyroidism [66-69].

GRC CLEL 4Grade of Recommendation C (Level of Evidence – 4)

2.4 Instrumental Diagnostics

• All patients are recommended to undergo a comprehensive abdominal ultrasound for the diagnosis of cholelithiasis and NAFLD [48, 49, 70, 71].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• In the presence of clinical manifestations of OSA, it is recommended to perform overnight cardiorespiratory monitoring [72].

GCR BLEL 5Grade of Recommendation B (Level of Evidence – 5)

• To examine patients with hypertension, coronary artery disease (CAD), or chronic heart failure (CHF), it is recommended to perform an ECG and/or echocardiography [73-75].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

2.5 Other Procedures

• From the moment obesity treatment begins, every patient is recommended to have a consultation (examination, consultation) with a nutritionist/dietitian to receive information on healthy eating and proper meal planning [76].

GCR ALOE 2Grade of Recommendation A (Level of Evidence – 2)

• All female patients with obesity and menstrual irregularities, infertility, or symptoms of hyperandrogenism (acne, hirsutism, or androgenetic alopecia) are recommended an evaluation to rule out polycystic ovary syndrome (PCOS) [81, 82].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For patients with obesity and hypertension who fail to achieve the target blood pressure level, it is recommended to have a consultation (examination, consultation) with a cardiologist to prescribe or adjust antihypertensive therapy [73-75].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For patients with obesity and dyslipidemia who fail to achieve target lipid metabolism parameters, it is recommended to have a consultation (examination, consultation) with a cardiologist to prescribe or adjust lipid-lowering therapy [73-75].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For patients with obesity and clinical signs of coronary artery disease, or obesity and chronic heart failure, it is recommended to have a consultation (examination, consultation) with a cardiologist to determine indications for additional examinations, and to prescribe or adjust therapy [73-75].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• For all patients with obesity, after ruling out secondary causes of weight gain, it is recommended to have a consultation (examination, consultation) with a psychiatrist or psychotherapist specializing in somatic diseases and psychosomatic disorders [85, 86].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients with obesity, NAFLD, and risk factors for the development of NASH and liver cirrhosis, it is recommended to have a consultation (examination, consultation) with a gastroenterologist to address the need for a liver needle biopsy [87].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients who have indications for surgical treatment of obesity, it is recommended to have a consultation (examination, consultation) with an endocrinologist to rule out contraindications [88-89].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients who have indications for surgical treatment of obesity, it is recommended to have a consultation (examination, consultation) with a general practitioner/internist to rule out contraindications [88-89].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients who have indications for surgical treatment of obesity, it is recommended to have a consultation (examination, consultation) with a cardiologist to rule out contraindications [88-89].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients who have indications for surgical treatment of obesity, it is recommended to have a consultation (examination, consultation) with a nutritionist/dietitian to modify their diet [88-89].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• For patients who have indications for surgical treatment of obesity, it is recommended to have a consultation (examination, consultation) with a psychiatrist to rule out contraindications [90-95].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

Comments: consultations with medical specialists are performed to identify contraindications to bariatric surgery or to prescribe treatment in preparation for bariatric surgery.

• Prior to bariatric surgery, patients with obesity are recommended to undergo duplex scanning of the lower extremity veins to assess the condition of deep veins of the extremities and detect signs of their incompetence, current or past thrombosis [96].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• Performance of esophagogastroduodenoscopy, microbiological (culture) examination of a gastric wall biopsy specimen for Helicobacter pylori, and detection of Helicobacter pylori DNA in gastric mucosa biopsy specimens by PCR are recommended to prescribe preventive therapy prior to surgical treatment of obesity [97].

LeRR CLoE 4Level of recommendation confidence C (level of evidence – 4)

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Conservative Treatment

Weight loss is indicated for all patients with obesity, as well as for overweight patients with one or more cardiovascular disease (CVD) risk factors or concomitant diseases whose clinical course is associated with obesity. Overweight patients without concomitant obesity-associated diseases or CVD risk factors are advised to prevent further weight gain. The goals of obesity treatment are to reduce body weight to a level that achieves the maximum possible reduction in health risks and improves the course of obesity-associated diseases; to maintain the achieved result; and to improve the patients' quality of life.

Comments: considering that obesity is a chronic disease, its management must be carried out throughout life under constant supervision to prevent weight regain and to monitor risks or treatment of comorbid conditions (e.g., type 2 diabetes mellitus, cardiovascular diseases).

Table 3. Target weight loss parameters during obesity treatment depending on the presence of comorbid conditions in the patient [106, 107]

3.1.1 Non-pharmacological therapy

• Non-pharmacological therapy (lifestyle modification through dietary changes and increased physical activity) is the foundation of obesity treatment and is recommended as the first, mandatory, and continuous stage of obesity treatment [98-107].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

• All patients suffering from obesity are recommended a hypocaloric diet (a deficit of 500-700 kcal from physiological requirements taking into account body weight, age, and gender), balanced in food ingredients, to achieve weight loss; during the weight maintenance phase, an eucaloric diet balanced in food ingredients [108-112].

GCR ALEL 2Grade of Recommendation A (Level of Evidence – 2)

Comments: A caloric restriction of 500-1000 kcal per day from the calculated requirement leads to a weight loss of 0.5-1.0 kg per week. Such a rate of weight loss is maintained for 3-6 months. Subsequently, moderate weight loss leads to a reduction in energy expenditure by 16 kcal/kg per day in men and 12 kcal/kg per day in women due to a decrease in lean body mass, as a result of which weight loss plateaus. Most different types of diets are equally effective provided that the principle of total calorie restriction is followed. The main predictor of diet success – systematic adherence to this diet. Fasting is not recommended due to the lack of data on its efficacy and safety in the long-term treatment of obesity.

• To facilitate the control of calorie intake and diet balance, it is recommended to use specialized clinical and dietary preventive nutrition products in the form of hypocaloric food products balanced in food ingredients, providing at least 16 g of protein per 200 kcal per meal. Specialized food products can be used as the sole source of nutrition or as a replacement for one or two meals [113-119].

GCR BLEL 2Grade of Recommendations B (Level of Evidence – 2)

• Patients with obesity are recommended individual or group therapeutic education aimed at lifestyle modification, conducted by a qualified medical specialist following a structured program in a group or individual format [120-122].

GCR CLEL 3Grade of Recommendation C (Level of Evidence – 3)

• Physical activity is recommended as an integral part of obesity treatment and the maintenance of weight achieved during treatment. Regular aerobic exercise for at least 150 minutes per week is indicated for all overweight and obese individuals [123-127].

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

Comments: increased physical activity reduces visceral fat mass and increases muscle mass, while attenuating the diet-induced decrease in resting energy expenditure, lowers blood pressure, improves glucose tolerance, insulin sensitivity, and the lipid profile, and has a favorable effect on long-term weight maintenance. Increased physical activity (predominantly aerobic) of ≥150 min per week (equivalent to ≥30 min on most days) is recommended during the weight loss phase; more intense physical activity (200 to 300 min per week) may be recommended for long-term weight maintenance. Combined lifestyle modification (dietary changes in addition to exercise) leads to more significant weight loss compared to "monotherapy" (diet or exercise alone).

• Obese patients are recommended daily physical activity in the form of moderate-intensity aerobic exercise lasting from 225 to 420 minutes per week [123-127].

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

• Obese patients are recommended physical rehabilitation programs lasting at least 12 weeks [128-131].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

Physical therapy for obese patients consists of two interrelated and mutually reinforcing areas: optimization of physical activity and physical rehabilitation. The goal of physical activity optimization is to increase energy expenditure for a gradual, steady reduction in the patient's weight (5–10% per year) to an optimal level and maintaining the achieved results over the long term. This is achieved by determining the volume, intensity, nature, and regimen of exercise. A personalized exercise program should be developed based on the diagnostics of the functional state of relevant organs and systems of the patient: physical examination, anthropometric measurements (body weight, height, waist, hip, calf, and arm circumferences); measurement of joint range of motion and spinal flexibility; determination of posture type and postural disorders; assessment of static and dynamic postural control using stabilometry in the Romberg position or stabiloplatforms; measurement of physical performance (6-minute walk test with cardiorespiratory testing and strength endurance tests for major muscle groups); body composition analysis by bioelectrical impedance analysis (if necessary equipment for muscle and fat mass is not available, the Matiegka formula is used); measurement of basal metabolic rate, exercise energy expenditure, and determination of the aerobic threshold through ergometry (metabolography).

• Obese patients with obstructive sleep apnea syndrome are recommended to undergo CPAP therapy (continuous positive airway pressure ventilation) [132-133].

Level of Evidence AGrade of Evidence 2Level of Recommendations A (Grade of Evidence – 2)

3.1.2. Pharmacotherapy

• The prescription of drugs registered as medications for the treatment of obesity (A08A: Antiobesity preparations, excluding diet products) is recommended for patients who cannot achieve clinically significant weight loss with non-pharmacological treatments and/or during the weight maintenance phase. Furthermore, in the presence of at least one obesity-associated complication, pharmacotherapy is indicated immediately alongside non-pharmacological treatments [134-137].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

• The prescription of antiobesity medications, excluding diet products, is recommended for a BMI ≥ 30 kg/m² or a BMI ≥ 27 kg/m² in the presence of risk factors and/or comorbid conditions [134-137].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

• Evaluation of the efficacy of pharmacotherapy for obesity is recommended 3 months after initiating treatment. Weight loss of less than 5% of baseline over 3 months may be considered ineffective [134-137].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• Evaluation of therapy safety is recommended 1 to 3 months after drug initiation and at least every 3 months thereafter [134-137].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• Treatment of obesity-associated diseases is carried out within the framework of relevant standards in accordance with clinical guidelines. In this context, it is recommended to prescribe medications that do not affect body weight or medications that promote weight loss [134-137].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Currently, the following drugs for the treatment of obesity (excluding diet products) are registered in the Russian Federation: orlistat, sibutramine, liraglutide, sibutramine + metformin, semaglutide.

• Orlistat (A08AB01) is a peripherally acting antiobesity drug, recommended for patients with a BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m² in the presence of risk factors and/or comorbid conditions at a dose of 120 mg 3 times daily during meals or no later than one hour after a meal for weight loss. The approved maximum duration of treatment is 4 years [134, 135, 138-139].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

Comments: orlistat, being a specific, long-acting inhibitor of gastrointestinal lipases, exerts its therapeutic effect within the gastrointestinal tract and has no systemic effects: it prevents the hydrolysis and subsequent absorption of dietary fats (about 30%), thereby creating an energy deficit that leads to weight loss. Orlistat also helps reduce hypercholesterolemia, regardless of the degree of weight loss. If a meal is missed or contains no fat, the dose of the drug can be skipped. The use of orlistat in obese patients can significantly improve the risk factor profile for type 2 diabetes, cardiovascular diseases, and other obesity-associated conditions, which may favorably affect the life expectancy in this category of patients. There are currently no data allowing an assessment of the effect of orlistat on overall mortality or cardiovascular mortality. An important advantage of the drug is its peripheral action confined strictly to the gastrointestinal tract and the absence of systemic effects. Orlistat is contraindicated in acute pancreatitis and conditions accompanied by diarrhea, chronic malabsorption syndrome, and cholestasis. Orlistat increases the likelihood of gallstone formation, though rational fat intake does not impair gallbladder motility. Given its mechanism of action, side effects of the drug include fatty stools, oily spotting from the rectum, fecal urgency, increased frequency of bowel movements, fecal incontinence, abdominal pain, and flatulence with some discharge. The severity and duration of side effects directly depend on patient adherence to treatment and compliance with recommendations to restrict dietary fat. If multivitamins are recommended, they should be taken no earlier than 2 hours after taking orlistat or at bedtime.

• Sibutramine (A08AA10) is a centrally acting antiobesity drug, recommended for patients with a BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² in the presence of risk factors and/or comorbid conditions; as a starting dose of sibutramine, including sibutramine + microcrystalline cellulose, it is recommended to take 10 mg in the morning, daily, regardless of meals. If body weight has decreased by less than 2 kg during the first month of treatment, it is recommended to increase the dose to 15 mg of sibutramine, provided it is well tolerated. If body weight decreases by less than 5% from baseline over 3 months of intake, treatment is considered ineffective. The approved maximum duration of treatment is 1 year [134, 135, 140-143].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

Comments: Sibutramine, being a serotonin, noradrenaline, and, to a lesser extent, dopamine reuptake inhibitor in CNS synapses (including in combination with microcrystalline cellulose), has a dual mechanism of action: on the one hand, it accelerates the feeling of satiety, reducing food intake; on the other hand, it increases energy expenditure, which together leads to a negative energy balance. Sibutramine provides effective weight loss regardless of sex, age, and comorbid conditions. The higher the baseline BMI, the more intensive weight loss can be expected. Sibutramine provides effective and sustained weight loss and improves metabolic parameters: it significantly reduces triglyceride, total cholesterol, and LDL-C levels, increases antiatherogenic HDL-C levels, decreases plasma uric acid, and reduces glycated hemoglobin levels. Obesity treatment with sibutramine requires mandatory medical supervision. Blood pressure and heart rate monitoring is necessary in all patients before starting treatment, then every 2 weeks from the 1st to the 3rd month of treatment, monthly from the 4th to the 6th month, and every 3 months from the 6th to the 12th month. The drug should be discontinued if heart rate increases by more than 10 beats per minute on two separate occasions, blood pressure increases by more than 10 mmHg, or if blood pressure exceeds 140/90 mmHg on two repeated measurements in previously controlled hypertension. The drug must not be prescribed to patients with uncontrolled hypertension (BP > 145/90 mmHg; controlled arterial hypertension is not a contraindication to sibutramine), coronary artery disease, decompensated chronic heart failure, cardiac arrhythmias, cerebrovascular diseases (stroke, transient ischemic attack), peripheral arterial occlusive disease, age over 65 years, severe hepatic and renal impairment (which may occur in association with obesity), concurrent use or use within less than 2 weeks of discontinuing monoamine oxidase inhibitors type A, monoamine oxidase inhibitors type B, or other centrally acting drugs (including antidepressants), severe eating disorders and psychiatric illnesses, thyrotoxicosis, pheochromocytoma, angle-closure glaucoma, or benign prostatic hyperplasia. Adverse effects such as nausea, loss of appetite, constipation, dry mouth, dysgeusia, insomnia, headache, agitation, and sweating are usually mild, occur only at the start of treatment, are transient, and generally do not require discontinuation of therapy.

• Liraglutide (A10BJ02) is a glucagon-like peptide-1 (GLP-1) analogue, recommended for patients with a BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m³ in the presence of risk factors and/or comorbid conditions; the starting dose is 0.6 mg subcutaneously once daily, followed by standard titration (the dose is increased by 0.6 mg at intervals of at least one week to improve gastrointestinal tolerance until the therapeutic dose of 3.0 mg daily is reached). If body weight does not decrease by 5% or more from baseline after 3 months of using liraglutide at a daily dose of 3.0 mg, treatment is discontinued [144-150].

Level of Evidence AGrade of Recommendation 1Level of Recommendation A (Level of Evidence — 1)

Comments: liraglutide regulates appetite by enhancing the feeling of gastric fullness and satiety while attenuating hunger and reducing prospective food consumption. Liraglutide does not increase 24-hour energy expenditure. Liraglutide 3.0 mg provides effective and sustained weight loss, and has a positive effect on the dynamics of cardio-metabolic risk factors in the setting of weight reduction. Liraglutide 3.0 mg may be considered a preferred option for patients with obesity and comorbid cardiovascular disease due to proven cardiovascular risk reduction, sustained weight loss over three years of therapy, reduction in the severity of sleep apnea, a significant decrease in the risk of type 2 diabetes, and a favorable safety and tolerability profile. The drug is contraindicated in patients with a history of medullary thyroid carcinoma (including familial), multiple endocrine neoplasia type 2, severe depression, suicidal ideation or behavior (including a history thereof), severe renal and hepatic impairment, and class IV heart failure (according to the NYHA classification), in patients aged ≥75 years. The use of liraglutide in patients with inflammatory bowel disease and diabetic gastroparesis is not recommended, as it is associated with transient gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea. Use with caution in patients with mild-to-moderate hepatic impairment, thyroid disorders, and a history of acute pancreatitis.

• Semaglutide (A10BJ06) is a glucagon-like peptide-1 (GLP-1) receptor agonist, acts as a physiological regulator of eating behavior and carbohydrate metabolism, and is recommended for patients with a BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² in the presence of risk factors and/or comorbid conditions such as prediabetes, type 2 diabetes, arterial hypertension, dyslipidemia, obstructive sleep apnea syndrome, or cardiovascular disease, as an adjunct to a low-calorie diet and physical activity. The starting dose of semaglutide is 0.25 mg subcutaneously once weekly, followed by standard titration (0.5 mg, 1 mg, 1.7 mg up to a therapeutic dose of 2.4 mg) at 4-week intervals to improve gastrointestinal tolerability. Semaglutide treatment should be discontinued if a weight loss of 5% or more from baseline is not achieved after 12 weeks of treatment at a dose of 2.4 mg or the maximum tolerated dose [151-155].

LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2)

Comments: Clinical studies have shown that semaglutide 2.4 mg leads to clinically meaningful and sustained weight loss in patients with obesity or overweight. This is achieved by reducing calorie intake, hunger, food cravings, and preference for high-fat foods. Treatment with semaglutide 2.4 mg was associated with decreased blood glucose levels and reduced glucagon secretion, as well as improvements in several cardiometabolic parameters, including waist circumference, glycated hemoglobin, blood pressure, lipid profile, liver function, and general physical condition [151–155]. In studies, semaglutide demonstrated not only improvements in anthropometric parameters, but also a reduction in cardiovascular mortality in patients with type 2 diabetes [156]. Efficacy has been demonstrated regardless of age, sex, race, ethnicity, baseline body weight, BMI, presence of type 2 diabetes, and renal function. Given its proven efficacy and favorable safety profile, semaglutide 2.4 mg can be considered an optimal option for long-term therapy in patients with obesity or overweight and high cardiovascular risk [151]. Contraindications to the use of semaglutide 2.4 mg include intolerance to semaglutide or any other components of the drug, a personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, type 1 diabetes mellitus, diabetic ketoacidosis, severe hepatic impairment, end-stage renal disease (creatinine clearance < 15 mL/min), and New York Heart Association (NYHA) functional class IV chronic heart failure. Semaglutide 2.4 mg is not recommended when using other weight-loss medications, in diabetic retinopathy, secondary obesity due to endocrine disorders, eating disorders, use of medications that may lead to weight gain, inflammatory bowel disease, or diabetic gastroparesis (delayed gastric emptying in diabetes). The drug should be used with caution in patients with mild to moderate hepatic impairment, thyroid disease, and a history of acute pancreatitis. There is limited experience with semaglutide 2.4 mg in patients aged 75 years and older. The most common adverse reactions with semaglutide (headache, nausea, vomiting, diarrhea, constipation, abdominal pain) typically occur at the start of treatment, are transient in nature, and do not require discontinuation of therapy.

Combination drugs for the treatment of obesity

• The drug Metformin + Sibutramine, which contains sibutramine (A08AA10), a centrally acting anti-obesity drug, and metformin** (A10BA02), a hypoglycemic agent (excluding insulins), is recommended for weight management and the improvement of lipid and carbohydrate metabolism in patients: with a BMI over 30 kg/m² (alimentary obesity); with a BMI of 27 kg/m² or more in combination with type 2 diabetes and dyslipidemia; with a BMI of 30 kg/m² or more with prediabetes and additional risk factors for type 2 diabetes in whom lifestyle modifications have failed to achieve adequate glycemic control [141-143].

GCR CLEL 4Grade of Recommendation C (Level of Evidence - 4)

Comments: the combined use of sibutramine and metformin**, either as concomitant administration or as a fixed-dose combination product, increases the therapeutic efficacy of the regimen in overweight patients with carbohydrate metabolism disorders. Sibutramine + metformin** enhances the effectiveness of obesity therapy and helps restore metabolic health even in patients without additional carbohydrate metabolism disorders. During therapy, weight loss is accompanied by a clinically significant reduction in waist circumference and an improvement in the lipid profile, which proves the efficacy of the drug in reducing the risk of complications and meets the primary goals of obesity treatment. The recommended duration of treatment with sibutramine and metformin, both as concomitant administration and as a combination product, is at least 6 months to establish healthy dietary habits and maintain the achieved weight loss results. Controlled arterial hypertension (blood pressure below 145/90 mm Hg) is not a contraindication to the use of the drug. The drug should not be taken in the presence of diabetic ketoacidosis, hepatic or renal impairment (creatinine clearance less than 45 mL/min), or in the presence of contraindications to sibutramine. Alcohol and ethanol-containing medicinal products should be avoided during treatment.

• If an obese patient has carbohydrate metabolism disorders, including conditions associated with insulin resistance (impaired fasting glucose, impaired glucose tolerance), in order to reduce the risk of developing type 2 diabetes or delay its onset, it is recommended to prescribe metformin**, liraglutide, or metformin + sibutramine [98, 105, 141-143].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• When prescribing medications for the treatment of obesity (A08A: Anti-obesity preparations, excluding diet products) at the stage of preconception care within a natural cycle or as part of preparation for assisted reproductive technologies (ART), it is recommended to inform the female patient about the need for contraception [157, 158].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• At the preoperative stage, patients with morbid obesity are recommended to correct vitamin D deficiency or insufficiency in accordance with current Clinical Guidelines [88, 159].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• During the preparation stage for bariatric surgery and for 12–24 months postoperatively, women of reproductive age are recommended to use contraception [88].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

3.2 Surgical Treatment

• Surgical treatment (A16.16.064 Gastric bypass, A16.16.065 Biliopancreatic diversion, A16.16.066 Laparoscopic gastroplication, A16.16.067 Laparoscopic gastric banding) is recommended for patients with morbid obesity aged 18–60 years when prior conservative measures have failed, in the presence of a BMI > 40 kg/m² (regardless of comorbidities) or a BMI > 35 kg/m² with severe comorbid conditions (type 2 diabetes, joint disease, obstructive sleep apnea) that can be ameliorated by weight loss [88, 160-162].

GRC BLEL 2Grade of Recommendation B (Level of Evidence – 2)

Comments: Weight loss achieved through intensive treatment directly during preparation for bariatric surgery (A16.16.064 Gastric bypass, A16.16.065 Biliopancreatic diversion, A16.16.066 Laparoscopic gastroplication, A16.16.067 Laparoscopic gastric banding) and a reduction in BMI below 35 kg/m² is not a contraindication for surgery. Bariatric surgery is also indicated for patients who successfully lost weight through conservative methods but were unable to maintain the results long-term and began to regain weight (even if their BMI has not reached 35 kg/m²). Typically, candidates for bariatric surgery are patients aged 18 to 60 years, although surgical indications may also be considered in other age groups.

• Surgical treatment of obesity is not recommended in the presence of acute gastric and duodenal ulcers, pregnancy, oncological diseases with a post-treatment remission period of less than 5 years, mental disorders (severe depression, psychoses including chronic ones, substance abuse such as alcohol, narcotics, and other psychotropics), certain types of personality disorders (psychopathies), life-threatening conditions in the short term, and severe irreversible organ dysfunction (class III–IV heart failure, hepatic or renal failure, etc.) [88, 160-162].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

Comments: Bariatric surgery (A16.16.064 Gastric bypass, A16.16.065 Biliopancreatic diversion, A16.16.066 Laparoscopic gastroplication, A16.16.067 Laparoscopic adjustable gastric banding) may be performed after a course of anti-ulcer therapy and confirmation of erosion/ulcer healing following treatment.

• If there are indications and no contraindications for surgical treatment of obesity, it is recommended to consult a surgeon performing bariatric surgeries [88, 160-162].

GDR CLE 5Grade of recommendation C (level of evidence – 5)

• Patients with morbid obesity are recommended to undergo the following surgeries: laparoscopic adjustable gastric banding (A16.16.067 Laparoscopic gastric banding), laparoscopic sleeve gastrectomy (A16.16.066 Laparoscopic gastroplication), laparoscopic gastric bypass (A16.16.064.001 Laparoscopic gastric bypass), as well as laparoscopic biliopancreatic diversion with duodenal switch (A16.16.065 Biliopancreatic diversion) [163-167].

LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2).

Comments: When choosing a specific type of bariatric surgery, it is recommended to consider the patient's age, degree of obesity, presence of comorbid and concomitant diseases, risk of surgical intervention, and the feasibility of ongoing regular postoperative monitoring. The use of modern staplers and meticulous anastomotic technique are recommended to reduce the risk of bleeding and anastomotic leakage.

• To achieve the best results of surgical treatment, it is recommended to prioritize following an enhanced recovery after surgery (ERABS or ERAS) protocol before, during, and after surgery [168, 169].

LoR CGoE 4Level of Recommendation C (Grade of Evidence - 4).

Comment: The ERABS protocol may include patient information preparation (standardized preoperative patient education and training with setting short- and long-term postoperative goals), preoperative preparation (avoiding premedication (patient sedation) and prolonged fasting), intraoperative care (standardized anesthesia (B01.003.004 Anesthesia care (including early postoperative management)), local anesthesia (B01.003.004.001 Local anesthesia), omission of nasogastric tube (A14.30.003 Feeding of a severely ill patient via mouth and/or nasogastric tube) and abdominal cavity drainage (A16.30.007 Peritoneal drainage) for prophylactic purposes, prevention of hypothermia, etc.), postoperative care (extubation immediately upon patient awakening, breathing exercises, prevention of vomiting and nausea, early removal of catheters and drains, early initiation of oral nutrition, avoiding nasogastric tubes, physical activity 2 hours after returning to the ward, standardized analgesia and thromboprophylaxis, early discharge), and post-discharge care (telephone contact with the patient on day 1 and 1 week after discharge, outpatient visits at the medical facility that performed the surgery 2 weeks after discharge). Examples of the protocol are provided in Appendix A3.

• Patients are not recommended to have a vena cava filter placed prior to surgery for the prevention of venous thromboembolism, as this procedure increases the risk of deep vein thrombosis [172].

LeveL of Recommendation AGrade of Evidence 2LeveL of Recommendation A (Grade of Evidence - 2).

• All patients are recommended to cease tobacco use, preferably 1 year and at least 6 weeks prior to surgery [88, 173, 174].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comments: It is also recommended not to resume tobacco use after surgery, as it increases the risk of poor wound healing, anastomotic ulcers, and leads to worse overall health status.

• Patients with obesity and type 2 diabetes mellitus are recommended to achieve glycemic control target levels during the preparation stage for bariatric surgery [88, 175].

LeveL of Recommendation AGrade of Evidence 2LeveL of Recommendation A (Grade of Evidence - 2).

• All patients who have undergone surgical treatment for obesity are recommended to receive thromboprophylaxis in the early postoperative period: early mobilization of patients from the first hours after surgery, elastic compression of the lower extremities, administration of unfractionated heparin (heparin sodium**, ATC code: B01AB01) or low-molecular-weight heparin (enoxaparin sodium** ATC code: B01AB05; nadroparin calcium ATC code: B01AB06) [88, 176].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• Patients with obesity suffering from type 2 diabetes mellitus are recommended to monitor blood glucose levels (A09.05.023 Blood glucose test) at least 4 times a day during the first days after surgery, with correction of glucose-lowering therapy if necessary [177, 178].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comments: In obese patients with concomitant type 2 diabetes mellitus after surgery, the issue of discontinuing or reducing the dose of hypoglycemic agents, except insulins (A10B) and insulin (A10AB, A10AC, A10AE, and its analogues (A10A) should be decided on an individual basis. Patients whose glycemia does not reach target levels after surgery are recommended to continue appropriate therapy.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Special rehabilitation methods are not provided.

5. Prevention and Dispensary Observation

• Patients who have achieved clinically significant weight loss (≥ 5% of baseline) through conservative treatment are recommended to maintain weight for 1-2 years [179-182].

GCR BLOE 3Grade of Recommendation B (Level of Evidence 3).

• During the weight maintenance stage after conservative treatment of obesity, it is recommended to regularly monitor body weight (weighing at least once a week), maintain or expand aerobic exercise regimens, and follow an eucaloric balanced diet [179-182].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• During the weight maintenance stage after conservative treatment of obesity, it is recommended to have regular appointments (examinations, consultations) (in-person or remote) with an endocrinologist, dietician, psychotherapist, or psychiatrist [179-182].

GCR CLOE 5Grade of Recommendation C (Level of Evidence – 5).

• All patients after bariatric surgery are recommended to have regular appointments (examinations, consultations) (in-person or remote) with an endocrinologist, surgeon, psychotherapist, or psychiatrist [88-95].

RG CLE 5Recommendation Grade C (Level of Evidence 5).

• All patients after bariatric surgery are recommended postoperative follow-up – a consultation (examination) with a dietician 1-2 weeks after surgery, then every 3 months during the first year and at least twice during the second year after surgery, and annually thereafter on an ongoing basis [183,184].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• If pregnancy occurs in a patient 12-18 months after surgery, it is recommended to consult a dietician to assess nutrition, the risk of deficiency states, and their correction [183, 184].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• All patients after bariatric surgery are recommended supplementation for vitamin, micronutrient, and macronutrient deficiencies under laboratory monitoring [184-188].

LoR CGoE 4Level of Recommendation C (Grade of Evidence - 4).

Comments: Despite the recommended multivitamin intake (A11BA), more than 60% of patients after bariatric surgery require additional prescription of one or more specific supplements. To detect the most common manifestations of vitamin and micronutrient deficiency, monitoring of the following parameters is recommended: vitamin B12, iron, folic acid, calcium, vitamin D, thiamine, copper, and zinc.

• 3-4 weeks after bariatric surgery, it is recommended to take calcium preparations at a dose of 1500-1800 mg per day and cholecalciferol** at a dose of 800 IU per day [88, 176, 189].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• 3 months after bariatric surgery, it is recommended to adjust the dose of calcium preparations and cholecalciferol** based on laboratory test results: blood 25-OH vitamin D level, total blood calcium level, inorganic blood phosphorus level, and blood albumin level [88, 184, 189].

GCR CLEL 5Grade of Recommendation C (Level of Evidence – 5)

• 6 months after bariatric surgery, it is recommended to test the blood PTH level [88, 176, 189-191].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• Patients who have undergone bariatric surgery are recommended to test blood 25-OH vitamin D and total calcium levels at least once every 6 months [88, 176, 189, 190].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• Patients who have undergone bariatric surgery are recommended to be prescribed cholecalciferol at a dose that maintains a normal blood 25-OH vitamin D level [88, 176, 189, 190].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Comments: The dose of vitamin D (cholecalciferol**) is selected individually. Achieving a normal serum calcium level and adequate vitamin D status are necessary conditions for reducing PTH levels and treating secondary hyperparathyroidism (SHPT).

• Two years after surgery, all bariatric patients are recommended to undergo dual-energy X-ray absorptiometry (A06.03.061 Osteodensitometry). When osteoporosis is diagnosed (T-score ≤ -2.5), appropriate treatment is indicated. If necessary, alphacalcidol** may be added to the therapy [88, 176].

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

• All patients who have undergone bariatric surgery are recommended to take oral iron supplements daily at a dose of at least 100 mg (calculated as elemental iron) starting from 6–8 weeks postoperatively [88, 190, 191].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• To assess protein deficiency in all patients 3 months after bariatric surgery, it is recommended to test blood total protein and blood albumin levels [88, 184, 190, 191].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• To prevent protein deficiency in all patients who have undergone bariatric surgery, starting from 3–4 weeks postoperatively, it is recommended to use a specialized high-protein whey-based formula with a low carbohydrate content (less than 7.5 g per 100 g: AM.01.48.01.004.R.000182.08.21, RU.77.99.32.007.E.004123.09.18, AM.01.01.01.003.R.000344.07.22), as well as enteral nutrition formulas in the form of shakes: AM.01.48.01.004.R.000145.07.21 [192].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

• Patients who have undergone bariatric surgery with suspected vitamin B12-deficiency anemia are recommended to have blood vitamin B12 (cyanocobalamin) and serum folic acid levels determined [88, 176, 189].

GCP CLEL 5Level of Evidence C (Level of Likelihood of Evidence - 5).

Comments: All patients with malabsorption syndrome, gastric resection, and intestinal resection are at risk for developing vitamin B12-deficiency anemia. To prevent the recurrence of vitamin B12-deficiency anemia, #intramuscular administration of cyanocobalamin** once every 3 months (1,000 mcg) under laboratory monitoring may be recommended [194-195]. In vitamin B12-deficiency anemia, serum iron and ferritin levels are typically high. However, patients with malabsorption syndrome may present with a combined cobalamin and iron deficiency. In such cases, the typical laboratory picture of vitamin B12-deficiency anemia may be masked, hindering timely diagnosis and delaying pathogenetic therapy.

• All patients during the weight loss phase after bariatric surgery are recommended to be prescribed oral #ursodeoxycholic acid** at a dose of 500–1000 mg for 6 months to prevent gallstone formation [160, 196].

GPP BLE 2Grade of Recommendations B (Level of Evidence 2).

6. Organization of Medical Care

Elective hospitalization. Inpatient / day hospital care.

Indications for planned hospitalization in a medical organization (day hospital, inpatient setting):

1. progressive weight gain, worsening of comorbid conditions, and/or decompensation of metabolic disorders associated with obesity (type 2 diabetes, cardiovascular diseases, obstructive sleep apnea syndrome, etc.);

2. performance of bariatric surgeries and preparation for them;

3. decompensation of metabolic disorders after bariatric surgeries;

Indications for patient discharge from a medical organization

1. weight loss;

2. improvement of comorbid conditions and/or compensation of obesity-associated metabolic disorders.

7. Additional Information

There is no additional information affecting the course and outcome of the disease/condition.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

LEADERS:

Dedov, I.I., Professor, Academician of the RAS, Moscow

Mokrysheva, N.G., Professor, Corresponding Member of the RAS, Moscow

Melnichenko, G.A., Professor, Academician of the RAS, Moscow

Troshina, E.A., Professor, Corresponding Member of the RAS, Moscow

TEXT AUTHORS:

Mazurina, N.V., MD, PhD, Moscow

Ershova, E.V., PhD in Medicine, Moscow

Komshilova, K.A., PhD in Medicine, Moscow

EXPERTS INVOLVED IN THE DISCUSSION AND APPROVAL OF THE CLINICAL GUIDELINES:

Andreeva, E.N., MD, PhD, Professor, Moscow

Antsiferov, M.B., MD, PhD, Professor, Moscow

Bardymova, T.P., MD, PhD, Professor, Irkutsk

Bordan, N.S., MD, PhD, Moscow

Vagapova, G.R., MD, PhD, Professor, Kazan

Volkova, A.R., MD, PhD, Associate Professor, Saint Petersburg

Volkova, N.I., MD, PhD, Professor, Rostov-on-Don

Volynkina, A.P., PhD in Medicine, Associate Professor, Voronezh

Vyuchnova, E.S., PhD in Medicine, Moscow

Demidova, T.Yu., MD, PhD, Professor, Moscow

Dzhgoeva, F.Kh., PhD in Medicine, Associate Professor, Moscow

Kiseleva, T.P., MD, PhD, Professor, Yekaterinburg

Mayev, I.V., MD, PhD, Professor, Academician of the RAS

Markova, T.N., MD, PhD, Moscow

Neimark, A.E., PhD in Medicine, Saint Petersburg

Ostroumova, O.D., MD, PhD, Professor, Moscow

Romantsova, T.I., MD, PhD, Professor, Moscow

Ruyatkina, L.A., MD, PhD, Professor, Novosibirsk

Suplotova, L.A., MD, PhD, Professor, Tyumen

Khalimov, Yu.Sh., MD, PhD, Professor, Saint Petersburg

Khatsiev, B.B., MD, PhD, Stavropol

Shestakova, E.A., MD, PhD, Moscow

Yashkov, Yu.I., MD, PhD, Professor, Moscow

Conflict of interest: none declared

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. endocrinologists

2. general practitioners (internal medicine)

3. general practitioners (family physicians)

4. cardiologists

5. obstetrician-gynecologists

6. surgeons

7. gastroenterologists

8. dermatovenereologists

9. cosmetologists

10. plastic surgeons

11. nutritionists

Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

None provided.

Appendix B. Physician Action Algorithms

Drug therapy algorithm for a patient with exogenous-constitutional obesity

Algorithm for choosing obesity treatment tactics

Algorithm for selecting drugs for obesity pharmacotherapy

ERABS protocol (option 1) [168, 169]

ERABS protocol (option 2) [168, 169]

Appendix C. Patient Information

1. How to properly assess your weight? To do this, calculate your body mass index (BMI) using the formula: BMI = weight (kg) ÷ height (m²). Check which group your BMI belongs to:

   BMI	Health risk
   18,5 – 24,9 Normal body weight	Eat healthy. Exercise. Monitor your weight.
   25 – 29,9 Overweight	There is a risk of complications. A comprehensive clinical examination is required. Think about your health. Modify your diet and physical activity levels.
   30 –39,9 Obesity	High risk of developing obesity-related diseases. You should consult a physician for an examination and a personalized weight loss program.
   More than 40 Morbid obesity	Health risk is very high. Diseases of various organs and body systems are already present. You should consult a doctor immediately. Urgent examination and treatment are required not only for obesity, but also for existing complications.

2. The following types of obesity are distinguished:

   • Abdominal (from the Latin abdomen – belly) type of obesity, characterized by excessive deposition of adipose tissue in the abdomen and upper body. This type of obesity is most dangerous for the development of cardiovascular and respiratory diseases and type 2 diabetes mellitus.

   • Gynoid (lower) type of obesity, characterized by predominant deposition of adipose tissue in the buttocks and thighs. Most often accompanied by the development of diseases of the spine, joints, and lower extremity veins.

   • Mixed type of obesity, characterized by an even distribution of fat throughout the body.

     To determine the type of obesity, find the waist-to-hip ratio (WHR). Measure the waist circumference at the midpoint between the lower rib margin and the pelvic bone, and the hip circumference at the widest part at the level of the buttocks. A WHR exceeding 1.0 in men and 0.85 in women indicates an abdominal type of obesity. A waist circumference greater than 94 cm in men and greater than 80 cm in women represents a real risk for developing type 2 diabetes mellitus and cardiovascular disease.

3. If you are overweight or obese, get a blood test once a year for total cholesterol and its fractions, triglycerides, and glucose, and monitor your blood pressure. The most severe diseases that develop in connection with obesity are arterial hypertension, type 2 diabetes mellitus, and atherosclerosis.

4. Lose weight slowly and gradually – this will yield positive results, will not disrupt the normal functioning of organs and systems, and will help avoid weight regain. Weight loss goals are 5–15% of the initial body weight within 3–6 months, followed by weight maintenance.

5. The key to successful weight loss is a combination of a rational balanced diet with an active lifestyle (at least 150 minutes per week)

6. How to calculate daily calorie intake:

   • Calculate the actual calorie content of your daily diet.

   • Calculate your physiological daily energy expenditure using the formula

     for women:

     18–30 years: (0.0621 × weight in kg + 2.0357) × 240

     31–60 years: (0.0342 × weight in kg + 3.5377) × 240

     over 60 years: (0.0377 × weight in kg + 2.7546) × 240

     for men:

     18–30 years: (0.0630 × weight in kg + 2.8957) × 240

     31–60 years: (0.0484 × weight in kg + 3.6534) × 240

     over 60 years: (0.0491 × weight in kg + 2.4587) × 240

     If you lead a sedentary lifestyle, multiply the resulting value by 1.1; for moderate physical activity, by 1.3; for physical labor or active sports, by 1.5.

   • Calculate the daily calorie intake required for weight loss. To do this, reduce the resulting daily calorie value by 20% (500–600 kcal). If your actual diet exceeds 3000 kcal per day, reduce food intake gradually – by 300–500 kcal per week until you reach your calculated individual calorie norm.

   • Calculate your daily fat requirement. Divide the calorie content of your diet required for weight loss by 4, and then by 9.

   • Distribute the calorie content of the diet into 3–5 meals.

     • Breakfast – 25%

     • Second breakfast – 15%

     • Lunch – 35%

     • Afternoon snack – 10%

     • Dinner – 15%

Principles of dietary therapy at the preoperative preparation stage

Preoperative weight loss

Preoperative fasting

Solid food intake is restricted 6 hours, and liquids 2 hours before the start of anesthesia, in the absence of contraindications (e.g., gastroparesis, intestinal obstruction)

Stages of postoperative dietary therapy

Early postoperative period: from several hours to 6–8 weeks

From several hours to 1–2 days after surgery. Step one – “clear liquids”

Volume of room temperature liquid no more than 100 ml (½ cup) per serving, gradually increasing the volume up to 2 liters per day.

• Water, broth, herbal teas, liquid fruit kissel (sugar-free), fruit juice diluted 10 times

  3–7 days after surgery. Step two – “full/enriched liquids”

• Milk, plant-based milk alternatives, liquid yogurt, protein shakes (high protein content of 20–30 g per serving), enteral nutrition shakes.

  7–14 days after surgery. Step three – “pureed food”

  This period is recommended to begin with homogenous food and gradually transition to less homogenous pureed food. It is important to maintain an interval between meals and drinks (15 minutes before or 30 minutes after a meal)

• blended soups, baby meat, vegetable, and fruit purees, pureed vegetable mixtures with the addition of white poultry meat (with a sufficient amount of liquid to achieve the desired consistency)

  2–4 weeks after surgery – “soft food”

  During this period, patients can add soft-consistency foods to their diet

• soft meatballs*, omelet or boiled eggs; boiled, peeled vegetables; and soft peeled fruit, cottage cheese, and low-fat cream cheeses

  4–8 weeks after surgery. Step four – “solid food”

  2 months after surgery, patients can switch to a normal balanced diet. Food volume should not exceed 200 ml.

• after one month, it is recommended to add: legumes, fresh vegetables, fruits, and bread

2 months after surgery, patients can switch to a normal balanced diet

*Note: protein products must contain a sufficient amount of liquid to ensure proper digestion. The optimal cooking method for this period: steaming, poaching, stewing. If adverse events occur during the transition to the next diet stage, it is recommended to return to the previous stage for a few days.

Recommendations for eating rules

1. Thorough meal planning is necessary (4–6 small meals a day, depending on the postoperative stage)

2. Replace large plates and cups with smaller tableware

3. Eat slowly, cut solid food into small pieces, chew food thoroughly (25 to 30 times for each piece), stop eating as soon as you feel full

4. In the early postoperative period, avoid foods that can cause obstruction: persimmon, citrus membranes, nuts and seeds, popcorn, whole grain products, tough/dry meat

5. Exclude white flour products, pasta, and white rice

6. Drink sufficient fluids to maintain adequate hydration (≥1.5 L/day). It is recommended to refrain from drinking beverages 15 minutes before meals and/or 30 minutes after meals for up to 3 months postoperatively

7. Do not consume carbonated beverages, alcohol, or caffeine-containing beverages.

8. Restriction of simple sugars (milkshakes, ice cream, pastries, and cookies) to 10% of total daily caloric intake.

9. Restriction of saturated and trans fats in the diet

10. It is important to recommend that patients add omega-3 fatty acid-rich foods, vegetables and fruits, flavonoid- and antioxidant-rich foods, and high-calcium (low-fat) dairy products to their diet.

11. Adequate protein intake

12. Daily multivitamin supplementation

Recommendations for optimal protein intake

Protein deficiency is associated with muscle atrophy, asthenia, and alopecia.

• Preference should be given to high-protein foods (dairy products, eggs, fish, lean meat, soy products, and legumes)

• Thorough chewing of food improves the digestion of protein components

• A total protein intake of 60–80 g per day or 1.0–1.5 g/kg of ideal body weight is recommended, except for BPD, where 90 g of protein per day is recommended

• The highest quality protein sources are: whey (the best source of leucine, which helps preserve muscle mass), egg, and soy

• The optimal protein content is at least 20 g per serving

Table 1. Types of protein supplements.

Dietary therapy for frequent gastrointestinal disorders in the postoperative period

Table 2. Methods for the prevention and treatment of common gastrointestinal symptoms after bariatric surgery

Physical activity

Patients should engage in at least 150 minutes of aerobic activity per week, and incorporate additional resistance training at least twice a week once recovery is complete.

Postoperative follow-up with a clinical dietitian 1–2 weeks after surgery, then every 3 months during the first year, at least twice during the second year, and at least annually thereafter for the long term. If pregnancy occurs 12–18 months postoperatively, a nutritional consultation is recommended to assess dietary intake, evaluate the risk of nutritional deficiencies, and provide management.

An important part of postoperative follow-up is the creation of patient support groups to receive valuable information from specialists and share valuable experiences with one another.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not applicable.