The choice of treatment of diabetes mellitus type 2 is personalized, based on modern Russian and international algorithms for management of such patients. Given the initial level of decompensation of the disease at the time of diagnosis (at the level of glycated hemoglobin), most patients with type 2 diabetes at the time of initiation of therapy requires the combined treatment, at least two antidiabetic drugs. In modern conditions, on the basis of evidence-based medicine, priority should be given to drugs with a low risk of hypoglycemic conditions and do not affect or reduce body weight. In this article we consider a class of inhibitors of dipeptidyl peptidase 4, which entered into clinical practice since 2006 for the treatment of patients suffering from diabetes mellitus type 2, with an emphasis on drugs used in the Russian Federation. Today in our country there are seven members of the class of inhibitors of dipeptidyl peptidase 4. The results of the major randomized clinical trials (SAVOR-TIMI 53, EXAMINE, TECOS, CAROLINA), which studied the cardiovascular safety of dipeptidyl peptidase 4 inhibitors, showed the intra class heterogeneity with respect to data on the frequency of hospitalizations due to chronic heart failure. Have proven cardiovascular neutrality in relation to the primary combined cardiovascular outcome was MACE, including cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. A major problem is the choice of effective glucose-lowering therapy to special patient groups. Assign their profession the safety of drugs plays a key role. With its high efficiency and unique glucosidation mechanism of action, guaranteeing a low risk of hypoglycemia and high safety, the drugs of this group has firmly taken its niche among the priority hypoglycemic drugs.

Introduction. Today, non-alcoholic fatty liver disease (NAFLD) is increasingly associated with the presence or risk of developing type 2 diabetes (D2). The term “hepatogenic diabetes”, proposed to refer to SD2 in patients with cirrhosis of the liver (CP), has acquired a new meaning, since this combination is of growing interest. The authors analyzed the current literature and summarized data on the pathogenesis, risk factors, and possible therapy of NAFLD.

Objective: to evaluate the effectiveness of L-ornithine-L-aspartate (HEPA-Merz, Merz Pharma GmbH & Co) in combination with biguanides in the treatment of NAFLD patients in combination with D2.

Materials and methods. The study included 30 patients aged 26 to 60 years with a verified diagnosis of NAFLD of varying degrees of activity in combination with D2. All patients were prescribed combination therapy with the drug HEPA-Merz (“Merz Pharma GmbH and Co”) at a dose of 3 grams 3 times a day in combination with biguanides. The examination was performed on the 1st, 28-th and 56-th days of treatment. In order to determine the effectiveness of therapy, we evaluated the dynamics of clinical symptoms (asthenovegetative, dyspeptic syndromes, pain syndrome in the ball system), biochemical parameters of liver function (changes in markers of cytolysis, cholestasis), lipidogram indicators, glucose levels, glycated hemoglobin, and ultrasound results of abdominal organs.

Results. On day 56, asthenovegetative, dyspeptic and pain syndrome were stopped during therapy. Most patients showed a decrease in body weight from 3 to 5 kg. When evaluating changes in biochemical parameters on the 28-th day, the activity of ALT, AST, GGTP and glucose levels significantly decreased against the background of the therapy. On the 56th day of treatment, the activity of transaminases, bilirubin, GGTP and GFR in all patients were within the reference values.

Conclusion. Understanding the multifactorial nature of NAFLD and the mechanisms of associated diseases, including D2, will allow us to assess the prognosis of the disease and prescribe adequate timely therapy. The effectiveness of the original ornithineaspartate (Merz Pharma GmbH & Co.) is manifested by a decrease in the processes of cytolysis of hepatocytes, normalization of lipid and carbohydrate metabolism.

Verification of the type of diabetes mellitus in young people is of high clinical significance in the clinical practice since the purpose of treatment depends on this: from the correction of carbohydrate metabolism by a rational diet to the administration of oral hypoglycemic drugs and insulin therapy. The chosen therapy has a significant impact on the quality of life of the patient. With the most common types of diabetes in young people the appointment of therapy is not in doubt, since with type 1 diabetes mellitus there is an absolute need for the maintenance of exogenous insulin, and with type 2 the administration of metformin is pathogenetically substantiated. In more rare forms of diabetes which MODY belongs to sulfonylurea preparations are recommended in most cases and there are few conflicting data on the effects of newer classes (DPP4, SGLT2 inhibitors, GLP1 agonists) with monogenic forms. Using the method of continuous monitoring of glucose (CGMS) and glycemic variability indicators it is possible to determine the effectiveness of various classes of sugar-lowering drugs for rare types of diabetes mellitus which will help practitioners in choosing therapy. In the literature single studies using CGMS have been described in this group of patients. In Turkey CGMS was performed for 8 patients with GCK-MODY; it was shown that in 50% of patients the glucose values during the day exceeded the normal ranges. Italian scientists conducted a study in which they diagnosed glycemic variability, in particular episodes of hypoglycemia, in patients with HNF4AMODY diabetes (MODY1) using CGMS. The clinical consequence of episodes of asymptomatic hypoglycemia in the MODY cohort remains unknown. Diagnosing the predominance of fasting or postprandial hyperglycemia, the determination of hypoglycemia can help in the appointment of pathogenetic therapy and improve the quality of life of people diagnosed with MODY-diabetes.

Type 2 diabetes mellitus (T2DM) is closely associated with the risk of developing cardiovascular complications. A new approach to treatment of T2DM, based on the inhibition of the sodium-glucose cotransporter type 2 (SGLT2) ensures reliable insulin-independent glycemic control with quick overcome of glucotoxicity, reduction of insulin resistance, and positive effects on body mass, blood pressure and other rates. Besides, pronounces clinical efficacy of SGLT2 inhibitor is marked by its use safety and minimized frequency of adverse events. Along with this, the results of carried-out, randomized clinical studies of cardiovascular safety of different SGLT2 inhibitors showed, that apart from bearing on the risk factors, the inhibition of sodium-glucose cotransporter type 2 leads to cardioand renoprotective effects. In addition, their influence on cardiovascular and renal outcomes is the stronger the more different the pre-existing status of cardiovascular diseases of the patient is, the condition of his renal function and the severity of albuminuria. This article summarizes the main results of carried-out randomized clinical studies of SGLT2 inhibitors, which demonstrate their cardiovascular advantages and compile encouraging results of multicentered studies VERTIS, examining different aspects of the use of the ertugliflazine SGLT2 inhibitor in patients with type 2 diabetes. There is data provided demonstrating a powerful glucoselowering, body-mass lowering and hypotensive impacts of ertugliflazine comparable to the same performance of the best representatives of the class. This article describes an evidence base of the use of the drug in monotherapy and its ability to be combined with other oral hypoglycemic agentsand highlightes a high level of safety of the use of ertugliflazine correspondinding to minimized frequency of adverse outcomes of SGLT2 inhibition and so the potential of SGLT2 inhibitors as a new promising class for the treatment of patients with type 2 diabetes and established cardiovascular disease is revealed.

Alogliptin, a dipeptidylpeptidase-4 inhibitor, is an oral hypoglycemic agent approved in many countries for the treatment of patients with type 2 diabetes, including the United States, Europe, and Japan. The drug is effective both as a monotherapy, and as an additional or combined treatment of type 2 diabetes. Alogliptin is well tolerated by patients, including the elderly, as well as those suffering from kidney and / or liver failure or having a high risk of cardiovascular events. The low risk of hypoglycemia, weight gain, acute pancreatitis, and side gastrointestinal events. During treatment with alogliptin has been demonstrated in both long-term (up to 4.5 years) studies and in actual clinical practice. Alogliptin increases postprandial levels of the glucagon-like peptide-1, which leads to insulin secretion and normalization of glucose homeostasis. Treatment with alogliptin is associated not only with improved glucose metabolism, but also with a decrease in blood pressure and arterial rigidity in patients with arterial hypertension and diabetes, as well as normalizing the lipid profile. In patients with diabetes mellitus who have recently undergone acute coronary syndrome and received alogliptin, the frequency of serious adverse cardiovascular events does not increase. Experimental data show that alogliptin reduces ventricular hypertrophy, interstitial fibrosis, and diastolic dysfunction. Alogliptin has a number of unique properties. It is assumed that it can increase the number of circulating endothelial progenitor cells that play an important role in endothelial repair and neovascularization. Alogliptin preserves the functionality and structure of the mitochondria of cardiomyocytes. The drug may be a potential treatment for patients with MODY1 diabetes at an early stage of the disease, when residual insulin secretion is preserved. Treatment with a fixed combination of Alogliptin + Metformin results in better glycemic control than monotherapy and is well tolerated. There is evidence that treatment with alogliptin is not associated with an increased risk of pancreatitis or pancreatic cancer.

Type 2 diabetes mellitus (T2DM) is a progressive disease accompanied by a gradual worsening of β-cell function. With a long course of T2DM, a significant proportion of patients develop absolute insulinopenia and there is a need to transfer the patient from oral hypoglycemic drugs (OHD) to basal insulin therapy in combination with OHD or to the basal-bolus regimen of insulin therapy (IT). More than 80% of patients with T2DM are obese or overweight and the addition of insulin, which is a lipogenetic hormone, to the therapy contributes to even greater weight gain, which serves as a prerequisite for increasing cardiovascular risks, as well as the appearance and progression of biomechanical problems such as arthrosis of the joints, venous insufficiency. In this review article, we will consider and evaluate the benefits of administering combinations of basal insulin glargine in combination with glucagonlike peptide-1 receptor agonists (GLP-1ra) lixisenatide to one of the most rational treatment regimens for patients with T2DM insulin deficiency and persistent insulin resistance. Also, the article focuses on the variability of glycemia, which according to research can play an important role in the pathogenesis of atherosclerosis and can be an independent risk factor for cardiovascular complications in patients with diabetes. Due to the fact that glycemic control is based on the determination of predominantly glycated hemoglobin (HbA1c) as a measure of average glucose concentration, it is known that this marker does not accurately reflect glycemic variability, which is characterized by the amplitude, frequency and duration of hypo- and hyperglycemic fluctuations. A fixed combination of insulin preparations glargin 100 and GLP-1ra lixisenatide allows to select individually effective dosage for a patient with type 2 diabetes and obesity, will help to achieve several goals at the same time - from improving glycemic parameters without increasing body weight and without increasing the risk of hypoglycemia, to significantly reduce the need for insulin with its previous use, as well as reduce the risk of cardiovascular complications.

Diabetic polyneuropathy (DPN) is the most common and earliest complication of diabetes mellitus and it may occur much earlier in patients with type-2 diabetes than in patients with type-1. Distal polyneuropathy can develop not only in diabetes mellitus, but also at the stage of prediabetes and even in patients with metabolic syndrome without impaired glycemic state. Hyperglycemia viewed as a major, but not the sole factor, responsible for development and progression DPN. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. Damage of peripheral nervous system in prediabetes and in the initial stages of diabetes mainly affects small nerve fibers, which also leads to disorders of the autonomic nervous system. Cardiac autonomic neuropathy diagnosed in 5-7.7% of patients at the time of diagnosis of type 1 and type 2 diabetes mellitus. For the early diagnosis of DPN, both routine assessment of peripheral sensation can be used, as well as specialized methods (sympathetic skin reactions, skin biopsy, confocal corneal microscopy, quantitative sensory tests) and validated questionnaires (Utah Early Neuropathy Scale) focused on assessing the function of small nerve fibers. Non-electrophysiological studies also were tested for early diagnosis of DPN: peripheral nerve sonoelastography, optical coherence tomography, MRI neurography, spiral positron emission CT (SPECT) with 123I-MIBG. DPN diagnosis in the pre-clinical stage very important, because treatment with diet and lifestyle intervention may be successful. The correlation between the severity of oxidative stress and the activity of antioxidant defense is considered as a potential mechanism for early nerves damage with hyperglycemia and as a possible target for therapeutic intervention. In this work, we will review prevalence, diagnostic approaches and potential treatment options for early diabetic polyneuropathy.

Introduction. The results of a 25-year observational program to assess the effect of glycated hemoglobin variability on the development of microvascular complications in patients with type 1 diabetes mellitus are presented.

Objective: This study aimed to evaluate the effect of glycated hemoglobin (HbA1c) variability on the development of microvascular complications in patients with type 1 diabetes mellitus (DM1) and disease duration of 25 years.

Materials and methods: A retrospective analysis of the database of patients with DM1 was performed from the moment of the disease manifestation until the time of the last visit. Determination of HbA1c level is carried out using parameters certified in accordance with the National Standard for Glycohemoglobin Standardization (NGSP) or the International Federation of Clinical Chemists (IFCC). HbA1c variability was determinated by average current HbA1c, average of longitudinal HbA1c (from the manifestation to the last visit – 2019), median and maximum of difference in changes of HbA1c (median and max∆HbA1c). Statistical analysis was performed by IBM SPSS Statistics ver.22. A statistically significant difference is the value p < 0.05.

Results. A total of 88 patients were enrolled in this study, they were divided in 3 groups depending on the registered microvascular complications (MVC): without MVC (n = 38), isolated MVC (retinopathy or nephropathy) (n = 25) and multiple MVC (retinopathy and nephropathy) (n = 25). Clinical characteristics [median (25; 75 percentile)]: age of manifestation of DM1 is 9 years (5; 12), age of patients at the time of the last visit is 33 years (29; 35), duration of DM1 is 24 years (20; 27), body mass index 24 kg/m2 (21; 25). Medication: basal-bolus insulin therapy (n = 82) or pump insulin therapy (n = 6). The average level of longitudinal HbA1c for the three groups was: 8% (7.6; 8.9), 8.5% (7.9; 8.9), 8.6% (7.8; 10), p = 0.2. Average of current (at the time of the last visit) HbA1c – 8.2% (7.2; 9.0), 8.1% (7.5; 9.0), 8.4% (7.3; 9.7), p = 0.4. Statistically significant differences were determined in the group without complications and in the group with multiple complications between the levels of maxΔ HbA1c 2.3% (1.8; 2.8) vs 4.7% (3.2; 5.6), p < 0.0001 and median Δ HbA1c 0.7% (0.6; 0.9) vs 1.4% (1; 1.7), р < 0.0001. There were no statistically significant relationships between the maximum and medianΔ HbA1c in the groups without complications and in the group with isolated complications.

Conclusions: Longitudinal HbA1c and current HbA1c are not associated with the development of microvascular complications. The potential role in the development of microvascular complications was determined for the maximum and median Δ HbA1c.

Introduction. Among phenotypic variants of osteoarthritis (OA), a special place is occupied by OA with a comorbidity. A therapy of a pain in OA patients with the comorbid for diabetes mellitus type 2 (DM2) should be carried out with account for its effectiveness and safety.

Objective. Perform comparative analysis of the clinical and laboratory characteristics of gonarthrosis and their therapeutic dynamics in moderate comorbid risk groups.

Methods. The clinical and laboratory characteristics of gonarthrosis were studied in 386 women (mean age 61.3 ± 7.8 years), of which 162 ones had DM2. We evaluated several characteristics of the pain, which were summarized in the rating of pain (R_P). The level of C-reactive protein (CRP) in the blood serum was determined. An analysis of 75 samples of a synovial fluid (SF) obtained by a puncture of knee joints (KJ) in patients with severe synovitis was performed. An open-label controlled short-term trial of the analgesic and anti-inflammatory activity of diclofenac sodium in gonarthrosis was performed in 30 people in the euglycemic group and in the comorbid one according to DM2.

Results. R_P for concomitant DM2 was 22.2% (p = 0.0001) lower than for isolated gonarthrosis, but the concentration of CRP in serum and SF did not differ between groups. The glucose level in the SF with concomitant DM2 was 46.6% (p = 0.0001) higher. NSAIDs were used according to the needs of more than 75% of patients, but women with concomitant diabetes mellitus type 2 used non-selective drugs 1.9 times (p = 0.008) more often. The efficacy and safety of the drug containing diclofenac sodium was comparable in the euglycemic group and in the concomitant diabetes mellitus type 2 group, but patients with comorbid DM2 achieved an effect of 23% less quantity NSAIDs.

Conclusions. The use of drugs containing diclofenac sodium in 87% of patients provides an analgesic and anti-inflammatory effect with the satisfactory tolerance and the low drug demand, including in patients comorbid for type 2 diabetes.

Introduction. Patients with type 2 diabetes are more likely to have concomitant depression. In addition, there are some studies that have alluded to a direct relationship between overweight and diabetes and daytime drowsiness.

The aim of this study was to study the relationship of metabolic disorders, anthropometric data with daytime sleepiness and depression in patients with type 2 diabetes.

Material and methods. A general clinical study consisted in interviewing the patient (complaints, medical history), obtaining physical data (anthropometry) – height (cm), weight (kg), neck circumference (cm), waist circumference (cm), hip circumference (cm). The object of the study was the whole blood and blood plasma of patients in order to determine the level of fasting plasma glucose, glycosylated hemoglobin and other blood biochemical parameters. To verify violations in the emotional-volitional sphere, the Beck Depression Inventory and the Epworth Sleepiness Scale were used.

Results. All patients had visceral obesity, the waist circumference is significantly higher than normal, both in men and women. In accordance with the Epworth drowsiness scale, on average, borderline insomnia was recorded in the examined patients with type 2 diabetes. Drowsiness rate correlated with waist circumference (r = 0,65) and hips (0,67), age (0.34) only in male patients. The level of depression correlated with age in female patients (r = 0.37, p < 0,05) and male (r = 0,6, p < 0,05) and did not correlate with drowsiness in both groups. The level of depression was 16, which corresponds to mild to moderate depression. However, the rate of depression is negligible, but higher among female patients (14.00 [6.00; 18.00] versus 19.00 [10.50; 20.00], p = 0,047).

Conclusions. Increased daytime sleepiness and depression accompany patients with type 2 diabetes, regardless of gender. The dependence between the severity of decreased daily activity and increased anthropometric indicators and age can be seen in male patients, which may illustrative of increasing androgen deficiency in men and its contribution to the development of metabolic disorders, including obesity. Depressive states have deeper manifestations in female patients with type 2 diabetes compared to male patients, which may indicate both emotional instability of female patients and a more pronouncedeffect of the disease itself on the psychoemotional background in women.

Introduction. Currently, there is a high prevalence of type 2 diabetes mellitus (DM2) and osteoarthritis (OA). DM2 worsens the prognosis of the results of arthroplasty for OA, and also becomes an additional insecurity factor in the administration of traditionally often used non-steroidal anti-inflammatory drugs (NSAIDs) and in local injections of glucocorticosteroids. It is considered safer to prescribe chondroitin sulfate.

Objective. Identification of clinical, radiological and arthrosonographic features of the manifestations of gonarthrosis with concomitant DM2 and related differences in the strategic conservative therapy.

Methods. The study included 386 women with OA of knee joints (mean age 61,3 + 7,8 years). Patients were divided into groups of euglycemic status (group “OA”, n = 224) and comorbid according to DM2 (group “OA + DM2”, n = 162). The amplitude of an active mobility of the knee joints (KJ), the severity of gonarthrosis using the Lequesnealgo-functional index (AFI_Lequesne) and the WOMAC questionnaire were assessed. Radiography and arthrosonography of the KJ were performed.

Results. In patients in group “OA + DM2” AFI_Lequesne were less by 18,2% (p = 0,0001), the total WOMAC index were less by 15,6% (p = 0,0001) compared with the “OA” group. In the group “OA + DM2”, the first x-ray stage was 2,6 times less common, and the third was 2 times more likely than the group “OA” (χ2 = 25,5; p = 0,001). The arthrosonography in the group “OA + DM2” detected a more pronounced thinning of the articular cartilage and more severe osteophytosis. The masking effect of DM2 on the symptoms of OA led to a rarer use of slowly acting symptom-modifying agents containing chondroitin in patients with “OA + DM2” in 1,7 times as compared with “OA” patients.

Conclusions. In patients with gonarthrosis, concomitant DM2 minimizes symptoms, but accelerates the degeneration of the knee joints tissues. There is no information on the deterioration of the carbohydrate metabolism with a prolonged use of chondroitin sulfate, which suggests the safety of such therapy for patients with OA and concomitant diabetes mellitus type 2.

The article presents the issues of epidemiology, classification, and clinic of hypothyroidism. The frequency of hypothyroidism increases significantly with age. The most common form is primary hypothyroidism, caused by a pathological process in the thyroid gland itself. Secondary hypothyroidism or tertiary hypothyroidism is caused by insufficient secretion of thyroid- stimulating hormone (TSH), or thyrotropin-releasing hormone. The article deals with the main causes of primary and secondary hypothyroidism. The most common cause of primary hypothyroidism is autoimmune thyroiditis, which can develop both separately and simultaneously with other autoimmune diseases, as part of polyglandular syndrome. Special attention should be paid to the change of thyroid status as a result of adverse side reactions when using a range of drugs. The questions about the mechanisms of thyroid insufficiency development as a result of unfavorable side reactions when using a number of drugs (lithium preparations, iodine-containing compounds, tyrosine kinase inhibitors, etc.) have been raised. Undiagnosed hypothyroidism is a risk factor for the progression of already existing cardiovascular diseases. The severity of clinical manifestations is determined by the severity of thyroid hormone deficiency. There are no significant clinical differences between the pronounced forms of primary and secondary hypothyroidism. Depending on the degree of lesion, secondary hypothyroidism may be complicated by other manifestations of hypothalamic-pituitary disorders, as well as the latter may include a decrease in the secretion of antidiuretic hormone at a certain stage of their development. Diagnostic difficulties are discussed, as hypothyroidism disrupts the functioning of most organs and systems of the body (musculoskeletal, cardiovascular, urinary, gastrointestinal, central and peripheral nervous systems) and can be masked by various diseases. The final diagnosis of hypothyroidism is clarified by a number of laboratory and instrumental studies. Substitution therapy with levothyroxine is used to treat hypothyroidism of any etiology.

The continuing growth in the prevalence of obesity in close connection with the tandem of a number of chronic diseases, each of which is in the nature of a non-infectious epidemic, indicates an obesity syndrome. This is one of the most complex and expensive diseases, taking into account its cardio-metabolic and oncological risk, chronic progressive course and recurrent nature. Such a situation dictates the necessity to clarify the pathogenetic approaches to the problem, based on the principles of early treatment, before the debut of comorbid nosology’s. With the multifactorial nature of obesity, it is difficult to single out the principal directions of intervention with the goal of not only reducing body weight, but especially its stabilization. The accumulated data on new pathogenesis links are analyzed: dysfunctions of the microbiota and entero-endocrine system of the gastrointestinal tract with impaired incretin synthesis, metainflammation, peripheral and central insulin resistance, which integrally changes intracellular energy metabolism through a change in the activity of the AMP-activated protein kinase and is associated with systemic inflammatory response. These links are interconnected by the axis: “intestine – brain – liver”, which explains the relationship of obesity with multiple multidisciplinary pathology and reflects the necessity for multidirectional effects. From the point of view of the definition of obesity as a brain disease, with an emphasis on the hypothalamus, the feasibility of an approach to weight loss only through lifestyle changes and the problem of the slipping effect is discussed. The necessity for weight loss is discussed along with the regulation of metabolic imbalance. The feasibility of combined pharmacological intervention is substantiated. ReduxinForte is considered as the drug of choice with a detailed analysis of its components, metformin and sibutramine, their ability to correct various parts of the pathogenesis of obesity and pleiotropic effects to achieve stable metabolic control and reduce the risks of complications.

Nowadays clinicians have access to high-quality diagnostic algorithms to determine the risk of fractures and the need for treatment, as well as the ability to choose the most advanced drug therapy that will be the most suitable, comfortable and safe for the patient with osteoporosis. This algorithm for the selection of therapy is based on an assessment of the fracture risk, which is determined by the presence and severity of low-energy fractures, the level of bone mineral density (BMD), and the 10-year probability of fractures. Patients with a moderate risk of osteoporotic fractures are the most controversial category of patients regarding the choice and assessment of the prognosis of treatment, since they either have no history of fractures or have suffered only one low-energy fracture due to osteopenia or normal BMD. In such cases, oral bisphosphonates with a planned treatment duration of 5 years were recommended as starting therapy for osteoporosis. Alendronic acid is the most well-known and widely prescribed oral bisphosphonate, characterized by financial availability and a favorable profile of clinical efficacy in the treatment of osteoporosis. The effectiveness of treatment with oral bisphosphonates is largely determined by the tolerability of the drug and patient adherence to treatment. Gastrointestinal side effects and the lack of patient motivation are the main reasons for the low adherence to anti-osteoporotic therapy. Due to the low incidence of adverse events and the convenient pharmacological form for enhancing treatment compliance, alendronate buffer solution in soluble effervescent tablets may be preferred in patients with a moderate risk of fractures. Solubilized in a buffer solution alendronate less contacts the mucous membrane of the esophagus and stomach, minimizing contact between the particles of the drug and the mucous membrane of the upper gastrointestinal tract, and ultimately reducing the local irritating effect and the likelihood of gastroesophageal reflux.

Hypoglycemic syndrome (HGS) is a significant decrease glucose in blood, manifested by neurological symptoms, and stopped by the introduction of glucose. Among the many causes of HGS the special place is taken by the factitious hypoglycemia, as one of the variants of Munchausen syndrome. Hypoglycemia in such cases is achieved by the intentional introduction of hypoglycemic drugs. The most commonly used medications are sulfonylurea derivatives, which are affordable, inexpensive and legal. The close collaboration of clinicians with the laboratory service plays a key role in the diagnosis of factitious hypoglycemia. Since the results of biochemical and hormonal analyzes in patients with hypoglycemia due to reception of oral hypoglycemic medications and pancreatogenous HGS are identical, the only way to differentiate these conditions is by detection of insulin secretagogue substances in the blood (or urine).

The determination of oral hypoglycemic medications in cases of suspicion of artificial reception is not implemented in Russia. Factitious hypoglycemia in most cases is the diagnosis of exclusion, and its confirmation if often based on detection of medications among the personal effects of patient. This is a significant difficulty given the ethical standards. However, since 2018 we conduct in our Centre the determination of 7 oral hypoglycemic medications (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in patient’s blood using the liquid chromatography–tandem mass spectrometry (LC-MS). This article presents a clinical case of a patient without diabetes mellitus taking glibenclamide and detection of this drug using highly selective LC-MS.

Introduction. Acromegaly is a severe multi-organ disease that negatively affects the quality and life expectancy of patients. The continuing complexity of acromegaly curation is due to the multiplicity of pathomorphological variants growth hormone-secreting adenomas and the lack of differentiated approach in choosing a therapeutic strategy. The high percentage of non-radical adenomectomy, due to the large size and invasive growth of somatotropin, involves the operative connection of adequate secondary drug therapy.

Purpose. The aim of the study is to compare the effectiveness of different classes of drugs, as well as algorithms of their combined use in the treatment of acromegaly.

Methods of treatment. The review uses information on factors affecting the results of clinical use of modern pharmacological preparations (somatostatin analogues, dopamine agonists, growth hormone receptor antagonists) used in secondary drug therapy of acromegaly. The indications for the administration of a drug are discussed taking into account the features of the pathomorphological structure of the tumor tissue, as well as the tactics of the therapeutic allowance in absolute or relative resistance to somatostatin analogues of the 1st generation (octreotide and lanreotide) and dopamine agonists (cabergoline). Data on efficiency of the new drug – pegvisomant providing stable control of acromegaly irrespective of secretory activity and receptor phenotype of tumor tissue are summed up.

Results. Interim reports of the ACROSTUDY observational project and other clinical studies regarding the therapeutic efficacy and safety of pegvisomant are presented. A relatively low risk of continued growth of tumor tissue and other adverse reactions against the background of treatment with this drug is shown. Prognostic factors of insufficient efficiency of pegvisomant include young age, increased BMI, high initial level of ИРФ-1, presence of diabetes mellitus. There is an advantage of combined use of pegvisomant and somatostatin analogues to maintain acromegaly control and prevent tumor growth. The topic of primary therapy of pegvisomant is touched upon. Based on the results of real clinical practice, modern international recommendations are presented, which indicate the place of pegvisomant in the algorithm of secondary drug therapy.

Conclusions. Due to the introduction into clinical practice of various therapeutic agents, which allow, regardless of the activity of the disease, the specificity of the pathomorphological structure of tumor tissue and somatic status, to achieve stable maintenance of biochemical remission, patients have real opportunities for improving the quality and life expectancy.