Instructions for use of "Glimekomb", analogs, composition, mechanism of action, release form, indications, contraindications, prices, reviews and side effects

"Glimecomb" is the trade name of a combined hypoglycemic drug that is used to treat type 2 diabetes mellitus (T2DM). In the article we will analyze the drug “Glimecomb” - instructions for use.

"Glymecombe"

Attention! In the anatomical-therapeutic-chemical (ATC) classification, Glimekomb is designated by code A10BB09. International nonproprietary name: Gliclazide.

Pharmacodynamics and pharmacokinetics: description

Diabetes mellitus is a metabolic disorder that requires long-term treatment. In this condition, it is necessary to maintain normal blood glucose levels as both hyperglycemia and hypoglycemia can lead to serious health consequences. Oral hypoglycemic agents continue to be the mainstay of treatment for type 2 diabetes. Gliclazide, a second-generation sulfonylurea, is the treatment of choice due to its selective inhibitory activity on pancreatic K+ATP.

A recent study assessed the effectiveness of a combination of substances in rats with non-insulin-dependent diabetic disorder. In a study using an animal model, it was found that induced diabetes may affect the pharmacodynamic response as well as the pharmacokinetics of gliclazide. However, in this experiment, the drug was administered as a suspension, whereas the most popular form is a tablet.

Diabetes

After eating a carbohydrate-rich meal, the pancreas releases insulin protein to maintain glycemia within the normal range. Sugars contained in food are digested in the gastrointestinal tract and absorbed in the form of monosaccharides. Circulating glucose in the blood is injected into target cells by insulin. Myocytes and hepatocytes can store excess monosaccharides and also easily release them into the bloodstream if necessary. In addition, the liver can also obtain glucose from other nutrients such as lipids and amino acids.

Glimekomb delays the absorption of glucose in the gastrointestinal tract and, therefore, reduces postprandial blood sugar levels. Glimekomb also has a beneficial effect on fat metabolism, so it is preferable in patients with severe obesity.

Metformin drug

After oral administration, approximately two-thirds of the drug is absorbed into the blood. "Glimecomb" is not metabolized in the body and is excreted through the kidney 7 hours after ingestion. The equilibrium concentration of the active ingredient in the body is established after 3 days of regular use.

The drug was found to be effective in preventing lung cancer caused by smoking. Some retrospective epidemiological and experimental studies have shown that the drug may have an anticarcinogenic effect in the context of prostate, breast, ovarian and pancreatic cancer.

The role and place of domestic drugs Gliformin and Glimecomb in the treatment of type 2 diabetes mellitus

Among the total number of patients with diabetes, patients with type 2 diabetes account for 85–90%, and approximately 80% of patients are overweight or obese. The main increase in patients with diabetes occurs mainly due to an increase in the number of patients with type 2 diabetes in older age groups of the population. According to WHO and the International Diabetes Federation, there are currently more than 280 million people with diabetes in the world, and by 2025 their number will exceed 360–380 million people [1]. Global trends in the incidence of diabetes are also observed in Russia. According to the domestic registry, in Russia there are 8 million patients with diabetes, or approximately 5% of the total population, 90% of them are patients with type 2 diabetes. By 2025, the number of patients is expected to increase to 13 million people. At the same time, the number of patients registered according to their attendance is usually 2–3 times less than what actually exists [2,3]. Close attention to type 2 diabetes by doctors of various specialties (internists, cardiologists, neurologists, surgeons, etc.) is associated with the development of vascular complications, which sharply increase the risk of developing cardiovascular diseases (CVD), coronary heart disease (CHD) and mortality. CVD in patients with type 2 diabetes is significantly more common than in the general population. According to international studies, the prevalence of ischemic heart disease in patients with type 2 diabetes is 2–4 times higher, the risk of developing acute myocardial infarction (MI) is 6–10 times higher, cerebral stroke is 4–7 times higher, and the survival rate of patients after acute vascular pathology – 2–3 times lower than in patients without diabetes [4]. The more frequent development of ischemic heart disease and acute myocardial infarction, especially painless forms of myocardial infarction in the presence of type 2 diabetes, is most often associated with long-term decompensation of diabetes mellitus and the development of diabetic polyneuropathy with damage to the vessels supplying the nerves [5], as well as destabilization of atherosclerotic plaques, which is more often observed in diabetes mellitus . The cause of death in patients with type 2 diabetes in 75–80% of cases is CVD and acute vascular accidents: of these, ~60% are cardiovascular and ~10% are cerebrovascular lesions [6,3]. Almost 50% of patients with type 2 diabetes die from acute MI [4]. The leading role of early cardiovascular mortality in reducing life expectancy in the vast majority of patients with type 2 diabetes allowed the American Heart Association to classify type 2 diabetes as a CVD. The development of diabetic complications is associated with chronic hyperglycemia, which has been convincingly proven in many years of large-scale scientific studies, such as the DCCT for type 1 diabetes [7] and the UKPDS - British Prospective Study of Type 2 Diabetes [8]. The UKPDS study proved that to compensate for metabolic disorders in type 2 diabetes in order to prevent the progression of atherosclerosis and macrovascular complications, it is necessary to take into account not only glycemia, but also the lipid spectrum and blood pressure, which are also significant risk factors for the development of vascular complications. Diabetes is a chronic, severe, progressive disease characterized by the presence of two fundamental pathological defects: insulin resistance and dysfunction of pancreatic β-cells. Insulin resistance (IR) is a decrease in the sensitivity to insulin of peripheral tissues, primarily muscles, which make up the bulk of the human body. In type 2 diabetes, glucose uptake by peripheral tissues is approximately halved. IR of skeletal muscles in patients with diabetes or obesity is associated with dysfunction and a decrease in the number of glucose transporters - GLUT-4, which was proven by studying muscle biopsies in vitro. The function of glucose transporters is increased under the influence of insulin and exercise. With a sedentary lifestyle, to normalize glycemia, insulin secretion increases. Hyperinsulinemia increases appetite and contributes to the development of obesity. Type 2 diabetes and IR are characterized by abdominal/visceral obesity with an increase in waist circumference in men >94 cm, in women >80 cm. Adipose tissue is an active endocrine organ and secretes more than 90 biologically active substances, including adipokines, cytokines, angiotensin, a number of hormones: leptin, adiponectin, etc. Leptin is involved in the regulation of energy metabolism, control of hematopoiesis, immune system function, angiogenesis, and the amount of adipose tissue. The level of leptin in blood plasma is proportional to the amount of adipose tissue [9]. Adiponectin, which is considered as one of the markers of metabolic syndrome, plays an important role in the development of IR [10]. It is inversely related to the severity of obesity, BMI, severity of metabolic syndrome, type 2 diabetes, IR, dyslipidemia, fasting hyperinsulinemia and cardiovascular disease and is likely to play a protective role in these conditions. Reducing body weight, especially due to abdominal obesity, leads to an increase in adiponectin levels and a decrease in the risk of cardiovascular pathology. Scientific research in recent years has shown that adipose tissue also plays an important role in the development of inflammatory mechanisms, stimulating the synthesis of pro-inflammatory cytokines, such as IL-6, TNF-α, PAI-1 [11], which contribute to the development of IR, and is one of the key mediators its development is tumor necrosis factor-α (TNF-α). Thus, an increase in the expression of the TNF-α gene in adipocytes during obesity and an increase in its secretion by adipose tissue cells was accompanied by a proportional increase in the severity of IR. The anti-insulin effect of TNF-α is due to a direct effect on glucose transporters and insulin receptors and is associated with a decrease in the expression of GLUT-4 and blockade of insulin receptor tyrosine kinase in target tissues. During treatment with metformin in patients with diabetes and obesity after 3 months. There was a significant decrease in the initially elevated TNF-α from 47.75±2.98 to 24.34±3.15 pg/ml (p<0.05) [12,13]. Impaired fat metabolism in obesity and type 2 diabetes is characterized by an increase in the blood plasma level of atherogenic lipids and a decrease in the level of lipids that prevent the development of atherosclerosis. An increase in the blood level of total cholesterol, low and very low density lipoproteins, triglycerides and free fatty acids leads to their accumulation in various organs and tissues of the body, disrupting their function. Excessive production of free fatty acids (FFA) by visceral adipose tissue against the background of IR leads to a decrease in the sensitivity of the liver to the blocking effect of insulin on the processes of gluconeogenesis and glucose production by the liver, resulting in fasting hyperglycemia. The accumulation of lipids in muscles leads to IR, in the liver - to its fatty degeneration, in β-cells of the pancreas - to a decrease in insulin secretion and an increase in the death of β-cells by 7 or more times (lipotoxicity effect). Currently, more than 90% of patients with type 2 diabetes have overweight or obesity and IR. IR is directly proportional to obesity and precedes the development of diabetes. For example, IR is detected in first-degree relatives of patients with type 2 diabetes 7–12 years before the disease is diagnosed in them. It has been proven that IR is an independent risk factor for the development of atherosclerosis and CVD: hypertension, coronary artery disease, myocardial infarction, ischemic cerebral disease, stroke. Hyperinsulinemia, lipid metabolism disorders and hyperglycemia are also risk factors for the development of atherosclerosis and CVD, which develop in patients with type 2 diabetes several times more often than in patients without diabetes. To maintain normal glycemic levels under IR conditions and reduce glucose uptake by muscles, pancreatic β-cells have to work harder to secrete more insulin. Initially, hyperproduction of insulin (hyperinsulinemia) is enough to keep glucose levels within normal limits, but over time, hyperinsulinemia cannot overcome IR. β-cell function is depleted, and clinical signs of insulin deficiency appear, which is manifested by increased glycemia and the development of impaired glucose tolerance, and then type 2 diabetes. Impaired synthesis and secretion of insulin, as well as its action at the level of peripheral target cells, lead to a decrease in glucose utilization after meals and a decrease in glycogen synthesis in muscles and liver, resulting in the development of the cardinal symptom of type 2 diabetes - postprandial hyperglycemia. An increase in blood glucose levels after a meal >7.9 mmol/l (with a norm of <7.8 mmol/l) leads to the development of “glucotoxicity”, manifested in the glycosylation of proteins in various organs and tissues of the body, which inevitably leads to disruption of their function and development diabetic complications: retinopathy, nephropathy, polyneuropathy, atherosclerosis and cardiovascular pathology. A feature of the clinical development of type 2 diabetes is the long asymptomatic course of the disease, as a result of which the diagnosis of type 2 diabetes, according to international studies, is delayed by 7–12 years from the onset of the disease. The long-term “silent” course of diabetes leads to the fact that more than 50% of patients at the first diagnosis of type 2 diabetes already have various complications [14]: macroangiopathies: • arterial hypertension – 39%; • IHD, ischemic cerebral disease, stroke – 25–30%; • heart attack – 8%; • damage to the blood vessels of the legs – 30%; microangiopathy: • retinopathy, decreased vision – 15%; • nephropathy, decreased renal function: – microalbuminuria – 30%, – proteinuria – 5–10%, – chronic renal failure – 1%; – neuropathy – 15%. Diabetic complications occur only when diabetes has not been compensated for a long time and blood glucose levels remain elevated. Once they occur, diabetic complications gradually progress, significantly reducing the quality of life and shortening its duration. 75–80% of all deaths from diabetes are associated with vascular complications - heart attack, stroke, diabetic gangrene, chronic renal failure. However, as shown in the UKPDS study, reducing or normalizing glycemia reduces the risk of developing diabetic complications and helps prevent their progression. With good compensation of diabetes, there was a decrease in the frequency of: • all diseases associated with diabetes – by 12%; • microangiopathies – by 25%; • myocardial infarction – by 16%; • retinopathy – by 21%; • nephropathy – by 33%. Treatment of type 2 diabetes, given the complex mechanism of its development and the heterogeneity of this group of patients, is a difficult task. 76% of patients with diabetes in the Russian Federation do not reach the target values ​​of HbA1c<7%. Currently, it is impossible to cure diabetes, but it can be well managed and you can live a full life for many years, maintaining your ability to work, good health and a low risk of vascular complications. According to the recommendations of the European Group on Policy Formation in the Field of Type 2 Diabetes (European Diabetes Polisi Group, 1998–1999), the Federal Target Program “Diabetes Mellitus” recommends therapeutic goals for type 2 diabetes to reduce the risk of developing micro- and macrovascular complications, presented in the table 1. In this regard, the main goal of treatment of diabetes is the most complete compensation of carbohydrate metabolism disorders, which can only be achieved as a result of complex, step-by-step and pathogenetically based treatment, taking into account the chronic course of the disease, the heterogeneity of metabolic disorders, a progressive decrease in β-cell mass, a decrease in their function, the age of the patient, the risk of developing hypoglycemia, as well as the need to achieve long-term effective glycemic control in order to reduce the risk of developing cardiovascular diseases, coronary artery disease and mortality in patients with type 2 diabetes. The main goals of treatment of type 2 diabetes include: 1. Achieving good metabolic control: eliminating symptoms of hyperglycemia and dyslipidemia. 2. Prevention of acute complications: hypoglycemia and decompensation of diabetes. 3. Prevention of the development of late vascular complications. Treatment must begin with lifestyle changes, which include diet and increased physical activity. Since 80–90% of patients with type 2 diabetes are overweight, and many are also elderly, have high blood pressure, concomitant cardiovascular and other diseases, special attention should be paid to nutrition. The goals of the diet are to eliminate postprandial hyperglycemia, fasting hyperglycemia, and reduce excess body weight, since obesity contributes to the progression of diabetic complications. The second important factor in the treatment of type 2 diabetes is increasing physical activity. Physical activity not only has a positive effect on glycemic indicators, promoting the utilization of glucose, but also improves fat metabolism, has a beneficial effect on the cardiovascular system, causes positive emotions and helps to withstand stressful situations, and leads to a decrease in insulin resistance and hyperinsulinemia. Physical activity should be individualized taking into account the patient’s age, complications of diabetes and concomitant diseases. The success of treatment largely depends on how involved the patient is in the therapy program, on his knowledge about his disease, motivation, behavior, and training in the principles of self-control. In the early stages of carbohydrate metabolism disorders, lifestyle changes can be quite effective and reduce the risk of developing type 2 diabetes by 58%. However, in the later stages of type 2 diabetes, when it is most often detected, only 6% of patients achieve acceptable HbA1c levels (<7%) [15]. As practice shows, the vast majority of patients require active glucose-lowering therapy, since rapid compensation of diabetes is necessary to prevent the progression of diabetic complications. The sensational result of the UKPDS study was that the best results were achieved in patients with type 2 diabetes who began treatment for the disease with a drug from the biguanide class, metformin. It has been proven that the use of metformin reduces the risk of developing diabetic complications in patients with type 2 diabetes with obesity: – the incidence of all diseases associated with diabetes is reduced by 32%; – incidence of myocardial infarction – by 39%; – incidence of stroke – by 41%; – mortality from diabetes – by 42%; – overall mortality – by 36%. In 2006, the American Diabetes Association (ADA), together with the European Association for the Study of Diabetes (EASD), developed an algorithm for the treatment of type 2 diabetes, which provides, when diagnosing type 2 diabetes, along with the recommendation of lifestyle changes, to prescribe metformin (in the absence of specific contraindications) – a first-line drug for the treatment of type 2 diabetes, affecting IR. In the absence of proper glycemic control for 2–3 months. It is recommended to add a second drug. According to consensus, at this stage of treatment it is possible to add any second glucose-lowering drug from the group of sulfonylureas (SMU) to metformin. Thus, the first drug of choice to achieve good metabolic glucose control in the absence of sufficient effectiveness of diet and increased physical activity in patients with type 2 diabetes with overweight and obesity is metformin. It has some anorexigenic effects on easily digestible carbohydrates. By slowing down the absorption of carbohydrates, metformin does not lead to a sharp increase in blood sugar levels after meals and an increase in body weight, but, on the contrary, helps to stabilize it. Treatment with metformin in overweight patients leads to a moderate weight loss of an average of 5–7 kg over 3–4 months. The drug does not stimulate the release of insulin by β-cells of the pancreas, therefore it does not lead to hyperinsulinemia, does not cause the development of hypoglycemia, which is especially dangerous in patients with type 2 diabetes due to the possible development of acute cardiovascular pathology - heart attack or stroke. Slowing down the absorption of glucose into the blood under the influence of metformin facilitates the functioning of the pancreas and protects it from overstrain and exhaustion. Metformin has been found to increase the sensitivity of peripheral tissues to insulin. With long-term use, it leads to a flattening of the daily glycemic curve, a decrease in the average daily glycemic level and fasting glycemic level, as well as a decrease and normalization of the level of glycated hemoglobin (HbA1c), which helps prevent late complications of diabetes. By reducing postprandial hyperglycemia, metformin reduces the risk of developing atherosclerosis in patients with hyperinsulinemia and IR. Metformin improves the uptake of glucose into tissues by increasing sensitivity to insulin, reduces glucose production in the liver, as well as glucose absorption in the intestine, increases cell sensitivity to insulin and reduces IR: increases glucose consumption by cells, improves nutrition of cells of organs and tissues and at the same time reduces the concentration of glucose in blood plasma. Improving cell nutrition, metformin helps to reduce the level of glycemia on an empty stomach, which indicates an improvement in carbohydrate metabolism. Unlike PSM, metformin reduces the level of glucose in the blood not by stimulating the secretion of insulin with pancreatic β -cells, but by increasing glucose absorption with peripheral tissue cells. The lack of stimulation of insulin secretion leads to a decrease in appetite, a lack of risk of developing hypoglycemia, as well as to a decrease in hyperinsulinemia and IR. Reducing usually increased appetite in patients with type 2 diabetes, metformin contributes to a gradual weight loss, and reducing the absorption of glucose in the intestine, prevents the increase in blood sugar after eating and further increase in body weight. Therefore, metformin is especially effective in patients with type 2 diabetes with an excess body weight. In addition, scientific studies have shown that metformin effectively reduces the appetite, body weight and insulin resistance already at the stage of only overweight, preventing or significantly reducing the risk of developing glucose tolerance and type 2 diabetes. Thus, metformin acts pathogenetically: - gently reduces blood sugar; - Unlike PSM, it does not stimulate insulin secretion and does not cause the development of hypoglycemia; - increases the sensitivity of peripheral tissues to insulin, enhances the absorption of glucose with cells and reduces IR; - inhibits glucose products with liver, which helps to reduce glycemia on an empty stomach; - slows down the absorption of carbohydrates in the intestines, reduces appetite, which leads to a decrease in PPG; - helps to reduce body weight in patients with obesity; - has a favorable effect on lipid metabolism: reduces the level of general cholesterol, low density lipoproteins and triglycerides, as a result of which the progression of atherosclerosis decreases; - Promotes a decrease in blood pressure. Metformin is highly effective both in monotherapy and with combined therapy of type 2 diabetes, in combination with PSM or insulin preparations. From the side effects of Metformin, there are sometimes violations of the gastrointestinal tract: diarrhea, a decrease in appetite, a metal taste in the mouth, which usually quickly pass without treatment. The most formidable complication is lactacidosis, since the suppression of neo -Soglyucogenesis by beiguanides leads to an increase in the concentration of lactate, pyruvat and alanine, which are the predecessors of glucose formation in this process. However, studies conducted in recent years have proven metformin safety. Metformin’s metformin in the form of monotherapy or in combination with other drugs, performed in 2003, the meta -analysis of 176 -analysis, has shown that the frequency of lactacidosis was lower than in a control group or in groups with other drugs [16]. Metformin is the only Biguanide allowed for use at the present time. Its safety is confirmed not only in adults, but also in children [17], which served as the basis for the resolution in 2000 of the use of this drug in the United States in children aged 10 years and older. Although Metformin is a relatively safe drug, its large doses by increasing anaerobic glycolysis can enhance chronic hypoxia in patients with heart diseases, lungs, and therefore this drug is not recommended for patients over 60 years old. Currently, practical healthcare is used by metformin preparations of various (Russia) analogue of metformin - the drug glyformin in dosages of 500, 850 and 1000 mg, which is fully consistent with imported analogues and allows you to choose the necessary treatment scheme. Indications for the use of a glyphone: • is a drug of choice for patients with type 2 diabetes with obesity with ineffectiveness of a diet and increasing physical activity; • improves glycemic control in combination with PSM and insulin, especially with a severe degree of obesity and the presence of IR; • reduces the risk of diabetic complications in patients with type 2 diabetes; • In combination with insulin, it prevents an increase in body weight of patients with type 2 diabetes. They begin treatment with 1 tablet 500 mg 1-2 times/day. During or after eating, without chewing. After 10-15 days, the dose of glyphorin can be gradually increased under the control of glycemia to the necessary. The average therapeutic dose is usually 1500–2000 mg/day, the maximum is 3000 mg/day. Contraindications: • Diabetic ketoacidosis, Precom, Coma; • severe diseases of the heart, lungs, circulatory failure; • excessive consumption of alcoholic beverages; • impaired liver and kidney function. Glyformin has passed large -scale clinical studies, including at the Department of Endocrinology and Diabetology of RMAPO, in which he proved its high efficiency. Clinical studies of the effectiveness and safety of the drug glyformin conducted in 1 MGMA named after I.M. Sechenov based on DCC No. 1 of Moscow, showed that it not only has a positive effect on carbohydrate and lipid metabolism, but also has antioxidant properties, reliably reducing the activity of small dyilladehyde (MDA) from 0.13 ± 0.05 to 0.09 ± 0.04 (p <0.001). Glyformin was therapeutically equivalent to Glucopaus [18]. Clinical studies of the glystrom conducted on the basis of the DCC No. 1 of the Department of Health of Moscow in 2010 E.M. Klebanova and J.I. Variychuk [19] also showed the positive effect of the drug on carbohydrate and lipid metabolism and on weight loss. In addition, against the background of the treatment of glyformin, a reliable increase in the functional activity of β -cells (FAB index) was observed from 70.38 ± 67.13 to 79.53 ± 92.67 (p <0.05) and a decrease in C -peptide from 2, from 2, 41 ± 1.06 to 2.37 ± 0.86 ng/ml (p <0.05). It should be especially noted the beneficial effects of glympholine on the hormones of adipose tissue. The therapy with glyformin led to a reliable reduction in FNO - α from 17.18 ± 18.56 to 15.08 ± 16.3 (p <0.05) and an increase in adiponectin content from 7.37 ± 3.31 to 8.06 ± 5 , 31 (p <0.05). Its content with diabetes is usually reduced. Adiponectin reduces the expression of adhesive molecules with endothelial vessel cells and the rate of formation of the number of cytokines by macrophages, improves endothelium - dependent vasodilation vascular vasodilation. Adiponectin refers to endogenous anti -atherogenic compounds, therefore, increasing its content under the influence of treatment with glyformin will contribute to a decrease in the risk of developing and progression of vascular complications of type 2 diabetes. In the case of contraindications to metformin or its intolerance, in the absence of proper glycemic control already at the first stage of treatment of type 2 diabetes, according to consensus, the use of PSM or clay that stimulates insulin secretion, since, despite the number of patients with hyperinSulinemia at the beginning of the disease , its own insulin is not enough to overcome insulin resistance, and it is necessary to increase its concentration in the blood. Among the oral sugar -lowering drugs, PSM is most popular. They act through the ATP -dependent potassium channels of the β -cells of the pancreas, which have a complex structure and consist of four Kir 6.2 prayer subunits, facing the ion channel, and the SUR sulfonyl gross receptor (SUR). PSM close the catf -dependent channels, which leads to the depolarization of the cell membrane, the discovery of potential -dependent calcium channels and the receipt of Ca2+ ions into the cytoplasm of β cells with the subsequent release of the finished insulin into the blood. An increase in the concentration of insulin in blood plasma leads to a decrease in both postprandial glycemia and glycemia on an empty stomach. With the progression of the disease or when identifying type 2 diabetes at the stage of more pronounced metabolic disorders to metformin, PSM is added, which stimulate insulin secretion and effectively reduce blood sugar. One of the best PSM is glyclazide. It gently stimulates the secretion of insulin, restores a two -phase profile of insulin secretion in response to food intake, reduces glucose products with liver, reduces insulin resistance, has a low risk of hypoglycemia, and there is no body weight gain when it is used. Glycraside improves the rheological properties of blood - reduces thrombosis, and most importantly - the risk of cardiovascular complications, protects the heart and blood vessels with prolonged use. Given the need for the constant use of two preparations for the treatment of type 2 diabetes, pharmaceutical companies began to create combined drugs containing metformin and PSM in one tablet. This made it possible to reduce the number of tablets taken by 2 times and significantly increased the compliance of patients, that is, their commitment to treatment, the desire to be treated. In addition, the connection of two drugs in one tablet made it possible to use the smallest concentrations with the best effect due to the mutual increase in the action of the components included in it. OJSC Chemical and Pharmaceutical Plant Akrikhin first created the only drug in Russia containing two highly effective and safe drugs: glyclazide and metformin. A new drug for the treatment of type 2 diabetes is called glimekombs and contains an original fixed combination: glyclazide 40 mg + metformin 500 mg in one tablet. The advantage of the glimecomb compared to the combinations of glibenclamide and metformin existing on the market is the high selectivity of glyclazide, which gently stimulates the pancreatic β cells, without causing a sharp decrease in blood sugar and not having a negative effect on the cardiovascular system. Glycraside is recommended by the American and European Associations of Diabetes as one of the best drugs of choice due to the minimum risk of hypoglycemia. Unlike the existing fixed combinations of glibenclamide and metformin, an increase in the maximum daily dosage of the glimekom to 5 tablets in terms of glyclazide (200 mg) allows you to minimize the risks of developing hypoglycemia, especially in elderly patients. In 2008, the drug successfully passed large -scale clinical studies, in which the Department of Endocrinology and Diabetology of the GBOU DPO of the Russian Medical Academy of Postgraduate Education (RMAPO) of the Ministry of Health and Social Development of the Russian Federation (head of the department - prof. A.S. Ametov) was also involved. The studies conducted by us showed the high efficiency of the glimecomb and the advantage of a fixed combination over separate intake of glyclazide and metformin in similar dosages. So, after 3 months. The treatment of glimekomb has a reliable decrease in glycemia on an empty stomach - from 8.2 ± 0.2 to 6.5 ± 0.2 (p <0.001), glycemia 2 hours after eating - from 12.85 ± 0.3 to 8.97 ± 0.2 mmol/l (p <0.001), glycated hemoglobin (NVA1C) - from 8.25 ± 0.3% to 7.07 ± 0.1% (with a norm of 4–6%, p <0.001). The intake of the drug glimekombs did not cause weight gain and was accompanied by a low risk of hypoglycemia. Throughout the study period, all patients who received the drug Glimeomb noted its high efficiency and good tolerance. There were no negative reactions, deviations from the norm in the clinical and biochemical analysis of the blood either in any patient, nor a single case of ketoacidosis or hypoglycemia, as well as allergic reactions, which indicates the safety of taking the drug. Most patients had a tendency to reduce cholesterol and triglycerides. A study of the effectiveness of type 2 diabetes using a continuous glucose monitoring system (Continwoous Glucose Monitoring System (CGMS) showed a higher effective combination of the Glimeomb drug compared to a separate administration of the drugs that are part of it. In addition, the glimekombs eliminated the pathological variability of glycemia during the day in lower dosages compared to the separate intake of these drugs. Similar data were obtained in clinical research by Glimekomb in Irkutsk A.V. Davydova et al. (2010) [20]. In 3 months. A reliable decrease in nouric glycemia was observed - from 8.9 ± 1.6 to 6.0 ± 0.7 mmol/l (p <0.0001), glycated hemoglobin (HBA1S) - from 8.9 ± 1.6% to 7 to 7 , 4 ± 1.1% (at a rate of 4–6%, p <0.0001), and the proportion of patients with HBA1C ≤7% increased against the background of glymecomb treatment by 10 times - from 5.3% to 54.4 %. The intake of the drug Glimeks did not cause body weight gain (BMI 32.1 ± 4.9 and 31.8 ± 4.8 kg/m2, p = 0.11) and was not accompanied by the risk of hypoglycemia. Thus, domestic drugs glyformin and glimekombs are effective and safe drugs for the treatment of type 2 diabetes. Glyformin can be a first choice in the early stages of a violation of carbohydrate metabolism and type 2 diabetes, used to treat obesity, metabolic syndrome and other diseases in which metformin is used. Glimekomb - a unique combined drug containing glyclazide and metformin, can also be used in the treatment of type 2 diabetes as a drug of choice already in the early stages of therapy. Glimekomb is a drug with a modern mechanism of action, characterized by the convenience of taking, which can also be used when replacing therapy with monopolformin and sulfonymic chaste, which increases the compliance of patients and helps to prevent and slow down the progression of vascular complications of type 2 diabetes.

Literature 1. Ametov A.S. Diabetes mellitus type 2. Tutorial. – M., 2003. – P. 7–62. 2. Suntsov Yu.I., Dedov I.I., Kudryakova S.V. State register of diabetes mellitus: epidemiological characteristics of non-insulin-dependent diabetes mellitus. // Diabetes. – 2002. – No. 1. – P. 41–43. 3. Structure of cardiovascular morbidity and mortality in the Russian Federation for 2004 // Clinical Medicine. – 2005. – No. 1. – P. 3–8. 4. Haffner SM, Lehto S., Ronnemaa T., Mortality from coronary artery disease in subject with type 2 diabetes and nondiabetic subjects with and without myocardial infarction. // N Engl. J Med. 1998;339:229–234. 5. Mychka V.B., Chazova I.E. Cardiovascular complications of type 2 diabetes. // Consilium Medicum. – 2003. – T. 5 (9). – pp. 504–509. 6. Neaton JD, Wentworth DN, Cutler J., Kuller L. Risk factors for death from different types of stroke. Multiple Risk Factor Intervention trial Research Group. // Ann Epidemiol. 1993;3:493–499. 7. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long–term complications in insulin–dependent diabetes mellitus. // N. Engl. J Med. 1993;Vol. 329:977–986. 8. UK Prospective Diabetes Study Group. Tight Blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: (UKPDS 38) BMJ 1998; 317:703–13. 9. Fruhbeek G., Salvador J. // Relation between leptin and regulative of glucose metabolism. // Diabetologia. 2000;43(1):3–12. 10. Trujillo ME, Scherer PE Adiponectin: journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. // J Intern Med. 2005;257:167–175. 11. Wisse BE The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. // J Am Soc Nephrol. 2004;15:2792–80. 12. Rosen ED, Spiegelman BM Tumor necrosis factor as a mediator of insulin resistance of obesity. // Curr opin Endocrinol Metab. 1999. – Vol. 6. – P. 170–176. 13. Sevter CP, Digby JE at al. Regulation of tumor necrosis factor–alpha release from human adipose tissue in vitro. // J Endocrinol. 1999. – Vol. 163. – P. 33–38. 14. UK Prospective Diabetes Study Group. Effect of intensive blood–glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS). // Lancet. 1998;352:854–65. 15. Tuomilehto J., Lindstrom J., Ericsson J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. // N Eng J Med. 2001;344:1343–50. 16. Salpeter SR, Greyber E. et al. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta–analysis. //Arch Intern Med. 2003;163(21):2594–602. 17. Buck ML Use of Metformin in Htdiatric Patients. // Pediatr Pharm. 2004;10 (7). 18. Morgun I.A., Petunina N.A., Nedosugova L.V., Klebanova E.M. Evaluation of the effectiveness of domestic gliclazide and metformin in various treatment regimens for type 2 diabetes mellitus. // Attending doctor. – 2011. – No. 3. 19. Klebanova E.M., Variychuk Zh.I. The role of metformin (Gliformin) in the treatment of patients with type 2 diabetes mellitus. // RMJ. – 2010. – T. 18. – No. 10. 20. Davydova A.V., Kazantseva S.N., Alekseychikova N.V., Goryashina M.E., Khisamova S.A., Zaslavskaya A.V., Voloshin A.V. Experience of using the combination drug Glimekomb in the treatment of patients with type 2 diabetes mellitus in outpatient practice. // Endocrinology. – 4/20.

Indications and contraindications

Glimekomb is approved for use in diabetics as an oral antidiabetic agent. The drug is prescribed if the concentration of sugar in the blood does not decrease as a result of physical activity or a change in diet.

The drug is also used to treat prediabetes and gestational diabetes. In most cases, the drug is used in the long term to correct patients' glycemia.

Polycystic testicular syndrome is a hormonal disorder in women that, among other things, can lead to infertility. Some studies and individual case reports have shown that metformin can reduce symptoms of the disorder. It can treat existing insulin resistance and abnormally elevated testosterone production, allowing patients to become pregnant.

Contraindications:

• Hypersensitivity to product ingredients;
• Insulin-dependent diabetes (juvenile diabetes);
• Ketoacidosis (metabolic disorder due to increased degradation of fatty acids and amino acids);
• Severe renal, adrenal, thyroid or liver failure;
• Precoma or diabetic coma.

General information, composition and release form

This drug is a hypoglycemic agent taken orally.
The product has a combined effect. In addition to the hypoglycemic effect, Glimecomb has a pancreatic effect. In some cases, the medicine has an extrapancreatic effect. The drug contains Metformin Hydrochloride in an amount of 500 mg and Gliclazide - 40 mg, as well as excipients sorbitol and croscarmellose sodium. The medicine contains magnesium stearate and povidone in small quantities.

The drug is available in the form of flat-cylindrical tablets in white, cream or yellow shades. Marbling is acceptable for tablets. The tablets are scored and chamfered.

Glimecomb is sold in 10 tablets in blister packs. One pack contains 6 packs.

Side effects

Side effects usually occur only at the beginning of therapy and disappear after a few days or weeks. Very often (in more than 1 in 10 patients) digestive system disorders occur - nausea, vomiting, diarrhea and abdominal pain. Adverse effects can be avoided if you take Glimekomb with food.

Every 10 out of 100 patients experience changes in taste. They do not cause life-threatening disorders and disappear within 2-3 days.

Very rarely (less than 1 in 10,000 patients) the life-threatening metabolic disorder lactic acidosis occurs. Patients experience increased acidity, which is mainly observed in patients with kidney disease. Signs of lactic acidosis include muscle pain, malaise, abdominal pain, breathing problems and low body temperature. If you suspect lactic acidosis, you should contact your doctor immediately.

Lactic acidosis

History of the drug

In 1929, it was discovered that blood sugar levels could be effectively lowered with metformin. Due to the advent of insulin, studies on the effectiveness of the drug were stopped for a certain time.

It was not until the 1950s that interest in metformin returned. At the same time, the first studies were carried out. Diabetologist Jean Stern published his research in 1957, after which metformin has been marketed since 1958 as a hypoglycemic agent. Metformin was approved in the United States in 1994. In 2005, Glimekomb entered the market.

Instructions for use and special instructions

The dosage of the medicine is individual for each patient. It is recommended to take 1-3 tablets per day. In subsequent days of treatment, it is possible to increase the dose, based on the patient’s blood sugar levels and the degree of manifestation of his disease. The maximum dosage for Glimekomb is 5 tablets per day.

It is recommended to take the drug in the morning and evening. The medicine is taken during or after meals.

The product is not recommended for patients over 60 years of age who work in difficult physical conditions. With hard work and taking Glimekomb, older people may develop lactic acidosis.

Pregnancy is one of the contraindications to taking this drug. When pregnancy occurs, as well as before planning it, it is necessary to replace the drug with insulin therapy.

Breastfeeding is also a contraindication due to the high absorption of the drug components into breast milk. It is necessary to stop breastfeeding while the mother is taking Glimekomb or stop taking the drug itself during lactation.

This medicine should be taken with caution in patients with:

• fever;
• problems with the thyroid gland;
• adrenal insufficiency.

The drug should not be taken by patients with liver disease, as well as kidney problems accompanied by shock, dehydration and other severe phenomena.

The drug is taken only if patients follow a low-calorie diet with low carbohydrate intake. In the first days of treatment, monitoring blood sugar levels is required. Drug therapy is carried out only in those patients who receive regular nutrition.

Sulfonylureas contained in the drug can cause hypoglycemia. It occurs with low-calorie diet and physical activity. It is necessary to constantly adjust the dose of the drug, especially in elderly patients.

Hypoglycemia may occur in patients taking:

• ethyl alcohol;
• non-steroidal anti-inflammatory drugs.

Fasting also increases the risk of hypoglycemia in patients, and drugs such as Reserpine with Clonidine mask it.
In cases of surgical operations in patients, if they have burns, injuries, infections with fever, as well as myalgia, lactic acidosis, immediate cessation of taking the drug is required.

The drug may affect driving. Caution must be exercised.

It is required to stop taking Glimekomb 2 days before and after introducing a radiocontrast agent with iodine into the patient’s body.

Interaction

The drug was studied in controlled clinical trials in children and adolescents aged 6 years and older. No specific side effects have been identified, but treatment should be monitored by a doctor.

Pregnancy is not an absolute contraindication. It is important to understand that Glimecomb is rarely used for diabetes in pregnant women. Insulin therapy is most often prescribed because it has no negative effects on the fetus.

If breastfeeding, the drug should be avoided as the active substances pass into breast milk. If the patient needs to take the drug, breastfeeding should be discontinued.

It is not recommended to take Glimekomb and the following medications:

• Medicines that affect the blood - glucocorticoids (cortisone) and drugs that stimulate the sympathetic nervous system (sympathomimetics);
• Some diuretics (loop diuretics);
• Experts recommend avoiding alcohol consumption during treatment with the drug.

Treatment of diabetes with this drug requires regular glycemic monitoring. Regular use of the substance may impair the ability to actively participate in traffic.

Cortisone

Drug interactions and analogues

The drug interacts with other medications as follows:

• the hypoglycemic effect is enhanced when taken together with Enalapril, Cimetidine, Miconazole, Clofibrate, Ethionamide, anabolic steroids, Cyclophosphamide, Tetracycline, Reserpine and other drugs that have a hypoglycemic effect;
• the hypoglycemic effect decreases when taken together with Clonidine, Phenytoin, Acetazolamide, Furosemide, Danazol, Morphine, Glucagon, Rifampicin, nicotinic acid in a large dose, estrogens, lithium salts, oral contraceptives;
• simultaneous use with Nifedipine slows down the withdrawal of metformin;
• combined use with cationic agents increases the maximum concentration of metformin in the blood by 60%;
• Co-administration of the drug with Furosemide increases the concentration of metformin.

Glimekomb has analogs and synonyms:

• Glidiab;
• Gliformin;
• Glidiab Mv;
• Gliformin Prolong;
• Metglib;
• Formetin;
• Gliclazide Mv;
• Diabetalong;
• Gliclazide-Akos.

The video program “Tablet” is dedicated to the symptoms and treatment of diabetes:

Reviews

Opinion of a practicing physician and patient.

Glimekomb is an inexpensive combination medication that is used when metformin monotherapy is ineffective. The drug can cause severe hypoglycemia, so it is not recommended to change the dosage without consulting your doctor. The effectiveness of the drug has been proven in clinical trials.

Valery Valentinovich, diabetologist

I tried 3 drugs before Glimekomb was prescribed. I have been taking the drug for 4 months now and feel improvements. Glycemia returned to normal and dizziness disappeared. Sometimes hypoglycemia occurs (slight tremor), but it goes away if you take a sugar cube.

Stanislav, 32

Price (in Russia)

The average cost of the drug is 547 rubles. Price may vary depending on pharmacy. It is recommended to check the price with your pharmacist.

Important! The drug is available with a doctor's prescription.

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