Galvus Met pills coated 50mg + 850mg N30
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Active ingredients
Vildagliptin + Metformin
Release form
Pills
Composition
1 tablet contains: Vildagliptin 50 mg Metformin hydrochloride 850 mg Auxiliary substances: Hyprolosis - 84.15 mg, magnesium stearate - 9.85 mg, hypromellose - 18.58 mg, titanium dioxide (E171) - 2.9 mg, macrogol 4000 - 1.86 mg, talc - 1.86 mg, iron yellow oxide (E172) - 0.82 mg.
Pharmacological effect
The preparation Galvus Met consists of two hypoglycemic agents with different mechanisms of action: vildagliptin, belonging to the class of inhibitors of dipeptidyl peptidase-4 (DPP-4), and metformin (in the form of hydrochloride), a representative of the class of biguanides. The combination of these components makes it possible to more effectively control the concentration of blood glucose in patients with type 2 diabetes for 24 hours. Wilddagliptin, a member of the class of pancreatic islet apparatus stimulants, selectively inhibits the enzyme DPP-4, which destroys glucagon-like peptide 1 type (GLP-1) and glucose-dependent insulinotropic polypeptide (HIP). Metformin decreases hepatic glucose production, decreases the absorption of glucose in the gut and reduce insulin resistance due to capture and enhance glucose utilization by peripheral tkanyami.Metformin induces intracellular glycogen synthesis by acting on glikiencintetazu, and enhances the transport of glucose some membrane proteins, glucose transporters (GLUT-1 and GLUT -4). Wilddagliptin Rapid and complete inhibition of the activity of DPP-4 after taking vildagliptin causes an increase in both basal and food-stimulated secretion GLP-1 and HIP from the intestine into the systemic circulation throughout the day. By raising the concentration of GLP-1 and HIP, vildagliptin causes an increase in the sensitivity of β-cells of the pancreas to glucose, which leads to an improvement in glucose-dependent insulin secretion. The degree of improvement in β-cell function depends on the degree of their initial damage, so in individuals without diabetes mellitus (with a normal glucose concentration in blood plasma), vildagliptin does not stimulate insulin secretion and does not decrease glucose concentration. While raising the concentration of endogenous GLP-1, vildagliptin increases β sensitivity cells to glucose, which leads to an improvement in glucose-dependent regulation of glucagon secretion.A decrease in elevated glucagon concentration after a meal, in turn, causes a decrease in insulin resistance. An increase in the insulin / glucagon ratio during hyperglycemia, due to an increase in the concentration of GLP-1 and HIP, causes a decrease in glucose production by the liver both during and after meals, which leads to decrease in plasma glucose concentration. Furthermore, against the background of vildagliptin, there was a decrease in plasma lipid concentration after a meal, but this effect is not related to its effect on GLP- 1 or HIP and improved function of pancreatic islet cells. It is known that an increase in the concentration of GLP-1 may lead to a slower gastric emptying, however, this effect is not observed when using vildagliptin. When using vildagliptin in 5759 patients with type 2 diabetes mellitus for 52 weeks in monotherapy or in combination with metformin sulfonylurea , thiazolidinedione, or insulin showed a significant long-term decrease in the concentration of glycated hemoglobin (HbA1c) and fasting blood glucose. Methformin Methtformin improves glucose tolerance in patients ntov with diabetes mellitus type 2, reducing the concentration of glucose in plasma, both before and after a meal. Unlike sulfonylurea derivatives, metformin does not cause hypoglycemia in patients with type 2 diabetes or in healthy individuals (except in special cases). Drug therapy does not lead to the development of hyperinsulinemia. When using metformin, insulin secretion does not change, while insulin plasma concentrations on an empty stomach and during the day may decrease. When using metformin, there is a beneficial effect on lipoprotein metabolism: a decrease in total cholesterol, low-density lipoprotein cholesterol and triglycerides that is not associated with the effect of the drug on the concentration of glucose in the blood plasma. Wildagliptin + metformin. When using combination therapy with vildagliptin and metformin in daily doses of 1500-3000 mg of metfor ina and 50 mg of vildagliptin 2 times / day for 1 year there was a statistically significant persistent decrease in blood glucose concentration (determined by a decrease in HbA1c) and an increase in the proportion of patients whose decrease in HbA1c concentration was at least 0.6-0.7% (compared to patients who continued to receive only metformin). In patients who received the combination of vildagliptin and metformin, there was no statistically significant change in body weight compared with the initial state.24 weeks after the start of treatment in groups of patients receiving vildagliptin in combination with metformin, there was a decrease in systolic and diastolic blood pressure in patients with arterial hypertension. When using a combination of vildagliptin and metformin as the initial therapy of patients with type 2 diabetes mellitus, 24 dose-dependent reduction of HbA1c in comparison with monotherapy with these drugs. Cases of hypoglycemia were minimal in both groups of therapy. When using vildagliptin (50 mg 2 times / day) simultaneously with / without metformin in combination with insulin (average dose of 41 U) in patients in a clinical study, HbA1c was statistically significantly reduced by 0.72% ( the initial rate, an average of 8.8%). The frequency of hypoglycemia in patients treated was comparable to the frequency of hypoglycemia in the placebo group. When using vildagliptin (50 mg 2 times / day) concurrently with metformin (more than 1500 mg) in combination with glimepiride (more than 4 mg per day) in patients with clinical In the study, HbA1c was statistically significantly reduced by 0.76% (from an average of 8.8%).
Pharmacokinetics
Vildagliptin Absorption When ingested on an empty stomach, vildagliptin is rapidly absorbed, and its maximum plasma concentration (Cmax) is reached within 1.75 hours after ingestion. With simultaneous ingestion with food, the absorption rate of vildagliptin decreases slightly: there is a decrease in Cmax by 19% and an increase in the time it reaches to 2.5 h. However, food intake does not affect the degree of absorption and the area under the concentration-time curve (AUC). Wildaglaptin is rapidly absorbed, its absolute bioavailability after oral administration is 85%. Cmax and AUC in the therapeutic range of doses increase approximately in proportion to the dose. Distribution The degree of vildagliptin binding to plasma proteins is low (9.3%). The drug is distributed evenly between the plasma and red blood cells. The distribution of vildagliptin occurs presumably extravascularly, the volume of distribution in the equilibrium state after intravenous administration (Vss) is 71 l. Metabolism Biotransformation is the main route of excretion of vildagliptin. In the human body, 69% of the drug dose is converted.The main metabolite is LAY151 (57% of the dose) is pharmacologically inactive and is the product of hydrolysis of the cyano component. About 4% of the dose of the drug undergoes amide hydrolysis. In experimental studies, DPP-4 has a positive effect on the hydrolysis of the drug. Vildagliptin is not metabolized with the participation of cytochrome P450 isoenzymes. According to in vitro studies, vildagliptin is not a substrate of P (CYP) 450 isoenzymes, does not inhibit and does not induce CYP450 cytochrome isoenzymes. . With i / v administration, the average half-life of T1 / 2 reaches 2 h, the total plasma clearance and renal clearance of vildagliptin are 41 l / h and 13 l / h, respectively. T1 / 2 after ingestion is about 3 hours, regardless of dose. Pharmacokinetics in special cases Sex, body mass index and ethnicity do not affect vildagliptin pharmacokinetics. Patients with impaired liver function in patients with mild and moderately impaired liver function (6- 10 points according to the Child-Pugh classification) after a single use of the drug, there is a decrease in bioavailability of vildagliptin by 8% and 20%, respectively. In patients with severely impaired liver function (12 points according to Child-Pugh classification), bioavailability of vildagliptin is increased by 22%. The maximum change in bioavailability of vildagliptin, an increase or decrease of up to 30% on average, is not clinically significant. There was no correlation between the severity of liver dysfunction and the bioavailability of the drug. Patients with impaired renal function In patients with impaired mild, moderate or severe AUC, vildagliptin increased in comparison with healthy volunteers 1.4, 1.7 and 2 times, respectively. The AUC of the LAY151 metabolite increased 1.6, 3.2, and 7.3 times, and the metabolite BQS867 increased 1.4, 2.7, and 7.3 times in patients with mild, moderate and severe renal impairment, respectively. Limited data in patients with end-stage chronic kidney disease (CKD) indicate that the indicators in this group are similar to those in patients with severe renal impairment.The concentration of the metabolite LAY151 in patients with end-stage CKD increased by 2-3 times compared with the concentration in patients with severe renal impairment. Vidagliptin excretion in hemodialysis is limited (3% during the procedure lasting more than 3-4 hours 4 hours after a single dose of the drug). Use in patients aged ≥ 65 years Maximal increase in the bioavailability of the drug by 32% (increase in Cmax by 18%) in patients older 70 years is not clinically significant and does not affect the inhibition of DPP-4. The use in patients under the age of 18 years The pharmacokinetic features of vildagliptin in children and adolescents under 18 years of age have not been established. Metformin Absorption Absolute Bio The availability of metformin when administered at a dose of 500 mg fasting was 50-60%. The maximum plasma concentration (Cmax) is reached at 1.81-2.69 h after administration. When increasing the dose of the drug from 500 mg to 1500 mg, or in doses from 850 mg to 2250 mg orally, a slower increase in pharmacokinetic parameters was noted (than would be expected for a linear relationship). This effect is due not so much to a change in the elimination of the drug as to a slowdown in its absorption. Against the background of food intake, the extent and rate of absorption of metformin also decreased somewhat. So, with a single dose of the drug at a dose of 850 mg, along with food, there was a decrease in Cmax and AUC by about 40% and 25% and an increase in the time to reach the maximum concentration (Tmax) by 35 minutes. The clinical significance of these facts has not been established. Distribution When administered orally at a dose of 850 mg, the apparent volume of distribution of metformin is 654 ± 358 l. The drug is practically not bound to plasma proteins, while sulfonylurea derivatives bind to them by more than 90%. Metformin enters the red blood cells (probably an increase in this process over time). When using metformin according to the standard scheme (standard dose and frequency of administration), the equilibrium concentration of the drug in the blood plasma is reached within 24-48 hours and, as a rule, does not exceed 1 μg / ml. During controlled clinical studies, Cmax of plasma metformin did not exceed 5 µg / ml (even when taken in high doses). Metabolism With a single IV injection of metformin to healthy volunteers, it is excreted by the kidneys in unchanged form.At the same time, the drug is not metabolized in the liver (no metabolites are detected in humans) and is not excreted in the bile. Excretion As the renal clearance of metformin is about 3.5 times higher than the creatinine clearance (CK), the main route of excretion of the drug is tubular secretion. On ingestion, approximately 90% of the absorbed dose is eliminated by the kidneys during the first 24 hours; at the same time, T1 / 2 of blood plasma is about 6.2 hours. T1 / 2 of metformin from whole blood is about 17.6 h, which indicates the accumulation of a significant part of the drug in erythrocytes. Pharmacokinetics in special cases The gender of patients does not affect the pharmacokinetics of metformin. Patients with hepatic impairment In patients with hepatic insufficiency, the pharmacokinetic features of metformin were not studied. Patients with impaired renal function Patients with impaired renal function (as assessed by KK) T1 / 2 metformin from plasma and whole blood increases, and its renal clyg Osen decreases in proportion to the decrease in QC. Use in patients aged ≥ 65 years old According to limited data from pharmacokinetic studies in healthy people aged ≥65 years, there was a decrease in total plasma clearance of metformin and an increase in T1 / 2 and Cmax compared with young individuals. These features of pharmacokinetics of metformin in people over 65 years old are probably primarily related to changes in kidney function, and therefore patients older than 80 years can use the drug Galvus Met only with normal CC. Use in patients younger than 18 years oldPharmacokinetic features of metformin in children and adolescents under 18 years old have not been established. The use of patients of different ethnicity There is no evidence of the influence of patients' ethnicity on the pharmacokinetic features of metformin. At the end Controlled clinical studies of metformin in patients with type 2 diabetes of different ethnicity. The hypoglycemic effect of the drug was equally pronounced. Wilddagliptin + Metformin The studies showed bioequivalence in AUC and Cmax of Galvus Met in three different dosages (50 mg + 500 mg, 50 mg + 850 mg and 50 mg + 1000 mg) and vildagliptin and metformin, taken in appropriate doses as separate pills. Food intake does not affect the degree and rate of absorption of vildagliptin in the preparation and Galvus Met. The values of Cmax and AUC of metformin in the composition of the drug Galvus Met, while taking it with food, decreased by 26% and 7%, respectively.In addition, against the background of food intake, the absorption of metformin was slowed down, which led to an increase in Tmax (from 2.0 to 4.0 h). A similar change in Cmax and AUC during food intake was also noted when using metformin separately, but in the latter case, the changes were less significant. The effect of food on the pharmacokinetics of vildagliptin and metformin as part of Galvus Met did not differ from that when taking both drugs separately.
Indications
Type 2 diabetes mellitus (in combination with diet therapy and exercise): - with insufficient effectiveness of monotherapy with vildagliptin or metformin; - in patients who have previously received combination therapy with vildagliptin and metformin in the form of monotherapy; - in combination with sulfonylurea derivatives (triple combination therapy) patients previously treated with sulfonylurea and metformin derivatives without achieving adequate glycemic control; - in triple combination therapy with insulin in patients, receiving it in a stable dose of insulin and metformin without achieve adequate glycemic control - as initial therapy in patients with type 2 diabetes mellitus with inadequate efficiency dietetics, exercise, and the need to improve glycemic control.
Contraindications
- hypersensitivity to vildagliptin or metformin or any other components of the drug; - renal failure or renal dysfunction (when serum creatinine is greater than 1.5 mg% (greater than 135 μmol / L) for men and greater than 1.4 mg% (greater than 110 μmol / l) for women) - acute conditions, with the risk of developing impaired renal function: dehydration (with diarrhea, vomiting), fever, severe infectious diseases, hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases); - acute and chronic heart disease not enough accuracy, acute myocardial infarction, acute heart failure (shock), respiratory failure, - impaired liver function; - acute or chronic metabolic acidosis (including diabetic ketoacidosis in combination with or without coma). Diabetic ketoacidosis should be adjusted by insulin therapy. Lactic acidosis (includingand in history); - the drug should not be used 48 hours before surgery, radioisotope, X-ray studies with the introduction of contrast agents and within 48 hours after their implementation; - pregnancy and breastfeeding period; - type 1 diabetes; - chronic alcoholism , acute alcohol poisoning; - observance of low-calorie diet (less than 1000 kcal / day); - efficacy and safety of use of the drug in children under 18 years of age has not been established; - as in patients with impaired liver function, in some cases I lactic acidosis, possibly one of the side effects of metformin, Galvus Met should not be used in patients with liver disease or impaired biochemical indicators of liver function.
Precautionary measures
With caution: drugs containing metformin are recommended to be used with caution in patients over 60 years old when performing heavy physical work, due to an increased risk of developing lactic acidosis in them.
Use during pregnancy and lactation
Pregnancy Experimental studies in animals with the use of vildagliptin in doses 200 times higher than recommended, the drug did not cause disruption of the early development of the embryo and had no teratogenic effect. When using vildagliptin in combination with metformin in a ratio of 1: 10, no teratogenic effect was also detected. Since there are no sufficient data on the use of Galvus Met in pregnancy, the use of the drug in pregnancy is contraindicated. Breastfeeding Metformin penetrates into breast milk. It is not known whether vildagliptin is excreted in breast milk. Use of the drug Galvus Met during breastfeeding is contraindicated.
Dosage and administration
The drug is used inside. Dosing regimen Galvus Met should be selected individually, depending on the effectiveness and tolerability of therapy. When using Galvus Met, do not exceed the recommended maximum daily dose of vildagliptin (100 mg). The recommended starting dose of Galvus Met should be selected taking into account the duration of diabetes and glycemia, the patient’s condition, and vidagliptin and / or metformin already used in the patient .To reduce the severity of side effects from the organs of the gastrointestinal tract, characteristic of metformin, Galvus Met is taken with food. The initial dose of Galvus Met with vildagliptin monotherapy is ineffective. Treatment with Galvus Met can be started with one tablet 50 mg + 500 mg 2 times per day; After evaluating the therapeutic effect, the dose can be gradually increased. The initial dose of the drug Galvus Met with the ineffectiveness of metformin monotherapy Depending on the dose of metformin already taken, treatment with Galvus Met can be started with one tablet dosage of 50 mg + 500 mg, 50 mg + 850 mg or 50 mg + 1000 mg 2 times / day. Initial dose of Galvus Met in patients who have previously received combination therapy with vildagliptin and metformin as separate pills Depending on the doses already taken vildagliptin or metformin, treatment With the Galvus Met drug, you should start with a tablet as close as possible to the existing treatment, 50 mg + 500 mg, 50 mg + 850 mg or 50 mg + 1000 mg, and adjust the dose depending on the effectiveness. The starting dose of Galvus Met is as initial therapy in patients with type 2 diabetes with insufficient effectiveness of diet therapy and exercise As a starting therapy, Galvus Met should be used in an initial dose of 50 mg + 500 mg 1 time / day and after evaluating the therapeutic effect, gradually increase the doses at up to 50 mg + 1000 mg 2 times / day. Combination therapy with Galvus Met and sulfonylurea derivatives or insulin The dose of Galvus Met is calculated based on the dose of vildagliptin 50 mg x 2 times / day (100 mg per day) and metformin at a dose equal to previously taken as a single product.
Side effects
During therapy with vildagliptin, abnormal liver function (including hepatitis) of an asymptomatic course was rarely observed. In most cases, these disorders and abnormalities in liver function indicators from the norm were resolved independently without complications after cessation of drug therapy. When using vildagliptin at a dose of 50 mg 1 or 2 times / day, the frequency of increased activity of liver enzymes ALT or AST 3 times higher than the upper limit of normal (VGN) was 0.2% or 0.3%, respectively (compared to 0.2% in the control group).Hepatic enzyme activity increased in most cases was asymptomatic, did not progress and was not accompanied by cholestasis or jaundice. The following criteria were used to estimate the incidence of adverse events (AE): very often (more than 1/10), often (more than / 100, less than / 10) , infrequently (more than 1/1000, less than 1/100), rarely (more than 1/10 000, less than 1/1000), very rarely (less than 1/10 000), including isolated cases. Adverse reactions, possibly associated with the use of combination therapy with vildagliptin and metformin ( frequency of development of which in grams Upevildagliptin and metformin differed from that compared with placebo and metformin by more than 2%) are presented below. Violations of the nervous system: often - headache, dizziness, tremor. When using vildagliptin in combination with metformin in various doses, hypoglycemia was observed in 0.9% of cases (for comparison, in the placebo group in combination with metformin, it was 0.4%). The incidence of NA from the gastrointestinal tract during combination with vildagliptin and metformin was 12.9% . When using metformin, similar AEs were observed in 18.1% of patients. In groups of patients treated with metformin in combination with vildagliptin, disorders of the gastrointestinal tract were observed with a frequency of 10-15%, and in the group of patients treated with metformin in combination with placebo, with a frequency of 18%. Long-term clinical studies of up to 2 years did not reveal any additional deviations of the safety profile or unforeseen risks when using vildagliptin in monotherapy. The study of the combination of vildagliptin and metformin as a starting therapy for type 2 diabetes did not reveal any risks and no additional safety data.
Overdose
Vildagliptin Wilddagliptin is well tolerated at a dose of up to 200 mg / day. When using the drug at a dose of 400 mg / day, pain in the muscles can be observed, rarely - mild transient paresthesia, fever, edema, and a transient increase in lipase activity (higher than VGN). By increasing the dose of vildagliptin to 600 mg / day, it is possible to develop edema of the extremities, accompanied by paresthesias and an increase in the concentration of CPK, C-reactive protein and myoglobin, AST activity.All symptoms of overdose and changes in laboratory parameters disappear after discontinuation of the drug. Removal of the drug from the body through dialysis is unlikely. However, the main hydrolytic metabolite of vildagliptin (LAY151) can be removed from the body by hemodialysis. MetforminTen have been several cases of overdose with metformin, including as a result of ingestion of the drug in an amount of more than 50g. however, its connection with taking the drug has not been established); lactic acidosis was observed in 32% of cases. Early symptoms of lactic acidosis are nausea, vomiting, diarrhea, decrease in body temperature, abdominal pain, muscle pain, and there may be an increase in breathing, dizziness, impaired consciousness, and coma. Metformin is eliminated from the blood by hemodialysis (with clearance up to 170 ml / min) without the development of hemodynamic disturbances. Thus, hemodialysis can be used to remove metformin from the blood in case of overdose with the drug. In case of overdose, it is necessary to carry out appropriate symptomatic treatment based on the patient's condition and clinical manifestations.
Interaction with other drugs
Vildagliptin + Metformin In the simultaneous use of vildagliptin (100 mg 1 time / day) and metformin (1000 mg 1 time / day), there were no clinically significant pharmacokinetic interactions between them. Neither during clinical studies nor in the course of widespread clinical use of Galvus Met in patients who received other drugs and substances at the same time, there were no unexpected interactions. Wildaglyptin Wildeagliptin has a low potential for drug interaction. Since vildagliptin is not a substrate of cytochrome P450 (CYP) enzymes and also does not inhibit and does not induce these isoenzymes, its interaction with drugs, which are substrates, inhibitors or induc proof operation P450 (CYP), it is unlikely. With simultaneous use of vildagliptin does not affect the metabolic rate of drugs that are enzyme substrates: CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 / 5. Clinical significant interaction of vildagliptin with drugs,most commonly used in the treatment of type 2 diabetes mellitus (glibenclamide, pioglitazone, metformin) or having a narrow therapeutic range (amlodipine, digoxin, ramipril, simvastatin, valsartan, warfarin) is not established. clearance. Metformin reduces Cmax and AUC of furosemide and also does not affect its renal clearance. Nifedipine increases the absorption, Cmax and AUC of metformin; in addition, it increases its excretion by the kidneys. Metformin has virtually no effect on the pharmacokinetic parameters of nifedipine. Glibenclamide does not affect the pharmacokinetic / pharmacodynamic parameters of metformin. Metformin, in general, reduces the Cmax and AUC of glibenclamide, but the magnitude of the effect varies greatly. For this reason, the clinical significance of this interaction remains unclear. Organic cations, such as amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, vancomycin, etc., can be secreted by the kidney by tubular secretion can theoretically interact with metformin, due to competition for common renal tubular transport systems. So, cimetidine increases both the concentration of metformin in the blood plasma, and its AUC by 60% and 40%, respectively. Metformin does not affect the pharmacokinetic parameters of cimetidine. Care should be taken when using the drug Galvus Met along with drugs that affect kidney function or the distribution of metformin in the body. Other drugs: some drugs can cause hyperglycemia and can reduce the effectiveness of hypoglycemic agents. These drugs include thiazides and other diuretics, glucocorticosteroids, phenothiazines, thyroid hormone drugs, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium antagonists and isoniazid. With simultaneous use of such drugs or, on the contrary, if they are canceled, it is recommended to carefully monitor the effectiveness of metformin (its hypoglycemic effect) and, if necessary, adjust the dose of the drug. It is not recommended to take danazol at the same time to avoid hyperglycemic action of the latter.If necessary, treatment with danazol and after discontinuation of the latter requires a dose adjustment of metformin under the control of the concentration of blood glucose. Chlorpromazine when used in large doses (100 mg per day) increases glycemia, reducing insulin release. When treating neuroleptics and after discontinuation of the latter, a dose adjustment of the drug Galvus Met is required under control of blood glucose concentration. beta2-sympathomimetics: increase glycemia due to stimulation of β2-adrenergic receptors. In this case, glycemia control is necessary. If necessary, the use of insulin is recommended. With simultaneous use of metformin with sulfonylurea derivatives, insulin, acarbose, salicylates, hypoglycemic effect may increase. when treating with Galvus Met should refrain from the use of alcohol and medicines containing ethyl sleep. t.
special instructions
Galvus Met cannot replace insulin in patients treated with insulin. Wilddagliptin Liver dysfunction As the use of vildagliptin, an increase in the activity of aminotransferases (usually without clinical manifestations) was noted more often than in the control group before using Galvus Met and also during drug treatment, it is recommended to determine the biochemical parameters of liver function. If an increase in the activity of aminotransferases is detected, a repeated study should be conducted to confirm the result, and then the biochemical parameters of the liver function should be regularly determined until their normalization. If the excess of AST or ALT activity is 3 or more times higher than VGN is confirmed by repeated research, the drug is recommended to be canceled. Metformin Lactic acidosis Lactic acidosis is a very rare but severe metabolic complication that occurs when metformin accumulates in the body.Lactic acidosis with metformin was observed mainly in patients with diabetes mellitus with severe renal impairment. The risk of developing lactic acidosis increases in patients with diabetes mellitus that is difficult to treat, with ketoacidosis, prolonged fasting, prolonged alcohol abuse, abnormal liver function and diseases causing hypoxia. Dyspnea, abdominal pain and hypothermia followed by lactic acidosis, followed by coma. The following laboratory parameters are of diagnostic value: a decrease in blood pH, serum lactate concentration above 5 nmol / l, as well as an increased anion interval and an increase in the lactate / pyruvate ratio. If lactic acidosis is suspected, the drug should be canceled and the patient should be immediately hospitalized. The kidney function is under control. Since metformin is largely eliminated by the kidneys, the risk of its accumulation with the development of lactic acidosis increases in proportion to the severity of renal impairment. When using the drug Gal