Metformin inhibits gluconeogenesis in the liver, reduces the absorption of glucose from the intestine, increases peripheral glucose utilization, and also increases the sensitivity of tissues to insulin. It does not have an effect on insulin secretion by pancreatic beta cells, does not cause hypoglycemic reactions. Lowers triglycerides and low density linoproteins in the blood. Stabilizes or reduces body weight. It has a fibrinolytic effect due to the suppression of a tissue-type plasminogen activator inhibitor.
After oral administration, metformin is absorbed from the gastrointestinal tract. Bioavailability after taking the standard dose is 50-60%. Cmax in plasma is achieved 2.5 hours after ingestion. Practically does not bind to plasma proteins. It accumulates in the salivary glands, muscles, liver and kidneys. Excreted unchanged by the kidneys. T1 / 2 is 9-12 hours. In case of impaired renal function, drug accumulation is possible.
Indications for use
Type 2 diabetes in adults (especially in patients with obesity) with the ineffectiveness of diet and exercise, as monotherapy or in combination with other oral hypoglycemic agents or insulin. Type 2 diabetes in children from 10 years of age - both as a monotherapy and in combination with insulin.
- diabetic ketoacidosis, diabetic precoma, coma;
- impaired renal function;
- acute diseases that are at risk of developing renal dysfunction: dehydration (with diarrhea, vomiting), fever, serious infectious diseases, hypoxia (shock, sepsis, renal infections, bronchopulmonary diseases);
- clinically significant manifestations of acute and chronic diseases that can lead to the development of tissue hypoxia (cardiac or respiratory failure, acute myocardial infarction);
- serious surgery and trauma (when insulin therapy is indicated);
- abnormal liver function;
- chronic alcoholism, acute alcohol poisoning;
- use for at least 2 days before and within 2 days after conducting radioisotope or x-ray studies with the introduction of iodine-containing contrast agent;
- lactic acidosis (including history);
- adherence to a low-calorie diet (less than 1000 calories / day);
- lactation period;
- hypersensitivity to the drug.
It is not recommended to use the drug in persons older than 60 years who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.
Dosage and administration
Tablets should be taken orally, swallowing whole, without chewing, during or immediately after a meal, drinking plenty of water.
Monotherapy and combination therapy with other oral hypoglycemic agents The recommended initial dose is 1000-1500 mg / day. To reduce side effects from the gastrointestinal tract, the dose should be divided into 2-3 doses. After 10-15 days, in the absence of adverse effects from the gastrointestinal tract, a further gradual increase in dose is possible depending on the concentration of glucose in the blood. Slowly increasing the dose may help improve the gastrointestinal tolerance of the drug.
Maintenance daily dose is 1500-2000 mg. The maximum daily dose is 3000 mg, divided into 3 doses.
When planning a transition from taking another oral hypoglycemic agent to the drug Metformin, you must stop taking another hypoglycemic agent and start taking Metformin Canon in the above doses.
Combined Insulin Therapy.The recommended initial dose of the drug Metformin 500 mg and 850 mg - 1 tablet 2-3 times a day, Metformin 1000 mg - 1 tablet 1 time per day, while the insulin dose is selected based on the blood glucose concentration.
Children over 10 years old
Metformin Canon is used in monotherapy and in combination therapy with insulin. The recommended initial dose of Metformin is 500 mg 1 time per day in the evening with meals. After 10-15 days, the dose of the drug must be adjusted based on the concentration of glucose in the blood. Maintenance dose is 1000-1500 mg / day in 2-3 doses. The maximum daily dose is 2000 mg in 3 doses.
Due to the possible reduction in renal function, the dose of Metformin should be selected under regular monitoring of indicators of renal function (control of serum creatinine at least 2-4 times a year).
The duration of treatment is determined by the doctor. It is not recommended to interrupt the administration of the drug without the indication of the attending physician.
Use during pregnancy and lactation
The drug is contraindicated for use during pregnancy and during breastfeeding. When planning or having a pregnancy, Metformin Canon should be discontinued and insulin therapy should be applied. The patient should be warned about the need to notify the doctor in case of pregnancy. Mother and child should be monitored. It is not known whether metformin is excreted in breast milk. If necessary, the use of the drug during lactation, breastfeeding should be stopped.
On the part of the digestive system: nausea, vomiting, metallic taste in the mouth, lack of appetite, diarrhea, flatulence, abdominal pain. These symptoms are particularly common at the beginning of treatment and, as a rule, go away on their own. These symptoms can be reduced by prescribing anthocytes, atropine derivatives, or antispasmodics.
Metabolism: in rare cases - lactacidosis (requires discontinuation of treatment); with long-term treatment - hypovitaminosis B12 (absorption disorder).
From the side of blood-forming organs: in some cases - megaloblastic anemia.
On the part of the endocrine system: hypoglycemia.
Allergic reactions: skin rash.
During the period of treatment, it is necessary to monitor renal function. At least 2 times a year, as well as the appearance of myalgia should determine the content of lactate in the plasma. In addition, 1 time in 6 months control of serum creatinine level is necessary (especially in patients of advanced age). Metformin should not be administered if the level of creatinine in the blood is higher than 135 µmol / L in men and 110 µmol / L in women.
Perhaps the use of the drug Metformin in combination with sulfonylurea derivatives. In this case, especially careful control of blood glucose level is necessary.
48 h before and within 48 h after radiopaque (urography, in / in angiography) should stop taking Metformin.
When a patient has a bronchopulmonary infection or an infection of the urinary organs, you should immediately inform the attending physician.
During treatment, you should refrain from taking alcohol and drugs containing ethanol.
Influence on ability to drive motor transport and control mechanisms
The use of the drug in monotherapy does not affect the ability to drive and work with mechanisms.
When Metformin is combined with other hypoglycemic agents (sulfonylurea derivatives, insulin), hypoglycemic states can develop, which impair the ability to control vehicles and engage in other potentially hazardous activities that require increased attention and quick psychomotor reactions.
Contraindications. Radiological studies with the use of iodine-containing radiopaque drugs can cause the development of lactic acidosis in patients with diabetes mellitus on the background of functional renal failure. The use of metformin should be discontinued 48 hours before and should not be resumed earlier than 48 hours after x-ray examination with the use of contrast media.
Combinations not recommended. With simultaneous use of metformin with alcohol and ethanol-containing drugs, during acute alcohol intoxication, with fasting or following a low-calorie diet, as well as with liver failure, the risk of developing lactic acidosis increases.
Combinations requiring special care. With the simultaneous use of metformin with danazol may develop hyperglycemic effect. If necessary, treatment with danazol and after discontinuation of its administration requires a dose adjustment of metformin under the control of the concentration of glucose in the blood.
Chlorpromazine in high doses (100 mg / day) reduces insulin release and increases the concentration of glucose in the blood. With simultaneous use with neuroleptics and after discontinuation of their administration, dose adjustment of metformin is required under the control of glucose concentration in the blood.
When parenteral and topical administration, glucocorticosteroids (GCS) reduce glucose tolerance and increase the concentration of glucose in the blood, in some cases causing ketosis. If necessary, the use of such a combination and after discontinuation of the GCS requires a dose adjustment of metformin under the control of glucose concentration in the blood.
With the simultaneous use of "loop" diuretics and metformin, there is a risk of developing lactic acidosis due to the possible appearance of functional renal failure.
The use of beta2-adrenomimetik in the form of injections reduces the hypoglycemic effect of metformin due to the stimulation of beta2-adrenergic receptors. In this case, the concentration of glucose in the blood should be monitored and, if necessary, insulin should be used.
Angiotensin-converting enzyme inhibitors and other antihypertensive drugs can reduce the concentration of glucose in the blood. If necessary, adjust the dose of metformin.
With simultaneous use of metformin with sulfonylurea derivatives, insulin, acarbose and salicylates, hypoglycemic action may be enhanced.
Nifedipine increases the absorption and Cmax of metformin, which must be considered when using them simultaneously.
"Loopback" diuretics and nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of reducing kidney function. In this case, care must be taken when using metformin.
Symptoms: when using metformin at a dose of 85 g, hypoglycemia was not observed, but the development of lactic acidosis was noted. 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. Treatment: In case of signs of lactic acidosis, treatment with the drug should be stopped immediately, the patient should be urgently hospitalized and, after determining the concentration of lactate, the diagnosis should be clarified. The most effective measure for the elimination of lactate and metformin from the body is hemodialysis. Symptomatic treatment is also performed.