If you believe the reviews and instructions, Metformin is an effective and reliable means of correcting diabetes. Pills are designed to lower the concentration of sugar in the circulatory system. They belong to the category of biguanides, are available in oral form. "Metformin" has found its use in the treatment of the second type of diabetic disease. The most pronounced effect is shown against the background of obesity, excess weight with adequate renal function.
general information
Metformin has proven itself best in type 2 diabetes mellitus, but some scientists suggest that the remedy may be effective in case of a diabetic disease while carrying a child due to hormonal imbalance, as well as in case of polycystic ovary syndrome, accompanied by a specific syndrome. Currently, tests are still being conducted to prove the effectiveness or to establish the failure of the tablets in these conditions. Previously, experiments were organized to determine the possibility of using Metformin for the treatment of conditions in which the patient suffers from increased insulin resistance.
As can be seen from the reviews and instructions for use, Metformin rarely provokes an unwanted response from the body if the drug is taken correctly. Since the experience of use and clinical practice of application are quite voluminous, these responses can be trusted - the sample is large enough to be accurate. Patients taking the pills noted that sometimes against the background of treatment, disorders in the work of the stomach and intestines occurred. At the same time, there is a likelihood of hypoglycemia, but such a danger is assessed as minimal.
Taking Metformin can cause lactic acidosis, a condition in which lactic acid accumulates in the circulatory system. The risks of its occurrence are higher against the background of an overdose, as well as the use of the drug in the presence of contraindications.
Efficiency Proven
Nowadays, among the best hypoglycemic drugs is Metformin, which effectively reduces the concentration of harmful cholesterol, triglycerides, and low-density lipoproteins in the circulatory system. The drug does not provoke weight gain. Medical statistics made it possible to identify: against the background of the use of the pills in question, the risk of death due to complications caused by diabetes is significantly reduced.
The effectiveness of Metformin in diabetes has led to the inclusion of funds in the number of important drugs. The medication is included in the thematic list of WHO, which includes another remedy for diabetes - Glibenclamide.
Application practice: how it all began
It was suggested that Metformin can be used for diabetes in 1922. The first official description of the substance was made by the scientists Bell and Werner, who received the drug as a result of the reaction of N-dimethylguanidine. After another seven years, the ability of the compound to lower the blood sugar in experimental rabbits was proved. The new product was the most effective biguanide known at that time. True, this information has lost relevance against the background of the demand for insulin.
In 1950, scientists revealed: “Metformin” does not lower blood pressure, which distinguishes it against the background of many hypoglycemic drugs. Animal tests have shown no effect on heart muscle contractions. Then, “Metformin” was first used in a therapeutic course against influenza and confirmed its effectiveness as a method of lowering the concentration in the circulatory system to a physiological minimum. In addition, practice has shown no toxic effect. At the same time, it was suggested that Metformin possesses a number of important properties: the ability to combat the pathogen of malaria, alleviate heartburn, destroy viruses, as well as bacteriostatic, analgesic effects.
In 1954, most of the assumptions were not confirmed during the tests of the scientist Supnevsky, although they still managed to get some activity against viruses.
Idea development: medicine does not stand still
How can you take "Metformin", how to achieve a pronounced effect from it, studied the French doctor Stern. Initially, his research was devoted to the galegin obtained during the processing of a pharmaceutical goat's goat, the structure of which has common features with metmorphine, the main substance of the modern drug Metformin. Even before the appearance of the first synthalins, he recorded the effectiveness of Metformin against diabetes.
Stern, subsequently going to the Paris research laboratories, confirmed that Metformin with type 2 diabetes shows good results. In addition to this substance, he studied other biguanides. Stern was the first physician to formally attempt to use Metformin in clinical practice in the fight against diabetes. He owns the copyright in the name "Glucophagus". The results of the observations were officially published in 1957. A year later, the tool became available in the national form of Great Britain, appeared in English pharmacies.
Progress of the pharmacy assortment
In the 1970s, virtually all biguanides were seized from pharmacies, and it was then that the era of the Metformin drug began. Canadian doctors approved it in 1972, in 1994, for the second type of diabetes, the drug was taken as therapeutic in America. For the first time in the USA, the medicine was sold under the name Glucophagus, the start of sales was in March 1995. Currently, various generics based on matformin are represented in different powers. Medical statistics suggest that drugs on metformin these days around the planet are the most commonly prescribed remedy for diabetics.
Synthesis and pharmaceuticals
For the first time, the manufacture of a substance was officially described in 1922: it is the result of the interaction of dimethylamine hydrochloride and dicyandiamide. The reaction requires an increase in temperature. A patent issued in 1975, as well as an encyclopedia dedicated to pharmaceuticals, contain the following recommendations: equimolar volumes of the components must be dissolved in toluene, cooled, a high level of concentration achieved, then diluted with hydrogen chloride. The resulting composition boils on its own, then cools. The precipitate formed during the reaction is metformin. The reaction efficiency is 96%.
More recently, a more efficient and safe method for producing a compound has been invented. To work, you need a few milligrams of components, a few drops of liquid. The reaction lasts five minutes, proceeds under the influence of microwave radiation.
Dynamics
To understand the main mechanism of action of Metformin, you should carefully study the instructions that are included with the composition: manufacturers describe in detail how the substance works. Studies have shown that a marked decrease in glucose concentration in the circulatory system is explained by inhibition of the glucose generation reaction, which normally occurs in liver cells. Against the background of the second type of diabetes, the reaction rate of glucose production in the patient’s body is on average three times higher than normal, and taking the drug can reduce the parameter by about a third.
According to the instructions “Metformin” (“Canon”, “Teva” and other release options), when it enters the human body, it activates the liver enzyme AMPK, which is indispensable in the insulin signaling procedure. This controls the energy balance, metabolic reactions involving lipids, sugars. Activation of the liver enzyme allows you to achieve a pronounced effect of inhibition of gluconeogenesis.
Details: New and Verified
Not so long ago, fresh studies were published on the mechanism of action of metformin. Scientists have found that the activation of AMPA leads to protein expression, inhibiting the expression of substances necessary for the production of glucose by the liver cells: glucose-6-phosphatase, phosphoenolpyruvic acid.
Due to its mechanism of action, metformin has become an important participant in reactions involving AICA ribonucleotides, playing the role of an AMPK antagonist. While scientists do not know exactly why biguanides can activate the enzyme produced by the liver, but studies show that the concentration of cytosolic AMP is growing.
Tests have proven: the substance on which the popular diabetes drug is based has a mild inhibitory effect on the first respiratory complex. It is believed that this quality is one of the basic ones that ensure the effectiveness of the product.
Performance Features
The mechanism of action of Metformin is associated with an increase in the sensitivity of organic tissues to the hormone insulin. Under the influence of the drug, the activity of peripheral uptake of sugars increases due to the phosphorylation of one of the glucose transporters. Oxidative reactions with the participation of fatty acids become more active, the ability of the gastrointestinal mucosa to absorb glucose decreases. The activity of peripheral utilization is probably due to the better ability of hormones to bind to insulin receptors.
It was revealed that the hepatic enzyme AMPK becomes more active in muscle support of the skeleton, which is also due to the mechanism of action of Metformin. This enzyme affects glucose transporters, initiating their incorporation into the plasma membrane, which allows sugar absorption reactions to proceed without the participation of insulin. It is believed that the metabolism of Metformin is not dependent on AMPK. Research conducted in 2008 clearly showed: in the muscle of the heart, the effectiveness of the compound is observed regardless of the level of liver enzymes.
The nuances of action
According to the instructions, Metformin lowers triglycerides, low-density lipoproteins in the circulatory system, while other types of these substances remain stable. The drug helps to stabilize weight and reduce it. If there is no insulin in the circulatory system, it has no effect. The tool does not provoke a hypoglycemic response, increases fibrinolytic blood qualities, as it inhibits plasminogen.
Using the Metformin instructions, you can reduce the sugar concentration by one fifth, and glycosylated hemoglobin - by about one and a half percent. The use of only the drug in question without a combination with other substances to lower glucose in the circulatory system reduces the risk of heart attack. A similar effect was revealed in comparison with the placebo control group and patients on a diet who took insulin. The drug has significantly reduced the risk of death against the background of the second type of diabetic disease. Research results confirming this fact were published in 2005. Statistics were summarized for 29 works.
Kinetics
When taken on an empty stomach 500 mg of Metformin, the bioavailability of the drug is 50-60%. The use of the drug with food reduces the rate by 10%. The highest concentration in the circulatory system is observed within 1-3 hours after taking the pill, when consumed with food - for half an hour longer. When choosing a prolonged form, the highest concentration is fixed in the interval 4-8 hours after using the product. The medication is practically not able to bind to plasma proteins. The approximate volume of distribution is estimated at 654 liters. A stable level of concentration in the patient’s body is observed on 2-3 days of regular use.
When taking Metformin (500 mg, 850 mg and another dosage option), metabolic reactions are not initiated. The substance is eliminated with urine in its original form through the tubules of the kidneys. In the blood serum, a day after a single use is not detected. The average elimination half-life is 6.2 hours. Basically, the compound is distributed in red blood cells, from which it is eliminated more slowly; suggest that metformin can accumulate in these blood cells. With a single dose, the half-life of erythrocytes can reach 31.5 hours. Analyzes were conducted with the participation of patients without diabetes.
The absorption level of analogues of drugs on metformin is estimated at an average of 50% with a deviation of about 2% up and down. The compound is absorbed fairly quickly when passing through the digestive tract. In the blood serum, the concentration of 24-48 hours is maintained at about 1 μg / ml.
Diabetes: how will it help?
The drug itself and analogues on metformin are intended for the treatment of the second type of diabetes. The medication is more recommended for overweight people. Decades of research have shown: the substance effectively reduces the risk of diabetic complications and the frequency of deaths by one third in comparison with the control group that took drugs on sulfonylurea, insulin. Regarding people who followed a diet but avoided the drug course, those taking Metformin developed complications in 40% less often. After the study, the test participants were followed for another 5-10 years. During this period, the trend continued.
According to reviews, the use of "Metformin" does not pose serious difficulties: it is enough to take pills regularly, without missing the right time, monitoring the use of the product on an empty stomach. Such a course is considered to be intensive, reduces the risk of diabetes-related endpoints. The risk of a hypoglycemic attack is reduced. The difference in the frequency of hypoglycemic seizures is especially pronounced in comparison with a group of patients who used sulfonylurea agents. Hypoglycemia can accompany a therapeutic course against the background of excessive physical activity, high-calorie starvation, the use of other drugs to reduce blood sugar.
You can use, following the instructions for use, "Metformin" for weight loss. The drug is prescribed for obesity in combination with other medications, a nutrition program and physical activity. It is impossible to use the composition for weight loss on your own, without the doctor’s control - this can cause serious complications.
Experimentation and Efficiency
Recently, scientists have been working on the theory of using Metformin for polycystic ovary syndrome. Presumably, the drug can be used for fatty liver pathologies, if they are not associated with the use of screening. Metformin is practiced taking puberty ahead of time. Such indications are currently classified as experimental.
The main advantages of the composition under consideration under these conditions have not yet been officially proven. Several random studies were carried out, during which an improvement in the health of patients was detected while taking Metformin. So far, this information is not voluminous enough for the experiment to be considered proven.
Composition and shape
"Metformin" is produced on the same active substance. In addition to it, each tablet contains auxiliary components. The manufacturer provides a complete list of the substances used in the description of a specific product. As a rule, talc, povidone, starch, magnesium sterate, macrogol, titanium dioxide are used.
Metformin is available in tablet form. Instances are packaged in a dozen in a blister, one cardboard package contains three blisters. On the outside, the amount of the drug, the concentration of the main substance in one tablet, is indicated.
Application rules
When to use the medication, how and how much Metformin should be consumed, the doctor will tell you at the reception, issuing a prescription for the drug. The dosage is always selected individually, focusing on the indicators of sugars in the circulatory system. As a rule, they start with 0.5-1 g of the drug, that is, one tablet or two. After one and a half to two weeks, you can increase the number, if required by indicators of blood quality.
For most patients, Metformin in a maintenance dosage is 1.5-2 g per day, that is, no more than four tablets. Maximum per day is allowed to use 6 tablets, or 3 g of the composition. In old age, Metformin is taken in an amount of not more than 1 g in 24 hours.
Tablets are used without chewing, without violating the integrity of the shell. As a rule, the release is intended for use on an empty stomach, but the features of the shell of specific tablets may require use with or immediately after a meal. If necessary, the manufacturer shall indicate the relevant information in the accompanying instruction. "Metformin" should be washed down with liquid in reasonable volumes. To reduce the risk of a negative gastrointestinal tract response, it is reasonable to divide the daily dose into several doses (up to three).
Since the drug can cause lactic acidosis, in severe failures of metabolic reactions in the body, the dosage is reduced.
Strongly impossible!
"Metformin" is forbidden to take against the background of precoma, coma due to diabetes, ketoacidosis caused by it. The drug is not used for severe renal impairment and acute diseases, the course of which is highly likely to cause impaired renal function. "Metformin" is not prescribed for dehydration, fever and hypoxia, severe infection. The tool is forbidden to take if chronic, acute diseases are accompanied by an increased risk of tissue hypoxia.
"Metformin" can not be used before complex long-term operations, against the background of a serious injury. The drug is not used in cases of renal failure, amid acute alcohol poisoning or prolonged addiction to alcoholic beverages. If tests are shown with the introduction of contrast agents containing iodine into the body, two days before the Metformin event, they are canceled, and they continue to be taken two days after the procedure.
"Metformin" is prohibited on the background of lactic acidosis, including previously transferred. The medicine is not prescribed for pregnant and lactating mothers, people who have hypersensitivity to the drug. It is forbidden to combine Metformin and a diet with a reduced calorie content (up to 1,000 calories per day).
Do not use Metformin for patients of the age group 60 years and older, if it is necessary to regularly endure heavy physical exertion, since such a course is accompanied by an increased risk of lactic acidosis.
The nuances of safe use
The therapeutic course with Metformin requires monitoring renal function. Twice a year in the general case, and with the symptoms of myalgia - immediately clarified the concentration of lactate in the serum. Twice a year, creatinine clearance should be monitored. This is especially important for the elderly. If the creatinine concentration in the male patient is more than 135 μmol / L, in the female - 110 μmol / L, Metformin is canceled.
It is allowed to combine the drug in question and sulfonylurea processing products, but only if it is possible to regularly monitor the sugar content in the circulatory system.
If an infection of the bronchi, lungs, infectious pathology localized in the reproductive system is detected, it is necessary to consult a doctor. The therapeutic course is categorically not combined with alcohol and drugs that contain ethanol.
The use of the drug in question alone, as the only treatment drug, is not associated with a deterioration in the ability to concentrate, therefore, does not affect the ability to work with machines, devices, and vehicles. If Metformin is combined with other medicines to lower the concentration of glucose in the circulatory system, there is a danger of hypoglycemia, which is associated with a deterioration in the ability to concentrate and control the work of dangerous objects.
When is it prescribed?
"Metformin" is indicated for the second type of diabetes, if the patient is not prone to ketoacidosis. The drug is used if the diet does not show the desired result. You can combine the drug with insulin in the second type of diabetes. It is especially effective for overweight and secondary hormone resistance.
Mutual influence
The appointment of “Metformin” and “Danazole” at the same time should be avoided, since such a combination is associated with an increased risk of hypoglycemia. If it is necessary to use Danazol, and also shortly after stopping its use, Metformin is used in a reduced dosage. Volume adjustment is done by an experienced doctor.
Special care requires the simultaneous use of the composition in question and high dosages of Chlorpromazine (from 100 mg per day or more). This combination leads to a decrease in insulin release, which increases the risk of glycemia. The use of antipsychotics, as well as the period shortly after the completion of such a program, oblige you to adjust the volume of Metformin, focusing on the indicators of sugars in the patient's circulatory system.
Note!
The combination of Metformin and IMAO, ACE inhibitors, insulin, beta-blockers, clofibrate products, non-hormonal anti-inflammatory drugs, acarbose, oxytetracycline, cyclophosphamide and preparations made on sulfonylurea is associated with an increased hypoglycemic effect of the drug in question.
The simultaneous ingestion of a patient with hormonal anti-inflammatory, hormonal contraceptives, sympathomimetics, nicotinic acid products, diuretics can cause a weakening of the effectiveness of Metformin. A similar result is possible with the use of phenothiazine processing products, hormonal compounds similar to those produced by the thyroid gland, glucagon, and epinephrine.
Special accent
Tests have shown: "Metformin" can make the effect of coumarin derivatives less pronounced.
The use of alcohol against the background of a therapeutic course increases the risk of lactic acidosis. Particularly high is the likelihood of developing such a state against the background of acute alcohol poisoning, during the fasting phase and, if necessary, adhere to a diet with minimal calorie content.
Too much
Excessive use of "Metformin" is associated with the danger of lactic acidosis, which can lead to death of the patient. It is known that a fatal outcome is possible due to the cumulative effect due to renal dysfunction. Poisoning can be suspected by violation of the stool, lowering temperature, pain in the abdomen. The patient's muscles respond with pain, he vomits and feels sick, breathing becomes more frequent, his head is spinning. Possible loss of consciousness, coma.
With the symptoms of lactic acidosis, it is necessary to immediately cancel "Metformin" and hospitalize the victim. The initial analysis is aimed at clarifying the content of lactate and confirming the diagnosis, after which blood dialysis and treatment are prescribed based on the nuances of the symptoms of a particular case.