If you believe the reviews and instructions, "Metformin" is an effective and reliable means of correcting diabetes. Tablets are designed to lower the concentration of sugar in the circulatory system. Belong to the category of biguanides, are available in the form for oral use. "Metformin" has found its application 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 functionality.
General information
Metformin has proven itself best in type 2 diabetes, but some scientists suggest that the remedy may be effective in diabetic disease during childbearing due to hormonal imbalance, as well as in polycystic ovaries, accompanied by a specific syndrome. At present, trials are still being carried out to prove the effectiveness or establish the ineffectiveness of tablets in these conditions. Experiments were previously organized to determine the possibility of using Metformin for the treatmentconditions in which the patient suffers from increased insulin resistance.
As can be seen from the reviews and instructions for use, Metformin rarely provokes an undesirable body response if the drug is taken correctly. Since the experience of use, clinical practice of application is quite voluminous, these responses can be trusted - the sample is large enough to be accurate. The patients who took the pills noted that sometimes during the treatment there were disorders in the work of the stomach, intestinal tract. At the same time, there is a possibility of hypoglycemia, but this risk is assessed as minimal.
Metformin can cause lactic acidosis, a condition in which lactic acid builds up in the bloodstream. Higher risks of its occurrence on the background of an overdose, as well as the use of the drug in the presence of contraindications.
Proven effectiveness
Today, 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 cause weight gain. Medical statistics have revealed: against the background of the use of the tablets in question, the risk of death due to complications caused by diabetes is significantly reduced.
The effectiveness of "Metformin" in diabetes mellitus has led to the inclusion of the drug among the most important drugs. The drug is included in the WHO thematic list, which includes another remedy for diabetes -Glibenclamide.
Practice of application: how it all began
Suggested that you can use "Metformin" in diabetes, in 1922. The author of the first official description of the substance was the scientists Bell, Werner, who received the remedy as a result of the reaction of N-dimethylguanidine. After another seven years, the ability of the compound to lower the blood sugar content of guinea pigs was proven. The new product was the most effective biguanide known at the time. True, this information has lost its relevance against the background of the demand for insulin.
In 1950, scientists found: "Metformin" does not lower blood pressure, which distinguishes it from the background of many hypoglycemic drugs. Animal tests have proven no effect on the heart muscle contraction rate. At the same time, 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 the absence of a toxic effect. At the same time, it was suggested that Metformin had a number of important properties: the ability to fight the causative agent of malaria, relieve 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 some activity against viruses was still obtained.
Development of the idea: medicine does not stand still
How can I take Metformin, how can I achievefrom it a pronounced effect, studied the French doctor Stern. Initially, his research was devoted to galegin obtained by processing the pharmacy goat's rue, the structure of which has common features with metmorphine, the main substance of the modern drug Metformin. Even before the first synthalins appeared, he recorded the effectiveness of Metformin against diabetes.
Stern, later moving to research laboratories in Paris, confirmed that Metformin shows good results in type 2 diabetes. In addition to this substance, he studied other biguanides. Stern became the first physician to officially attempt to use Metformin in clinical practice in the fight against diabetes. He owns the copyright for the name "Glucophage". The results of the observations were officially published in 1957. A year later, the remedy became available in the national formulary of Great Britain, appeared in English pharmacies.
Progress of the pharmacy assortment
In the 1970s, almost all biguanides were withdrawn 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 remedy was accepted as a therapeutic agent in America. For the first time in the United States, the drug was sold under the name "Glucophage", the start of sales took place in March 1995. Currently, numerous generics based on matformin are presented in different countries. Medical statistics suggest that metformin-based drugs are the most frequently prescribed drug for diabetics today on the entire planet.
Synthesis andpharmaceuticals
For the first time, the manufacture of the substance was described officially 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, reached a high level of concentration, 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%.
Relatively recently, a more efficient and safer method of 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 attached to the composition: manufacturers describe in some detail how the substance works. Studies have shown that a pronounced decrease in glucose concentration in the circulatory system is due to inhibition of the glucose generation reaction that 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 of "Metformin" ("Kanon", "Teva" and other release options) when it entersthe human body activates the liver enzyme AMPK, which is indispensable in the insulin signaling process. This controls the energy balance, metabolic reactions involving lipids, sugars. Activation of the liver enzyme allows to achieve a pronounced effect of inhibition of gluconeogenesis.
Information: new and tested
Recent studies have been published on the mechanism of action of metformin. Scientists have found that AMPK activation leads to protein expression, suppressing the expression of substances necessary for the production of glucose by liver cells: glucose-6-phosphatase, phosphoenolpyruvic acid.
Due to its mechanism of action, metformin has become an important participant in reactions involving AICA ribonucleotide, playing the role of an AMPK antagonist. While scientists do not know exactly why the biguanides can activate the enzyme produced by the liver, but studies show that the concentration of cytosolic AMP is increasing.
Tests have proven that the substance on which the popular remedy for diabetes is based has a moderate inhibitory effect on the first respiratory complex. It is assumed that this quality is one of the basic ones that ensure the effectiveness of the tool.
Efficiency 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 sugar uptake increases due to the phosphorylation of one of the glucose transporters. Oxidative reactions involving fatty acids become more active,the ability of the gastrointestinal mucosa to absorb glucose. The activity of peripheral utilization is probably due to the better ability of hormones to bind to insulin receptors.
The liver enzyme AMPK has been found to become more active in the muscular 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 makes it possible for sugar uptake reactions to occur without the participation of insulin. It is assumed that the metabolism of "Metformin" does not depend on AMPK. Research conducted in 2008 clearly showed that in the heart muscle, the effectiveness of the compound is observed regardless of the level of liver enzymes.
Nuances of action
According to the instructions, "Metformin" lowers the content of 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 effectiveness. The agent does not provoke a hypoglycemic response, increases fibrinolytic blood qualities, as it inhibits plasminogen.
Using Metformin according to the instructions, you can reduce the concentration of sugars by one fifth, and glycosylated hemoglobin by about one and a half percent. The use of only the considered agent without combination with other substances to lower glucose in the circulatory system reduces the risk of a heart attack. A similar effect was found in comparison withplacebo control group and patients on a diet taking insulin. The drug allowed to significantly reduce the risk of death against the background of the second type of diabetic disease. The results of studies confirming this fact were published in 2005. The statistics were summed up on 29 works.
Kinetics
When taken on an empty stomach 500 mg "Metformin" bioavailability of the drug - 50-60%. The use of medication with food reduces the rate by 10%. The highest concentration in the circulatory system is observed within 1-3 hours from the moment of 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 of 4-8 hours after the use of the drug. The drug is practically incapable of binding 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 for 2-3 days of regular use.
When taking "Metformin" (500 mg, 850 mg and other dosage options), metabolic reactions are not initiated. The substance is eliminated in the 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 half-life is on average 6.2 hours. Basically, the compound is distributed in erythrocytes, it is excreted from them more slowly; suggest that metformin may accumulate in these blood cells. With a single dose, the half-life from erythrocytes can reach 31.5 hours. Analyzes were performed in patients notdiabetics.
The level of absorbability of Metformin analogues is estimated at an average of 50% with a deviation of about 2% up and down. The compound is fairly rapidly absorbed when passing through the gastrointestinal tract. In blood serum, the concentration of 24-48 hours is maintained at about 1 μg / ml.
Diabetes: how will it help?
The drug itself and metformin analogues are intended for the treatment of type 2 diabetes. The drug is more recommended for people who are overweight. Decades of research have shown that the substance effectively reduces the risk of diabetic complications and the frequency of deaths by a third in comparison with the control group who used sulfonylurea drugs, insulin. Relative to persons who adhered to a diet, but avoided a drug course, those who took Metformin were 40% less likely to develop complications. After the study, the participants in the trials were followed for another 5-10 years. During this period, the trend continued.
According to reviews, the use of "Metformin" is not a serious difficulty: it is enough to take the pills regularly, without missing the right time, watching the use of the drug on an empty stomach. Such a course is considered intensive, lowers the risk of diabetes-related endpoints. Reduces the risk of a hypoglycemic attack. The difference in the frequency of hypoglycemic attacks is especially pronounced in comparison with the group of patients who used sulfonylurea drugs. Hypoglycemia may accompany the therapeutic course against the background ofexcessive physical activity, calorie starvation, use of other means to reduce blood sugars.
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 supervision of a doctor - this can cause serious complications.
Experimentation and efficiency
Recently, scientists have been working on the theory of the use of "Metformin" in polycystic ovary syndrome. Presumably, the drug can be used for fatty liver pathologies, if they are not associated with the use of sieve. Practicing the reception of "Metformin" during puberty ahead of time. Such indications are currently classified as experimental.
The main advantages of the composition in question under these conditions have not yet been officially proven. Several random studies were conducted, during which an improvement in the he alth of patients was revealed 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 active substance of the same name. In addition to it, each tablet contains auxiliary components. The manufacturer gives 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 the formtablets. Copies are packed ten in a blister, one carton contains three blisters. On the outside, the amount of the product is indicated, the concentration of the main substance in one tablet.
Rules of application
When to use the medication, how and how much "Metformin" you need to use, the doctor will definitely tell you at the appointment, 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, the amount can be increased if blood quality indicators require it.
For most patients, Metformin at a maintenance dosage is 1.5-2 g per day, that is, no more than four tablets. A maximum of 6 tablets per day, or 3 g of the composition, is allowed. In old age, Metformin is taken in an amount of no more than 1 g per 24 hours.
Pills are consumed without chewing, without violating the integrity of the shell. As a rule, the release is intended to be taken on an empty stomach, but the characteristics of the shell of specific tablets may require use with or immediately after a meal. If necessary, the manufacturer indicates the relevant information in the accompanying instructions. "Metformin" should be washed down with liquid in reasonable volumes. To reduce the risk of a negative gastrointestinal response, it is reasonable to divide the daily dose into several doses (up to three).
Since the agent can cause lactic acidosis, with severe failuresmetabolic reactions in the body, reduce the dosage.
Absolutely not allowed
"Metformin" is forbidden to take against the background of precoma, coma due to diabetes, caused by it's ketoacidosis. The drug is not used for severe renal disorders and acute diseases, the course of which with a high degree of probability can cause a violation of renal functionality. "Metformin" is not prescribed for dehydration, fever and hypoxia, severe infection. It is forbidden to take the remedy 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 case of failure of renal functionality, against the background of acute alcohol poisoning or prolonged addiction to alcoholic beverages. If tests with the introduction of contrast agents containing iodine into the body are indicated, two days before the event, Metformin is canceled, and continues to be taken two days after the procedure.
"Metformin" is prohibited against the background of lactic acidosis, including the previous one. The drug is not prescribed to pregnant and lactating mothers, persons who have shown hypersensitivity to the drug. It is forbidden to combine Metformin and a reduced calorie diet (up to 1,000 calories per day).
Metformin should not be used by patients in the age group of 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.
Nuancessafe use
The therapeutic course with "Metformin" requires monitoring of renal functionality. Twice a year in the general case, and with the symptoms of myalgia, the clarification of the concentration of lactate in the serum is immediately shown. Creatinine clearance should be monitored twice a year. This is especially important for the elderly. If the concentration of creatinine in a male patient is more than 135 µmol / l, in a female patient - 110 µmol / l, Metformin is canceled.
It is allowed to combine the agent in question and sulfonylurea processing products, but only if it is possible to regularly monitor the sugar content in the circulatory system.
When detecting infection of the bronchi, lungs, infectious pathology localized in the reproductive system, you must consult a doctor. The therapeutic course is categorically not combined with alcohol and drugs that contain ethanol.
The use of the agent in question on its own, as the only treatment drug, is not associated with a deterioration in the ability to concentrate, therefore it does not affect the ability to work with machines, apparatus, and transport. If "Metformin" is combined with other medicines to lower the concentration of glucose in the circulatory system, there is a risk of hypoglycemia, which is associated with a deterioration in the ability to concentrate, control the work of dangerous objects.
When appointed?
"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 remedy with insulin in the second type of diabetes. It is especially effective for overweight and secondary hormone resistance.
Mutual influence
You should avoid prescribing Metformin and Danazol to the patient at the same time, 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 administration, "Metformin" is used in a reduced dosage. Adjustment of volumes is made 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 and more). This combination leads to a decrease in insulin release, resulting in an increased risk of glycemia. The use of antipsychotics, as well as the period shortly after the completion of such a program, oblige to adjust the volumes of Metformin, focusing on the sugars in the patient's circulatory system.
Pay attention
The combination of Metformin and MAOIs, ACE inhibitors, insulin, beta-blockers, clofibrate products, non-hormonal anti-inflammatory drugs, acarbose, oxytetracycline, cyclophosphamide and sulfonylurea preparations is associated with an increased hypoglycemic effect of the agent in question.
Simultaneous ingestion of hormonal anti-inflammatory, hormonal contraceptives, sympathomimetics, nicotinic acid products, diuretics into the patient's body can cause a weakening of the effectiveness of Metformin. A similar result is possiblewhen using products of phenothiazine processing, hormonal compounds similar to those produced by the thyroid gland, glucagon, epinephrine.
Special accent
Tests have shown: "Metformin" can reduce the effect of coumarin derivatives.
Drinking alcohol against the background of a therapeutic course increases the risk of lactic acidosis. The likelihood of developing such a condition is especially high against the background of acute alcohol poisoning, in the stage of starvation and, if necessary, adhere to a diet with a minimum calorie content.
Too much
Excessive use of "Metformin" is associated with the risk of lactic acidosis, which can cause death of the patient. It is known that death is possible due to the cumulative effect due to renal dysfunction. Poisoning can be suspected by a violation of the stool, a decrease in temperature, and abdominal pain. The patient's muscles respond with pain, he vomits and feels sick, breathing becomes faster, and his head is spinning. Possible loss of consciousness, coma.
With symptoms of lactic acidosis, it is necessary to immediately cancel Metformin and hospitalize the victim. The initial analysis is aimed at clarifying the lactate content and confirming the diagnosis, after which blood dialysis and treatment are prescribed based on the nuances of the symptoms of a particular case.
