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Currently, Metformin is considered as one of the main medication's in the treatment of type 2 diabetes. Why?

First, because Metformin has sufficient hypoglycemic capacity, comparable to the effectiveness of the main groups of hypoglycemic medication's. And also because the combination of Metformin with other oral hypoglycemic medication's or insulin significantly increases the ability to achieve target levels of carbohydrate metabolism compensation in patients with type 2 diabetes.

Secondly, it is necessary to remember the unique property of Metformin for hypoglycemic medication's to significantly reduce the incidence of myocardial infarction and cerebral circulatory disorders in patients with type 2 diabetes, which was shown in the UKPDS-the basic study for type 2 diabetes.

Third, the idea of the unique cardiovascular properties of Metformin is particularly attractive against the background of data on the safety of its use. This is manifested, on the one hand, in the almost complete absence of dangerous hypoglycemia when using it, and on the other — in the fact that such a severe complication as lactate acidosis is extremely rare when using Metformin.

However, in clinical practice, the doctor each time faces an individual, specific patient. Therefore, when planning treatment tactics, it is necessary each time, evaluate the acceptability of using General recommendations when choosing therapy for a specific patient. Thus, the doctor faces with the need to answer a few simple questions, the main of which is whether this medication is suitable for this patient, will it (the medication) have the desired effect in this particular patient?

What is the basis of the hypoglycemic action of Metformin?

The effect of Metformin on carbohydrate metabolism is represented by several mechanisms that do not directly affect the release of insulin by beta cells. The main action of Metformin can be defined as antihyperglycemic, not hypoglycemic. Metformin suppresses the production of glucose by the liver (mainly by suppressing gluconeogenesis and, to a lesser extent, glycogenolysis). Since the hepatic glucose synthesis in patients with diabetes is increased by about 2-3 times compared to healthy people, Metformin is the only oral hypoglycemic agent that helps normalize the level of fasting glycemia.

In addition, Metformin increases the sensitivity of peripheral tissues to insulin. In insulin-sensitive tissues (liver, muscles, adipose tissue) the medication improves glucose transport by increasing the activity of tyrosine kinase in insulin receptors, and also improves glucose transport by carrier proteins-GLUT — 1 in the plasma membrane and GLUT-4 in intracellular membranes.

The medication has a weak anorexigenic effect due to direct contact of the medication with the gastrointestinal mucosa. Reduced appetite leads to a decrease in glucose intake from food, gradual weight loss, and eventually-to a decrease in insulin resistance. Metformin also slows down the rate of absorption of carbohydrates in the intestine, which leads to a decrease in postprandial glycemia. It is believed that this is due to a decrease in motility of the small intestine and the rate of gastric emptying.

Are there additional benefits of using Metformin as one of the main medication's in the treatment of type 2 diabetes?

The effect of Metformin on the development of complications of diabetes mellitus and mortality can be explained by its pathogenetic effect, and primarily by a decrease in the underlying development of diabetes mellitus insulin resistance, i.e. the causes of carbohydrate metabolism disorders, dyslipidemia, hypertension and vascular complications of the disease. For this medication, there are undeniable laboratory and clinical results on proven cardiovascular protection. So, conducted since the 60s. Twentieth-century work aimed at studying the effects of Metformin in relation to experimental atherosclerosis, revealed that the introduction of Metformin in laboratory animals prevented vascular damage, typical for developing diabetes. There was also a decrease in the risk of developing and progression of microangiopathies when the medication is added to mice with insulin resistance or impaired carbohydrate tolerance.

In addition to the above effects, Metformin in laboratory animals has been shown to enhance vascular relaxation by potentiating the effects of substances acting through NO. It was found that by affecting insulin resistance and reducing the levels of atherogenic lipids, Metformin weakens the inclusion of lipids in the vascular wall and the proliferation of smooth muscle cells.

Metformin improves fibrinolysis by reducing visceral fat and insulin resistance, reducing the activity and production of a plasminogen activator inhibitor. It was also found that Metformin inhibits the activity of clotting factor XIII, reducing the formation of blood clots.

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Myth 1 - Diabetes mellitus is a disease of our Millennium.
The problem of high blood sugar has been known since ancient times. There are types 1 and 2 diabetes mellitus. Type 2 diabetes is one of the most common diseases. It has a great social significance not only because of its high prevalence, but also because of the steady increase in the number of patients, which, according to experts, will continue to increase.
Myth 2 - Skinny diabetes does not threaten.
This is not quite true, we need clarification: thin people are most likely not at risk of type 2 diabetes, since it is most often associated with overweight. The risk of developing type 2 diabetes is greatest with obesity, which is characterized by fat deposits in the abdomen. But patients with type 1 diabetes, on the contrary, are usually thin.

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Myth 3 - Diabetes mellitus is a rare inherited disease.
Medicine has accumulated a sufficient number of facts proving the hereditary predisposition of diabetes mellitus. But it's not that simple. If both parents have type 1 diabetes, their child has a 7% chance of developing the disease.
The risk increases if the parents have type 2 diabetes, as adults will probably pass on inherited factors that lead to the development of the disease — a tendency to obesity, high blood pressure and impaired fat metabolism. Knowing this, you can prevent the development of type 2 diabetes. It is necessary to eat properly, maintaining the level of physical activity and normal weight, as well as monitor the state of blood pressure.

What are the clinical benefits of Metformin?

As noted above, hyperglycemia and underlying type 2 diabetes mellitus insulin resistance are powerful and independent factors that lead to the development of macro and microvascular pathology, violation of neurological regulation. All this leads to a decrease in life expectancy and working capacity in people with diabetes. Most patients with type 2 diabetes die from cardiovascular disease. However, enough data has been accumulated to show the need to influence both arterial hypertension and blood lipids in diabetes mellitus or initial disorders of carbohydrate metabolism. This is due to the fact that type 2 diabetes, being a component of the metabolic syndrome, requires not only the normalization of glycemia, but also the elimination of factors that affect the formation or progress of atherosclerosis. In the UKPDS study Metformin had a significantly better effect on reducing mortality or the incidence of vascular complications compared to insulin or sulfonylurea derivatives at similar HbA1c values.

The cardioprotective effect of Metformin today can be explained by a lot of additional effects aimed at improving the state of the endothelium, blood rheology, capillary blood flow, and so on. These data allow us to recommend Metformin both for the treatment of hyperglycemia and to improve the prognosis in patients with diabetes mellitus for vascular complications.

How to start treatment with Metformin?

The starting dose of the medication should be 500-850 mg during or after meals (preferably in the evening) with a gradual increase of 500-850 mg weekly. The average effective dose in the United States is 2000-2500 mg, in Europe-3000 mg of Metformin per day. The first control point for the effectiveness of therapy is the normalization of fasting glycemia. However, Metformin has a good effect throughout the day, since, in addition to reducing the production of glucose by the liver at night, the medication improves the sensitivity of tissues to insulin throughout the day.

Important is the possibility of combining Metformin with other oral hypoglycemic agents or insulin without losing its hypoglycemic effectiveness. Thus, Metformin monotherapy reduces HbA1c by 1-1. 5 %, and the combined administration of Metformin and sulfonylureas in patients who are subcompensated against the background of diet and physical activity, allows you to double the effectiveness of treatment (reducing the level of HbA1c by 1.5–2.5 % of the original).

What are the main side effects of Metformin? How do I reduce them?

Metformin is generally well tolerated, with no serious side effects. The main problem of Metformin tolerance is side effects from the gastrointestinal tract, which are observed in 20-30 % of patients. Although these side effects usually resolve within 2 weeks of treatment or when the Metformin dose is reduced, in some patients they can be a serious barrier to successful therapy. Frequency of side effects the effect is dose-dependent and is more common in the range of 1000 to 2000 mg of the medication per day.

The second point that somewhat restricts the use of Metformin is the need to use it several times a day. A medication form of Metformin, which could be taken once a day, would be more convenient for both doctors and patients, especially against the background of the fact that medication's that are taken once a day are becoming the accepted norm.

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Myth 4 - People with diabetes should eat special food for diabetics.
The statement does not correspond to reality. The rules for making a daily diet for a patient with diabetes are the same as for a healthy person: limiting the consumption of fat, moderate intake of sugar and salt, sufficient consumption of vegetables, fruits, cereals, carbohydrates, vitamins, and proteins.
International experience shows that nutrition based on special products for diabetics containing glucose substitutes (sucrose) does not have the expected effect from them.

Safety of Metformin use. How often does lactate acidosis occur when taking the medication?

Numerous data indicate a low risk of developing lactate acidosis during Metformin therapy, which is less than 3 sluchev per 100 thousand patients. Thus, the risk of developing this complication is almost minimal if the recommendations regarding existing contraindications are strictly followed, especially those related to kidney disorders and conditions accompanied by hypoxia.

What are the contraindications to Metformin?

The most serious contraindication to the use of Metformin is the risk of developing lactate acidosis. From the point of view of the clinic, the most important contraindications to the appointment of Metformin are the following indicators:

  • Kidney failure. Metformin administration is contraindicated for creatinine clearance < 60 ml/min. Given that in 80-90% of cases, lactate acidosis develops in renal failure, this is one of the most important contraindications;
  • Chronic impairment of lung function. Metformin is contraindicated if there are symptoms confirming a violation of the function of external respiration, expressed radiological signs of pathology of the bronchopulmonary system;
  • Acute myocardial infarction. Metformin is contraindicated in the first 21-28 days after acute myocardial infarction. In the future when in the absence of heart failure, it is possible to prescribe Metformin or continue therapy, if Metformin was prescribed and used previously;
  • Heart failure. Left ventricular ejection fraction less than 40 % is a contraindication to Metformin treatment;
  • Chronic liver failure. Increased by more than 3 times the level of transaminases and alkaline phosphatase, decompensated cirrhosis of the liver;
  • Alcoholism;
  • Acute infections, injuries, operations under General anesthesia;
  • Administration of iodized radiopaque agents to patients with renal insufficiency may lead to acute functional deterioration of kidney function.

If the patient is diabetic and takes Metformin, the risk of developing lactate acidosis is high. Therefore, Metformin is suspended for 48 hours and can be resumed 2 days after the radiopaque examination, if the renal function and creatinine clearance remain normal.

Are there additional (non-antihyperglycemic) effects of Metformin?

Along with the hypoglycemic effect, Metformin has a number of other metabolic effects, including an effect on fat metabolism.

Metformin has the ability to reduce the oxidation of free fatty acids by 10-30 %. By reducing the concentration of free fatty acids, it not only improves insulin sensitivity, but also helps to correct impaired insulin secretion, reducing lipotoxicity. Treatment with Metformin is accompanied by a decrease in the concentration of triglycerides (by 10-20 %) and, as a result, a decrease in hepatic synthesis, an increase in the clearance of lipoproteins very low densities. In addition, Metformin increases the concentration of high-density anti-atherogenic lipoproteins. It is also known that Metformin has its own additional cardioprotective mechanisms of action, among which there are improvements in endothelial function, effects on hemostasis, oxidative stress, protein glycosylation and other cellular processes underlying the progression of atherosclerosis.

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Myth 5 - The use of insulin in type 2 diabetes increases blood pressure, increases body weight and leads to the development of vascular atherosclerosis.
Modern clinical studies prove that the introduction of insulin does not increase blood pressure and does not lead to the development of vascular atherosclerosis.
It has been proved that effective control of blood glucose levels significantly exceeds the negative consequences of possible weight gain in terms of its beneficial effect.

Metformin outside the treatment of type 2 diabetes

Polycystic ovary syndrome is a problem of 5-10 % of women of reproductive age and one of the most common causes of infertility. In addition, polycystic ovary syndrome is associated with the risk of cardiovascular complications due to severe insulin resistance. According to data for example, when using Metformin in this category of patients, there is a decrease in the level of testosterone, Androstenedione, dihydroepiandrosterone sulfate in the blood serum in comparison with placebo. Currently, Metformin is not included in the international standards of medical care for this disease due to the still insufficient and ambiguous evidence base, but the convincing results of a number of clinical studies have led to the fact that in some European countries and in the United States in recent years, their own recommendations for prescribing Metformin to patients with polycystic ovarian syndrome, especially women with obesity and clinical manifestations of insulin resistance.

One of the most common pathological conditions currently associated with insulin resistance and the associated risk of cardiovascular complications is non-alcoholic steatohepatosis. There is evidence of a significant decrease in body mass index, plasma insulin and C-peptide levels, insulin resistance, and normalization of ALT and AST levels during 6 months of treatment with Metformin compared to placebo.

Metformin use in children and adolescents

Speaking about the spread of type 2 diabetes in the world, we must not forget that the proportion of children and adolescents is steadily growing. In the United States, according to recent data, there are about 0.2–0.4 % of adolescents aged 12-19 years who suffer from type 2 diabetes.

It is obvious that in this category of individuals, the normalization of carbohydrate metabolism should be made as quickly as possible in order to reduce the likelihood of developing late complications of the disease at a young age. In addition, an additional adverse factor contributing to the development of type 2 diabetes in children and adolescents, along with the classic (high-calorie diet, obesity, low physical activity, genetic factors and it is actually physiological (puberty) insulin resistance. And in this situation, Metformin has found its use as a medication whose main mechanism of action is to reduce insulin resistance.

Currently, the medication is recommended for use in adolescents and children over 10 years of age with type 2 diabetes in Europe and the maximum dose is 2000 mg/day, either as monotherapy or in combination with insulin.

In summary, I would like to emphasize the following features of Metformin, which allowed it to take a leading place in the treatment of type 2 diabetes:

  • Good glycemic reduction (-1.5 % HbA1c);
  • Good tolerability;
  • Absence of hypoglycemia in monotherapy;
  • Despite the effect on the absorption of vitamin B12, long-term therapy with Metformin practically does not lead to anemia;
  • Neutrality in relation to weight gain or a mild decrease in it;
  • Data from UKPDS in reducing cardiovascular disorders in diabetes mellitus of the 2nd type;
  • High safety in terms of the risk of developing lactate acidosis.

Dear readers, we do not promote self-medication do not self-medicate, this page describes General information, before changing any medication, be sure to consult a doctor. Take care of yourself and your family and be healthy!