Metformin tablets for weight loss: how to take correctly?

How does metformin help you lose weight?

Initially, the product was developed for patients with diabetes. Then, research revealed indications such as overweight and obesity.

The medicine belongs to the group of biguanides. It has a hypoglycemic effect and does not stimulate insulin secretion. Taking metformin causes the following changes:

• decreased glucose absorption;
• decrease in basal blood sugar levels;
• increased sensitivity of peripheral receptors to insulin;
• stimulation of glucose deposition;
• inhibition of sugar synthesis from fats and proteins;
• increased high density lipoproteins;
• reducing the amount of cholesterol.

Thus, the medicine leads to optimal glucose absorption and prevents insulin from being produced in large quantities. This allows you to get rid of excess fat. The pills also reduce appetite. Metformin is successfully used for metabolic syndrome and for the prevention of aging.

Metformin in the treatment of metabolic disorders: glycemic and non-glycemic effects

Endocrinology: news, opinions, training. 2021. No. 2. pp. 22-27.

Metformin has been used in clinical practice as a hypoglycemic agent for about 60 years, but for clinicians, the use of this drug for the correction of other components of the metabolic syndrome, as well as in the treatment of conditions associated with it, is of significant interest.

Cellular and molecular mechanisms of action of metformin

It is currently known that the hypoglycemic effect of metformin is associated primarily with highly specific inhibition of complex 1 of the mitochondrial respiratory chain [1], however, the pleiotropic effects of the drug are due to another mechanism: activation of AMP-activated protein kinase (AMPK). Activation of AMPK switches cells from an anabolic to a catabolic state by closing synthetic ATP consumption pathways and restoring energy balance.

This regulatory mechanism involves AMPK phosphorylation of key metabolic enzymes and transcription factors activators of gene expression modulation. As a result, the synthesis of glucose, lipids and proteins, as well as cell growth, is suppressed and the oxidation of glucose and fatty acids is simultaneously stimulated [1].

Metformin exhibits the greatest activity in hepatocytes, interacting with the organic cation transporter-1, due to which metformin accumulates in the liver in larger quantities than in other tissues - its level exceeds 100 mmol/kg in the periportal zone. Apparently, this is precisely what determines the positive effect of the drug on the functional state of the liver in patients with non-alcoholic steatohepatitis [2].

Metformin in the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is currently a global health problem. In developed countries, signs of non-alcoholic steatohepatitis are detected in 20-30% of the adult population [3]. It should be emphasized that the concept of NAFLD includes a wide range of histological abnormalities from fatty liver to hepatocellular carcinoma (Fig. 1) [4].

The development of NAFLD is closely associated with a number of metabolic diseases. Obesity and impaired glucose tolerance (IGT) in patients with fatty hepatosis are 5.3 and 3.6 times more common, respectively, than in the general population [5]. Since insulin resistance plays a key role in the pathogenesis of NAFLD, the use of insulin sensitizers, in particular metformin, as part of complex therapy for this pathology seems very promising. In hepatocytes, metformin suppresses lipogenesis and stimulates fatty acid oxidation, suppressing palmitate production. This leads to a decrease in the severity of fatty liver disease and, as a rule, reduces the anti-inflammatory activation of macrophages caused by excess fat deposition. In both hepatocytes and macrophages, metformin inhibits low-grade inflammation by suppressing the production of proinflammatory cytokines (Fig. 2).

A recent meta-analysis of 9 studies, including 417 patients with NAFLD, showed that patients treated with metformin had improvements in alanine and aspartate aminotransferase levels: -8.12 U/L (p = 0.03) and -4.52 U/L ( p=0.04), which reliably indicates an improvement in the functional state of the liver [6]. Thus, the addition of metformin to the complex therapy of NAFLD has the potential to improve the course of the disease.

Metformin in weight loss therapy

It is now known that the most significant reduction in body weight while taking metformin is observed in patients with severe insulin resistance. Apparently, the basis for weight loss during metformin therapy, in addition to improving insulin sensitivity, is a decrease in intestinal glucose absorption and a decrease in serum leptin levels [7]. In addition, the ability of metformin to reduce body weight is partly due to the anorexigenic effect of the drug, which is associated with its effect on the incretin system. Recently published by A. Maida et al. Evidence suggests that metformin significantly increases plasma levels of glucagon-like peptide-1 (GLP-1) and induces pancreatic islet incretin receptor gene expression through a mechanism involving peroxisome proliferator-activated receptor alpha (PPARa) [8]. S. Kappe et al. showed that metformin improves the secretion of GLP-1 in GLP-producing cells in
vitro
[9], therefore, increased levels of GLP-1 are observed in the plasma of patients receiving long-term metformin.

According to the results of a meta-analysis of 31 studies conducted from 1966 to 2006, taking metformin is accompanied by an average reduction in body weight of 5.3% over an average study duration of 1.8 years [10]. At the same time, metformin promotes the healthy distribution of fatty tissue in the body. Thus, in a study using radionuclide scanning, it was shown that after 6 months of treatment with metformin, body weight decreased by 4%, adipose tissue mass - by 9%, visceral fat volume - by 15%, subcutaneous fat mass decreased by 7%, with In this case, no decrease in muscle mass was recorded [11].

Metformin in the prevention of type 2 diabetes mellitus

For the first time, the assumption that type 2 diabetes mellitus (T2DM) can be prevented or slowed down its development in people at high risk was confirmed within the framework of the T2DM Diabetes Prevention Study (DPP, 2002) [12].

In the context of this study, the importance of a sedentary lifestyle and excess body weight in the development of insulin resistance and early carbohydrate metabolism disorders with subsequent progression to T2DM was convincingly demonstrated. The DPP study showed that treatment with metformin 850 mg twice daily could slow or prevent the development of T2DM by 31% in people with IGT, especially those with excess body weight [13]. The 10-year follow-up (DPPOS) after randomization to DPP showed that those in the lifestyle intervention group experienced initial weight loss followed by weight gain, and most patients in the metformin group maintained their weight loss. The most frequent development of T2DM in subsequent years was observed in the group of active lifestyle changes - 5.9 per 100 patient-years. In the metformin group, the average incidence of T2DM was 4.9, in the placebo group -5.6 per 100 patient-years (Fig. 3) [14].

In another study, in patients with metabolic syndrome and a high risk of developing T2DM (average 3-year risk - 60%), metformin at a dose of 850 mg twice a day reduced the absolute risk by 20% over 3 years of observation [15].

Metformin in the treatment of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is also a common endocrine pathology and one of the common causes of anovulatory infertility in women. In most cases, PCOS is associated with severe metabolic disorders. It is now recognized that its development is based on impaired insulin sensitivity. Although the molecular mechanisms of insulin resistance in PCOS are not fully understood, excess insulin-independent serine phosphorylation of the β-subunit of the insulin receptor was found in some patients, and therefore insulin sensitizers have been proposed for the treatment of such variants of PCOS.

The positive effects of metformin are primarily due to a decrease in serum levels of insulin, which stimulates a number of enzymes involved in steroidogenesis: CYP17, 3β-HSD and StAR protein. By improving insulin sensitivity, metformin reduces CYP17 activity. In addition, metformin suppresses the production of androstenedione in the theca cells of the ovaries and reduces the FSH-stimulated activity of the enzymes 3β-HSD, StAR, and CYP11A1 [16].

Metformin has been used as a therapeutic option for the treatment of PCOS since 1994. Since then, more than 100 randomized clinical trials have been conducted on the effectiveness and safety of its use. A meta-analysis of 31 clinical trials showed that treatment with metformin in PCOS patients stimulates ovulation, improves menstrual cycles, reduces serum androgen levels, and reduces the severity of hirsutism [17]. In another study, metformin therapy was associated with clinically significant changes in the levels of follicle-stimulating (p>0.01) and luteinizing hormones (p>0.001), as well as vistafine (p>0.001) [18]. In a recent meta-analysis of 433 women with PCOS, metformin significantly reduced C-reactive protein levels [19].

According to currently available data, taking metformin most often significantly improves clinical outcomes in patients with PCOS, but does not always lead to normalization of laboratory metabolic and hormonal parameters [20].

In particular, in women with obesity and PCOS, the use of metformin in combination with lifestyle changes and the prescription of clomiphene reliably leads to a decrease in ovarian volume, restoration of menstrual function, ovulation and fertility. Interestingly, when taking metformin, the risk of premature termination of pregnancy is significantly reduced in women with a high risk of intra- and neonatal complications. In addition, metformin affects factors that increase the risk of abortion: the expression of the androgen receptor in the endometrium, PAI-1 and plasma endothelin-1 [21].

According to the recommendations of the Androgen Excess Society, all women with PCOS, regardless of their body weight, undergo a glucose tolerance test immediately after diagnosis and every subsequent 2 years to timely detect early disorders of carbohydrate metabolism. According to the recommendations of the American Association of Clinical Endocrinologists, metformin should be used as the drug of choice in the treatment of PCOS [22].

Metformin: antioxidant properties and vascular effects

Metabolic syndrome is invariably accompanied by a number of different systemic disorders and pathophysiological defects, which traditionally include oxidative stress, chronic nonspecific inflammation, atherogenic dyslipidemia and hemocoagulation disorders. Metformin has the ability to neutralize or significantly reduce the severity of these disorders, primarily reducing the adverse effect of oxidative stress on the development of vascular complications. Metformin can directly intercept free radicals or indirectly reduce their content by inhibiting the intracellular formation of oxygen superoxide radical, the main source of which is the oxidation of NADPH, activation of the AMPK system and acceleration of fatty acid metabolism [23].

It has been suggested that by inhibiting NF-kB, metformin has the potential to suppress the inflammatory response. This may be partly due to the improvement in cardiovascular outcomes with the drug [24]. In addition, metformin reduces apoptosis of pancreatic β-cells by eliminating glucose and lipotoxicity [25]. Metformin reduces the systemic production of tissue plasminogen activator, von Willebrand factor and plasminogen activator inhibitor [26]. Moreover, metformin significantly improves the condition of the endothelium even in patients without diabetes [27].

Another long-known property of the drug is its lipid-lowering effect. According to a 2004 meta-analysis, metformin reduces total cholesterol levels by an average of 0.26 mmol/L, low-density lipoproteins by 0.22 mmol/L, and triglycerides by 0.13 mmol/L [28].

Today, despite a significant number of new antidiabetic drugs, metformin occupies a central place in the treatment of metabolic disorders. The scope of its application is not limited to the treatment of T2DM on a long-term basis, but involves its use for the correction of early disorders of carbohydrate metabolism. In addition, metformin has the potential to improve the course of various pathological conditions associated with insulin resistance, including NAFLD and PCOS, which may soon lead to an expansion of indications for its use.

Information about authors

Kondratieva Larisa Vasilievna

Degree/grade: Candidate of Medical Sciences

Position: Associate Professor, Department of Endocrinology

Place of work: Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuing Professional Education" of the Ministry of Health of Russia, Moscow

e-mail

Ivanova Lyudmila Pavlovna

Degree/grade: Candidate of Medical Sciences

Position: Associate Professor, Department of Endocrinology

Place of work: Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuing Professional Education" of the Ministry of Health of Russia, Moscow

e-mail

Unique properties of the drug

The drug is being studied in many countries around the world. The Internet is replete with information about its unique properties. The following statements are relevant today:

• Metformin has been successfully used in the field of oncology and vascular diseases.
• A decrease in glucose occurs approximately 7-10 days after the first dose.
• The drug is combined with insulin and maninil.
• The pills promote the growth of new neurons in the brain.
• Metformin reduces the risk of death from diabetic complications by 30%.
• The medicine stabilizes weight, the excess of which is caused by antipsychotic drugs.
• Sometimes the drug is used in the absence of ovulation in the case of a diagnosis of infertility.
• Taking metformin helps create new memories. Therefore, the tablets can be taken for Alzheimer's disease.

Experts continue to debate the issue of weight loss with metformin. It cannot be perceived as an ideal anti-aging remedy. The main indication for the tablets remains type 2 diabetes.

General information about the drug for weight loss

Metformin is a compound that lowers blood sugar levels. The drug is intended for the treatment of type 2 diabetes mellitus.

The product allows healthy people to lose weight even when diet and exercise do not help.

If you follow the treatment regimen, the risk of side effects is minimal.

Release form

Pharmaceutical companies produce Metformin in the form of tablets of 10, 30, 60, 100 or 120 pieces.
packaged. The content of the active substance in 1 tablet is 500 mg, 800 mg or 1000 mg.

Properties of metformin.

Operating principle

Taking the drug leads to a decrease in the concentration of sugar in the bloodstream. At the same time, the level of hemoglobin decreases, and all metabolic processes in the body take place in such a way that there is no excess glucose. Insulin production by pancreatic cells occurs as usual.

If a person has diabetes, then while taking the drug, the composition of the plasma is normalized, cholesterol levels are reduced, and adenosine triphosphoric acid is produced in small quantities.

The concentration of glucose in the blood returns to normal due to the following processes:

• in non-carbohydrate compounds, the processes of glucose production stop;
• body cells actively neutralize excess glucose;
• tissues become more sensitive to insulin;
• glucose is slowly absorbed by the small intestine.

The drug is quickly absorbed into the walls of the gastrointestinal tract, its full bioavailability in the blood occurs 2 hours after use.
While taking Metformin, the absorption of carbohydrates is blocked, and there is no feeling of hunger or discomfort. The product does not have a fat burning effect. The main purpose of use is to reduce appetite.

Course duration

The course can last no more than 20 days.
After this, they take a break for 30-60 days so that the body does not get used to the drug. But even during withdrawal, diet and physical activity are recommended. You should not take the drug for longer than the specified period, because after 20 days Metformin does not provide the desired weight loss effect. Long-term use of tablets helps the body become accustomed to the active substance.

How to take metformin

The drug is available in tablets with different dosages:

• 1000 mg;
• 850 mg;
• 750 mg;
• 500 mg.

Initially, it is permissible to take 500 mg per day. Take tablets after or during meals 2-3 times a day. After a couple of weeks, the dose is increased based on glucose levels. The maximum amount per day is 2000 mg.

The duration of use depends on the purpose. Metformin is usually discontinued immediately after weight loss. Recommended course – 3 weeks. After this, you need to take a month's break so that the body does not get used to the active substance. In addition, the main component can accumulate in the kidneys, muscles and liver.

The drug is not prescribed together with medications containing iodine. While losing weight, it is prohibited to drink alcohol-containing drinks. It is not recommended to combine the medicine with glucocorticosteroid hormones and diuretics.

It is important to monitor your blood fluid levels and get tested periodically. This is because metformin can reduce vitamin B12 levels. A doctor's prescription is not required to purchase the medication.

Clinical trial result

In addition to reviews from those losing weight, it is worth studying the opinions of people who participated in clinical trials of the drug. American experts selected 2 thousand overweight volunteers. They were divided into 3 groups. The first lost weight through diet and exercise, the second took metformin, the third combined taking pills with sports and changes in nutritional diet. A month later the result was as follows:

• Group 1 – minus 5 kg;
• Group 2 – minus 3 kg;
• Group 3 – minus 7 kg.

The study has proven that you should not rely entirely on medicine. It is important to combine all effective methods of losing weight.

Experts' opinions

Nutritionists warn that increasing the daily dosage can have serious consequences. There is a risk of being poisoned by lactic acidosis. As a result, the person will experience nausea and vomiting. In this case, you need to call a doctor. A severe overdose can cause coma. Therefore, it is important to monitor the amount of substance taken.

Experts advise losing weight on metformin and following the following rules:

• It is important to exclude sweets and canned flour dishes from the menu.
• You should include oatmeal, chicken fillet, kefir, cottage cheese and celery in your diet.
• Daily calorie intake should be reduced to 1200 calories.
• You need to drink 2 liters of water per day.
• Every day you need to do exercises.

Many doctors recommend taking pills for people whose weight reaches 90-100 kg. If a person has 3-5 extra pounds, you can do without metformin and rely more on diet and exercise. In any case, you will need to consult a doctor. It is not necessary to make an appointment with an endocrinologist. A therapist can advise on this issue.

Metformin analogues

If metformin is not suitable for the patient or shows insufficient effectiveness, analogues of the drug are taken:

• Bagomet . The drug is similar to metformin in terms of limitations and side effects. It helps reduce the absorption of glucose by the intestine.
• Formetin . Contains metformin hydrochloride. Prohibited for use by children and pregnant women.
• Novoformin . The therapeutic component is metformin hydrochloride. The medicine has similar limitations.
• Merifatin . Has the same active substance. Sometimes used in children's practice.
• Gliformin . The tablets do not differ from their analogues in pharmacokinetics, contraindications and side effects.
• Siofor . The foreign drug should not be used by pregnant and nursing mothers.
• Glucophage . Available in tablet form. Use with care in nursing patients.

The price of metformin varies between 106-543 rubles.

Side effects

Manufacturers talk about the complete safety of the drug, but you should not believe this one hundred percent. This is a medicine that, like all other medicines, tends to cause side effects. Thanks to research by doctors, it was found that the most dangerous moment for the development of side effects is the first days. Symptoms of developed reactions go away on their own, but in severe cases it is better to seek help from specialists.

Possible consequences:

• Headache;
• Spasmodic pain in the abdominal area;
• Nausea;
• Anemia;
• Development of impotence;
• Lactic acidosis;
• Hives;
• Gastrointestinal disorders, which are manifested by vomiting, diarrhea and loss of appetite.

Under the influence of metformin, the body’s normal activities are disrupted. Lactic acidosis is the most life-threatening side effect. The cause of the disease is a violation of lactic acid metabolism and its further, uncontrolled accumulation.

Clinical picture of lactic acidosis:

• Nausea;
• Vomit;
• Dizziness;
• Loss of consciousness;
• Diarrhea.

At the first appearance of such signs, immediately seek help from a doctor.

Side effects may develop in case of overdose. Women and men, in pursuit of quick weight loss results, try to increase the dosage. Some increased the permissible dose to 1500 mg per day. Lactic acidosis in this case is inevitable. And it can be fatal. Without the help of specialists, a person first falls into a coma and then dies.

Hemodialysis is considered the most effective way to combat overdose. After this, complex symptomatic therapy is carried out.