Metformin was introduced into medicine in the 20th century. Despite previous controversy about it, it is now the "gold standard" in the treatment of type 2 diabetes. Clinicians are still discovering its application, and recent discoveries have broadened the reimbursement indications of metformin. Check the action of this substance!

Metformin - action

Metforminbelongs to the group of drugs that lower blood glucose levels.The action of metformin is based on 3 mechanisms:

  1. metformin affectshepatic glucose production in the bodyby inhibiting gluconeogenesis and glycogenolysis. These processes increase blood glucose levels. Their inhibition has the opposite effect, which is desirable in the treatment of diabetes.
  2. metforminincreases the sensitivity of tissues to insulin.Increases the uptake of glucose by these tissues, and thus reduces blood sugar levels. It is especially important to increase the insulin sensitivity of skeletal muscles, heart, liver and adipose tissue,
  3. metforminreduces the absorption of glucose and other sugars in the intestine .

This action causes metformin to reduce fasting and postprandial glycemia in diabetics and to reduce the amount of insulin produced by the pancreas.

Contrary to other hypoglycaemic drugs, metformindoes not directly affect insulin secretion . This makes it safer than other drugs for diabetics, as it does not cause hypoglycaemia. The state of lowered blood sugar can only occur when the patient is taking other antidiabetic drugs or insulin therapy at the same time, or when the patient drinks alcohol.

Metformin causes weight loss in some patients by reducing insulin requirements . . This effect is very desirable, in particular when treating obese patients. There has been a decrease in BMI in patients, especially those with increased body weight. Unfortunately, this does not apply to all patients and usually the weight loss effect is exacerbated by the change in eating habits by the patient.

Metformin has a positive effect on the lipid profile. Decreases in total cholesterol, LDL and triglyceride levels have been reported in patients during long-term therapy.

Saysaboutcardioprotective properties of metformin. Researchers noticed improvements in vascular function and structure following administration of the drug to patients.

An anti-inflammatory effect of metformin as manifested by a reduction in the amount of C-reactive protein was also noted in diabetics participating in clinical trials.

The drug in question also has apreventive effect against the further development of diabetesin people with pre-diabetes. The following effects of metformin therapy have been documented in type 2 diabetes mellitus with obesity:

  • mortality decrease,
  • decline in deaths from diabetes,
  • fewer episodes of heart attacks.

The research results were documented by the UKPDS (United Kingdom Perspective Diabetes Study) in 1998.

Metformin - indications

Currently, metformin is the first drug to be introduced into thetreatment of newly diagnosed type 2 diabetes . It is also used as a pre-diabetes medication that slows disease progression and helps the patient achieve better results when combined with exercise and diet.

Metformincan be used alone or with other medications.Often used with sulfonylureas or insulin. If the patient is prescribed multi-drug therapy, the diabetologist should warn the patient about the risk of hypoglycaemia and teach the patient how to recognize this condition. The specialist should also encourage the patient to measure blood glucose as often as possible.

Researchers agree that metformin can be used to treat other disorders that are associated with increased insulin resistance.

The treatment of polycystic ovary syndrome has been added to the reimbursement indications of metforminIt has been proven that the combination of clomiphene and metformin in patients with overweight polycystic ovary syndrome gives a better therapeutic effect than treatment with clomiphene alone or the solution surgical. The positive therapeutic effect of metformin in this situation is argued by the researchers with the very etiology of polycystic ovary syndrome. In overweight patients, an increase in insulin resistance is observed, the body is forced to increase insulin production in order to maintain proper carbohydrate metabolism. High insulin levels increase the production of androgens, including testosterone. This is what causes the clinical symptoms of polycystic ovary syndrome. The effect of metformin treatment is:

  • increase in the frequency of ovulation in treated women,
  • improved cycle regularity,
  • reduction of hyperandrogenism,
  • increased fertility,
  • to facilitateimplantation of the egg in the uterus,
  • additionally, clinicians noticed weight loss in patients.

Currently, there is a dispute in the world of diabetology about the legitimacy of using metformin in type 1 diabetics. Despite the fact that metformin does not affect insulin secretion, which is practically non-existent in type 1 diabetics, it influences insulin resistance in diabetic tissues. Low sensitivity to this hormone affects both type 2 and type 1 diabetics. In these patients, weight gain increases the tissue demand for insulin, which forces the patient to increase insulin doses and more frequent injections. Increased insulin resistance impedes the control of type 1 diabetes, and therefore the addition of metformin to their insulin therapy was considered. Positive effects of such a combination have been observed in small-scale studies.

Additionally, metforminmay help to combat the "dawn hyperglycemia effect"in this group of patients. Decreased absorption of glucose into the blood from the gut also lowers postprandial glucose levels. The arguments against introducing the drug in question into insulin therapy are the increased risk of hypoglycaemia and the development of lactic acidosis when metformin is used with insulin.

Read also: First symptoms of diabetes. Check if you have them too

Metformin - dosage

The typical treatment regimen of metformin is to administer the lowest dose initially and then gradually increase it. The smallest dose of meformin available on the market is500 mg and this is the dose that starts thetherapy. While taking the drug, the patient is obliged to control glycaemia and after 10-15 days the dose is adjusted.

If the metformin dose of 500 mg is unsuccessful, it is increased to 750 mg, then 1 g. The maximum dose is 2 g. The extended-release formulation is usually taken once daily, while the immediate-release tablets are usually taken two times a day. This gradual increase in dose increases the body's tolerance to the drug and reduces its side effects.

Metformin - contraindications

The contraindications of metformin includehypersensitivity to the active substanceor any excipients present in the drug. Metformin cannot be prescribed if the patient has ketoacidosis or is in a pre-coma.

Contraindication is also the use of metformin in patients with renal failureor impaired renal functionci (where creatinine clearance is<60 ml/min). Do powyższego tyczą się również ostre stany chorobowe, których następstwem mogą być zaburzenia w funkcjonowaniu nerek, są to: odwodnienie, ciężkie zakażenie lub wstrząs.

The drug cannot be used in states of heart failure, failureor a recent heart attack. These conditions are characterized by increased tissue hypoxia, and during these conditions the administration of metformin is prohibited.

Do not take the drug withliver failureoralcohol poisoning . Patients suffering from alcoholism should not take metformin.

Metformin - precautions

A particularly dangerous condition that may occur with metformin is lactic acidosis . This is not a common side effect, but without reacting quickly enough, it could be fatal. This complication may occur as a result of metformin accumulation in the body. Kidney failure significantly increases the risk of developing lactic acidosis.Other risk factors include:

  • uncontrolled diabetes,
  • ketosis,
  • starving yourself,
  • alcohol abuse,
  • liver failure,
  • conditions associated with increased tissue hypoxia.

The addition of metformin to the treatment of elderly people already taking antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs should be performed with caution, as the renal function of these patients may be impaired. Laboratory tests should be performed to rule out the possibility of acidosis before starting treatment with this drug.

The intravenous administration of iodinated contrast media for radiological examinations may result in patient renal failure. Therefore, metformin should be discontinued during the study and treatment continued after 48 hours. In order to determine the appropriate therapy strategy in this case, it is best to ask the attending physician about the details of the procedure.

Metformin is not recommended in pregnant and lactating women. Clinical studies in animals are not conclusive. Pregnant, diabetic and nursing women should only use insulin therapy during pregnancy and be under the constant supervision of a diabetologist.

Read also: Creatinine - norms in blood tests. Low and high creatinine levels. How to read the result?

Metformin - side effects

Despite its characteristic side effects,metformin is a drug with a relatively high safety profile .

The most commonly reported side effects, especially at initiation of therapy, are:

  • nausea,
  • vomiting,
  • diarrhea,
  • loss of appetite.

These symptoms resolve spontaneously in most patients during treatment or drug discontinuation.

In diabeticstaking metformin, a very common occurrence isa decrease in the absorption of vitamin B12 . This information is especially important for patients with megaloblastic anemia. There are preparations available on the market specially designed to supplement vitamin B12 deficiency in these patients.

Taste disturbances may appear frequently, manifested bymetallic aftertasteinmouth .

Hepatic dysfunction is very rarely observed in patients. In order to properly control the safety of the therapy, liver enzymes should be tested periodically.

There may beskin reactions, possibly allergic . In this case, the drug should be discontinued.

Sources

  • K. Strojek, M. Wróbel, A. Szymborska-Kajanek, D. Rokicka,Metformin - new reimbursement indications,access: June 28, 2021
  • Artur J. Jakimiuk,The role of metformin in the treatment of polycystic ovary syndrome (PCOS),accessed: June 28, 2021
  • A. Zawada, B. Wierusz-Wysocka,The use of metformin in type 1 diabetes mellitus , accessed on June 28, 2021
  • Summary of Product Characteristics for Metformin, accessed June 28, 2021.

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