Description
Metformin Pharmacodynamics
Metformin belongs to the hypoglycemic agents of the biguanide group, it reduces hyperglycemia without leading to the development of hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and has no hypoglycemic effect in a healthy person. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells (especially in muscle tissue). Reduces glucose production by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays the absorption of glucose in the intestine. Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases transport capacity of all types of membrane glucose transporters.
In addition, it has a favorable effect on lipid metabolism: it reduces the concentration of total cholesterol, low-density lipoproteins and triglycerides.
While taking metformin, the patient’s body weight either remains stable or decreases moderately.
Clinical studies have also shown the effectiveness of metformin for the prevention of diabetes in patients with prediabetes with additional risk factors for obvious type 2 diabetes, in whom lifestyle changes have not allowed to achieve adequate glycemic control.
Indications
Type 2 diabetes mellitus, especially in obese patients with ineffectiveness of diet therapy and physical activity:
In adults as monotherapy or in combination with other oral hypoglycemic agents, or with insulin;
In children from 10 years of age, as monotherapy or in combination with insulin.
Prophylaxis of diabetes mellitus type 2 in patients with prediabetes with additional risk factors of development of diabetes mellitus type 2, in whom changes of life style did not allow to achieve adequate glycemic control.
Contraindications
– Hypersensitivity to metformin or any excipient of the drug;
– Diabetic ketoacidosis, diabetic precoma, coma;
– Renal insufficiency or impaired renal function (CKR less than 30 ml/min);
– acute conditions with risk of renal dysfunction: dehydration (diarrhea, vomiting), severe infectious diseases, shock;
– clinically expressed manifestations of acute or chronic diseases that may lead to the development of tissue hypoxia (including acute heart failure, chronic heart failure with unstable hemodynamic parameters, respiratory failure, acute myocardial infarction);
– major surgical operations and injuries, when insulin therapy is indicated (see section “Special Indications”);
– hepatic insufficiency, liver dysfunction;
– chronic alcoholism; acute alcohol poisoning;
– pregnancy;
– lactoacidosis (including in anamnesis);
– use for less than 48 hours before and within 48 hours after radioisotopic or radiological studies with the introduction of iodine-containing contrast agent (see section “Interaction with other medicinal products”);
– compliance with a hypocaloric diet (less than 1000 kcal/day);
– children under 10 years of age.
How to use and dosages.
- Inside.
- Adults
Monotherapy and combined therapy in combination with other oral hypoglycemic agents in type 2 diabetes mellitus:
– The usual starting dose is 500 mg or 850 mg 2-3 times daily after or during meals.
– Every 10-15 days, it is recommended that the dose be adjusted based on the results of plasma glucose concentration measurements. Slowly increasing the dose helps to reduce the number of gastrointestinal (GI) side effects.
– The maintenance dose of metformin is usually 1500-2000 mg/day. To reduce gastrointestinal side effects, the daily dose should be divided into 2-3 doses. The maximum dose is 3000 mg/day divided into three doses.
– Patients taking metformin at doses of 2000-3000 mg/day may be switched to a dose of 1000 mg. The maximum recommended dose is 3000 mg/day divided into three doses. - If switching from another hypoglycemic drug is planned: the other drug should be discontinued and Metformin should be started at the dose indicated above.
- Combination with Insulin
To achieve better blood glucose control, metformin and insulin in patients with type 2 diabetes can be used as a combination therapy. The usual starting dose of Metformin is 500 mg or 850 mg 2-3 times a day, while the dose of insulin is adjusted based on blood glucose concentrations. - Children and adolescents: In children from the age of 10 years, Metformin can be used as monotherapy or in combination with insulin. Usual starting dose is 500 mg or 850 mg once a day after or with a meal. The dose should be adjusted after 10-15 days on the basis of blood glucose concentration. The maximum daily dose is 2000 mg divided into 2-3 doses.
- Monotherapy in prediabetes.
The usual dose is 1000-1700 mg daily after or during meals, divided into 2 doses. Regular glycemic control is recommended to assess the need for further use of metformin. - Patients with renal impairment
Metformin may be used in patients with renal insufficiency with a creatinine clearance of 30-59 mL/min only if there are no conditions/risk factors that may increase the risk of lactoacidosis. - Renal function (RF) should be assessed before starting therapy with metformin and then at least once a year. In patients at increased risk of progression of renal failure and in the elderly, renal function should be monitored more frequently (every 3-6 months).
- If creatinine clearance is below 30 ml/min, the drug should be stopped immediately.
Creatinine clearance (mL/min) Maximum daily dose (divided into 2-3 doses per day) - Additional information
60-89 3000 mg - Reduction of metformin dose should be considered due to decreased renal function
45-59 2000 mg - Factors that increase the risk of lactoacidosis should be investigated before starting therapy with metformin (see “Special Precautions”).
30-44 1000 mg - The starting dose is half of the maximum daily dose.
<30 - Metformin administration is contraindicated.
Elderly patients: because of possible decrease of renal function, metformin dose should be adjusted under regular renal function monitoring (determine plasma creatinine concentration at least 2-4 times per year). - Duration of therapy
The drug should be taken daily, without interruption. If therapy is discontinued, the patient should inform the physician.
