Pharmacological action
Oral hypoglycemic drug – a third-generation sulfonylurea derivative.
Glimepiride reduces blood glucose concentrations mainly by stimulating insulin release from pancreatic β-cells. Its effect is primarily associated with improving the ability of pancreatic β-cells to respond to physiological stimulation with glucose. Compared with glibenclamide, glimepiride in low doses causes the release of less insulin while achieving approximately the same decrease in blood glucose concentration. This fact indicates that glimepiride has extrapancreatic hypoglycemic effects (increased tissue sensitivity to insulin and insulinomimetic effect).
Insulin secretion. Like all other sulfonylurea derivatives, glimepiride regulates insulin secretion by interacting with ATP-sensitive potassium channels on β-cell membranes. Unlike other sulfonylurea derivatives, glimepiride selectively binds to a protein with a molecular weight of 65 kilodaltons, located in the membranes of pancreatic β-cells. This interaction of glimepiride with the protein that binds to it regulates the opening or closing of ATP-sensitive potassium channels.
Glimepiride closes potassium channels. This causes depolarization of β-cells and leads to the opening of voltage-sensitive calcium channels and the entry of calcium into the cell. As a result, an increase in the intracellular calcium concentration activates insulin secretion by exocytosis.
Glimepiride binds to and is released from its binding protein much faster and, accordingly, more often than glibenclamide. It is assumed that this property of the high rate of exchange of glimepiride with the protein that binds to it causes its pronounced effect of sensitizing β-cells to glucose and protecting them from desensitization and premature exhaustion.
The effect of increasing tissue sensitivity to insulin. Glimepiride enhances the effects of insulin on glucose uptake by peripheral tissues.
Insulin-mimetic effect. Glimepiride has effects similar to the effects of insulin on glucose uptake by peripheral tissues and glucose release from the liver.
Glucose uptake by peripheral tissues is carried out by its transport into muscle cells and adipocytes. Glimepiride directly increases the number of glucose-transporting molecules in the plasma membranes of muscle cells and adipocytes. Increased glucose influx into cells activates glycosylphosphatidylinositol-specific phospholipase C. As a result, the intracellular calcium concentration decreases, causing a decrease in protein kinase A activity, which in turn stimulates glucose metabolism.
Glimepiride inhibits glucose release from the liver by increasing the concentration of fructose-2,6-bisphosphate, which inhibits gluconeogenesis.
Effect on platelet aggregation. Glimepiride reduces platelet aggregation in vitro and in vivo. This effect is apparently associated with selective inhibition of COX, which is responsible for the formation of thromboxane A, an important endogenous factor in platelet aggregation.
Antiatherogenic effect. Glimepiride helps normalize lipid levels, reduces the level of malonic aldehyde in the blood, which leads to a significant decrease in lipid peroxidation. In animals, glimepiride leads to a significant decrease in the formation of atherosclerotic plaques. Reduction of oxidative stress, which is constantly present in patients with type 2 diabetes. Glimepiride increases the level of endogenous α-tocopherol, the activity of catalase, glutathione peroxidase and superoxide dismutase.
Cardiovascular effects. Sulfonylurea derivatives also affect the cardiovascular system through ATP-sensitive potassium channels. Compared with traditional sulfonylurea derivatives, glimepiride has a significantly smaller effect on the cardiovascular system, which can be explained by the specific nature of its interaction with the ATP-sensitive potassium channel protein that binds to it.
In healthy volunteers, the minimum effective dose of glimepiride is 0.6 mg. The effect of glimepiride is dose-dependent and reproducible. The physiological response to physical activity (decreased insulin secretion) is preserved when taking glimepiride.
There are no significant differences in effect depending on whether the drug was taken 30 minutes before a meal or immediately before a meal. In patients with diabetes mellitus, sufficient metabolic control can be achieved for 24 hours with a single dose of the drug. Moreover, in a clinical study, sufficient metabolic control was also achieved in 12 of 16 patients with renal insufficiency (CC 4-79 ml/min).
Combination therapy with metformin. In patients with insufficient metabolic control when using the maximum dose of glimepiride, combination therapy with glimepiride and metformin can be initiated. In two studies, improved metabolic control was demonstrated with combination therapy compared with that with treatment with each of these drugs separately.
Combination therapy with insulin. In patients with insufficient metabolic control when taking glimepiride in maximum doses, concomitant insulin therapy can be initiated. According to the results of two studies, the combination achieved the same improvement in metabolic control as insulin alone. However, a lower insulin dose is required in combination therapy.
Indications for Amaryl®
Type 2 diabetes mellitus (as monotherapy or in combination therapy with metformin or insulin).
Contraindications for use
Type 1 diabetes mellitus;
Diabetic ketoacidosis, diabetic precoma and coma;
Severe liver dysfunction (no clinical experience with use);
Severe renal dysfunction, including patients on hemodialysis (no clinical experience with use);
Pregnancy;
Lactation (breastfeeding);
Childhood (no clinical experience with use);
Rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption;
Hypersensitivity to the components of the drug;
hypersensitivity to other sulfonylurea derivatives and sulfonamide drugs (risk of developing hypersensitivity reactions).
Warning: Always consult a doctor before using medications.
