Glimepiride, Glyburide and Glicazide Metabolization
The sulfonylureas have an acute hypoglycemic effect acting on the β cells of the pancreas and stimulating the insulin secretion, and a chronic hypoglycaemic effect that is due to the potentiation of the action of insulin, through an increase in the number of receptors for insulin or its binding to them in sensitive tissues.
Sulfonylureas are the drugs of choice in patients with type II diabetes mellitus (DM2) who do not tolerate metformin and who do not have a special risk of hypoglycemia. Some patients with DM2 do not respond to the sulfonylureas (Primary Failure), it seems that in relation to the level of hyperglycemia. And some patients who work well with sulfonylureas can eventually stop responding (Secondary Failure) due to pancreatic β cells depletion or the presence of intercurrent processes (infections, stress, etc.). Sometimes the ability to respond to sulfonylureas is recovered with temporary insulinization of these patients.
Within the sulfonylureas group there is a large number of drugs among which are: glycazide, glyburide (glibenclamide), glimepiride, glipizide, tolbutamide, etc. The failures that sometimes occur in the pharmacological response between different patients may be due to several factors. Among these factors, the genetic difference between patients in those genes related to transport, interaction, insulin signaling and the metabolization by the cytochromes that bioconvert these drugs in the liver is being more relevant during the last years. This item deals with the effectiveness of glicazide, glimepiride and glyburide (or glibenclamide) associated with the presence of polymorphisms in the CYP2C9 cytochrome, which is the main enzyme that metabolizes these drugs.
Diabetes mellitus 1, pregnancy and lactation, kidney failure (gliquidone, glipizide, gliclazide and glimepiride can be prescribed in mild-moderate renal failure), adverse reactions to sulfonylureas, allergy to sulfamides and severe hepatic failure.
The risk of hypoglycemia is increased by: substances that displace sulfonylureas from albumin binding sites (such as aspirin, fibrates and trimethoprim), substances that competitively inhibit the metabolism of sulfonylureas (such as alcohol, H2-blockers and anticoagulants), substances that inhibit the urinary elimination of sulfonylureas (such as probenecid and allopurinol), substances that enhance the properties of oral hypoglycemic agents (such as alcohol and aspirin), beta-blockers and sympatholytics.
Hypoglycaemia (glyburide or glibenclamide is the sulphonylurea that produces more hypoglycaemia, more severe and longer), hematological alterations (medullar aplasia, agranulocytosis, hemolytic anemia and thrombocytopenia), skin disorders (purple, pruritus, erythema nodosum, erythema multiforme, Steven-Johnson, photosensitivity), Gastrointestinal disorders (nausea, vomiting, cholestasis), Thyroid disorders (transient subclinical hypothyroidism), renal effect (inadequate secretion of ADH (hyponatremia), diuretic effect), Diffuse pulmonary reactions (pneumonitis), Weight gain, Hyperinsulinemia .
The frequency of adverse effects is low (2-5%). The main side effect is hypoglycaemia, which has been more frequently associated with the use of long-lived sulfonylureas, such as chlorpropamide and glibenclamide. Mild-moderate hypoglycaemias occur in 14% of patients-year and severe hypoglycemia in 0.6% patients-year. Glimepiride, modified-release gliclazide and glipizide of shorter duration have less hypoglycaemia risk.
- Glimepiride (Amaryl®, Roname®)
- Gliburide or glibenclamide (Daonil®, Euglucon®, Glucolon®, Norglicem 5®)
- Glicazide (Diamicron®)
Gene or region studied