Glibenclamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreatic beta cells. In addition glibenclamide produces a mild diuresis by enhancement of renal free water clearance.

As an adjunct to diet to lower the blood glucose in patients with type II diabetes mellitus whose hyperglycemia can not be satisfactory controlled by diet alone.

All sulfonylureas are capable of producing severe hypoglycemia. Renal or hepatic insufficiency may cause elevated drug levels of glibenclamide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemia.

The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including NSAID, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probencid, coumarins, MAOs, and beta adrenergic blocking agents.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, OCPs, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid.

Hypoglycemia; cholestatic jaundice and hepatitis may occur rarely; Gastrointestinal disturbances eg, nausea, epigastric fullness, and heartburn are the most common reaction; Dermatologic reactions; hematologic reactions eg, Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia; Metabolic reactions; hyponatremia.

The usual initial dose in type II diabetes mellitus is 2.5 to 5 mg daily with breakfast, adjusted every 7 days by increments of 2.5 mg daily up to 15 mg daily. Although increasing the dose above 15 mg is unlikely to produce further benefit, doses of up to 20 mg daily have been given. Doses greater than 10 mg daily may be given in 2 divided doses.
Because of the relatively long duration of action of glibenclamide, it is best avoided in the elderly.