GLYBURIDE AND METFORMIN HYDROCHLORIDE

12.1 Mechanism of Action Glyburide primarily lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin. Metformin is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may decrease.

Contraindications

• • including diabetic ketoacidosis
• • with or without coma. Concomitant administration of bosentan [see Drug Interactions (7) ]. Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) (4
• • 5.1) Hypersensitivity to metformin or glyburide. (4) Acute or chronic metabolic acidosis
• • including diabetic ketoacidosis
• • with or without coma. (4) Concomitant administration of bosentan. (4