Gliclazide

Chemical compound

Gliclazide, sold under the brand name Diamicron among others, is a sulfonylurea type of anti diabetic medication, used to treat type 2 diabetes. It is taken by mouth. Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems. It is on the World Health Organization's List of Essential Medicines. It is not available for sale in the United States.

Gliclazide is used for control of hyperglycemia in gliclazide responsive diabetes mellitus of stable, mild, non ketosis prone, type 2 diabetes. It is used when diabetes cannot be controlled by proper dietary management and exercise and when metformin has already been tried. National Kidney Foundation (2012 Update) claims that Gliclazide does not require dosage up titration even in end stage kidney disease.

Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and Monitoring.

Gliclazide selectively binds to sulfonylurea receptors (SUR 1) on the surface of the pancreatic beta cells. It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors (SUR 2A) in the heart. This binding effectively closes these K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca2+ ion channels to open increasing the Ca2+ influx. The calcium can then bind to and activate calmodulin which in turn leads to exocytosis of insulin vesicles leading to insulin release. The mouse model of Maturity onset diabetes of the young (MODY) diabetes suggested that the reduced gliclazide clearance stands behind their therapeutic success in human MODY patients, but Urbanova et al. found that human MODY patients respond differently and that there was no consistent decrease in gliclazide clearance in randomly selected HNF1A MODY and HNF4A MODY patients. Its classification has been ambiguous, as literature uses it as both a first generation and second generation sulfonylurea.

According to the Biopharmaceutical Classification System (BCS), gliclazide falls under the BCS Class II drug, which is poorly soluble and highly permeable. Water solubility = 0.027mg/L
Hypoglycemic sulfonylurea, restoring first peak of insulin secretion, increasing insulin Sensitivity. No active circulating Metabolites. But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.