Gliclazide, sold under the brand name Diamicron among others, is an anti-diabetic medication used to treat diabetes mellitus type 2. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth. Gliclazide, sold under the brand name Diamicron among others, is an anti-diabetic medication used to treat diabetes mellitus type 2. It is used when dietary changes, exercise, and weight loss are not enough. It is taken by mouth. Side effect may include low blood sugar, vomiting, abdominal pain, rash, and liver problems. Use by those with significant kidney problems, liver problems, or who are pregnant is not recommended. Gliclazide is in the sulfonylurea family of medications. It works mostly by increasing the release of insulin. Gliclazide was patented in 1966 and approved for medical use in 1972. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$2.46–3.92 per month. In the United Kingdom a month of medication costs the NHS about 2.12 pounds. 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 or when insulin therapy is not appropriate.National Kidney Foundation (2012 Update) claims that Gliclazide does not require dosage uptitration even in end stage kidney disease. Hyperglycemic action may be caused by danazol, chlorpromazine, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone, alcohol, fluconazole, β-blockers, and possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo. 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 the K+ ion channels. This decreases the efflux of potassium from the cell which leads to the depolarization of the cell. This causes voltage dependent Ca++ ion channels to open increasing the Ca++ 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 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.