Gliclazide
Encyclopedia
Gliclazide is an oral hypoglycemic (anti-diabetic drug
) and is classified as a sulfonylurea
. It is marketed as Glizid, Glyloc and Reclide in India and Diamicron in Canada. In the Philippines, Servier markets it as Diamicron MR, like in most countries across the world. Many generic equivalents are also available e.g. Glubitor-OD, Clizid. It is not marketed in the United States. A modified-release formulation is also marketed. Its classification has been ambiguous, as literature uses it as both a first-generation and second-generation sulfonylurea. Gliclazide was proven to protect human pancreatic beta-cells from hyperglycemia-induced apoptosis. It was also proven to have a potent antiatherogenic effect in type 2 diabetes.
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.
, 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.
Anti-diabetic drug
Anti-diabetic medications treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents...
) and is classified as a sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...
. It is marketed as Glizid, Glyloc and Reclide in India and Diamicron in Canada. In the Philippines, Servier markets it as Diamicron MR, like in most countries across the world. Many generic equivalents are also available e.g. Glubitor-OD, Clizid. It is not marketed in the United States. A modified-release formulation is also marketed. Its classification has been ambiguous, as literature uses it as both a first-generation and second-generation sulfonylurea. Gliclazide was proven to protect human pancreatic beta-cells from hyperglycemia-induced apoptosis. It was also proven to have a potent antiatherogenic effect in type 2 diabetes.
Form and composition
Each immediate-release tablet contains 80 mg. Modified release formulations contain 30 mg and 60 mg of gliclazide. In the Philippines, all three formulations are available.Indication
Gliclazide is used for control of hyperglycemia in gliclazide-responsive diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
of stable, mild, non-ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
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.
Mode of action
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 exocystosis of insulin vesicles leading to insulin release.Dosage
The dosage for the 80 mg formulation is 40 to 320 mg daily in two divided doses, while the 30 mg and 60 mg modified release formulation may be given at a dose of 30 to 120 mg once daily at breakfast.Properties
- Hypoglycemic sulfonylurea, restoring first peak of insulin secretion, increasing insulin sensitivity.
- Glycemia-independent hemovascular effects, antioxidant effect.
- No active circulating metabolites.
Contraindications
- Type 1 diabetes
- Hypersensitivity to sulfonylureas
- Severe renal or hepatic failure
- Pregnancy and lactation
- MiconazoleMiconazoleMiconazole is an imidazole antifungal agent, developed by Janssen Pharmaceutica, commonly applied topically to the skin or to mucus membranes to cure fungal infections. It works by inhibiting the synthesis of ergosterol, a critical component of fungal cell membranes...
coprescription
Metabolism
Gliclazide undergoes extensive metabolism to several inactive metabolites in humans, mainly methylhydroxygliclazide and carboxygliclazide. CYP2C9 is involved in the formation of hydroxygliclazde in human liver microsomes and in a panel of recombinant human P450sin vitro. But the pharmacokinetics of gliclazide MR are affected mainly by CYP2C19 genetic polymorphism instead of CYP2C9 genetic polymorphism.Interactions
Hyperglycemic action may be caused by danazolDanazol
Danazol is a derivative of the synthetic steroid ethisterone, a modified testosterone. Also known as 17alpha-ethinyl testosterone. Before becoming available as a generic drug, Danazol was marketed as Danocrine in the United States. It was approved by the U.S. Food and Drug Administration as the...
, chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic action may be potentiated by phenylbutazone
Phenylbutazone
Phenylbutazone, often referred to as bute, is a non-steroidal anti-inflammatory drug for the short-term treatment of pain and fever in animals. In the United States, it is no longer approved for human use.-In humans:...
, alcohol, fluconazole
Fluconazole
Fluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
, β-blockers, and possibly ACE inhibitors. It has been found that rifampin increases gliclazide metabolism in humans in vivo.
Adverse effects
- HypoglycemiaHypoglycemiaHypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
- while it was proven to have the same efficacy as glimepiride, one of the newer sulfonylureas, the European GUIDE study has shown that it has approximately 50% fewer confirmed hypoglycaemic episodes in comparison with glimepiride. - Gastrointestinal disturbance (reported)
- Skin reactions (rare)
- Hematological disorders (rare)
- Hepatic enzyme rises (exceptional)
Overdosage
Gliclazide overdose may cause severe hypoglycemia, requiring urgent administration of glucose by IV and monitoring.External links
- Official website for Diamicron MR
- SERVIER
- Advance clinical trial on diabetes