Gliclazide is an oral hypoglycemic and is classified as a sulfonylurea.
Gliclazide is the product of research done by Servier - a French pharmaceutical company.
In India original Gliclazide is marketed in original brand name as " Diamicron XR 60 " by
Servier subsidiary Serdia Pharmaceuticals, while other companies promote copies are "Glizid"
,"Glyloc" and "Reclide" in India . 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 shown to protect human pancreatic beta-cells from hyperglycemia-induced apoptosis.
It was also shown to have an 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.
Indication 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 claims that Gliclazide doesn't requires dosage uptitration even in
end stage Kidney disease.
Mechanism of action Gliclazide selectively binds to sulfonylurea
receptors on the surface of the pancreatic beta-cells.
It was shown to provide cardiovascular protection as it does not bind to sulfonylurea receptors
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 Water Solubility = 0.027 mg/L
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 Miconazole 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 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.
Adverse effects Hypoglycemia - while it was shown 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 Skin reactions
Hematological disorders Hepatic enzyme rises
Overdosage Gliclazide overdose may cause severe hypoglycemia,
requiring urgent administration of glucose by IV and monitoring.
References
External links Official website for Diamicron MR
SERVIER Advance clinical trial on diabetes