Gliclazide

Gliclazide is a hypoglycaemic sulfonylurea antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond.

Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment.

In addition to these metabolic properties, gliclazide has haemovascular properties.

Effects on insulin release

In type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose.

Haemovascular properties

Gliclazide decreases microthrombosis by two mechanisms which may be involved in complications of diabetes:

• a partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet activation (beta thromboglobulin, thromboxane B₂),
• an action on the vascular endothelium fibrinolytic activity with an increase in tPA activity.

The drug is well absorbed and its half-life in man is approximately 10-12 hours. Gliclazide is metabolised in the liver; less that 5% of the dose is excreted unchanged in the urine.

Preclinical data reveal no special hazards for humans based on conventional studies of repeated dose toxicity and genotoxicity. Long term carcinogenicity studies have not been done. No teratogenic changes have been shown in animal studies, but lower fetal body weight was observed in animals receiving doses 9.4 fold higher than the maximum recommended dose in humans.