Glibenclamide is a sulfonylurea antidiabetic. Sulfonylureas appear to have several modes of action, apparently mediated by inhibition of ATP-sensitive potassium channels. Initially, secretion of insulin by functioning islet beta cells is increased. However, insulin secretion subsequently falls again but the hypoglycaemic effect persists and may be due to inhibition of hepatic glucose production and increased sensitivity to any available insulin.
Metformin Hydrochloride is a biguanide hypoglycaemic agent. The biguanide antidiabetics are a class of hypoglycaemic drugs used in the treatment of type 2 diabetes mellitus. They do not stimulate insulin release but require that some insulin be present in order to exert their hypoglycaemic effect. Possible mechanisms of action include delay in the absorption of glucose from the gastro-intestinal tract, an increase in insulin sensitivity and glucose uptake into cells, and inhibition of hepatic gluconeogenesis.
Glibenclamide is readily absorbed from the gastro-intestinal tract, peak plasma concentrations usually occuring within 2 to 4 hours, and is extensively bound to plasma proteins. Absorption may be slower in hyperglycaemic patients and may differ according to the particle size of the preparation used. It is metabolised almost completely, in the liver, the principle metabolite being only very weakly active. Approximately 50% of a dose is excreted in the urine and 50% via the bile into the faeces.
Metformin hydrochloride is slowly and incompletely absorbed from the gastro-intestinal tract; the absolute bioavailability of a single 500mg dose is reported to be about 50 to 60%, although this is reduced somewhat if taken with food. Once absorbed plasma protein binding is negligible, and it is excreted unchanged in the urine. The plasma elimination half-life is reported to range from about 2 to 6 hours after oral doses. Metformin is distributed into breast milk in small amounts.
It is indicated as initial therapy, as an adjunct to diet and excercise , to improve glycaemic control in patients with type 2 diabetes whose hyperglycaemia cannot be satisfactorily managed with diet and excercise alone.
It is indicated as second-line therapy when diet, excercise, and initial treatment with a sulfonylurea or metformin do not result in adequate glycaemic control in patients with type 2 diabetes.
DOSAGE AND ADMINISTRATION:
Starting dose: 1.25mg / 250mg once or twice daily with meals.
Starting dose: 2.5mg / 500mg or 5mg / 500mg twice daily with meals.