NAME OF THE MEDICINAL PRODUCT
Glucovance 250/1.25 mg
Glucovance 500/2.5 mg
Glucovance 500/5 mg
NAME AND STRENGTH OF ACTIVE INGREDIENTS
Each film-coated tablet of Glucovance 250 mg/1.25 mg contains 250 mg metformin hydrochloride, equivalent to 195 mg metformin, and 1.25 mg of glibenclamide.
Each film-coated tablet of Glucovance 500 mg /2.5 mg contains 500mg metformin hydrochloride, equivalent to 390 mg metformin, and 2.5 mg of glibenclamide.
Each film-coated tablet of Glucovance 500 mg /5 mg contains 500 mg metformin hydrochloride, equivalent to 390 mg metformin, and 5 mg of glibenclamide.
Glucovance 250 mg/1.25 mg are pale yellow capsule shaped, biconvex, film coated tablets with "250" engraved on one side and "1.25" on the other side.
Glucovance 500 mg/2.5 mg tablets are pale orange capsule-shaped, biconvex, film-coated tablets with "2.5" engraved on one side.
Glucovance 500 mg/5 mg tablets are yellow capsule-shaped, biconvex, film-coated tablets with "5" engraved on one side.
Pharmacotherapeutic group: Biguanides and sulphonamide(s) in combination. ATC code: A10BD02
Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Metformin may act via 3 mechanisms:
(1) by reducing hepatic glucose production by inhibiting gluconeogenesis and 9
(2) in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and utilisation
(3) and by delaying intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase. Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
In humans, independently of its action on glycaemia, metformin has favourable effects on lipid metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies: metformin reduces total
cholesterol, LDL-cholesterol and triglyceride levels. In clinical trials conducted so far with combination therapy with metformin and glibenclamide, these favourable effects on lipid metabolism have not been shown.
Glibenclamide is a second generation sulphonylurea with a medium half-life: it causes acute lowering of blood glucose by stimulating the release of insulin by the pancreas, this effect being dependent on the presence of functioning beta cells in the islets of Langerhans.
The stimulation of insulin secretion by glibenclamide in response to a meal is of major importance.
The administration of glibenclamide to diabetics induces an increase in the postprandial insulin-stimulating response. The increased postprandial responses in insulin and C-peptide secretion persist after at least 6 months of treatment. Metformin and glibenclamide have different mechanisms and sites of action, but their action is complementary. Glibenclamide stimulates the pancreas to secrete insulin, while metformin reduces cell resistance to insulin by acting on peripheral (skeletal muscle) and hepatic sensitivity to insulin.
Results from controlled, double blind clinical trials versus reference products in the treatment of type 2 diabetes inadequately controlled by monotherapy with metformin or glibenclamide combined with diet and exercise, have demonstrated that the combination had an additive effect on glucose regulation.
Paediatric patients: In a 26-week, active controlled, double-blind, clinical study performed in 167 paediatric patients aged 9 to 16 years with type 2 diabetes not adequately controlled with diet and exercise, with or without an oral antidiabetic treatment, a fixed combination of metformin hydrochloride 250 mg and glibenclamide 1.25 mg was not shown more effective to either metformin hydrochloride or glibenclamide in reducing HbA1c from baseline.