Glucoxit XR Mechanism of Action

ORAL ANTI-DIABETIC. ATC code: A10BA02: Gastrointestinal tract and metabolism.
Pharmacology: Pharmacodynamics: Metformin is a biguanide with anti-hyperglycaemic 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. Reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis.
2. In muscle by increasing insulin sensitivity, improving peripheral glucose uptake and utilisation.
3. And delay of 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).
Pharmacokinetics: Absorption: After an oral dose of the extended-release tablet, metformin absorption is significantly delayed compared to the immediate release tablet with a T_max at 7 hours (T_max for the immediate release tablet is 2.5 hours). At steady state, similar to the immediate release formulation, C_max and AUC are not proportionally increased to the administered dose. The AUC after a single oral administration of 2000 mg of metformin extended-release tablets is similar to that observed after administration of 1000 mg of metformin immediate release tablets.
Intrasubject variability of C_max and AUC of metformin extended-release is comparable to that observed with metformin immediate release tablets. When the extended-release tablet is administered in fasting conditions the AUC is decreased by 30% (both C_max and T_max are unaffected).
Metformin absorption from the extended-release formulation is not altered by meal composition. No accumulation is observed after repeated administration of up 2000 mg of metformin as extended-release tablets.
Distribution: Plasma protein binding is negligible. Metformin partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean V_d ranged between 63-276 L.
Metabolism: Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination: Renal clearance of metformin is >400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
Characteristics in specific groups of patients: Renal impairment: The available data in subjects with moderate renal insufficiency are scarce and no reliable estimation of the systemic exposure to metformin in this subgroup as compared to subjects with normal renal function could be made. Therefore, the dose adaptation should be made upon clinical efficacy/tolerability considerations.