RiteMED Metformin Extended-Release Tablet 1 g Mechanism of Action

Blood Glucose Lowering Drug (Biguanide).
Pharmacology: Pharmacodynamics: Metformin is a biguanide antidiabetic agent that reduces both basal and postprandial plasma glucose concentrations in patients with type 2 diabetes mellitus by improving both peripheral and hepatic sensitivity to insulin. It does not stimulate insulin secretion and therefore does not produce hypoglycemia when used alone. Fasting insulin levels and day-long insulin response remain the same or may even decrease with metformin therapy.
Metformin may act via three mechanisms: it reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; increases insulin sensitivity in the skeletal muscles and adipocytes, improving peripheral glucose uptake and utilization; delays intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase. It also increases the transport capacity of all types of membrane glucose transporters.
Metformin has demonstrated modest favorable effects on lipid metabolism in patients with type 2 diabetes. It lowers total cholesterol, mean fasting serum triglycerides and low-density lipoprotein cholesterol levels; it has no adverse effects on other lipid levels.
Pharmacokinetics: Extended-release Tablet: Metformin HCl extended-release tablet is intended for once-a-day dosing. Once-a-day dosing is possible through control of metformin release rate and prolonging absorption in the upper gastrointestinal tract.
At steady-state, after administration of metformin HCl extended-release tablet, the AUC and peak plasma concentrations are not dose proportional within the range of 500 mg to 2,000 mg. Time to reach maximum plasma concentrations (T_max) is approximately 7 hours (range from 4 to 8 hours). The extent of metformin absorption (based on AUC) for metformin HCl extended-release tablet at 2,000 mg once a day dose is similar as that for metformin HCl immediate-release tablet at 1,000 mg twice a day dose.
Metformin distributes rapidly to peripheral body tissues and fluids. It also appears to distribute slowly into erythrocytes and into a deep tissue compartment. Metformin is negligibly bound to plasma proteins. Steady-state plasma concentrations of metformin are generally <1 mcg/mL and are reached within 24 to 48 hours at usual clinical doses and dosing schedules.
Renal elimination of metformin is via glomerular filtration and secretion by the proximal convoluted tubules as unchanged drug. The principal plasma elimination half-life of metformin is about 6.2 hours with 90% of the total dose being cleared within 24 hours in patients with normal renal function. In the blood, the elimination half-life is about 17.6 hours.
Special Populations: Renal Insufficiency: The plasma and blood half-life of metformin is prolonged and the renal clearance decreased in proportion to the decrease in creatinine clearance in patients with decreased renal function (based on measured creatinine levels).
Geriatrics: The limited pharmacokinetic data of metformin in healthy elderly subjects suggest that total plasma clearance of metformin is decreased, half-life is prolonged, and C_max is increased, compared to healthy young subjects. It appears that the change in metformin pharmacokinetics with aging is primarily related to a change in renal function.
Pediatrics: The safety and efficacy of metformin HCl extended-release tablet has not been established in pediatric patients. Pharmacokinetic studies have not been conducted in these patients.