Pharmacotherapeutic Group: Blood glucose lowering drugs, excl. insulins. Biguanides. ATC Code: A10BA02.
Pharmacology: Pharmacodynamics: Metformin is a biguanide antidiabetic. Unlike sulfonylureas, metformin does not stimulate insulin secretion from pancreatic beta cells. It does not have a hypoglycemic effect in nondiabetic subjects. In diabetics, it allows reductions of hyperglycemia without causing hypoglycemic accidents (except in cases of fasting or synergistic association). Metformin lowers both basal (fasting) and postprandial plasma glucose concentration in patients with type II (non-insulin dependent) diabetes mellitus (NIDDM). The peripheral mode of action of metformin is evidenced by increased cellular utilization of glucose, improved binding of insulin to its receptor and probably a post-receptor effect, inhibition of hepatic glucose synthesis and reduction of intestinal absorption of glucose. Independent of its antidiabetic action, metformin has favorable effects on lipoprotein metabolism which are often abnormal in NIDDM patients. In contrast to sulfonylureas, body weight of individuals on metformin therapy tends to remain stable or may even decrease somewhat.
Pharmacokinetics: Metformin hydrochloride is slowly and incompletely absorbed from the gastrointestinal tract; the absolute bioavailability of a single 500 mg dose is reported to be about 50 to 60%, although this is somewhat reduced 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 hydrochloride is distributed into breast milk in small amounts.