Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin reduces hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis, and stimulates intracellular glycogen synthesis by acting on glycogen synthase. In muscle, it increases insulin sensitivity, improving peripheral glucose uptake and utilization. Metformin also delays intestinal glucose absorption. Metformin increases the transport capacity of all types of membrane glucose transporters (GLUTs) known to date.
In humans, independently of its action on glycemia, metformin has favorable 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 triglycerides levels. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and daylong plasma insulin response may actually decrease.
Dosage & Administration
Metformin 500 mg tablet: Initial dosage is 500 mg tablet 2-3 times daily with or after meals, gradually increased if necessary to 2 to 3 gm daily.
Metformin 850 mg tablet: Initial dosage is 850 mg tablet once or twice daily with or after meals, gradually increased if necessary to 2 to 3 gm daily.
Metformin extended release or long acting tablet: The usual starting dose of Metformin extended release tablet is 500 mg once daily with the evening meal. Dosage increases should be made in increments of 500 mg weekly, up to a maximum of 2000 mg once daily with the evening meal. If glycemic control is not achieved on Metformin extended release tablet 2000 mg once daily, a trial of Metformin extended release tablet 1000 mg twice daily should be considered. The maximum recommended dose of metformin is 3 gm daily.
Transfer from other antidiabetic therapy: When transferring patients from standard oral hypoglycemic agents other than Chlorpropamide to Metformin HCl, no transition period generally is necessary. When transferring patients from Chlorpropamide, care should be exercised during the first two weeks because of the prolonged retention of Chlorpropamide in the body, leading to overlapping drug effects and possible hypoglycemia.
Children and adolescents-
Monotherapy and combination with insulin
- Metformin tablets can be used in children from 10 years of age and adolescents.
- The usual starting dose is one tablet of 500 mg or 850 mg once daily, given during meals or after meals.
After 10 to 15 days the should be adjusted on the basis of blood glucose measurements. A slow increase of dose may improve gastrointestinal tolerability. The maximum recommended dose of metformin is 2 g daily, taken as 2 or 3 divided doses.
Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.
Concomitant use not recommended-
Alcohol: Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of: fasting or malnutrition, hepatic insufficiency. Avoid consumption of alcohol and alcohol-containing medications.
Iodinated contrast agents: Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.