The maximum recommended daily dose of Metformin is 2550mg in adults and 200mg in pediatric patients (10-16 years of age). Metformin should be given in divided doses with meals. Metformin should be started at a low dose with gradual dose escalation to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.
During treatment initiation and dose tritration, fasting plasma glucose should be used to determine the therapeutic response to Metformin and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 months. The therapeutic goal should be to decrease both fasting plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of Metformin when used as monotherapy or in combination with sulfonylurea or insulin. Monitoring of blood glucose and glycosylated hemoglobin will also permit detection of primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication and secondary failure, i.e., loss of an adequate blood glucose lowering responses after an initial period of effectiveness. Short-term administration of metformin may be sufficient during periods of transient loss of control in patients usually well-controlled on diet alone.
Adults: The usual starting dose of metformin tablets is 500 mg twice a day or 850 mg once a day, given with meals. In general, clinically significant responses are not seen at doses below 1500 mg per day. Dosage increases should be made in increments of 500 mg weekly or 850 mg every 2 weeks, up to a total of 2000 mg per day, given in divided doses. The dosage of metformin must be individualized on the basis of both effectiveness and tolerability. Patients can also be titrated from 500 mg twice a day to 850 mg twice a day after 2 weeks. For those patients requiring additional glycemic control, Metformin may be given to a maximum daily dose of 2550 mg per day. Doses above 2000 mg may be better tolerated given 3 times a day with meals.
Pediatrics: The usual starting dose of Metformin is 500 mg twice a day, given with meals. Dosage increases should be made in increments of 500 mg weekly up to a maximum of 2000 mg per day, given in divided doses. The dosage of Metformin must be individualized on the basis of both effectiveness and tolerability.
Renal impairment: Assess renal function prior to initiation of Metformin and periodically thereafter.
Contraindicated in patients with estimated glomelular filtration rate below 30mL/minute/1.73m2.
In patients with glomelular filtration rate between 30-45 mL/minute/1.73m2 is not recommended.
In patients whose glomelular filtration rate later falls below 45 mL/minute/1.73m2, assess the benefit risk of continuing therapy.
Discontinue if the patient's glomelular filtration rate later falls below 30 mL/minute/1.73m2.
Discontinue Metformin at the time of or prior to an iodinated contrast imaging procedure in patients with an glomelular filtration rate between 30 and 601 mL/min/1.73m2; in patients with history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate glomelular filtration rate 48 hours after the imaging procedure; restart metformin if renal function is stable.
If patients have not responded to 4 weeks of the maximum dose of metformin monotherapy, consideration should be given to gradual addition of an oral sulfonylurea while continuing metformin at the maximum dose, even if prior primary or secondary failure to a sulfonylurea has occurred. Clinical and pharmacokinetic drug-drug interaction data are currently available only for metformin plus glyburide (glibenclamide).
With concomitant Metformin and sulfonylurea therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. In a clinical trial patients with type 2 diabetes and prior failure on glyburide, patients started on metformin 500 mg and glyburide 20 mg were titrated to 1000/20 mg, 1500/20 mg, 2000/20 mg or 2500/20 mg of Metformin and glyburide, respectively, to reach the goal of glycemic control as measured by FPG, HbA1c and plasma glucose response. However attempts should be made to identify the minimum effective dose of each drug to achieve this goal with concomitant metformin and sulfonylurea therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken.
If patients have not satisfactorily responded to 1 to 3 months of concomitant therapy with the maximum dose of metformin and the maximum dose of an oral sulfonylurea, consider therapeutic alternatives including switching to insulin with or without metformin.
The current insulin dose should be continued upon initiation of metformin therapy. Metformin therapy should be initiated at 500 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of metformin should be increased by 500 mg after approximately 1 week and by 500mg every week thereafter until adequate glycemic control is achieved. The maximum recommended daily dose is 2500 mg for metformin. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120mg/dL in patients receiving concomitant insulin and metformin. Further adjustment should be individualized based on glucose-lowering response.
Pregnancy: Metformin is not recommended for use in pregnancy.
Metformin is not recommended in patients below the age of 10 years.
The initial maintenance dosing of metformin should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment should be based on a careful assessment of renal function.