DOSAGE AND ADMINISTRATION
Dosage of METAGLIP must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glipizide/2000 mg metformin. METAGLIP should be given with meals and should be initiated at a low dose, with gradual dose escalation as described below, in order to avoid hypoglycemia (largely due to glipizide), to reduce GI side effects (largely due to metformin), and to permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.
With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to METAGLIP and to identify the minimum effective dose for the patient. Thereafter, HbA1c should be measured at intervals of approximately 3 months to assess the effectiveness of therapy. The therapeutic goal in all patients with type 2 diabetes is to decrease FPG, PPG, and HbA1c to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA1c (glycosylated hemoglobin), which is a better indicator of long-term glycemic control than FPG alone.
No studies have been performed specifically examining the safety and efficacy of switching to METAGLIP therapy in patients taking concomitant glipizide (or other sulfonylurea) plus metformin. Changes in glycemic control may occur in such patients, with either hyperglycemia or hypoglycemia possible. Any change in therapy of type 2 diabetes should be undertaken with care and appropriate monitoring.
METAGLIP as Initial Therapy
For patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone, the recommended starting dose of METAGLIP is 2.5 mg/250 mg once a day with a meal. For patients whose FPG is 280 mg/dL to 320 mg/dL a starting dose of METAGLIP 2.5 mg/500 mg twice daily should be considered. The efficacy of METAGLIP in patients whose FPG exceeds 320 mg/dL has not been established. Dosage increases to achieve adequate glycemic control should be made in increments of one tablet per day every two weeks up to maximum of 10 mg/1000 mg or 10 mg/2000 mg METAGLIP per day given in divided doses. In clinical trials of METAGLIP as initial therapy, there was no experience with total daily doses greater than 10 mg/2000 mg per day.
METAGLIP as Second-Line Therapy
For patients not adequately controlled on either glipizide (or another sulfonylurea) or metformin alone, the recommended starting dose of METAGLIP is 2.5 mg/500 mg or 5 mg/500 mg twice daily with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of METAGLIP should not exceed the daily doses of glipizide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.
Patients previously treated with combination therapy of glipizide (or another sulfonylurea) plus metformin may be switched to METAGLIP 2.5 mg/500 mg or 5 mg/500 mg; the starting dose should not exceed the daily dose of glipizide (or equivalent dose of another sulfonylurea) and metformin already being taken. The decision to switch to the nearest equivalent dose or to titrate should be based on clinical judgment. Patients should be monitored closely for signs and symptoms of hypoglycemia following such a switch and the dose of METAGLIP should be titrated as described above to achieve adequate control of blood glucose.
Specific Patient Populations
METAGLIP is not recommended for use during pregnancy or for use in pediatric patients. The initial and maintenance dosing of METAGLIP should be conservative in patients with advanced age, due to the potential for decreased renal function in this population. Any dosage adjustment requires a careful assessment of renal function. Generally, elderly, debilitated, and malnourished patients should not be titrated to the maximum dose of METAGLIP to avoid the risk of hypoglycemia. Monitoring of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in the elderly. (See WARNINGS.)