Metaglip Information
Metaglip (Glipizide) Description
Metaglip (Glipizide) (glipizide and metformin HCl) Tablets contain 2 oral antihyperglycemic drugs used in the management of type 2 diabetes, glipizide and metformin hydrochloride.
Glipizide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glipizide is 1-cyclohexyl-3-[[-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl]sulfonyl]urea. Glipizide is a whitish, odorless powder with a molecular formula of CHNOS, a molecular weight of 445.55 and a pK of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 NaOH; it is freely soluble in dimethylformamide. The structural formula is represented below.
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride (,-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of CHClN (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pK of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown:
Metaglip (Glipizide) is available for oral administration in tablets containing 2.5 mg glipizide with 250 mg metformin hydrochloride, 2.5 mg glipizide with 500 mg metformin hydrochloride, and 5 mg glipizide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, and magnesium stearate. The tablets are film coated, which provides color differentiation.
Metaglip (Glipizide) Clinical Pharmacology
Metaglip (Glipizide) combines glipizide and metformin hydrochloride, 2 antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes.
Glipizide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment.
Metformin hydrochloride is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Metaglip (Glipizide) Indications And Usage
Metaglip (Glipizide) (glipizide and metformin HCl) Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Metaglip (Glipizide) Contraindications
Metaglip (Glipizide) is contraindicated in patients with:
Metaglip (Glipizide) should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function. (See also .)
Metaglip (Glipizide) Warnings
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to 1 of 4 treatment groups ( 19 (Suppl. 2):747-830, 1970).
UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and benefits of glipizide and of alternative modes of therapy.
Although only 1 drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
Metaglip (Glipizide) Precautions
Periodic fasting blood glucose (FBG) and HbA measurements should be performed to monitor therapeutic response.
Initial and periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell indices) and renal function (serum creatinine) should be performed, at least on an annual basis. While megaloblastic anemia has rarely been seen with metformin therapy, if this is suspected, vitamin B deficiency should be excluded.
Of the 345 patients who received Metaglip (Glipizide) 2.5 mg/250 mg and 2.5 mg/500 mg in the initial therapy trial, 67 (19.4%) were aged 65 and older while 5 (1.4%) were aged 75 and older. Of the 87 patients who received Metaglip (Glipizide) in the second-line therapy trial, 17 (19.5%) were aged 65 and older while 1 (1.1%) was at least aged 75. No overall differences in effectiveness or safety were observed between these patients and younger patients in either the initial therapy trial or the second-line therapy trial, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Metformin hydrochloride is known to be substantially excreted by the kidney and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, Metaglip (Glipizide) should only be used in patients with normal renal function (see , , and ). Because aging is associated with reduced renal function, Metaglip (Glipizide) should be used with caution as age increases. Care should be taken in dose selection and should be based on careful and regular monitoring of renal function. Generally, elderly patients should not be titrated to the maximum dose of Metaglip (Glipizide) (see also and ).
Metaglip (Glipizide) Adverse Reactions
In a double-blind 24-week clinical trial involving Metaglip (Glipizide) as initial therapy, a total of 172 patients received Metaglip (Glipizide) 2.5 mg/250 mg, 173 received Metaglip (Glipizide) 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in .
In a double-blind 18-week clinical trial involving Metaglip (Glipizide) as second-line therapy, a total of 87 patients received Metaglip (Glipizide) , 84 received glipizide, and 75 received metformin. The most common clinical adverse events in this clinical trial are listed in .
Metaglip (Glipizide) Dosage And Administration
Dosage of Metaglip (Glipizide) 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.
With initial treatment and during dose titration, appropriate blood glucose monitoring should be used to determine the therapeutic response to Metaglip (Glipizide) and to identify the minimum effective dose for the patient. Thereafter, HbA 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 HbA to normal or as near normal as possible. Ideally, the response to therapy should be evaluated using HbA, 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 (Glipizide) 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.
For patients not adequately controlled on either glipizide (or another sulfonylurea) or metformin alone, the recommended starting dose of Metaglip (Glipizide) 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 (Glipizide) 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 (Glipizide) 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 (Glipizide) should be titrated as described above to achieve adequate control of blood glucose.
Metaglip (Glipizide) How Supplied
Metaglip (Glipizide) tablet is a pink oval-shaped, biconvex film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Metaglip (Glipizide) tablet is a white oval-shaped, biconvex film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Metaglip (Glipizide) tablet is a pink oval-shaped, biconvex film-coated tablet with "" debossed on one side and "" debossed on the opposite side.
Metaglip (Glipizide)
Metaglip (Glipizide)
Metaglip (Glipizide)
Metaglip (Glipizide)
