Metaglip Information
Metaglip (Glipizide; metformin hydrochloride) Description
Metaglip (Glipizide; metformin hydrochloride) (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; metformin hydrochloride) 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; metformin hydrochloride) Clinical Pharmacology
Metaglip (Glipizide; metformin hydrochloride) 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; metformin hydrochloride) Indications And Usage
Metaglip (Glipizide; metformin hydrochloride) (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; metformin hydrochloride) Contraindications
Metaglip (Glipizide; metformin hydrochloride) is contraindicated in patients
with:
Metaglip (Glipizide; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride)
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; metformin hydrochloride) 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; metformin hydrochloride) should only be used in patients with normal renal
function (see , , and ). Because aging is associated with reduced
renal function, Metaglip (Glipizide; metformin hydrochloride) 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; metformin hydrochloride) (see also and ).
Metaglip (Glipizide; metformin hydrochloride) Adverse Reactions
In
a double-blind 24-week clinical trial involving Metaglip (Glipizide; metformin hydrochloride) as initial therapy,
a total of 172 patients received Metaglip (Glipizide; metformin hydrochloride) 2.5 mg/250 mg, 173 received Metaglip (Glipizide; metformin hydrochloride)
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; metformin hydrochloride)
as second-line therapy, a total of 87 patients received Metaglip (Glipizide; metformin hydrochloride) , 84 received
glipizide, and 75 received metformin. The most common clinical adverse events
in this clinical trial are listed in .
Metaglip (Glipizide; metformin hydrochloride) Dosage And Administration
Dosage of Metaglip (Glipizide; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride) 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; metformin hydrochloride)
should be titrated as described above to achieve adequate control of blood
glucose.
Metaglip (Glipizide; metformin hydrochloride) How Supplied
Metaglip (Glipizide; metformin hydrochloride) tablet is a pink oval-shaped, biconvex film-coated tablet
with "" debossed on one side and "" debossed
on the opposite side.
Metaglip (Glipizide; metformin hydrochloride) tablet
is a white oval-shaped, biconvex film-coated tablet with ""
debossed on one side and "" debossed on the opposite side.
Metaglip (Glipizide; metformin hydrochloride) tablet is a pink oval-shaped, biconvex film-coated tablet
with "" debossed on one side and "" debossed
on the opposite side.
Metaglip (Glipizide; metformin hydrochloride)
Metaglip (Glipizide; metformin hydrochloride)
Metaglip (Glipizide; metformin hydrochloride)
Metaglip (Glipizide; metformin hydrochloride)
