Title: Glibenclamide-metformin combination for the
treatment of diabetes mellitus of type II
United States Patent: RE37,330
Inventors: Barelli; Giulio (Pisa, IT); De Regis; Massimo
Assignee: Abiogen Pharma S.p.A. (Pisa, IT)
Appl. No.: 610548
Filed: July 5, 2000
PCT Filed: November 7, 1996
PCT NO: PCT/EP96/04860
371 Date: May 13, 1998
102(e) Date: May 13, 1998
PCT PUB.NO.: WO97/17975
PCT PUB. Date: May 22, 1997
Foreign Application Priority Data: Nov 14, 1995[IT]
Non-insulin dependent diabetes mellitus in cases of secondary failure
is treated with a combination of glibenclamide and metformin.
DETAILED DISCLOSURE OF THE INVENTION
According to a first preferred embodiment of the present
invention, the combination of the two active ingredients is used in a
medicament in the form of tablets with a dosage of 5 mg of glibenclamide
and 500 mg of metformin. This medicament is useful for the treatment of
diabetes mellitus of type II.
The balance of said doses makes the therapeutical effect optimum at any
time of the progression of the disease, starting from minor cases to the
most severe ones, and particularly, when it is necessary to increase
progressively with time the doses of the two substances.
On the contrary, when combination ratios different from those of the
present invention are used, the following cases are likely to occur:
when the ratios are lower than the recommended ones, the number of
metabolically controlled diabetic patients will definitely be lower,
when the recommended doses are exceeded, there will be an actual risk of
Therefore, the target area of the patients responding to the therapy will
increase and at the same time the onset of therapeutical risks will be
highly decreased only when the two medicaments are administered in
combination at the doses present in the tablet, or at multiple and
submultiple doses of the same.
Moreover, it has been proved that a dose increase beyond the maximum
limits herein recommended of 15 mg of glibenclamide and 1500 mg of
metformin daily causes no further favourable therapeutical effects.
Finally, it should be stressed that the above mentioned doses can
theoretically be attained also using the two medicaments separately.
However, this involves the need of taking twice as many tablets a day,
with clear compliance problems, especially in the elderly patients which
require concomitant therapies for other pathologies which are frequently
connected with diabetes, such as hypertension and vascular diseases.
Said combination of dosages can be used starting from the onset of the
disease in NID diabetics since the ratio of 5 mg of glibenclamide +500 mg
of metformin will always be balanced, in both the multiple and submultiple
dosages. In fact, when the tablets are subdivided, thus obtaining minor
and/or fractional daily dosages, the fixed ratio, which is the balanced
one, is always maintained. Therefore, according to a second embodiment of
the present invention, the medicament is in the form of a divisible tablet
containing the combination described above.
Alternatively, tablets containing fractions of the preferred dosage can be
prepared, always keeping the 1:100 ratio between the two active
Analogously, in the most severe cases of diabetes with metabolic
decompensation, which cannot be controlled with the commercially available
combination medicaments, (so that the patients should turn to insulin
therapy), the combination of the invention allows to treat them, still and
for a long time, with the oral therapy, with obvious benefits for the
Claim 1 of 7 Claims
1. A method of treating non-insulin dependent diabetes mellitus in cases
of secondary failure .[.comprising administering to a subject a need of
same.]. .Iadd.to a treatment utilizing .Iaddend.a combination of .[.glibenclamide
and metformin, expressed as the.]. .Iadd.glibenclamide-metformin
hydrochloride in a weight ratio higher than 1:100, comprising
administering to a subject in need of same a combination of glibenclamide
and metformin, expressed as the .Iaddend.hydrochloride, in a weight ratio
.[.higher than.]. .Iadd.of .Iaddend.1:100.
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