Title:  Glibenclamide-metformin combination for the treatment of diabetes mellitus of type II

United States Patent:  RE37,330

Assignee:  Abiogen Pharma S.p.A. (Pisa, IT)

Filed:  July 5, 2000

PCT NO:  PCT/EP96/04860

102(e) Date:  May 13, 1998

PCT PUB. Date:  May 22, 1997

Foreign Application Priority Data:  Nov 14, 1995[IT] (MI95A2337)

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 untoward effects.

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 principles.

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 patients themselves.

Claim 1 of 7 Claims

We claim:

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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