GLP-1 AND METHODS FOR TREATING DIABETES

• US 20140187483A1
• Filed: 02/10/2014
• Published: 07/03/2014
• Est. Priority Date: 07/04/2002
• Status: Abandoned Application

• Current Assignee: ZP Holding SPV K/S (Zealand Pharma A/S)
• Original Assignee: Zealand Pharma A/S
• Inventors: Steiness, Eva
• Application Number:
  US14/177,132
• Publication Number:
  US 20140187483A1
• Time in Patent Office: Days
• US Class Current: 514/7.2
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 31/64 Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
• CPC Class Codes: A61K 31/702 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/31 Somatostatins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to use of GLP-1 or a related molecule having GLP-effect for the manufacture of a medicament for preventing or treating diabetes in a mammal. The amount and timing of administration of said medicament are subsequently reduced to produce a “drug holiday”. Practice of the invention achieves effective therapy without continuous drug exposure and without continuous presence of therapeutic levels of the drug. The invention also discloses a method of treating diabetes and related disorders in a mammal by administering glucagon like peptide (GLP-1) or a related molecule having GLP-1 like effect and thereby providing a therapeutically effective amount of endogenous insulin.

Claims

1. A method for preventing or treating diabetes in a mammal, the method comprising administering to the mammal a therapeutically effective amount of at least one GLP-1 or a related molecule having GLP-1, wherein the amount and timing of administration are such as to prevent or treat diabetes in the mammal without the continuous presence of the molecule.

2. The method of claim 1, wherein the method further comprises reducing administration of the GLP-1 or related molecule below about the therapeutically effective amount for a time conducive to producing a drug holiday, the method being sufficient to prevent or treat the diabetes or related disorder in the mammal.

3. The method of claim 2, wherein administration of the GLP-1 or related molecule is reduced during the drug holiday by at least about 50% below the therapeutic amount.

4. The method of claim 3, wherein administration of the GLP-1 or related molecule is reduced during the drug holiday by at least about 90% below the therapeutic amount.

5. The method of claim 4, wherein administration of the GLP-1 or related molecule is stopped during the drug holiday.

6. The method of claim 1, wherein during the drug holiday is further defined as a time interval between a first endpoint following the reduction in administering the GLP-1 or related molecule and a second endpoint.

7. The method of claim 6, wherein the second endpoint is identified by a standard FBG or glycosylated hemoglobin test.

8. The method of claim 1, wherein the drug holiday is for about one day to about twenty five weeks.

9. The method of claim 8, wherein the drug holiday is for between from about three to four weeks.

10. The method of claim 1, wherein the GLP-1 or related molecule is administered as a depot formulation.

11. The method of claim 1, wherein the GLP-1 or related molecule is administered to the mammal bolus at least about once daily.

12. The method of claim 11, wherein the GLP-1 or related molecule is administered to the mammal bolus at least once a week.

13. The method of claim 1, wherein the administration of the GLP-1 or related molecule is about twice daily (i. v. or subQ) for between from about one to about twenty weeks.

14. The method of the claim 1, wherein the method further comprises administering to the mammal a second therapeutically effective amount of GLP-1 or a related molecule following the drug holiday.

16. The method of claim 1, wherein the administration and reducing steps are repeated at least once.

22. The method of claim 1, wherein the GLP-1 or related molecule is exendin-4, exendin-3;

or an analog or derivative thereof.

36. The method of claim 1, wherein the mammal is a human subject who has or is suspected of having diabetes mellitus or a related disorder.

37. The method of claim 36, wherein the diabetes mellitus is selected from the group consisting of insulin-dependent diabetes millitus (IDDM or type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM, or type II diabetes).

39. The method of claim 36, wherein the disorder related to diabetes mellitus is selected from the group consisting of impaired glucose tolerance (IGT), maturity-onset diabetes of youth (MODY);

leprechaunism (insulin receptor mutation), tropical diabetes, diabetes secondary to a pancreatic disease or surgery;

diabetes associated with a genetic syndrome (eg., Prader-Willi syndrome);

pancreatitis; and

diabetes secondary to endocrinopathies;

adipositas; and

metabolic syndrome (syndroma X).

15. (canceled)

17-21. -21. (canceled)

23-35. -35. (canceled)

38. (canceled)

40-78. -78. (canceled)