Method of regulating glucose metabolism, and reagents related thereto
View Patent ↗The present invention provides methods for modification and regulation of glucagon-like peptide 1 (GLP-1) metabolism by administering therapeutically effective amounts of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof, where the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; and the inhibitor is administered in an amount sufficient to inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
1. A method for modifying metabolism of glucagon-like peptide 1 (GLP-1), comprising administering orally to an animal in need thereof a therapeutically effective amount of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof once daily, wherein the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; the duration of the therapeutic effect is at least about 24 hours; and the inhibitor is administered in an amount sufficient to inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.
2. The method of claim 1 , wherein the inhibitor has a Ki for inhibition of DPIV of 1.0 nM or less.
3. The method of claim 2 , wherein the inhibitor has a Ki for inhibition of DPIV of 0.1 nM or less.
4. The method of claim 3 , wherein the inhibitor has a Ki for inhibition of DPIV of 0.01 nM or less.
5. The method of claim 1 , wherein the inhibitor has an EC 50 for modification of GLP-1 metabolism at least one order of magnitude less than its EC 50 for immunosuppression.
6. The method of claim 5 , wherein the inhibitor has an EC 50 for modification of GLP-1 metabolism at least two orders of magnitude less than its EC 50 for immunosuppression.
7. The method of claim 1 , wherein the inhibitor has a molecular weight less than 5000 amu.
8. The method of claim 7 , wherein the inhibitor has a molecular weight less than 2000 amu.
9. The method of claim 8 , wherein the inhibitor has a molecular weight less than 1000 amu.
10. The method of claim 1 , wherein said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
11. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours.
12. The method of claim 1 , wherein the animal is a human.
13. The method of claim 1 , wherein the inhibitor is administered in the form of a tablet.
14. The method of claim 1 , wherein the inhibitor is administered in the form of a coated tablet.
15. The method of claim 1 , wherein the animal is a human; and the duration of the therapeutic effect is about 24 hours.
16. The method of claim 1 , wherein the animal is a human; and the inhibitor has a molecular weight less than 1000 amu.
17. The method of claim 1 , wherein the animal is a human; and the inhibitor is administered in the form of a tablet.
18. The method of claim 1 , wherein the animal is a human; and the inhibitor is administered in the form of a coated tablet.
19. The method of claim 1 , wherein the inhibitor has a molecular weight less than 1000 amu; and the duration of the therapeutic effect is about 24 hours.
20. The method of claim 1 , wherein the inhibitor has a molecular weight less than 1000 amu; and the inhibitor is administered in the form of a tablet.
21. The method of claim 1 , wherein the inhibitor has a molecular weight less than 1000 amu; and the inhibitor is administered in the form of a coated tablet.
22. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; and the inhibitor is administered in the form of a tablet.
23. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; and the inhibitor is administered in the form of a coated tablet.
24. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a tablet; and the inhibitor has a molecular weight less than 1000 amu.
25. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a coated tablet; and the inhibitor has a molecular weight less than 1000 amu.
26. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a tablet; the inhibitor has a molecular weight less than 1000 amu; and said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.
27. The method of claim 1 , wherein the duration of the therapeutic effect is about 24 hours; the animal is a human; the inhibitor is administered in the form of a coated tablet; the inhibitor has a molecular weight less than 1000 amu; and said inhibition of DPIV proteolysis of GLP-1 treats Type II diabetes.