Chemosensory receptor ligand-based therapies
Provided herein are methods for treating conditions associated with a chemosensory receptor, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administrating a composition comprising a chemosensory receptor ligand, such as a bitter receptor ligand. Also provided herein are chemosensory receptor ligand compositions, including bitter receptor ligand compositions, and methods for the preparation thereof for use in the methods of the present invention. Also provided herein are compositions comprising metformin and salts thereof and methods of use.
1. A method of lowering blood glucose levels in a subject in need thereof, comprising administering to said subject a composition comprising metformin or a salt thereof, wherein said composition is adapted for delivery to enteroendocrine cells distal of the duodenum, and wherein said composition provides a lower average bioavailability of metformin as compared to an immediate-release formulation of an equivalent amount of metformin.
2. The method according to claim 1 , wherein said metformin salt is metformin hydrochloride.
3. The method according to claim 1 , wherein said composition is adapted to release a therapeutically effective amount of metformin downstream of the jejunum.
4. The method according to claim 3 , wherein said composition is adapted to release a therapeutically effective amount of metformin to the ileum and/or lower intestine.
5. The method according to claim 1 , wherein said composition releases metformin at an onset of about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration to said subject.
6. The method according to claim 5 , wherein said composition releases metformin at an onset of about pH 6.0 following administration to said subject.
7. The method according to claim 5 , wherein said composition releases metformin at an onset of about pH 6.5 following administration to a subject.
8. The method according to claim 5 , wherein said composition releases metformin at an onset of about pH 7.0 following administration to said subject.
9. The method according to claim 1 , wherein said composition comprises about 1 mg to about 2000 mg of metformin or a salt thereof.
10. The method according to claim 9 , wherein said composition comprises about 1500 mg, or about 2000 mg of metformin or a salt thereof.
11. The method according to claim 1 , wherein said composition further comprises a second antidiabetic agent or an antiobesity agent.
12. The method according to claim 11 , wherein said second antidiabetic agent is selected from thiazolidinediones, sulfonylureas, meglitinides, alphaglucosidase inhibitors, DPP-IV inhibitors, incretin mimetics, and SGLT inhibitors.
13. The method according to claim 11 , wherein said antiobesity agent is selected from phentermine, fenfluramine, sibutramine, rimonabant, topiramate, zonisamide, bupropion, naltrexone, lorcaserin, and orlistat, and combinations thereof.
14. The method according to claim 11 , wherein said antiobesity agent or said second antidiabetic agent is co-formulated with said composition and administered simultaneously in a combined formulation.
15. The method according to claim 14 , wherein said combined formulation is provided in the form of a delayed release component coupled with an immediate release component in a unitary dosage form.
16. The method according to claim 5 , wherein said composition comprises an enteric coating.
17. The method according to claim 5 , wherein said composition is formulated with a timed release system.
18. The method according to claim 1 , wherein said composition further comprises a chemosensory receptor ligand selected from a sweet receptor ligand, a bitter receptor ligand, an umami receptor ligand, a fat receptor ligand, a sour receptor ligand, and a bile acid receptor ligand.
19. The method according to claim 2 , wherein said composition releases metformin at an onset of about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration to said subject.
20. The method according to claim 19 , wherein said composition releases metformin at an onset of about pH 6.0 following administration to said subject.
21. The method according to claim 19 , wherein said composition releases metformin at an onset of about pH 6.5 following administration to a subject.
22. The method according to claim 19 , wherein said composition releases metformin at an onset of about pH 7.0 following administration to said subject.
23. The method according to claim 1 , wherein said composition comprises an enteric coating.
24. The method according to claim 2 , wherein said composition comprises an enteric coating.
25. The method according to claim 2 , wherein said composition is adapted to release a therapeutically effective amount of metformin downstream of the jejunum.
26. The method according to claim 25 , wherein said composition is adapted to release a therapeutically effective amount of metformin to the ileum and/or lower intestine.
27. The method according to claim 9 , wherein said composition releases metformin at an onset of about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration to said subject.
28. The method according to claim 27 , wherein said composition releases metformin at an onset of about pH 6.0 following administration to said subject.
29. The method according to claim 27 , wherein said composition releases metformin at an onset of about pH 6.5 following administration to a subject.
30. The method according to claim 27 , wherein said composition releases metformin at an onset of about pH 7.0 following administration to said subject.
31. The method according to claim 9 , wherein said composition comprises about 1500 mg of metformin or a salt thereof.
32. The method according to claim 31 , wherein said composition releases metformin at an onset of about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration to said subject.
33. The method according to claim 9 , wherein said composition comprises about 2000 mg of metformin or a salt thereof.
34. The method according to claim 33 , wherein said composition releases metformin at an onset of about pH 6.0, about pH 6.5, about pH 7.0, or a combination thereof following administration to said subject.
35. The method according to claim 10 , wherein said composition comprises an enteric coating.
36. The method according to claim 16 , wherein said metformin salt is metformin hydrochloride.
37. The method according to claim 16 , wherein said composition is adapted to release a therapeutically effective amount of metformin downstream of the jejunum.
38. The method according to claim 37 , wherein said composition is adapted to release a therapeutically effective amount of metformin to the ileum and/or lower intestine.
39. The method according to claim 5 , wherein said composition comprises an enteric coating.
40. The method according to claim 6 , wherein said composition comprises an enteric coating.
41. The method according to claim 6 , wherein said composition comprises an enteric coating.