Biguanide compositions and methods of treating metabolic disorders
Provided herein are methods for treating certain conditions, including diabetes, obesity, and other metabolic diseases, disorders or conditions by administrating a composition comprising a biguanide or related heterocyclic compound, e.g., metformin. Also provided herein are biguanide or related heterocyclic compound 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 for treating a disorder of glucose metabolism in a patient in need thereof, comprising administering to the patient a pharmaceutical dosage form comprising metformin or a salt thereof, wherein said pharmaceutical dosage form is adapted to have an onset of release of said metformin or a salt thereof distal of the duodenum and to provide at least 20% less relative bioavailability of metformin as measured by plasma area under curve (AUC) resulting from administration of said pharmaceutical dosage form, compared to an immediate release composition having the same amount of said metformin or a salt thereof, and wherein the daily dose of said metformin or a salt thereof is between about 1500 mg and about 2000 mg.
2. The method according to claim 1 , wherein said pharmaceutical dosage form is adapted to provide at least 30% less relative bioavailability of metformin compared to an immediate release composition having the same amount of said metformin or a salt thereof.
3. The method according to claim 1 , wherein said pharmaceutical dosage form is adapted to provide at least 40% less relative bioavailability of metformin compared to an immediate release composition having the same amount of said metformin or a salt thereof.
4. The method according to claim 1 , wherein said pharmaceutical dosage form is adapted to provide at least 50% less relative bioavailability of metformin compared to an immediate release composition having the same amount of said metformin or a salt thereof.
5. The method according to claim 1 , wherein said pharmaceutical dosage form is adapted to provide at least 60% less relative bioavailability of metformin compared to an immediate release composition having the same amount of said metformin or a salt thereof.
6. The method according to claim 1 , wherein the pharmaceutical dosage form minimizes the circulating plasma concentration of metformin in said patient below about 1.0 μg/mL.
7. The method according to claim 1 , wherein the pharmaceutical dosage form minimizes the circulating plasma concentration of metformin in said patient below about 0.5 μg/mL.
8. The method according to claim 1 , wherein the pharmaceutical dosage form minimizes the circulating plasma concentration of metformin in said patient below about 0.25 μg/mL.
9. The method according to claim 1 , wherein said metformin or a salt thereof is metformin hydrochloride.
10. The method according to claim 1 , wherein said pharmaceutical dosage form further comprises a second antidiabetic agent or an antiobesity agent.
11. The method according to claim 1 , wherein said disorder of glucose metabolism comprises diabetes.
12. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof at about pH 6.0.
13. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof at about pH 6.5.
14. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof at about pH 7.0.
15. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof from about pH 5.0 to about pH 6.0.
16. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof from about pH 6.0 to about pH 7.0.
17. The method according to claim 1 , wherein said pharmaceutical dosage form has an onset of release of said metformin or a salt thereof from about pH 7.0 to about pH 8.0.
18. The method according to claim 1 , wherein the daily dose of said metformin or a salt thereof is about 1500 mg.
19. The method according to claim 1 , wherein the daily dose of said metformin or a salt thereof is about 2000 mg.
20. The method according to claim 18 , wherein said metformin or a salt thereof is metformin hydrochloride.
21. The method according to claim 19 , wherein said metformin or a salt thereof is metformin hydrochloride.
22. The method according to claim 1 , wherein the disorder of glucose metabolism is gestational diabetes.
23. The method according to claim 22 , wherein said metformin or a salt thereof is metformin hydrochloride.