Methods of treating diabetes mellitus

1. A method of treating diabetes mellitus in a patient in need of such treatment, said method comprising:

orally administering an effective amount of an insulin polypeptide derivative to the patient within one hour of ingestion of a meal by the patient in order to treat diabetes mellitus in the patient, wherein the insulin polypeptide derivative has the following formula:

and wherein the effective amount of the insulin polypeptide derivative is administered so that it provides an insulin drug concentration in portal vein blood between 10 and 1,000 μU/ml within about 60 minutes of administration.

2. The method of claim 1 , wherein the oral administration of the effective amount of the insulin polypeptide derivative provides an insulin drug concentration in portal vein blood between 10 and 1,000 μU/ml within about 30 minutes of administration.

3. The method of claim 1 , wherein the effective amount of the insulin polypeptide derivative is between 0.05 and 10 mg per kilogram body weight.

4. The method of claim 1 , wherein the oral administration of the effective amount of the insulin polypeptide derivative provides a maximum insulin drug concentration in peripheral blood within about 60 minutes.

5. The method of claim 1 , wherein the oral administration of the effective amount of the insulin polypeptide derivative stabilizes peripheral glucose concentration to within +/−50 percent of an average peripheral glucose concentration measured over about a one hour time period beginning about 30 minutes after administration.

6. The method of claim 1 , wherein the insulin polypeptide derivative clears the bloodstream of the patient about 4 hours following administration.

7. The method of claim 1 , wherein the administration of the effective amount of the insulin polypeptide derivative reduces hepatic glucose production in the patient by at least 25 percent when compared to hepatic glucose production in the patient without administration.

8. The method of claim 7 , wherein the reduction in hepatic glucose production occurs about 90 minutes after administration.

9. The method of claim 1 , wherein the insulin polypeptide derivative is orally administered such that at least 25 percent of post-prandial glucose resulting from ingestion of a meal by the patient is hepatically absorbed about 120 minutes after ingestion of the meal.

10. The method of claim 1 , wherein the insulin polypeptide derivative is orally administered less than one hour prior to ingestion of a meal by the patient.

11. The method of claim 1 , wherein the insulin polypeptide derivative is orally administered substantially contemporaneously with the ingestion of a meal by the patient.

12. The method of claim 1 , wherein the insulin polypeptide derivative is orally administered about one hour after ingestion of a meal by the patient.

13. The method of claim 1 , wherein the insulin polypeptide in the insulin polypeptide derivative is human insulin.

14. The method of claim 1 , wherein the insulin polypeptide derivative is an insulin polypeptide-oligomer conjugate.

15. The method of claim 14 , wherein the insulin polypeptide-oligomer conjugate is an amphiphilically balanced insulin polypeptide-oligomer conjugate.

16. A method of treating diabetes mellitus in a patient in need of such treatment, said method comprising:

orally administering an effective amount of an insulin polypeptide derivative to the patient in order to treat diabetes mellitus in the patient, wherein the insulin polypeptide derivative has the following formula:

and wherein the effective amount of the insulin polypeptide derivative is administered so that it provides an insulin drug concentration in portal vein blood between 10 and 1,000 μU/ml within about 60 minutes of administration.

17. A method of treating diabetes mellitus in a patient in need of such treatment, said method comprising:

orally administering an effective amount of an insulin polypeptide derivative to the patient in order to treat diabetes mellitus in the patient, wherein the insulin polypeptide derivative has the following formula:

and wherein the effective amount of the insulin polypeptide derivative is administered so that it stabilizes peripheral glucose concentration to within +/−50 percent of an average peripheral glucose concentration measured over about a one hour time period beginning about 30 minutes after administration.

18. A method of treating diabetes mellitus in a patient in need of such treatment, said method comprising:

orally administering an effective amount of an insulin polypeptide derivative to the patient in order to treat diabetes mellitus in the patient, wherein the insulin polypeptide derivative has the following formula:

and wherein the effective amount of the insulin polypeptide derivative is administered so that it reduces hepatic glucose production in the patient by at least 25 percent when compared to hepatic glucose production in the patient without administration.

19. The method of claim 18 , wherein the reduction in hepatic glucose production occurs about 90 minutes after administration.

20. A method of treating diabetes mellitus in a patient in need of such treatment, said method comprising:

orally administering an effective amount of an insulin polypeptide derivative to the patient in order to treat diabetes mellitus in the patient, wherein the insulin polypeptide derivative has the following formula:

and wherein the effective amount of the insulin polypeptide derivative is administered so that about 25 percent of post-prandial glucose resulting from ingestion of a meal by the patient is hepatically absorbed about 120 minutes after ingestion of the meal by the patient.