USE OF ULTRARAPID ACTING INSULIN

• US 20100035795A1
• Filed: 08/11/2009
• Published: 02/11/2010
• Est. Priority Date: 08/11/2008
• Status: Active Grant

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Howard, Campbell, Petrucci, Richard, Mann, Alfred, Boss, Anders Hasager
• Granted Patent: US 8,258,095 B2
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/545 Heterocyclic compounds A61K47/558 takes precedence
• CPC Class Codes: A61K 9/0021 Intradermal administration, e.g. through microneedle arrays, needleless injectors mechanical aspects A61M
• CPC Class Codes: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• 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

Disclosed herein are improved methods of treating hyperglycemia with a combination of an ultrarapid acting insulin and insulin glargine comprising prandial administration of the ultrarapid insulin, and administration of a first dose of insulin glargine within 6 hours of waking for a day.

Claims

1. An improved method of treating hyperglycemia with a combination of an ultrarapid acting insulin and a long acting insulin analog comprising:

prandial administration of the ultrarapid insulin, and

administration of a dose of the long-acting insulin analog within 6 hours of waking for a day.

2. The method of claim 1 wherein the administration of the long acting insulin analog is within 3 hours of waking.

3. The method of claim 1 wherein the long acting insulin analog is insulin detemir or insulin glargine.

4. The method of claim 1 wherein the long acting insulin is insulin glargine and the method further comprises administering a second dose of insulin glargine and the second dose is administered from 8 to 14 hours after said morning dose.

5. The method of claim 1, wherein the ultrarapid acting insulin comprises a formulation comprising insulin and a diketopiperazine.

6. The method of claim 1 wherein the ultrarapid acting insulin comprises insulin-FDKP.

7. The method of claim 1 wherein the ultrarapid acting insulin is administered by inhalation into the lungs.

8. The method of claim 1 wherein the hyperglycemia is resultant of diabetes type 2.

9. An improved method of treating hyperglycemia with a combination of an ultrarapid acting insulin and an exogenous basal insulin comprising:

prandial administration of the ultrarapid insulin, and

continuous infusion of a short acting insulin with an insulin pump.

10. The method of claim 9 wherein the short-acting insulin is regular human insulin or a rapid acting insulin analog.

11. A method of controlling glycemia related to a daily meal without adjusting an insulin dose for meal content comprising the step of administering a predetermined dosage of an ultrarapid acting insulin formulation at mealtime for each daily meal.

12. The method of claim 11 wherein meal content is ≧

25% to ≦

200% of a usual meal content as used in determination of the predetermined dose.

13. The method of claim 11 wherein the ultrarapid-acting insulin formulation is insulin-FDKP.

14. A method of controlling glycemia related to a daily meal for a patient with delayed or prolonged nutrient absorption comprising the steps of:

selecting a patient with delayed nutrient absorption;

administering 50% to 75% of a predetermined dosage of an ultrarapid-acting insulin formulation at mealtime for the daily meal; and

administering the remainder of the predetermined dosage 30 to 120 minutes after beginning the daily meal.

15. The method of claim 14 wherein the ultrarapid acting insulin formulation is insulin-FDKP.

16. The method of claim 14 wherein the delayed nutrient absorption is related to a disease state.

17. The method of claim 14 wherein the delayed nutrient absorption is related to a meal content high in fat or fiber.

18. The method of claim 14 wherein the prolonged nutrient absorption is related to a prolonged meal.

19. A method of controlling glycemia related to a daily meal wherein insulin dosage is adjusted to the glycemic load of the meal consumed comprising the steps of:

administering an initial predetermined dose of an ultrarapid acting insulin formulation at mealtime for the daily meal;

determining postprandial blood glucose 1 to 2 hours after beginning the daily meal; and

if the postprandial blood glucose is >

140 mg/dl administering a second dose of the ultra rapid acting insulin formulation wherein the second dose is 25% to 100% of the initial dose.

20. The method of claim 19 wherein the ultrarapid acting insulin formulation is insulin-FDKP.

21. A method of treating diabetics with subcutaneous insulin resistance comprising the steps of:

selecting a patient with subcutaneous insulin resistance on the basis of atypically high insulin dosage;

discontinuing treatment with subcutaneously administered rapid-, short-, or intermediate-acting insulin formulations; and

initiating treatment by administration of prandial doses of insulin-FDKP by inhalation effective for the control of postprandial hypoglycemia.

22. The method of claim 21 wherein the atypically high insulin dosage is ≧

2 units/Kg/day.

23. The method of claim 21 wherein the selecting step further comprises selection of the basis that the patient has normal or near-normal levels of endogenous basal insulin.

24. The method of claim 23 wherein the level of endogenous basal insulin is ≦

50 μ

U/ml.

25. The method of claim 21 wherein the selecting step further comprises selection on the basis of injection site lipoatrophy or lipodystrophy.

26. The method of claim 21 wherein the selecting step further comprises selection of the basis of the patient having 2 HbA1c level determinations≧

9% in a 6 to 9 month period while on an intensified insulin regimen.

27. The method of claim 21 wherein the selecting step further comprises selection of the basis of the patient having life threatening glycemic instability characterized by periods of hyperglycemia and/or hypoglycemia despite adherence to their insulin regimen and any diet or exercise regimen.

28. The method of claim 21 further comprising the step of confirming the patient has subcutaneous insulin resistance by determining that a similar or improved degree of glycemic control is achieved with a substantially lower dosage of insulin after adjustment based on relative bioavailability.

29. A method for determining an individual'"'"'s dosage of an ultrarapid acting insulin for a daily meal comprising the steps of:

administering a low dose of the ultrarapid acting insulin at mealtime for the daily meal for which the dosage is being titrated each day for at least 3 days within a titration period of not more than a week;

iteratively increasing the dosage by the amount of the low dose in each subsequent titration period and administering at mealtime for the daily meal for which the dosage is being titrated each of at least three days in the titration period until a titration endpoint is reached.

30. The method of claim 29 wherein the low dose is 1-5 subQ eq units.

31. The method of claim 29 wherein the ultrarapid acting insulin comprises insulin-FDKP.

32. The method of claim 29 wherein the titration endpoint is selected from:

1) achieving a 2-hour post-prandial median glucose is between 70 and 110 mg/dl,

2) the dosage based on subcutaneous equivalent (subQ eq) units is a maximal dosage,

3) an episode of severe hypoglycemia with a confirmed SMBG<

36 mg/dl occurs and the dosage is decreased by the equivalent of one low-dose cartridge, and

4) an episode of mild to moderate hypoglycemia with a confirmed SMBG of <

70 mg/dl occurs, the dosage is decreased by the equivalent of one low dose cartridge for one week and then the titration is resumed until it reaches any of said endpoints 1-3 or the dosage is set at the level below that which again produces the mild to moderate hypoglycemia.

33. The method of claim 32 wherein the dosage for 2 or more daily meals are titrated concurrently.

34. The method of claim 32 wherein the dosage for 2 or more daily meals are titrated successively from the daily meal resulting in the highest 2-hour postprandial blood glucose to the daily meal resulting in the lowest 2-hour postprandial blood glucose.

35. The method of claim 32 wherein said maximal dosage is 24 subQ eq units.

36. The method of claim 32 wherein said maximal dosage is 32 subQ eq units.