Superior Control of Blood Glucose in Diabetes Treatment

• US 20110183901A1
• Filed: 03/31/2011
• Published: 07/28/2011
• Est. Priority Date: 03/31/2005
• Status: Abandoned Application

• Current Assignee: Mannkind Corporation
• Original Assignee: Mannkind Corporation
• Inventors: Cheatham, Wayman Wendell, Boss, Anders Hasager
• Application Number:
  US13/077,361
• Publication Number:
  US 20110183901A1
• Time in Patent Office: Days
• US Class Current: 514/6.5
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/545 Heterocyclic compounds A61K47/558 takes precedence
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin

Abstract

Methods related to the treatment of diabetes and improving the control of blood glucose levels are provided. In particular, methods are provided for effectively reducing postprandial glucose excursions while reducing the incidence of clinically significant late postprandial hypoglycemia by administered an insulin composition in a form suitable for pulmonary administration. Additionally, methods for effectively reducing post-prandial glucose excursions while reducing the incidence of clinically significant late postprandial hypoglycemia by administered an insulin composition in a form suitable for pulmonary administration along with a long-acting basal insulin.

Claims

1. A method of reducing postprandial glucose excursions in a patient with an insulin-related disorder comprising:

selecting a patient with an insulin-related disorder;

administering a dose of an insulin composition comprising fumaryl diketopiperazine in a form suitable for pulmonary administration in proximity to beginning a meal, wherein the patient'"'"'s total insulin exposure (INS-AUC_0-y, 3<

y<

6 hours) from said dose does not substantially exceed that produced by an appropriate subcutaneous dose of insulin; and

reducing the postprandial glucose excursions relative to treatment with the appropriate subcutaneous dose of insulin.

2. The method of claim 1 wherein the risk of late postprandial hypoglycemia is not increased.

3. The method of claim 1, wherein the insulin composition is administered by inhalation as a dry powder.

4. The method of claim 1, wherein the insulin composition is administered from approximately 10 minutes prior to beginning a meal to approximately 30 minutes after beginning a meal.

5. The method of claim 1, wherein the insulin-related disorder is diabetes mellitus.

6. The method of claim 1, wherein a mean glucose excursion is at least about 25% less than for said appropriate subcutaneous dose of insulin.

7. The method of claim 1, wherein glucose excursions are measured by a method selected from the group consisting of AUC_0-240, AUC_0-120, and maximum glucose excursion.

8. The method of claim 7, wherein the maximum glucose excursion does not exceed a blood glucose concentration of 180 mg/dL.

9. The method of claim 7, wherein the maximum glucose excursion does not exceed a premeal baseline blood glucose concentration by a value of more than 59 mg/dL.

10. The method according to claim 1 wherein as a result of said administering step, said patient exhibits a ratio of HbA1c after treatment to HbA1c before treatment less than for subcutaneous administration of a dose of insulin providing substantially similar insulin exposure.

11. A method of treating a patient with an insulin related disorder comprising:

administering an insulin composition comprising a diketopiperazine and insulin in a form suitable for pulmonary administration from between from 10 minutes prior to beginning a meal to 30 minutes after beginning a meal;

wherein said composition induces a maximum glucose elimination rate in said patient within 60 minutes of administration.

12. The method according to claim 11 wherein said glucose elimination rate falls to half-maximal within 80 minutes of reaching the maximum.

13. The method according to claim 11 wherein said diketopiperazine is fumaryl diketopiperazine.

14. The method according to claim 11 wherein said insulin-related disorder is diabetes mellitus.

15. The method according to claim 11 wherein the risk of late postprandial hypoglycemia is not increased.

16. The method according to claim 11 wherein as a result of said administering step, said patient exhibits a ratio of HbA1c after treatment to HbA1c before treatment less than for subcutaneous administration of a dose of insulin providing substantially similar insulin exposure.

17. A method of treating a patient with an insulin related disorder comprising:

administering an insulin composition comprising a diketopiperazine and insulin in a form suitable for pulmonary administration from between 10 minutes prior to beginning a meal to 30 minutes after beginning a meal;

wherein said composition induces a lower coefficient of variation at the 95% confidence interval of insulin exposure, (INS-AUC_o-x, x≦

3 hours) or glucose elimination ((GIR-)AUC_o-x, x≦

3 hours), in said patient than subcutaneously administered insulin, where the total insulin exposure [INS-AUC_o-y, 3≦

y≦

6] is substantially similar.

18. The method according to claim 17 wherein said diketopiperazine is fumaryl diketopiperazine.

19. The method according to claim 17 wherein said insulin-related disorder is diabetes mellitus.

20. The method according to claim 17 wherein the risk of late postprandial hypoglycemia is not increased.