Superior Control of Blood Glucose in Diabetes Treatment

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.

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.