Method for treating hyperglycemia

Abstract

A method for treating hyperglycemia and/or diabetes in a subject is provided. In particular, the method is directed for the treatment of patients with type 2 diabetes mellitus who have a fasting blood glucose concentration greater than about 8 mM, wherein the patient is administered a formulation comprising a GLP-1 molecule and a diketopiperazine by pulmonary inhalation with a dry powder inhalation system.

We claim: 
     
         1 . Use of a glucagon like peptide-1 (GLP-1) molecule in the manufacture of a medicament for treating hyperglycemia, wherein said medicament is administered to a subject having a fasting blood glucose concentration greater than about 7 mmol/L and said medicament comprises an inhalable dry powder formulation comprising a therapeutically effective amount of a GLP-1 molecule and a diketopiperazine. 
     
     
         2 . The use of  claim 1 , wherein the subject is a mammal having Type 2 diabetes mellitus. 
     
     
         3 . The use of  claim 1 , wherein the dry powder inhalable formulation comprises GLP-1 in an amount from about 0.01 mg to about 5 mg, or from about 0.02 mg to about 3 mg of GLP-1 in the formulation. 
     
     
         4 . The use of  claim 1 , wherein the inhalable dry powder formulation further comprises a DPP-IV inhibitor. 
     
     
         5 . The use of  claim 1 , wherein the diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The use of  claim 1 , wherein the GLP-1 molecule is selected from the group consisting of a native GLP-1, a GLP-1 metabolite, a GLP-1 analog, a GLP-1 derivative, a long acting GLP-1 analog, a GLP-1 mimetic, a GLP-1 peptide analog, or a biosynthetic GLP-1 analog, or combinations thereof and wherein said GLP-1 molecule has at least one biological activity of native GLP-1. 
     
     
         7 . Use of a GLP-1 molecule in the manufacture of a medicament for reducing glucose levels in a Type 2 diabetic patient, wherein the medicament is administered to said patient in need of treatment and wherein said medicament comprises a dry powder inhalable formulation for pulmonary administration comprising a therapeutically effective amount of a GLP-1 molecule, and a diketopiperazine or pharmaceutically acceptable salt thereof, wherein the Type 2 diabetic patient has a fasting blood glucose concentration greater than 8 mmol/L. 
     
     
         8 . The use of  claim 7 , wherein the glucose levels are reduced by about 0.1 mmol/L to about 3 mmol/L for a period of approximately four hours after administration of said inhalable formulation to said Type 2 diabetic patient. 
     
     
         9 . The use of  claim 7 , wherein the inhalable formulation is administered to said Type 2 diabetic patient prandially, preprandially, post-prandially or in a fasting state. 
     
     
         10 . The use of  claim 7 , wherein the GLP-1 formulation comprises from about 0.02 mg to about 3 mg of GLP-1 in the formulation. 
     
     
         11 . The use of  claim 7 , wherein the dry powder inhalable formulation comprises GLP-1 in an amount from about 0.01 mg to about 5 mg of GLP-1 in the formulation. 
     
     
         12 . The use of  claim 7 , wherein the inhalable dry powder formulation further comprises a DPP-IV inhibitor. 
     
     
         13 . The use of  claim 7 , wherein the diketopiperazine is 2,5-diketo-3,6-di(4-X-aminobutyl)piperazine; wherein X is selected from the group consisting of succinyl, glutaryl, maleyl, and fumaryl; or a pharmaceutically acceptable salt thereof. 
     
     
         14 . Use of a GLP-1 molecule in the manufacture of a medicament for inducing pulsatile insulin release in a subject, wherein said medicament is administered to a subject having a fasting blood glucose concentration greater than about 7 mmol/L and said medicament comprises an inhalable dry powder formulation comprising a therapeutically effective amount of a GLP-1 molecule and a diketopiperazine. 
     
     
         15 . An inhalable dry powder formulation for use in treating a patient having type 2 diabetes and a fasting blood glucose levels greater than 7 mmol/L characterized in that the formulation comprises a therapeutically effective amount of a GLP-1 molecule and a diketopiperazine. 
     
     
         16 . A method for treating hyperglycemia, comprising the step of administering to a subject having a fasting blood glucose concentration greater than about 7 mmol/L an inhalable dry powder formulation comprising a therapeutically effective amount of a GLP-1 molecule and a diketopiperazine.