Method of preventing adverse effects by glp-1

Abstract

A method for preventing or reducing adverse effects such as profuse sweating, nausea and vomiting, which normally are associated with subcutaneous and intravenous administration of glucagon-like peptide 1 (GLP-1) therapy is provided. In particular, the method comprises the rapid administration of a GLP-1 formulation into the pulmonary circulation such as by inhalation, directly into pulmonary alveolar capillaries using a dry powder drug delivery system.

We claim: 
     
         1 . A method for the treatment of hyperglycemia and/or diabetes in a patient, comprising the step of administering prandially to a patient in need of treatment an inhalable dry powder formulation, comprising a therapeutically effective amount of a GLP-1 molecule; wherein said administration does not result in at least one side effect selected from the group consisting of nausea, vomiting and profuse sweating. 
     
     
         2 . The method of  claim 1 , wherein the patient is a mammal suffering with Type 2 diabetes mellitus. 
     
     
         3 . The method of  claim 1 , wherein the GLP-1 formulation comprises about 0.5 mg to about 3 mg of GLP-1 in the formulation. 
     
     
         4 . The method of  claim 1 , wherein the inhalable dry powder formulation further comprises a DPP-IV inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the inhalable dry powder formulation comprises a diketopiperazine. 
     
     
         6 . The method of  claim 5 , 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. 
     
     
         7 . The method 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, an exendin, a GLP-1 peptide analog, or a biosynthetic GLP-1 analog, or combinations thereof. 
     
     
         8 . The method of  claim 1 , further comprising administering to a patient a therapeutically amount of an insulin molecule. 
     
     
         9 . The method of  claim 8 , wherein the inhalable dry powder formulation comprises the GLP-1 molecule co-formulated with the insulin molecule. 
     
     
         10 . The method of  claim 8 , wherein the insulin molecule is administered separately as an inhalable dry powder formulation. 
     
     
         11 . The method of  claim 1 , wherein the inhalable dry powder formulation lacks inhibition of gastric emptying. 
     
     
         12 . A kit for the treatment of diabetes and/or hyperglycemia comprising:
 a) a medicament cartridge operably configured to fit into a dry powder inhaler and containing a dry powder formulation comprises a GLP-1 molecule, and a diketopiperazine of the formula: 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 salt thereof, and   b) an inhalation device operably configured to receive/hold and securely engage said cartridge.   
     
     
         13 . A method for reducing glucose levels in a Type 2 diabetic patient suffering with hyperglycemia, the method comprising the step of administering to said patient in need of treatment a dry powder inhalable formulation for pulmonary administration comprising a therapeutically effective amount of GLP-1, and a diketopiperazine or pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 12 , wherein the glucose levels are reduced by from 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 patient. 
     
     
         15 . The method of  claim 12 , wherein the inhalable formulation is administered to said Type 2 diabetic patient prandially, preprandially, prandially, post-prandially or in a fasting state. 
     
     
         16 . The method of  claim 12 , wherein the GLP-1 formulation comprises from about 0.02 mg to about 2 mg of GLP-1 in the formulation. 
     
     
         17 . The method of  claim 12 , wherein the inhalable dry powder formulation further comprises a DPP-IV inhibitor. 
     
     
         18 . The method of  claim 12 , wherein the inhalable dry powder formulation comprises a diketopiperazine. 
     
     
         19 . The method of  claim 19 , 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. 
     
     
         20 . The method of  claim 12 , wherein the inhalable dry powder formulation comprises the GLP-1 molecule co-formulated with an insulin molecule. 
     
     
         21 . The method of  claim 19 , wherein the method further comprises administering insulin as an inhalable dry powder formulation. 
     
     
         22 . The method of  claim 21 , wherein the insulin is a rapid acting or a long acting insulin. 
     
     
         23 . The method of  claim 12 , further comprising administering a formulation comprising a long acting GLP-1 analog. 
     
     
         24 . The method of  claim 12 , wherein the inhalable dry powder formulation lacks inhibition of gastric emptying. 
     
     
         25 . A kit for the treatment of hyperglycemia in a type 2 diabetic patient, which comprises a pulmonary drug delivery system, comprising:
 a) a medicament cartridge operably configured to fit into a dry powder inhaler and containing a dry powder formulation comprises a GLP-1 molecule, and a diketopiperazine of the formula: 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 salt thereof, and   b) an inhalation device operably configured to adapt and securely engage said cartridge.