Methods for administering long-lasting hypoglycemic agents

Abstract

The present invention relates to methods and pharmaceutical compositions relating to administering hypoglycemic agents and/or GLP-1 agonists wherein the mean maximum plasma concentration (Cmax) and/or Area Under the Curve (AUC) values of the hypoglycemic agent are increased and/or sustained.

1 . A method for enhancing GLP-1 activity in a human, which method comprises administering to said human a composition comprising at least one polypeptide having GLP-1 activity, wherein said polypeptide provides a maximum plasma concentration of said polypeptide of at least about 0.6 nM and an Area Under the Curve value of said polypeptide which is at least about 3.5 nM× day over the period of one week. 
     
     
         2 . The method of  claim 1 , wherein said at least one polypeptide having GLP-1 activity comprises at least one GLP-1 agonist. 
     
     
         3 . The method of  claim 2 , wherein said at least one GLP-1 agonist is selected from the group of: incretin hormone and/or fragment, variant and/or conjugate thereof and incretin mimetic and/or fragment, variant and/or conjugate thereof. 
     
     
         4 . The method of  claim 1 , wherein said at least one polypeptide having GLP-1 activity comprises at least one fragment and/or variant of human GLP-1 fused with human serum albumin. 
     
     
         5 . The method of  claim 4 , wherein said at least one fragment and variant of GLP-1 comprises GLP-1(7-36(A8G)). 
     
     
         6 . The method of  claim 5 , wherein at least one fragment and variant of GLP-1 is genetically fused to human serum albumin. 
     
     
         7 . The method of  claim 6 , wherein at least one fragment and variant of GLP-1 comprises at least two GLP-1(7-36(A8G)) tandemly and genetically fused to the human serum albumin. 
     
     
         8 . The method of  claim 7 , wherein at least two GLP-1(7-36(A8G)) are genetically fused at the N-terminus of the human serum albumin. 
     
     
         9 . The method of  claim 1  wherein said at least one polypeptide having GLP-1 activity comprises SEQ ID NO.: 1. 
     
     
         10 . The method of  claim 1 , wherein said composition comprising at least one polypeptide having GLP-1 activity is administered to said human once every seven days. 
     
     
         11 . The method of  claim 1 , wherein said composition comprising at least one polypeptide having GLP-1 activity is administered to said human once every fourteen days. 
     
     
         12 . The method of  claim 1 , wherein said composition comprising at least one polypeptide having GLP-1 activity is administered to said human once every month. 
     
     
         13 . The method of  claim 1 , wherein said composition comprising said at least one polypeptide having GLP-1 activity provides a maximum plasma concentration of at least about 0.6 nM to about 319 nM of said at least one polypeptide having GLP-1 activity and an Area Under the Curve value of at least about 3.5 nM× day to about 1936 nM× day over the period of one week of said at least one polypeptide having GLP-1 activity. 
     
     
         14 . The method of  claim 1 , wherein said composition comprising said at least one polypeptide having GLP-1 activity provides a maximum plasma concentration of at least about 8 nM to about 54 nM of said at least one polypeptide having GLP-1 activity and AUC (Week 1) value of at least about 29 nM× day to about 245 nM× day over the period of one week of said at least one polypeptide having GLP-1 activity. 
     
     
         15 . The method of  claim 1 , wherein said composition comprising said at least one polypeptide having GLP-1 activity provides a maximum plasma concentration of at least about 8 nM to about 54 nM of said at least one polypeptide having GLP-1 activity and an AUC (0-∞) value after a single dose of at least about 99 nM× day to about 637 nM× day over the period of one week of said at least one polypeptide having GLP-1 activity. 
     
     
         16 . The method of  claim 1 , wherein said human has type II diabetes mellitus. 
     
     
         17 . The method of  claim 16 , wherein said at least one polypeptide having GLP-1 activity reduces plasma glucose in said human wherein the weighted mean for AUC 0-24h  of plasma glucose measured as a change from baseline when compared to placebo of said human is clinically and statistically significantly reduced over the time period of about one week after administration of said composition comprising said at least one polypeptide having GLP-1 activity. 
     
     
         18 . The method of  claim 16 , wherein said at least one polypeptide having GLP-1 activity reduces plasma glucose in said human wherein the fasting plasma glucose measured as a change from baseline when compared to placebo of said human is clinically and statistically significantly reduced over the time period of about one week after administration of said composition comprising at least one polypeptide having GLP-1 activity. 
     
     
         19 . A method for enhancing GLP-1 activity in a human, which method comprises administering to said human a composition comprising at least one GLP-1 agonist, wherein said at least one GLP-1 agonist provides a maximum plasma concentration of said at least one GLP-1 agonist of at least about 21.2 pM and an Area Under the Curve value of said at least one GLP-1 agonist which is at least about 149 pM× day over the period of one week. 
     
     
         20 . A pharmaceutical composition capable of enhancing GLP-1 activity in a human, comprising at least one polypeptide having GLP-1 activity, wherein said polypeptide provides a maximum plasma concentration of said polypeptide of at least about 0.6 nM and an Area Under the Curve value of said polypeptide which is at least about 3.5 nM× day over the period of one week when administered to a human.