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 pharmaceutical composition capable of enhancing GLP-1 activity in a human, comprising a polypeptide having the amino acid sequence of SEQ ID NO:1, wherein said pharmaceutical composition 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 at a time interval selected from: once every week, once every fourteen days, once every four weeks and once a month. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition is administered to said human once a week. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein said composition comprising a polypeptide having the amino acid sequence of SEQ ID NO:1 comprises about 0.25 mg to about 104 mg of said polypeptide. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition provides a maximum plasma concentration of at least about 0.6 nM to about 319 nM of the polypeptide having the amino acid sequence of SEQ ID NO:1 and an Area Under the Curve value of said polypeptide of at least about 3.5 nM×day to about 1936 nM×day over the period of one week. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition provides a maximum plasma concentration of at least about 8 nM to about 54 nM of the polypeptide having the amino acid sequence of SEQ ID NO:1 and providing AUC (Week 1) value of said polypeptide of at least about 29 nM×day to about 245 nM×day over the period of one week and wherein said pharmaceutical composition comprises about 16 mg to about 64 mg of said polypeptide. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition provides a serum half life of the polypeptide having the amino acid sequence of SEQ ID NO:1 of about 4 days to about 7 days. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein said pharmaceutical composition provides a Tmax value of the polypeptide having the amino acid sequence of SEQ ID NO:1 of about 1 day to about 5 days. 
     
     
         8 . The pharmaceutical composition of  claim 1 , further comprising mannitol, trehalose dihydrate, polysorbate 80, phosphate buffer and water for injection. 
     
     
         9 . The pharmaceutical composition of  claim 1  wherein the polypeptide having the amino acid sequence of SEQ ID NO:1 is present at a concentration in solution of 25 mg/mL. 
     
     
         10 . The pharmaceutical composition of  claim 1  wherein said polypeptide having the amino acid sequence of SEQ ID NO:1 is in an amount of about 0.25 mg to about 104 mg. 
     
     
         11 . The pharmaceutical composition of  claim 8  consisting of a polypeptide having the amino acid sequence of SEQ ID NO:1 at a concentration of 25 mg/mL from a lyophilized form 2.8% mannitol, 4.2% trehalose dihydrate, 0.01% polysorbate 80, 20 mM phosphate buffer at pH 7.2. 
     
     
         12 . A pharmaceutical composition for treating Type II diabetes in a human comprising about 24 mg to about 60 mg of a polypeptide having the amino acid sequence of SEQ ID NO:1, 2.8% mannitol, 4.2% trehalose dihydrate, 0.01% polysorbate 80, 20 mM phosphate buffer at pH 7.2 wherein said pharmaceutical composition provides a maximum plasma concentration of at least about 8 nM to about 54 nM of said polypeptide and an AUC (0-oc) value of said polypeptide after a single dose of at least about 99 nM×day to about 637 nM×day when said pharmaceutical composition is administered to said human at a time interval selected from: once every week, once every fourteen days, once every four weeks and once a month. 
     
     
         13 . The pharmaceutical composition of  claim 12  wherein said pharmaceutical composition is for subcutaneous injection. 
     
     
         14 . The pharmaceutical composition of  claim 13  wherein said pharmaceutical composition is administered to said human once a week. 
     
     
         15 . The pharmaceutical composition of  claim 14  comprising about 32 mg of said polypeptide.