Peptide agonists of glp-1 activity

Abstract

Novel peptide agonists of GLP-1 activity useful for lowering blood glucose levels. The novel peptides comprise variants of the GLP-1 or the exendin-4 polypeptide sequence and are pharmacologically active and stable. These peptides are useful in the treatment of diseases that benefit from regulation of excess levels of blood glucose and/or regulation of gastric emptying, such as diabetes and eating disorders.

1 . The compound desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A method for treating type 2 diabetes mellitus in a subject in need thereof, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective for the treatment of type 2 diabetes mellitus. 
     
     
         3 . A method for stimulating insulin release in a subject, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective to stimulate insulin release. 
     
     
         4 . A method for lowering the blood glucose level in a subject, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective to lower the blood glucose level. 
     
     
         5 . A method for treating type 1 diabetes mellitus in a subject in need thereof, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective for the treatment of type 1 diabetes mellitus. 
     
     
         6 . A method for reducing gastric motility in a subject, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective to reduce gastric motility. 
     
     
         7 . A method for treating obesity in a subject in need thereof, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective for the treatment of obesity. 
     
     
         8 . A method for treating insulin resistance syndrome in a subject in need thereof, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective for the treatment of insulin resistance syndrome. 
     
     
         9 . A method for delaying gastric emptying in a subject, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective to delay gastric emptying. 
     
     
         10 . A method for treating hyperglycemia in a subject in need thereof, said method comprising administering to said subject desPro 36 -exendin-4(1-39)-Lys 6 -NH 2 , or a pharmaceutically acceptable salt thereof, in an amount that is effective for the treatment of hyperglycemia.