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Abstract

The disclosure described herein provides for enzymatically stable and potent GLP-1 analogs (i.e., derivatives) for the treatment of metabolic disease or disorder in a subject. In some embodiments, the GLP-1 analog is a derivatized GLP-1 peptide, wherein the derivatized peptide has 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid differences from any one of GLP-1, GLP-1(7-39), GLP-1(7-36), GLP-1(7-37). In certain embodiments, the GLP-1 analog comprises at least one lysine substituent. The GLP-1 analogs described herein demonstrate potent receptor binding and extended plasma half-life. A pharmaceutical composition of the GLP-1 analogs is described herein for the treatment of metabolic disease or disorder in a subject, such as diabetes or obesity.

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