| abstract |
The invention relates to a derivative of a GLP-1 peptide, which peptide comprises a first K residue and a second K residue, at positions corresponding to position 26, and 34, respectively, of GLP-1(7-37) (SEQ ID NO:1), and a maximum of eight amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is Chem. 2: HOOC—C 6 H 4 -0-(CH 2 ) y —CO—*, in which y is an integer in the range of 6-13; and the linker comprises Chem. 3a: *—NH—(CH 2 ) q —CH[(CH 2 ) w —NR 1 R 2 ]—CO—*, wherein q is an integer in the range of 0-5, R 1 and R 2 independently represent *—H or *—CH 3 , and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptide and linker intermediates. The derivatives are potent, stable, protracted, and suitable for oral administration. |