| abstract |
The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve 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 selected from Chem. 1 : HOOC-(CH 2 ) x -CO-*, and Chem. 2: HOOC-C 6 H 4 -0-(CH 2 ) y -CO-*, in which x is an integer in the range of 6-18, and y is an integer in the range of 3-17; and the linker comprises Chem. 3: *-NH-(CH 2 ) q -CH[(CH 2 ) w -NH 2 ]-CO-*, wherein q is an integer in the range of 0-5, 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 peptides and side chain intermediates. The derivatives are potent, protracted, and suitable for oral administration. |