Double-acylated GLP-1 derivatives

The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue and a second K residue, at positions corresponding to position 26, and 37, 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 selected from Chem. 1: HOOC-(CH2)x-CO-*, and Chem. 2: HOOC-C6H4-O-(CH2)y-CO-*, in which x is an integer in the range of 8-16, and y is an integer in the range of 6-13; and the linker comprises Chem. 3: *-NH-(CH2)q-CH[(CH2)w-NR1R2]-CO-*, which is connected at its CO-* end to the epsilon amino group of the first or the second K residue of the GLP-1 analogue, and wherein q is an integer in the range of 0-5, R1 and R2 independently represent *-H or *-CH3, 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.