Glp-1r agonist / fgf21 fusion proteins

A fusion protein comprising a GLP-1R (glucagon-like peptide-1 receptor) agonistic peptide and a functionally active variant of human FGF21 (fibroblast growth factor 21),

• wherein the GLP-1R agonistic peptide is a variant of native GLP-1(7-36) comprising up to about 15 substitutions of amino acid residues in the amino acid sequence of native GLP-1(7-36) (SEQ ID NO:
• 260);
• wherein the functionally active variant of human FGF21 comprises an amino acid sequence being at least about 96% identical to the amino acid sequence of SEQ ID NO:
• 250 or SEQ ID NO:
• 251 and comprises
• (i) substitutions Q55C and P147C or substitutions Q55C and N149C, and
• (ii) a substitution or deletion of G198 and/or P199,
• wherein numbering of the amino acid residues is in accordance with SEQ ID NO:
• 250;
• and
• wherein the GLP-1R agonistic peptide and the functionally active variant of human FGF21 are linked via a linker molecule comprising a structure selected from the group consisting of L - Fc, Fc - L, L1 - Fc - L2 and Fc, wherein L, L1 and L2 are independently selected from the group consisting of single amino acids and peptides, and Fc is an Fc domain of an immunoglobulin or a variant thereof.