Fusion proteins of GLP-1 and GDF15 and conjugates thereof

A fusion polypeptide comprising, from N terminus to C terminus, GLP-1, a polypeptide linker and GDF15, wherein the polypeptide linker has a length of at least 80 amino acid residues;

• wherein the GLP-1 comprises the amino acid sequence of X7X8EGTFTSDVSSYLEX22QAAX26X27FIAWLVX34GX36G (SEQ ID NO:
• 325), wherein:
• the X7 is H;
• the X8 is A, G, S, V, or Aib;
• the X22 is G, or E;
• the X26 is K, or R;
• the X27 is E;
• the X34 is R, or K, and the X36 is K, R, or G;
• and
• wherein the GDF15 comprises a combination of substitutions selected from the group consisting of:
• 1) N3Q, M57L, K69R, K107R, and K91R;
• 2) N3Q, K69R, K107R, and K91R;
• 3) K69R, K107R, and K91R;
• 4) N3Q, M57L, K107R, and K91R;
• 5) N3Q, K107R, and K91R;
• 6) K107R, and K91R;
• 7) N3Q, M57L, K69R, and K91R;
• 8) Deletion of the first three amino acid residues from the N-terminus of GDF-15 and M57L;
• 9) N3Q, M57L, M86L, K69R, K107R, K91R;
• 10) N3Q, M57L;
• 11) M57L;
• and 12) M57L, K69R, K107R, K91R, relative to the amino acid sequence of SEQ ID NO:
• 248,
• wherein the fusion polypeptide comprises only one conjugatable residue, in which the conjugatable residue is present in the polypeptide linker;
• wherein the conjugatable residue is introduced to a position ranging from the 5th to the 51st residues in the amino acid sequence of the polypeptide linker, with the N terminal residue in the polypeptide linker being the 1st residue.