A complex comprising a first heterodimer and a second heterodimer, each of the first heterodimer and second heterodimer comprising: (i) a first polypeptide comprising from N-terminus to C-terminus: a human IgG Fc comprising a hinge region and a CH3 sequence comprising at least one engineered protuberance comprising at least one substitution of the corresponding amino acid in a human IgG 1 Fc sequence, wherein the substitution is selected from the group consisting of Q347W/Y, T366W/Y, and T394W/Y according to EU numbering; a linker, a GDF15 mutein comprising a contiguous amino acid sequence at least 98 amino acids long and at least 95% identical to the amino acid sequence of SEQ ID NO:1 wherein the C-terminal amino acid corresponds to Isoleucine at position 112 in SEQ ID NO:1, and the contiguous amino acid sequence does not comprise the first two amino acids present at the N-terminus of SEQ ID NO:1, and wherein the GDF15 mutein comprises a D5T substitution relative to the amino acid sequence of SEQ ID NO:1; and (ii) a second polypeptide comprising from N-terminus to C-terminus: a human IgG Fc sequence comprising a hinge region and a CH3 sequence comprising at least one engineered cavity comprising at least one substitution of the corresponding amino acid in a human IgG 1 Fc sequence, wherein the substitution is selected from the group consisting of T366S, L368A, T394S, F405T/V/A, and Y407T/V/A, according to EU numbering; wherein the first polypeptide dimerizes with the second polypeptide via positioning of the protuberance of the first polypeptide into the cavity of the second polypeptide; and wherein the GDF15 mutein in the first heterodimer dimerizes with the GDF15 mutein in the second heterodimer thereby forming the complex comprising the first heterodimer and second heterodimer. (i) a first polypeptide comprising from N-terminus to C-terminus: a human IgG Fc comprising a hinge region and a CH3 sequence comprising at least one engineered protuberance comprising at least one substitution of the corresponding amino acid in a human IgG 1 Fc sequence, wherein the substitution is selected from the group consisting of Q347W/Y, T366W/Y, and T394W/Y according to EU numbering; a linker, a GDF15 mutein comprising a contiguous amino acid sequence at least 98 amino acids long and at least 95% identical to the amino acid sequence of SEQ ID NO:1 wherein the C-terminal amino acid corresponds to Isoleucine at position 112 in SEQ ID NO:1, and the contiguous amino acid sequence does not comprise the first two amino acids present at the N-terminus of SEQ ID NO:1, and wherein the GDF15 mutein comprises a D5T substitution relative to the amino acid sequence of SEQ ID NO:1; and a human IgG Fc comprising a hinge region and a CH3 sequence comprising at least one engineered protuberance comprising at least one substitution of the corresponding amino acid in a human IgG 1 Fc sequence, wherein the substitution is selected from the group consisting of Q347W/Y, T366W/Y, and T394W/Y according to EU numbering; a linker, a GDF15 mutein comprising a contiguous amino acid sequence at least 98 amino acids long and at least 95% identical to the amino acid sequence of SEQ ID NO:1 wherein the C-terminal amino acid corresponds to Isoleucine at position 112 in SEQ ID NO:1, and the contiguous amino acid sequence does not comprise the first two amino acids present at the N-terminus of SEQ ID NO:1, and wherein the GDF15 mutein comprises a D5T substitution relative to the amino acid sequence of SEQ ID NO:1; and (ii) a second polypeptide comprising from N-terminus to C-terminus: a human IgG Fc sequence comprising a hinge region and a CH3 sequence comprising at least one engineered cavity comprising at least one substitution of the corresponding amino acid in a human IgG 1 Fc sequence, wherein the substitution is selected from the group consisting of T366S, L368A, T394S, F405T/V/A, and Y407T/V/A, according to EU numbering; <EOS>