Herein is reported an Fc-region fusion polypeptide or Fc-region conjugate comprising one to four incretin receptor ligand polypeptides and a variant human Fc-region with a mutation of the amino acid residue at position 329 and at least one further mutation of at least one amino acid selected from the group comprising amino acid residues at position 228, 233, 234, 235, 236, 237, 297, 318, 320, 322 and 331 to a different residue, wherein the residues in the Fc-region are numbered according to the EU index of Kabat and its use as a medicament.本發明揭示一種Fc區融合多肽或Fc區結合物，其包含1至4個腸促胰島素受體配體多肽及變體人類Fc區，該變體人類Fc區在329位置處具有胺基酸殘基之突變及至少一個選自包含在228、233、234、235、236、237、297、318、320、322及331位置處之胺基酸殘基之群的胺基酸至不同殘基之至少一個其他突變，其中該Fc區中之該等殘基係根據Kabat之EU索引編號；及其作為藥劑之用途。
