Gip derivatives and uses thereof

A method for reducing weight by administering a pharmaceutical composition to a subject in need thereof,

• wherein pharmaceutical composition comprises a glucose-dependent insulinotropic polypeptide (GIP) analogue derivative and a glucagon-like peptide-1 (GLP-1) receptor agonist;
• wherein the GIP analogue derivative comprises a GIP analogue and a modifying group;
• wherein the GIP analogue is (SEQ ID NO:
• 48):
• X1-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Aa-X14-Asp-X16-Ile-X18-Gln-X20-Asp-Phe-Val-Lys-Trp-Leu-Leu-Ala-Gln-Lys-X31;
• wherein
• X1 is Tyr, D-Tyr, Ac-Tyr, or Ac-D-Tyr;
• X2 is Aib, Ala, or D-Ala;
• X14 is Leu, Nle, Asp or Met;
• X16 is Lys or Ala;
• X18 is Arg or His;
• X20 is Gln, Glu or Aib;
• X31 is Gly or Pro;
• wherein the modifying group is A-B-C;
• wherein A is
• wherein p is an integer in the range of 14-20, and
• wherein * denotes the position of an amide bond connecting A- and B-;
• wherein B is
• wherein q is an integer in the range of 0-1,
• wherein r is an integer in the range of 1-3,
• wherein * denotes the position of the amide bond connecting A- and B-,
• wherein ** denotes the position of an amide bond connecting B- and C-;
• and
• wherein C is
• wherein s is an integer in the range of 1-3,
• wherein t is an integer in the range of 1-4,
• wherein u is an integer in the range of 1-3,
• wherein ** denotes the position of the amide bond connecting B- and C-, and
• wherein *** denotes the position of an amide bond connecting C- and the epsilon amino group of the lysine at position 24.