IP Library › Granted Patent US 12703729

Granted Patent B2

US 12703729 · App. 18/371,680 · Granted Aug 11, 2026

GIP agonist compounds and methods

Inventors: Anne Pernille Tofteng Shelton (Søborg, DK); Pia Nørregaard (Søborg, DK); Maria Alexandrovna Deryabina (Søborg, DK); Bjarne Due Larsen (Søborg, DK); Jacob Ulrik Fog (Søborg, DK)

Assignee: Zealand Pharma A/S

C07K14/575 A61K38/22 A61K45/06 A61K38/00

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Quick Facts

Patent No.: US 12703729
App. No.: 18/371,680
Granted: Aug 11, 2026
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention relates to acylated GIP analogues which have GIP agonist activity, and their use in the treatment of metabolic disorders.

Claims (505)

1 . A pharmaceutical composition formulated as a liquid suitable for administration by injection or infusion comprising a GIP analogue, or a pharmaceutically acceptable salt thereof, in admixture with a carrier, wherein the GIP analogue is represented by the general Formula I:

(SEQ ID NO: 42)

R 1 -Tyr-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-X10-X11-X12-

Glu-Leu-X15-X16-X17-X18-X19-X20-X21-Phe-X23-X24-

X25-Leu-X27-X28-X29-Y1-Y2-R 2 (I)

wherein

R 1 is H—, Ac or pGlu (pyroglutamic acid, (S)-(−)-2-pyrrolidone-5-carboxylic acid);

X2 is Aib, Ala, D-Ala, Gly, Ser, N-Me-Ser, Ac3c, Ac4c or Ac5c;

X10 is Tyr, Leu or Ser;

X11 is Ser or Leu;

X12 is Lys, Ψ or Ile;

X15 is Asp or Glu;

X16 is Ser, Glu, Lys or Ψ;

X17 is Ile, Lys, Gln, Arg or Ψ;

X18 is His, Arg or Ala;

X19 is Gln, Lys, Ala or Glu;

X20 is Gln, Lys, Ala, His or Arg;

X21 is Ala, Leu, Asp or Glu;

X23 is Val or Ile;

X24 is Asn or Glu;

X25 is Tyr or Trp;

X27 is Leu, Glu, Ser, Lys or Val;

X28 is Ala, Ser or Arg;

X29 is Aib, Gly, Ala, Gln, Thr, Ser or Lys or is absent;

Y1 is Lys-Gly, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO: 43), Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser (SEQ ID NO: 44), Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser (SEQ ID NO: 45), Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser (SEQ ID NO: 46), Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln (SEQ ID NO: 47) or absent;

Y2 is Ψ or is absent;

R 2 is —NH 2 or —OH;

wherein Ψ is a residue independently selected from Lys, Arg, Orn and Cys and wherein the side chain of said residue is conjugated to a lipophilic substituent;

and wherein the GIP analogue contains one and only one residue Ψ.

2 . The pharmaceutical composition according to claim 1 , wherein Ψ is a residue of Lys, Arg, Orn or Cys in which the side chain of said residue is conjugated to a lipophilic substituent having the formula —Z 1 or —Z 2 —Z 1 .

3 . The pharmaceutical composition according to claim 2 , wherein —Z 1 is a fatty chain having at a terminus a connection —X— to Ψ or to Z 2 ;

wherein —X— is a bond, —CO—, —SO—, or —SO 2 —;

and, optionally, Z 1 has a polar group at the end of the chain distal from connection —X—; said polar group comprising a carboxylic acid or a carboxylic acid bioisostere, a phosphonic acid, or a sulfonic acid group.

4 . The pharmaceutical composition according to claim 2 , wherein Z 1 is:

A-B—C 16-20 alkylene-(CO)— wherein A is H or —COOH and B is a bond, or wherein Z 1 is selected from:

17-carboxy-heptadecanoyl HOOC—(CH 2 ) 16 —(CO)—;

19-carboxy-nonadecanoyl HOOC—(CH 2 ) 18 —(CO)—;

Octadecanoyl H 3 C—(CH 2 ) 16 —(CO)—; and

Eicosanoyl H 3 C—(CH 2 ) 18 —(CO)—.

5 . The pharmaceutical composition according to claim 2 , wherein Z 2 is a spacer bound at one terminus by Y, which is a nitrogen, oxygen or sulfur atom, and at the other terminus by X, which is a bond or an acyl (—CO—), sulfinyl (—SO—), sulfonyl (—SO 2 —) or absent.

6 . The pharmaceutical composition according to claim 2 , wherein —Z 1 —Z 2 is:

7 . The pharmaceutical composition according to claim 1 , wherein the GIP analogue has the sequence;

(SEQ ID NO: 1)

Y-Aib-EGTFISDYSIELDK-K(Hexadecanoyl-isoGlu)-

HQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 2)

Y-Aib-EGTFISDYSIELD-K(Hexadecanoyl-isoGlu)-I

HQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 3)

Y-Aib-EGTFISDYSIELEK-K(Hexadecanoyl-isoGlu)-

HQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 4)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQGPSSGAPPPS-

K([19-carboxy-nonadecanoyl]-isoGlu-

Peg3-Peg3);

(SEQ ID NO: 5)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQGPSSGAPPPS-

K(Hexadecanoyl-isoGlu);

(SEQ ID NO: 6)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQ-

K(Hexadecanoyl-isoGlu);

(SEQ ID NO: 7)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQKG-K

(Hexadecanoyl-isoGlu);

(SEQ ID NO: 8)

Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

HQQDFVNYLLAQGPSSGAPPPS;

(SEQ ID NO: 9)

Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

HQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 10)

Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 11)

Y-Aib-EGTFISDYSIELEK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAKEFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 12)

Y-Aib-EGTFISDYSIELEK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFVEWLLAQGPSSGAPPPS;

(SEQ ID NO: 13)

Y-Aib-EGTFISDYSIELEKIAQRAFVEWLLAQ

GPSSGAPPPS-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3);

(SEQ ID NO: 141)

[[H-]]Y-Aib-EGTFISDYSIELEKIAQRAFV

EWLLAQ-K([19-carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 15)

[[H-]]Y-Aib-EGTFISDYSIELDK-K([19-

carboxy-nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAGPSSGAPPPS;

(SEQ ID NO: 142)

[[H-]]Y-Aib-EGTFISDYSIELDKIAAQDFVNWLL

AGPSSGAPPPS-K([19-carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 17)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFVEWLLAQGPSSGAPPPS;

(SEQ ID NO: 18)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 19)

Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQRAFIEWLLAQ

GPSSGAPPPS;

(SEQ ID NO: 20)

Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQRAFVEWLLA

QGPSSGAPPPS;

(SEQ ID NO: 21)

Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQKEFVEWLLA

AGPSSGAPPPS

(SEQ ID NO: 22)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQKEFVEWLLAAGPSSGAPPPS;

(SEQ ID NO: 23)

Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAGP

SSGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 24)

Y-Aib-EGTFISDYSIELDKIAQKEFIEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 25)

Y-Aib-EGTFISDYSIELDKIAAQDFIEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 26)

Y-Aib-EGTFISDYSIELDKIAAQDFIEWLLAGP

SSGAPPPS-K((19-Carboxy-nonadecanoyl)-

[(Piperazine-1-yl)-acetyl]-Peg3-

Peg3);

(SEQ ID NO: 27)

Y-Aib-EGTFISDYSIELDKIAAQDFVEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 28)

Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAQGP

SSGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3);

(SEQ ID NO: 29)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQAFVNWLLAGPSSGAPPPS;

(SEQ ID NO: 30)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAAGPSSGAPPPS;

(SEQ ID NO: 31)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFINWLLAGPSSGAPPPS;

(SEQ ID NO: 32)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFIEWLLAGPSSGAPPPS;

(SEQ ID NO: 33)

Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AAQDFIEWLLAGPSS

GAPPPS;

(SEQ ID NO: 34)

Y-Aib-EGTFISDYSIELD-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

IAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 35)

Y-Aib-EGTFISDYS-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

ELDKIAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 36)

Y-DAla-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 37)

Y-DAla-EGTFISDYSIELDKIAAQDFIEWLLAG

PSSGAPPPS-K((19-Carboxy-nonadecanoyl)-

[(Piperazine-1-yl)-acetyl]-Peg3-Peg3);

(SEQ ID NO: 38)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 39)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFINWLLAQGPSSGAPPPS;

(SEQ ID NO: 40)

Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 41)

Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AAQAFIEWLLAQGP

SSGAPPPS.

8 . The pharmaceutical composition according to claim 1 , wherein the GIP analogue is:

(SEQ ID NO: 89)

H-Y-Aib-EGTFISDYSIELDK-K(Hexadecanoyl-isoGlu)-

HQQDFVNWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 90)

H-Y-Aib-EGTFISDYSIELD-K(Hexadecanoyl-isoGlu)-I

HQQDFVNWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 91)

H-Y-Aib-EGTFISDYSIELEK-K(Hexadecanoyl-isoGlu)-

HQQDFVNWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 92)

H-Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQGPSSGAPPPS-

K([19-carboxy-nonadecanoyl]-isoGlu-

Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 93)

YH--Aib-EGTFISDYSIELDKIHQQDFVNWLLAQGPSSGAPPPS-

K(Hexadecanoyl-isoGlu)-NH 2 ;

(SEQ ID NO: 94)

H-Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQ-

K(Hexadecanoyl-isoGlu)-NH 2 ;

(SEQ ID NO: 95)

H-Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQKG-K

(Hexadecanoyl-isoGlu)-NH 2 ;

(SEQ ID NO: 96)

H-Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

HQQDFVNYLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 97)

H-Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

HQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 98)

H-Y-Aib-EGTFISDYSIELDK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 99)

H-Y-Aib-EGTFISDYSIELEK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAKEFVNWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 100)

H-Y-Aib-EGTFISDYSIELEK-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFVEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 101)

H-Y-Aib-EGTFISDYSIELEKIAQRAFVEWLLAQ

GPSSGAPPPS-K([19-carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 102)

H-Y-Aib-EGTFISDYSIELEKIAQRAFV

EWLLAQ-K([19-carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 103)

H-Y-Aib-EGTFISDYSIELDK-K([19-

carboxy-nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 104)

H-Y-Aib-EGTFISDYSIELDKIAAQDFVNWLL

AGPSSGAPPPS-K([19-carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 105)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFVEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 106)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 107)

H-Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQRAFIEWLLAQ

GPSSGAPPPS-NH 2 ;

(SEQ ID NO: 108)

H-Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQRAFVEWLLA

QGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 109)

H-Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AQKEFVEWLLA

AGPSSGAPPPS-NH 2

(SEQ ID NO: 110)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQKEFVEWLLAAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 111)

H-Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAGP

SSGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 112)

H-Y-Aib-EGTFISDYSIELDKIAQKEFIEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 113)

H-Y-Aib-EGTFISDYSIELDKIAAQDFIEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 114)

H-Y-Aib-EGTFISDYSIELDKIAAQDFIEWLLAGP

SSGAPPPS-K((19-Carboxy-nonadecanoyl)-

[(Piperazine-1-yl)-acetyl]-Peg3-

Peg3)-NH 2 ;

(SEQ ID NO: 115)

H-Y-Aib-EGTFISDYSIELDKIAAQDFVEWLLAGPS

SGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 116)

H-Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAQGP

SSGAPPPS-K([19-Carboxy-nonadecanoyl]-

isoGlu-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 117)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQAFVNWLLAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 118)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFVNWLLAAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 119)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFINWLLAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 120)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFIEWLLAGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 121)

H-Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AAQDFIEWLLAGPSS

GAPPPS-NH 2 ;

(SEQ ID NO: 122)

H-Y-Aib-EGTFISDYSIELD-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

IAQRAFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 123)

H-Y-Aib-EGTFISDYS-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

ELDKIAQRAFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 124)

H-Y-DAla-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AQRAFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 125)

H-Y-DAla-EGTFISDYSIELDKIAAQDFIEWLLAG

PSSGAPPPS-K((19-Carboxy-nonadecanoyl)-

[(Piperazine-1-yl)-acetyl]-Peg3-Peg3)-NH 2 ;

(SEQ ID NO: 126)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 127)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQDFINWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 128)

H-Y-Aib-EGTFISDYSIELDK-K([19-Carboxy-

nonadecanoyl]-isoGlu-Peg3-Peg3)-

AAQAFIEWLLAQGPSSGAPPPS-NH 2 ;

(SEQ ID NO: 129)

H-Y-Aib-EGTFISDYSIELDK-K((19-Carboxy-

nonadecanoyl)-[(Piperazine-1-yl)-

acetyl]-Peg3-Peg3)-AAQAFIEWLLAQGP

SSGAPPPS-NH 2 .

9 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is a unit dosage form.

10 . The pharmaceutical composition according to claim 9 , wherein the unit dosage form is a single dose injectable form.

11 . The pharmaceutical composition according to claim 10 , wherein the single dose injectable form is an injection pen.

12 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is suitable for subcutaneous, intramuscular, intravenous or transdermal administration.

13 . The pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition is suitable for administration by an injection pen.

14 . A pharmaceutical composition formulated as a liquid suitable for administration by injection or infusion comprising a GIP analogue, or a pharmaceutically acceptable salt thereof, in admixture with a carrier, wherein the GIP analogue is represented by the general Formula II:

(SEQ ID NO: 48)

R 1 -Tyr-X2-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-X12-

Glu-Leu-X15-X16-X17-X18-X19-X20-X21-Phe-X23-X24-

X25-Leu-X27-X28-X29-Y1-Y2-R 2 (II)

wherein

R 1 is H—, Ac or pGlu;

X2 is Aib, Ala, D-Ala, Gly;

X12 is Lys, Ψ or Ile;

X15 is Asp or Glu;

X16 is Ser, Glu, Lys or Ψ;

X17 is Ile, Lys, Gln, Arg or Ψ;

X18 is His, Arg or Ala;

X19 is Gln or Ala;

X20 is Gln, Lys, Ala, His or Arg;

X21 is Ala, Asp or Glu;

X23 is Ile or Val;

X24 is Asn or Glu;

X25 is Tyr or Trp;

X27 is Leu, Glu, Ser, Lys or Val;

X28 is Ala, Ser or Arg;

X29 is Aib, Gly, Ala, Gln, Thr, Ser or Lys or is absent;

Y2 is Ψ or is absent;

R 2 is —NH 2 or —OH;

wherein Ψ is a Lys residue wherein the side chain of said Lys residue is conjugated to a lipophilic substituent;

and wherein the GIP analogue contains one and only one residue Ψ.

15 . A pharmaceutical composition formulated as a liquid suitable for administration by injection or infusion comprising a GIP analogue, or a pharmaceutically acceptable salt thereof, in admixture with a carrier, wherein the GIP analogue is represented by the general Formula III:

(SEQ ID NO: 50)

R 1 -Tyr-Aib-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-

Glu-Leu-X15-X16-X17-X18-X19-X20-X21-Phe-Val-X24-

X25-Leu-Leu-Ala-X29-Y1-Y2-R 2 (III)

wherein

R 1 is H—, Ac or pGlu;

X15 is Asp or Glu;

X16 is Lys or Ψ;

X17 is Ile or Ψ;

X18 is His or Ala

X19 is Gln or Ala;

X20 is Gln, Lys or Arg;

X21 is Ala, Asp or Glu;

X24 is Asn or Glu;

X25 is Tyr or Trp

X28 is Ala, Ser or Arg;

X29 is Gln or is absent;

Y1 is Lys-Gly, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, Pro-Ser-Ser-Gly-Ala-Pro-Pro-Ser, Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln or absent;

Y2 is Ψ or is absent;

R 2 is-NH 2 or —OH;

wherein Ψ is a residue independently selected from Lys, Arg, Orn and Cys and wherein the side chain of said residue is conjugated to a lipophilic substituent;

and wherein the GIP analogue contains one and only one residue Ψ.

16 . A pharmaceutical composition formulated as a liquid suitable for administration by injection or infusion comprising a GIP analogue, or a pharmaceutically acceptable salt thereof, in admixture with a carrier, wherein the GIP analogue has the following sequence;

(SEQ ID NO: 51)

Y-Aib-EGTFISDYSIELDKΨHQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 52)

Y-Aib-EGTFISDYSIELDΨIHQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 53)

Y-Aib-EGTFISDYSIELEKΨHQQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 54)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQGPSSGAPPPSΨ;

(SEQ ID NO: 55)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQΨ;

(SEQ ID NO: 56)

Y-Aib-EGTFISDYSIELDKIHQQDFVNWLLAQKGΨ;

(SEQ ID NO: 57)

Y-Aib-EGTFISDYSIELDKΨHQQDFVNYLLAQGPSSGAPPPS;

(SEQ ID NO: 59)

Y-Aib-EGTFISDYSIELDKΨAAQDFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 60)

Y-Aib-EGTFISDYSIELEKΨAAKEFVNWLLAQGPSSGAPPPS;

(SEQ ID NO: 61)

Y-Aib-EGTFISDYSIELEKΨAQRAFVEWLLAQGPSSGAPPPS;

(SEQ ID NO: 62)

Y-Aib-EGTFISDYSIELEKIAQRAFVEWLLAQGPSSGAPPPSΨ;

(SEQ ID NO: 63)

Y-Aib-EGTFISDYSIELEKIAQRAFVEWLLAQΨ;

(SEQ ID NO: 64)

Y-Aib-EGTFISDYSIELDKΨAAQDFVNWLLAGPSSGAPPPS;

(SEQ ID NO: 65)

Y-Aib-EGTFISDYSIELDKIAAQDFVNWLLAGPSSGAPPPSΨ;

(SEQ ID NO: 130)

Y-Aib-EGTFISDYSIELDKKΨAQRAFVEWLLAQGPSSGAPPPS;

(SEQ ID NO: 131)

Y-Aib-EGTFISDYSIELDKKΨAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 68)

Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAGPSSGAPPPSKΨ;

(SEQ ID NO: 69)

Y-Aib-EGTFISDYSIELDKIAQKEFIEWLLAGPSSGAPPPSKΨ;

(SEQ ID NO: 70)

Y-Aib-EGTFISDYSIELDKIAAQDFIEWLLAGPSSGAPPPSKΨ;

(SEQ ID NO: 71)

Y-Aib-EGTFISDYSIELDKIAAQDFVEWLLAGPSSGAPPPSKΨ;

(SEQ ID NO: 72)

Y-Aib-EGTFISDYSIELDKIAQRAFIEWLLAQGPSSGAPPPSKΨ;

(SEQ ID NO: 132)

Y-Aib-EGTFISDYSIELDKKΨAAQAFVNWLLAGPSSGAPPPS;

(SEQ ID NO: 133)

Y-Aib-EGTFISDYSIELDKKΨAAQDFVNWLLAAGPSSGAPPPS;

(SEQ ID NO: 134)

Y-Aib-EGTFISDYSIELDKKΨAAQDFINWLLAGPSSGAPPPS;

(SEQ ID NO: 135)

Y-Aib-EGTFISDYSIELDKKΨAAQDFIEWLLAGPSSGAPPPS;

(SEQ ID NO: 78)

Y-Aib-EGTFISDYSIELDKΨIAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 136)

Y-Aib-EGTFISDYSKΨELDKIAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 137)

Y-DAla-EGTFISDYSIELDKKΨAQRAFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 81)

Y-DAla-EGTFISDYSIELDKIAAQDFIEWLLAGPSSGAPPPSKΨ;

(SEQ ID NO: 138)

Y-Aib-EGTFISDYSIELDKKΨAAQDFIEWLLAQGPSSGAPPPS;

(SEQ ID NO: 139)

Y-Aib-EGTFISDYSIELDKKΨAAQDFINWLLAQGPSSGAPPPS;

(SEQ ID NO: 140)

Y-Aib-EGTFISDYSIELDKKΨAAQAFIEWLLAQGPSSGAPPPS.

17 . A method of treating a metabolic disorder in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 1 to the subject wherein the metabolic disorder is increased fasting glucose, dyslipidemia, atherosclerosis, atherogenic dyslipidemia, osteoporosis including increased risk of bone fractures, or blood fat disorders.

18 . The method according to claim 17 , wherein:

(a) the blood fat disorder is high triglycerides, low HDL cholesterol, high LDL cholesterol, plaque buildup in artery walls, or a combination thereof; and/or

19 . A method of treating a metabolic disorder in a subject, the method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 1 wherein the pharmaceutical composition is administered as part of a combination therapy with a GLP-1 agonist.

20 . The method according to claim 17 , wherein the metabolic disorder is diabetes or a diabetes related disorder, or obesity or an obesity related disorder.

21 . The method according to claim 20 , wherein:

(a) the diabetes related disorder is insulin resistance, glucose intolerance, increased fasting glucose, hypoglycemia, pre-diabetes, type 1 diabetes, type 2 diabetes, gestational diabetes hypertension, dyslipidemia, or a combination thereof; or

(b) the diabetes related disorder is atherosclerosis, arteriosclerosis, coronary heart disease, peripheral artery disease, stroke, atherogenic dyslipidemia, a blood fat disorder, elevated blood pressure, or hypertension;

(d) the obesity related disorder is obesity linked inflammation, obesity linked gallbladder disease, obesity induced sleep apnea, or a combination thereof.