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1. WO2000034331 - ANALOGUES OF GLP-1

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

CLAIMS

What is claimed is:

1. A compound of formula (I),

(R2R3)-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27- A 28- A 29 - A 30- A 31- A 32- A 33- A 34- A 35- A 36 - A 37- A 38 - A 39-R1 ,

(l)

wherein

A7 is L-His, Ura, Paa, Pta, Amp, Tma-His, des-amino-His, or deleted;

A8 is Ala, D-Ala, Aib, Aec, N-Me-Ala, N-Me-D-Ala or N-Me-Gly;

A9 is Glu, N-Me-Glu, N-Me-Asp or Asp;

A10 is Gly, Aec, β-Ala or Aib;

A11 is Thr or Ser;

A12 is Phe, Aec, Aic, Aib, 3-Pal, 4-Pal, β-Nal, Cha, Trp or X1-Phe;

A13 is Thr or Ser;

A14 is Ser or Aib;

A15 is Asp or Glu;

A16 is Val, Aec, Aib, Leu, lie, Tie, Nle, Abu, Ala or Cha;

A17 is Ser or Thr;

A18 is Ser or Thr;

A19 is Tyr, Cha, Phe, 3-Pal, 4-Pal, Aec, β-Nal or X1-Phe;

A20 is Leu, Ace, Aib, Nle, lie, Cha, Tie, Val, Phe or X1-Phe;

A21 is is Glu or Asp;

A22 is Gly, Ace, β-Ala, Glu or Aib;

A23 is Gin, Asp, Asn or Glu;

A24 is Ala, Aib, Val, Abu, Tie or Aec;

A25 is Ala, Aib, Val, Abu, Tle, Aec, Lys, Arg, hArg, Om, HN-CH((CH2)n-N(R10R11))- C(O) or HN-CH((CH2)e-X3)-C(O);

A26 is Lys, Arg, hArg, Orn, HN-CH((CH2)n-N(R10R11))-C(O) or HN-CH((CH2)e-X3)- C(O);

A27 is Glu Asp, Leu, Aib or Lys;

A28 is Phe, Pal, β-Nal, X1-Phe, Aic, Aec, Aib, Cha or Trp;

A29 is lie, Aec, Aib, Leu, Nle, Cha, Tie, Val, Abu, Ala or Phe;

A30 is Ala, Aib or Ace;

A31 is Trp, β-Nal, 3-Pal, 4-Pal, Phe, Aec, Aib or Cha;

A32 is Leu, Ace, Aib, Nle, lie, Cha, Tie, Phe, X1-Phe or Ala;

A33 is Val, Ace, Aib, Leu, lie, Tie, Nle, Cha, Ala, Phe, Abu, Lys or X1-Phe;

A34 is Lys, Arg, hArg, Orn, HN-CH((CH2)n-N(R10R11))-C(O) or HN-CH((CH2)e-X3)-C(O);

A35 is Gly, β-Ala, D-Ala, Gaba, Ava, HN-(CH2)m-C(O), Aib, Ace or a D-amino acid;

A36 is L- or D-Arg, D- or L-Lys, D- or L-hArg, D- or L-Orn, HN-CH((CH2)n-N(R10R11))- C(O), HN-CH((CH2)e-X3)-C(O) or deleted;

A37 is Gly, β-Ala, Gaba, Ava, Aib, Aec, Ado, Arg, Asp, Aun, Aec, HN-(CH2)m-C(O), HN-CH((CH2)n-N(R10R11))-C(O), a D-amino acid, or deleted;

A38 is D- or L-Lys, D- or L-Arg, D- or L-hArg, D- or L-Orn, HN-CH((CH2)n-N(R10R11))- C(O), HN-CH((CH2)e-X3)-C(O) Ava, Ado, Aec or deleted;

A39 is D- or L-Lys, D- or L-Arg, HN-CH((CH2)n-N(R10R11))-C(O), Ava, Ado, or Aec;

X1 for each occurrence is independently selected from the group consisting of (C,-C6)alkyl, OH and halo;

R1 is OH, NH2, (C1-C30)alkoxy, or NH-X2-CH2-Z0, wherein X2 is a (Cr

C12)hydrocarbon moiety, and Z0 is H, OH, CO2H or CONH2;

-NH- CH2)2-NH-C(O)-R13


or -C(O)-NHR12, wherein X4 is, independently for each occurrence, -C(O)-, -NH- C(O)- or -CH2-, and wherein f is, independently for each occurrence, an integer from 1 to 29 inclusive;

each of R2 and R3 is independently selected from the group consisting of H, (C1- C30)alkyl, (C2-C30)aikenyl, phenyl(C1-C30)alkyl, naphthy(C1-C30) alkyl, hydroxy(C1- C30)alkyl, hydroxy(C2-C30)alkenyl, hydroxypheny(C1-C30) alkyl, and

hydroxynaphthyl(C1-C30)alkyl; or one of R2 and R3 is
H

C30)acyl, (C1-C30)alkylsulfonyl, C(O)X5,

; wherein Y is H, OH or NH2; r is 0 to 4; q is 0 to 4; and X5 is (C1-C30)alkyl, (C2-C30)alkenyl, phenyl(C1-C30)a lkyl, naphthyl(C1-C30)alkyl, hydroxy(C1-C30)alkyl, hydroxy(C2-C30)alkenyl, hydroxyphenyl(C1-C30)alkyl or hydroxynaphthyl(C1-C30)alkyl;

e is, independently for each occurrence, an integer from 1 to 4 inclusive;

m is, independently for each occurrence, an integer from 5 to 24 inclusive;

n is, independently for each occurrence, an integer from 1 to 5, inclusive;

each of R10 and R11 is, independently for each occurrence, H, (C1-C30)alkyl, (C1-

C30)acyl, ((C1-C30)alkylsulfonyl, -C((NH)(NH2)) or


R12 and R13 each is, independently for each occurrence, (C1-C30)alkyl;

provided that:

when A7 is Ura, Paa or Pta, then R2 and R3 are deleted;

when R10 is (C1-C30)acyl, (C1-C30)alkylsulfonyl, -C((NH)(NH2)) or


, then R11 is H or (C1-C30)alkyl;

(i) at least one amino acid of a compound of formula (I) is not the same as the native sequence of hGLP-1 (7-36, -37 or -38)NH2 or hGLP-1 (7-36, -37 or -38)OH; (ii) a compound of formula (I) is not an analogue of hGLP-1 (7-36, -37 or -38)NH2 or hGLP-1 (7-36, -37 or -38)OH wherein a single position has been substituted by Ala; (iii) a compound of formula (I) is not (Arg26,34, Lys38)hGLP-1 (7-38)-E, (Lys26(Nε- alkanoyl))hGLP-1 (7-36, -37 or -38)-E, (Lys34(Nε-alkanoyl))hGLP-1 (7-36, -37 or - 38)-E, (Lys26,34-bis(NE-alkanoyl))hGLP-1 (7-36, -37 or -38)-E, (Arg26, Lys34(NE- alkanoyl))hGLP-1 (8-36, -37 or -38)-E, (Arg26,34, Lys36(Nε-alkanoyl))hGLP-1 (7-36, -37 or -38)-E or (Arg26,34, Lys38(Nε-aikanoyl))hGLP-1 (7-38)-E, wherein E is -OH or -NH2; (iv) a compound of formula (I) is not Z1-hGLP-1 (7-36, -37 or -38)-OH, Z1-hGLP-1 (7- 36, -37 or -38)-NH2, wherein Z1 is selected from the group consisting of:

(e) (Arg26), (Arg34), (Arg26,34), (Lys36), (Arg26, Lys36), (Arg34, Lys36), (D-Lys36), (Arg35), (D-Arg36), (Arg26,34, Lys36) or (Arg26 ,36, Lys34);

(f) (Asp21);

(g) at least one of (Aib8), (D-Ala8) and (Asp9); and

(h) (Tyr7), (N-acyl-His7), (N-alkyl-His7), (N-acyl-D-His7) or (N-alkyl-D-His7);

(v) a compound of formula (I) is not a combination of any two of the substitutions listed in groups (a) to (d); and

(vi) a compound of formula (I) is not (N-Me-Ala8)hGLP-1 (8-36 or -37), (Glu15)hGLP-1(7-36 or -37), (Asp21)hGLP-1(7-36 or -37) or (Phe31 )hGLP-1 (7-36 or -37) or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein A11 is Thr; A13 is Thr; A15 is Asp; A17 is Ser; A18 is Ser; A21 is Glu; A23 is Gin or Glu; A27 is Glu; and A31 is Trp; or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2, wherein A9 is Glu, N-Me-Glu or N-Me-Asp; A12 is Phe, Aec or Aic; A16 is Val, Ace or Aib; A19 is Tyr; A20 is Leu, Ace or Cha; A24 is Ala, Aib or Ace; A25 is Ala, Aib, Ace, Lys, Arg, hArg, Orn, HN-CH((CH2)n-N(R10R11))-C(O) or HN-CH((CH2)e-X3)-C(O); A28 is Phe; A29 is lie or Ace; A30 is Ala or Aib; A32 is Leu, Ace or Cha; and A33 is Val or Aec; or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 3, wherein A8 is Ala, D-Ala, Aib, A6c, A5c, N-Me-Ala, N-Me-D-Ala or N-Me-Gly; A10 is Gly; A12 is Phe, A6c or A5c; A16 is Val, A6c or A5c; A20 is Leu, A6c, A5c or Cha; A22 is Gly, β-Ala or Aib; A24 is Ala or Aib; A29 is lie, A6c or A5c; A32 is Leu, A6c, A5c or Cha; A33 is Val, A6c or A5c; A35 is Aib, β-Ala, Ado, A6c, A5c or Gly; and A37 is Gly, Aib, β-Ala, Ado, D-Ala or deleted; or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 4 or a pharmaceutically acceptable salt thereof, wherein X4 for each occurrence is -C(O)-; e for each occurrence is independently 1 or 2; and R1 is OH or NH2.

6. A compound according to claim 5 or a pharmaceutically acceptable salt thereof, wherein R2 is H and R3 is (C1-C30)alkyl, (C2-C30)alkenyl, (C1-C30)acyl, (C1-C30)alkylsulfonyl,


7. A compound according to claim 5 or a pharmaceutically acceptable salt thereof, wherein R10 is (C1-C30)acyl, (C1-C30)alkylsulfonyl or


' , and R11 is H.

8. A compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein R10 is (C4-C20)acyl, (C4-C20)alkylsulfonyl or


9. A compound according to claim 1 wherein said compound is

(Aib8,35)hGLP-1(7-36)NH2,

((Nα-HEPES-His)7, Aib8,35)hGLP-1 (7-36)NH2,

((Nα-HEPA-His)7, Aib8,35)hGLP-1 (7-36)NH2,

(Aib8, β-Ala35)hGLP-1 (7-36)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2,

(Aib8,35, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2,

(Aib8,35,37, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-decanoyl))hGLP-1(7-36)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-dodecanesulfonyl))hGLP-1(7-36)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-(2-(4-tetradecyl-1 -piperazine)-acetyl)))hGLP-1 (7-36)NH2, (Aib8,35, Arg26,34, Asp36(1-(4-tetradecyl-piperazine)))hGLP-1 (7-36)NH2,

(Aib8,35, Arg26,34, Asp36(1-tetradecyiamino))hGLP-1 (7-36)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl),β-Ala37)hGLP-1 (7-37)-OH or

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)-OH, or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 9 wherein said compound is (Aib8,35)hGLP-1 (7-36)NH2,

(Aib8, β-Ala35)hGLP-1 (7-36)NH2,

(Aib8,35, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2,

(Aib8,35,37, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)NH2,

(Aib8,35, Arg26,34, Lys36(Nε-decanoyl))hGLP-1 (7-36)NH2, or

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl),β-Ala37)hGLP-1(7-37)-OH, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent.

12. A method of eliciting an agonist effect from a GLP-1 receptor in a subject in need thereof which comprises administering to said subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A method of treating a disease selected from the group consisting of Type I diabetes, Type II diabetes, obesity, glucagonomas, secretory disorders of the airway, metabolic disorder, arthritis, osteoporosis, central nervous system disease, restenosis and neurodegenerative disease, in a subject in need thereof which comprises administering to said subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

14. A method according to claim 13 wherein said disease is Type I diabetes or Type II diabetes.

15. A compound according to claim 1 wherein said compound is

(Aib35)hGLP-1 (7-36)NH2;

(β-Ala35)hGLP-1 (7-36)NH2;

((Nα-Me-His)7, Aib8,35)hGLP-1(7-36)NH2;

((Nα-Me-His)7, Aib8, β-Ala35)hGLP-1(7-36)NH2;

((Nα-Me-His)7, Aib8,35, Arg26'34)hGLP-1(7-36)NH2;

((Nα-Me-His)7, Aib8, Arg26,34, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, A6c35)hGLP-1 (7-36)NH2;

(Aib8, A5c35)hGLP-1(7-36)NH2;

(Aib8, D-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, A6c32)hGLP-1 (7-36)NH2;

(Aib8,35, A5c32)hGLP-1 (7-36)NH2;

(Aib8,35, Glu23)hGLP-1 (7-36)NH2;

(Aib8,24,35)hGLP-1 (7-36)NH2;

(Aib8,30,35)hGLP-1 (7-36)NH2;

(Aib8,25,35)hGLP-1 (7-36)NH2;

(Aib8,35, A6c16,20)hGLP-1 (7-36)NH2;

(Aib8,35, A6c16,29,32)hGLP-1 (7-36)NH2;

(Aib8,35, A6c20,32)hGLP-1 (7-36)NH2;

(Aib8,35, A6c20)hGLP-1(7-36)NH2;

(Aib8,35, Lys25)hGLP-1 (7-36)NH2;

(Aib8,24,35, A6c20)hGLP-1 (7-36)NH2;

(Aib8,35, A6c29,32)hGLP-1 (7-36)NH2;

(Aib8,24,35, A6c2932)hGLP-1 (7-36)NH2;

(Aib8,35, A6c12)hGLP-1 (7-36)NH2;

(Aib8,35, Cha20)hGLP-1 (7-36)NH2;

(Aib8,35, A6c33)hGLP-1 (7-36)NH2;

(Aib8,35, A6c20,32)hGLP-1 (7-36)NH2;

(Aib8, A6c16,20, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, β-Ala22)hGLP-1 (7-36)NH2;

(Aib8,22,35)hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, A6c32)hGLP-1 (7-36)NH2;

(Aib8,24,35, Glu23, A6c32)hGLP-1 (7-36)NH2;

(Aib8,24,25,35, Glu23, A6c32)hGLP-1 (7-36)NH2;

(Aib8,24,25,35, A6c16,20,32, Glu23)hGLP-1 (7-36)NH2;

(Aib8, A6c32, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, A5c32, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Glu23, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,24, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,30, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,25, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, A6c16,20, β-Ala35)hGLP-1 (7-36)NH2; (Aib8, A6c16,29,32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, A6c20,32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, A6c20, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys25, β-Ala35)hGLP-1(7-36)NH2;

(Aib8,24, A6c20, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, A6c29,32, β-Ala35)hGLP-1(7-36)NH2;

(Aib8,24, A6c29,32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, A6c12, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Cha20, β-Ala35)hGLP-1(7-36)NH2;

(Aib8 , A6c33, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, A6c20,32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, β-Ala22,35)hGLP-1 (7-36)NH2;

(Aib8,22, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Glu23, A6c32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,24, Glu23, A6c32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,24, Glu23, A6c32, Lys34(Nε-octanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,24,25, Glu23, A6c32, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,24,25, A6c16,20,32, Glu23, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, D-Arg36)hGLP-1 (7-36)NH2;

(Aib8,35, D-Lys36)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, D-Arg36)hGLP-1(7-36)NH2;

(Aib8, β-Ala35, D-Lys36)hGLP-1(7-36)NH2;

(Aib8,35, Arg26,34)hGLP-1 (7-36)NH2;

(Aib8, Arg26,34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34)hGLP-1 (7-36)NH2;

(Aib8, Arg25,26,34, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Arg26,34, β-Ala35, Lys36(NE-tetradecanoyl))hGLP-1 (7-36)OH;

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-37)OH;

(Aib8,35,37, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-37)OH;

(Aib8,35, Arg26,34, Lys36(Nε-tetradecanoyl), D-Ala37)hGLP-1 (7-37)OH;

(Aib8,35,37, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)OH;

(Aib8,35, Arg26,34, β-Ala37, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)OH;

(Aib8,35, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)OH;

(Aib8, Arg26,34, Lys36(Nε-tetradecanoyl), β-Ala37)hGLP-1(7-37)OH; (Aib8 37, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-37)OH;

(Aib8,35, Arg26,34, Ado37)hGLP-1 (7-37)OH;

(Aib8,35, Arg26,34, Ado37)hGLP-1 (7-37)NH2;

(Aib8, Arg26,34, Lys36(Nε-tetradecanoyl), D-Ala37)hGLP-1 (7-37)OH; (Aib8,37, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)OH;

(Aib8, Arg26,34, β-Ala37, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)OH;

(Aib8,35, Lys26(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,35, Lys26(Nε-hexadecanoyl))hGLP-1(7-36)NH2 ;

(Aib8, Lys26(Nε-octanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys26(NE-tetradecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys26(Nε-hexadecanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8,35, Lys26(Nε-octanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-tetradecanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-hexadecanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-decanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys25, Lys26(N£-octanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys25, Lys26(Nε-tetradecanoyl), Arg34)hGLP-1(7-36)NH2; (Aib8,35, Lys25, Lys26(Nε-hexadecanoyl), Arg34)hGLP-1(7-36)NH2;

(Aib8,35, Arg25,34, Lys26(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,34, Lys26(Nε-tetradecanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Arg25,34, Lys26(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,34, Lys26(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8, Lys26(Nε-octanoyl), Arg34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys26(Nε-tetradecanoyl), Arg34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys26(Nε-hexadecanoyl), Arg34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys26(Nε-decanoyl), Arg34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8 35, Arg25,26, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2; (Aib8,35, Arg25,26, Lys34(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys25, Arg26, Lys34(Nε-octanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Lys25, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys25, Arg26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2; (Aib8,35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,35, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-hexadecanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-octanoyl))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-decanoyl))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-hexadecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-octanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-decanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)NH2; (Aib8,35,37, Arg25, 26,34, Lys38(Nε-hexadecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35 37, Arg26,34, Lys38(Nε-octanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-decanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-hexadecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-octanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25, 26,34, Lys38(Nε-decanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-tetradecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25, 26,34, Lys38(Nε-hexadecanoyl))hGLP-1 (7-38)NH2;

(Aib8,35, Lys25, Arg26,34, Lys36(Nε-octanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Lys25, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2; (Aib8,35, Lys25, Arg26,34, Lys36(Nε-hexadecanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Arg25,26,34, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2; (Aib8,35, Arg25,26,34, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25 ,26,34, Lys36(Nε-decanoyl))hGLP-1(7-36)NH2;

(Aib8, Lys34(Nε-octanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys34(Nε-tetradecanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys34(Nε-hexadecanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, A6c32, Lys34(NE-octanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Glu23, Lys34(Nε-octanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Glu23, A6c32, Lys34(Nε-octanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Arg26, Lys34(Nε-octanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg26, Lys34(Ne-tetradecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg26, Lys34(Nε-hexadecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg26, Lys34(Nε-decanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg25,26, Lys34(Nε-octanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Arg25,26, Lys34(Nε-tetradecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg25,26, Lys34(Nε-hexadecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Arg25,26, Lys34(Nε-decanoyl), β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys25, Arg26, Lys34(Nε-octanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys25, Arg26, Lys34(Nε-tetradecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys25, Arg26, Lys34(Nε-hexadecanoyl), β-Ala35)hGLP-1 (7-36)NH2; (Aib8, β-Ala35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8, β-Ala35, Lys36(Nε-hexadecanoyl))hGLP-1(7-36)NH2;

(Aib8, Arg26, β-Ala35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg26, β-Ala35, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg26, β-Ala35, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg26,34, β-Ala35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg26,34, β-Ala35, Lys36(Nε-tetradecanoyl))hGLP-1(7-36)NH2;

(Aib8, Arg26,34, β-Ala35, Lys36(Nε- hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg26,34, β-Ala35, Lys36(Nε-decanoyl))hGLP-1(7-36)NH2;

(Aib8, Lys25, Arg26,34, β-Ala35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8, Lys25, Arg26,34, Lys36(Nε-tetradecanoyl), β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys25, Arg26,34, β-Ala35, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2; (Aib8, Arg25,26,34, β-Ala35, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg25,26,34, β-Ala35, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg25,26,34, β-Ala35, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8, Arg25,26,34, β-Ala35, Lys36(Nε-decanoyl))hGLP-1 (7-36)NH2; (Aib8,35, Lys26(Nε-octanoyl), A6c32, Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-tetradecanoyl), A6c32, Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,35, Lys26(Nε-hexadecanoyl), A6c32, Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,35, A6c32, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, A6c32, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8 35, A6c32, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, A6c32, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, A6c32, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, A6c32, Lys36(Nε-octanoyl))hGLP-1(7-36)NH2;

(Aib8,35, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,35, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Arg26, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, A6c32, Lys36(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Lys26(Nε-octanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,24,35, Lys26(Nε-tetradecanoyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,24,35, Lys26(Nε-hexadecanoyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,24,35, Arg26, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Arg26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Arg26,34, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,24,35, Arg26,34, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Glu23, A6c32, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Lys26(Nε-octanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Lys26(Nε-tetradecanoyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,35, Glu23, Lys26(Nε-hexadecanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, A6c32, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,35, Glu23, Lys36(Nε-hexadecanoyi))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26,34, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8 ,35, Glu23, Arg26,34, Lys36(Nε-hexadecanoyl))hGLP-1(7-36)NH2;

(Aib8 ,30,35, Lys26(Nε-octanoyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,30,35, Lys26(Nε-tetradecanoyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,30,35, Lys26(Nε-hexadecanoyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,30,35, Arg26, Lys34(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,30,35, Arg26, Lys34(Nε-tetradecanoyl))hGLP-1 (7-36)NH2;

(Aib8,30,35, Arg26, Lys34(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,30,35, Arg26,34, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,30,35, Arg26,34, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,30,35, Arg26,34, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,35, Glu23, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26,34, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Glu23, Arg26,34, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8 ,35, Glu23, Arg26,34, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2; (Aib8 ,24,35, Glu23, Arg26,34, A6c32, Lys36(Nε-octanoyl))hGLP-1 (7-36)NH2;

(Aib8,24,35, Glu23, Arg26,34, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,24,35, Glu23, Arg26,34, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2; (Aib8,24,30,35, Glu23, Arg26,34, A6c32, Lys36(Nε-octanoyl))hGLP-1(7-36)NH2;

(Aib8,24,30,35, Glu23, Arg26,34, A6c32, Lys36(Nε-tetradecanoyl))hGLP-1 (7-36)NH2 ;

(Aib8,24,30,35, Glu23, Arg26,34, A6c32, Lys36(Nε-hexadecanoyl))hGLP-1 (7-36)NH2;

((Nα-HEPES-His)7, Aib35)hGLP-1 (7-36)NH2;

((Nα-HEPES-His)7, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-HEPES-His)7, Aib8, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-HEPA-His)7, Aib35)hGLP-1 (7-36)NH2;

((Nα-HEPA-His)7, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-HEPA-His)7, Aib8, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8,35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8, β-Ala35)hGLP-1(7-36)NH2;

((Nα-tetradecanoyl-His)7, Arg26,34, Aib35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Arg26,34, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8,35 , Arg26,34)hGLP-1(7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8, Arg26,34, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Arg25,26,34, β-Ala35)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8,35 , Arg25,26,34)hGLP-1 (7-36)NH2;

((Nα-tetradecanoyl-His)7, Aib8, Arg25,26,34, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-octanesulfonyl), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Lys26(Nε-dodecanesulfonyl), Arg34)hGLP-1 (7-36)NH2 ;

(Aib8,35, Lys26(Nε-hexadecanesulfonyl), Arg34)hGLP-1(7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-octanesulfonyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-dodecanesulfonyl))hGLP-1 (7-36)NH2;

(Aib8 ,35, Arg26, Lys34(Nε-hexadecanesulfonyl))hGLP-1 (7-36)NH2;

(Aib8 ,35, Arg26,34, Lys36(Nε-octanesulfonyi))hGLP-1 (7-36)NH2;

(Aib8 ,35, Arg26,34, Lys36(Nε-hexadecanesulfonyl))hGLP-1 (7-36)NH2;

(Aib8,35, Asp26(1-(4-decylpiperazine)), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Asp26(1-(4-dodecylpiperazine)), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Asp26(1 -(4-tetradecylpiperazine)), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Asp26(1-(4-hexadecylpiperazine)), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Asp34(1-(4-decylpiperazine)))hGLP-1(7-36)NH2;

(Aib8,35, Arg26, Asp34(1 -(4-dodecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Asp34(1-(4-tetradecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Asp34(1-(4-hexadecylpiperazine)))hGLP-1 (7-36)NH2; (Aib8,35, Arg 26,34, Asp36(1 -(4-decylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34 , Asp36(1-(4-dodecylpiperazine)))hGLP-1(7-36)NH2;

(Aib835, Arg26,34 , Asp36(1-(4-hexadecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34 , Asp38(1 -(4-decylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34 , Asp38(1 -(4-dodecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34 , Asp38(1-(4-tetradecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34 , Asp38(1-(4-hexadecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34 , Asp38(1-(4-decylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34 , Asp38(1-(4-dodecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34 , Asp38(1-(4-tetradecylpiperazine)))hGLP-1 (7-38)NH2; (Aib8,35,37, Arg26,34 , Asp38(1-(4-hexadecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,34, Asp26(1-(4-decylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,34, Asp26(1-(4-dodecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,34, Asp26(1-(4-tetradecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,34, Asp26(1 -(4-hexadecylpiperazine)))hGLP-1 (7-36)NH2; (Aib8,35, Arg25,26, Asp34(1 -(4-decylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Asp34(1 -(4-dodecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Asp34(1-(4-tetradecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Asp34(1-(4-hexadecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Asp36(1-(4-decylpiperazine)))hGLP-1(7-36)NH2;

(Aib8,35, Arg25,26,34, Asp36(1-(4-dodecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Asp36(1-(4-tetradecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Asp36(1 -(4-hexadecylpiperazine)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Asp38(1-(4-decylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,26,34, Asp38(1-(4-dodecylpiperazine)))hGLP-1 (7-38)NH2; (Aib8,35, Arg25,26,34, Asp38(1-(4-tetradecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,26,34, Asp38(1-(4-hexadecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Asp38(1-(4-decyipiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Asp38(1-(4-dodecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Asp38(1-(4-tetradecylpiperazine)))hGLP-1 (7-38)NH2; (Aib8,35,37, Arg25,26,34, Asp38(1 -(4-hexadecylpiperazine)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Glu36(1-dodecylamino))hGLP-1 (7-36)NH2;

(Aib8,35, Glu26(1-dodecylamino), Arg34)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Glu34(1-dodecylamino))hGLP-1(7-36)NH2;

(Aib8,35,37, Arg26,34, Glu38(1-dodecylamino))hGLP-1 (7-38)NH2;

(Aib8,35, Arg34, Lys26(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1(7-36)NH2;

(Aib8,35, Arg34, Lys26(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 ((-36)NH2;

(Aib8,35, Arg34, Lys26(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg34, Lys26(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2; (Aib8,35, Arg26, Lys34(Nε-(2-(4-decyl-1 -piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-(2-(4-dodecyl-1-piperazine)-acetyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26, Lys34(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg26,34, Lys38(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2; (Aib8,35, Arg26,34, Lys38(Nε-(2-(4-hexadecyl-1 -piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg26,34, Lys38(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2; (Aib8,35, Arg25,34, Lys26(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25 ,34, Lys26(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1(7-36)NH2;

(Aib8,35, Arg25,34, Lys26(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

Aib8,35, Arg25,34, Lys26(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26, Lys34(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2; (Aib8,35, Arg25,26,34, Lys36(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Lys36(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Lys36(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-36)NH2;

(Aib8,35, Arg25,26,34, Lys36(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1(7-36)NH2; (Aib8,35, Arg25,26,34, Lys38(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,26,34 , Lys38(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,26,34, Lys38(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35, Arg25,26,34, Lys38(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-(2-(4-decyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2; (Aib8,35,37, Arg25,26,34, Lys38(Nε-(2-(4-dodecyl-1-piperazine)-acetyl)))hGLP-1 (7-38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-(2-(4-tetradecyl-1-piperazine)-acetyl)))hGLP-1 (7- 38)NH2;

(Aib8,35,37, Arg25,26,34, Lys38(Nε-(2-(4-hexadecyl-1-piperazine)-acetyl)))hGLP-1 (7- 38)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-decanoyl))hGLP-1 (7-36)OH;

(Aib8,35, Lys25, Arg26,34, Lys36(Nε-decanoyl))hGLP-1 (7-36)OH;

(Aib8,35,Arg26,34, Ava37, Ado38)hGLP-1 (7-38)NH2;

(Aib8,35,Arg26,34, Asp37, Ava38, Ado39)hGLP-1 (7-39)NH2;

(Aib8,35,Arg26,34, Aun37)hGLP-1 (7-37)NH2;

(Aib8,17,35,)hGLP-1(7-36)NH2;

(AiN8 ,Arg26,34, β-Ala35, D-Asp37, Ava38, Aun39)hGLP-1(7-39)NH2;

(Gly8, β-Ala35)hGLP-1 (7-36)NH2;

(Ser8, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Glu22,23, β-Ala35)hGLP-1 (7-36)NH2;

(Gly8, Aib35)hGLP-1 (7-36)NH2;

(Aib8, Lys18, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Leu27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys33, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys18, Leu27, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, D-Arg36)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, D-Arg37)hGLP-1 (7-37)NH2;

(Aib8,27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,27, β-Ala35,37, Arg38)hGLP-1(7-38)NH2;

(Aib8,27, β-Ala35,37, Arg38,39)hGLP-1 (7-39)NH2;

(Aib8, Lys18,27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, Arg38)hGLP-1 (7-38)NH2;

(Aib8, Arg26,34, β-Ala35,)hGLP-1 (7-36)NH2;

(Aib8, D-Arg35)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, Arg37)hGLP-1(7-37)NH2;

(Aib8, Phe31, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, Phe31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal28,31)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Nal31)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Phe31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal19,31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal12,31)hGLP-1(7-36)NH2;

(Aib8,35, Lys36(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg34, Lys26(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-dodecanoyl))hGLP-1 (7-36)NH2;

(Aib8,B-Ala35,Ser37(O-decanoyl))hGLP1(7-37)-NH2;

(Aib8,27, β-Ala35,37, Arg38, Lys39(Nε-octanoyl))hGLP-1 (7-39)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-octanoyl))hGLP-1 (7-37)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-decanoyl))hGLP-1(7-37)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-tetradecanoyl))hGLP-1(7-37)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-dodecanoyl))hGLP-1 (7-37)NH2; or

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-dodecanoyl))hGLP-1 (8-37)NH2;

or a pharmaceutically acceptable salt thereof.

16. A compound according to claim 15 wherein said compound is

(Aib8,35, A6c32)hGLP-1 (7-36)NH2;

(Aib8,35, Glu23)hGLP-1 (7-36)NH2;

(Aib8,2435)hGLP-1(7-36)NH2;

(Aib8,35, Glu23, A6c32)hGLP-1 (7-36)NH2;

(Aib8, Glu23, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-octanoyl))hGLP-1(7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-decanoyl))hGLP-1 (7-36)OH;

(Aib8,35, Lys25, Arg26,34, Lys36(Nε-decanoyl))hGLP-1(7-36)OH;

(Aib8, Arg26,34, β-Ala35, Lys36(Nε-Aec-decanoyl))hGLP-1 (7-36)NH2; (Aib8,35,Arg26,34, Ava37, Ado38)hGLP-1(7-38)NH2;

(Aib8,35,Arg26,34, Asp37, Ava38, Ado39)hGLP-1 (7-39)NH2;

(Aib8,35,Arg26,34, Aun37)hGLP-1 (7-37)NH2;

(Aib8,17,35,)hGLP-1 (7-36)NH2;

(Aib8 ,Arg26,34, β-Ala35, D-Asp37, Ava38, Aun39)hGLP-1 (7-39)NH2; (Gly8, β-Ala35)hGLP-1 (7-36)NH2;

(Ser8, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Glu2223, β-Ala35)hGLP-1 (7-36)NH2;

(Gly8, Aib35)hGLP-1(7-36)NH2;

(Aib8, Lys18, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Leu27, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys33, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, Lys18, Leu27, β-Ala35)hGLP-1(7-36)NH2;

(Aib8, D-Arg36)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, D-Arg37)hGLP-1 (7-37)NH2;

(Aib8,27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8,27, β-Ala35,37, Arg38)hGLP-1(7-38)NH2;

(Aib8,27, β-Ala35,37, Arg38,39)hGLP-1 (7-39)NH2;

(Aib8, Lys1827, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, Lys27, β-Ala35)hGLP-1 (7-36)NH2;

(Aib8, β-Ala35, Arg38)hGLP-1(7-38)NH2;

(Aib8, Arg26,34, β-Ala35,)hGLP-1 (7-36)NH2;

(Aib8, D-Arg35)hGLP-1(7-36)NH2;

(Aib8, β-Ala35, Arg37)hGLP-1(7-37)NH2;

(Aib8, Phe31, β-Ala35)hGLP-1(7-36)NH2;

(Aib8,35, Phe31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal28,31)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Nal31)hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Phe31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal19,31)hGLP-1 (7-36)NH2;

(Aib8,35, Nal12,31)hGLP-1 (7-36)NH2;

(Aib8,35, Lys36(Nε-decanoyl))hGLP-1 (7-36) NH2;

(Aib8,35, Arg34, Lys26(Nε-decanoyl))hGLP-1 (7-36)NH2;

(Aib8,35, Arg26,34, Lys36(Nε-dodecanoyl))hGLP-1 (7-36)NH2;

(Aib8,B-Ala35, Ser37 O-decanoyl))hGLPI(7-37)-NH2;

(Aib8,27, β-Ala35,37, Arg38, Lys39(Nε-octanoyl))hGLP-1 (7-39)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-octanoyl))hGLP-1 (7-37)NH2;

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-decanoyl))hGLP-1 (7-37)NH2; or

(Aib8, Arg26,34, β-Ala35, Lys37(Nε-tetradecanoyl))hGLP-1 (7-37)NH2;

or a pharmaceutically acceptable salt thereof.

17. Use of a compound as claimed in any of claims 1 to 10, or 15 or 16, in the preparation of a medicament for the treatment of disease.

18. Use as claimed in claim 17, in which the disease is selected from the group consisting of Type I diabetes, Type II diabetes, obesity, glucagonomas, secretory disorders of the airway, metabolic disorder, arthritis, osteoporosis, central nervous system disease, restenosis and neurodegenerative disease.