Details for Patent: 5,990,077

Title:	Glucagon-like peptide-2 and its therapeutic use
Abstract:	Glucagon-like peptide 2, a product of glucagon gene expression, has been identified as a gastrointestinal tissue growth factor. Its effects on the growth of small intestine and on pancreatic islets are described. Its formulation as a pharmaceutical, and its therapeutic use in treating bowel tissue disorders and in treating diabetes, are described.
Inventor(s):	Drucker; Daniel J. (Toronto, CA)
Assignee:	1149336 Ontario Inc. (Toronto, CA)
Filing Date:	Apr 14, 1995
Application Number:	08/422,540
Claims:	1. A pharmaceutical composition, comprising a GLP-2, or a pharmaceutically acceptable salt thereof, and a carrier, said carrier being a pharmaceutically acceptable carrier other than saline solution. 2. The pharmaceutical composition according to claim 1, wherein the GLP-2 has the amino acid sequence: His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Thr -Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp, SEQ ID NO: 3. 3. The pharmaceutical composition according to claim 2, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 4. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 2 to promote the growth of small intestine tissue. 5. The pharmaceutical composition according to claim 2, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 6. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 2 to promote the growth of pancreatic islets. 7. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 2 to promote the growth of pancreatic islets. 8. The pharmaceutical composition according to claim 2, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 9. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 2 to promote the growth of gastrointestinal tissue. 10. The pharmaceutical composition according to claim 1, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 11. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 1 to promote the growth of small intestine tissue. 12. The pharmaceutical composition according to claim 11, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 13. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 1 to promote the growth of pancreatic islets. 14. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 1 to promote the growth of pancreatic islets. 15. The pharmaceutical composition according to claim 1, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 4) wherein: aa1 is a neutral, polar, large and nonaromatic amino acid residue; aa2 is a neutral and polar amino acid residue; aa3 is a neutral amino acid residue; aa4 is a neutral, polar, large and nonaromatic amino acid residue; aa5 is a neutral or basic amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 16. The pharmaceutical composition according to claim 15, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 17. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 15 to promote the growth of small intestine tissue. 18. The pharmaceutical composition according to claim 15, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 19. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 15 to promote the growth of pancreatic islets. 20. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 15 to promote the growth of pancreatic islets. 21. The pharmaceutical composition according to claim 15, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 22. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 15 to promote the growth of gastrointestinal tissue. 23. The pharmaceutical composition according to claim 1, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 5) wherein: aa1 is Ile or Val; aa2 is Asn or Ser; aa3 is Ala or Thr; aa4 is Ile or Leu; aa5 is Gln or His; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 24. The pharmaceutical composition according to claim 23, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 25. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 23 to promote the growth of small intestine tissue. 26. The pharmaceutical composition according to claim 23, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 27. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 23 to promote the growth of pancreatic islets. 28. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 23 to promote the growth of pancreatic islets. 29. The pharmaceutical composition according to claim 23, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 30. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 23 to promote the growth of gastrointestinal tissue. 31. The pharmaceutical composition according to claim 1, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 6) wherein: aa3 is a neutral amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 32. The pharmaceutical composition according to claim 31, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 33. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 31 to promote the growth of small intestine tissue. 34. The pharmaceutical composition according to claim 31, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 35. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 31 to promote the growth of pancreatic islets. 36. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 31 to promote the growth of pancreatic islets. 37. The pharmaceutical composition according to claim 31, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 38. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 31 to promote the growth of gastrointestinal tissue. 39. The pharmaceutical composition according to claim 1, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 7) wherein: aa3 is Ala or Thr; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 40. The pharmaceutical composition according to claim 39, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 41. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 39 to promote the growth of small intestine tissue. 42. The pharmaceutical composition according to claim 39, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 43. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 39 to promote the growth of pancreatic islets. 44. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 39 to promote the growth of pancreatic islets. 45. The pharmaceutical composition according to claim 39, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 46. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 39 to promote the growth of gastrointestinal tissue. 47. The pharmaceutical composition according to claim 1, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 48. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 1 to promote the growth of gastrointestinal tissue. 49. A pharmaceutical composition, comprising a GLP-2, or a pharmaceutically acceptable salt thereof, other than human GLP-2(1-34), and a pharmaceutically acceptable carrier. 50. The pharmaceutical composition according to claim 49, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 51. The pharmaceutical composition according to claim 49, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 52. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 49 to promote the growth of pancreatic islets. 53. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 49 to promote the growth of pancreatic islets. 54. The pharmaceutical composition according to claim 49, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 55. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 49 to promote the growth of gastrointestinal tissue. 56. A pharmaceutical composition, comprising a GLP-2, or a pharmaceutically acceptable salt thereof, other than human GLP-2(1-34) or human GLP-2(1-33), and a pharmaceutically acceptable carrier. 57. The pharmaceutical composition according to claim 56, wherein the GLP-2 is present in an amount effective to promote the growth of small intestine tissue. 58. The pharmaceutical composition according to claim 56, wherein the GLP-2 is present in an amount effective to promote the growth of pancreatic islets. 59. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 56 to promote the growth of pancreatic islets. 60. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 56 to promote the growth of pancreatic islets. 61. The pharmaceutical composition according to claim 56, wherein the GLP-2 is present in an amount effective to promote the growth of gastrointestinal tissue. 62. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition as claimed in claim 56 to promote the growth of gastrointestinal tissue. 63. A method for promoting the growth of small intestine tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition comprising a GLP-2 or a pharmaceutically acceptable salt thereof to promote the growth of small intestine tissue. 64. A method for promoting the growth of pancreatic islets in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition comprising a GLP-2 or a pharmaceutically acceptable salt thereof to promote the growth of pancreatic islets. 65. A method for treating a patient suffering from type 1 diabetes, comprising the step of administering to the patient an effective amount of a pharmaceutical comprising a GLP-2 or a pharmaceutically acceptable salt thereof to promote the growth of pancreatic islets. 66. A method for promoting the growth of gastrointestinal tissue in a patient in need thereof, comprising the step of administering to the patient an effective amount of a pharmaceutical composition comprising a GLP-2 or a pharmaceutically acceptable salt thereof to promote the growth of gastrointestinal tissue. 67. A pharmaceutical composition comprising a GLP-2, or a pharmaceutically acceptable salt thereof, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 4) wherein: aa1 is a neutral, polar, large and nonaromatic amino acid residue; aa2 is a neutral and polar amino acid residue; aa3 is a neutral amino acid residue; aa4 is a neutral, polar, large and nonaromatic amino acid residue; aa5 is a neutral or basic amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group; wherein the GLP-2 is other than human GLP-2(1-34). 68. The pharmaceutical composition according to claim 67, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 5) wherein: aa1 is Ile or Val; aa2 is Asn or Ser; aa3 is Ala or Thr; aa4 is Ile or Leu; aa5 is Gln or His; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 69. The pharmaceutical composition according to claim 68, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 6) wherein: aa3 is a neutral amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 70. The pharmaceutical composition according to claim 69, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 7) wherein: aa3 is Ala or Thr; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 71. A pharmaceutical composition comprising a GLP-2, or a pharmaceutically acceptable salt thereof, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 4) wherein: aa1 is a neutral, polar, large and nonaromatic amino acid residue; aa2 is a neutral and polar amino acid residue; aa3 is a neutral amino acid residue; aa4 is a neutral, polar, large and nonaromatic amino acid residue; aa5 is a neutral or basic amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group; wherein the GLP-2 is other than human GLP-2(1-34) or human GLP-2 (1-33). 72. The pharmaceutical composition according to claim 71, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 5) wherein: aa1 is Ile or Val; aa2 is Asn or Ser; aa3 is Ala or Thr; aa4 is Ile or Leu; aa5 is Gln or His; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 73. The pharmaceutical composition according to claim 72, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 6) wherein: aa3 is a neutral amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 74. The pharmaceutical composition according to claim 73, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 7) wherein: aa3 is Ala or Thr; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 75. The method according to claim 63, 64, 65, or 66, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 4) wherein: aa1 is a neutral, polar, large and nonaromatic amino acid residue; aa2 is a neutral and polar amino acid residue; aa3 is a neutral amino acid residue; aa4 is a neutral, polar, large and nonaromatic amino acid residue; aa5 is a neutral or basic amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group; wherein the GLP-2 is other than human GLP-2(1-34). 76. The method according to claim 75, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-aa1-Leu-Asp-aa2-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-aa4-aa5-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 5) wherein: aa1 is Ile or Val; aa2 is Asn or Ser; aa3 is Ala or Thr; aa4 is Ile or Leu; aa5 is Gln or His; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 77. The method according to claim 76, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 6) wherein: aa3 is a neutral amino acid residue; X is Arg, Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 78. The method according to claim 77, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 7) wherein: aa3 is Ala or Thr; X is Arg or Lys, Arg-Lys or Lys-Lys; Y is Arg or Arg-Arg; m is 0 or 1; n is 0 or 1; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 79. The pharmaceutical composition according to claim 1, 2, 10, 16, 24, 12, 18, 26, 15, 23, 31, 39, 32, 40, 3, 34, 42, 5, 49, 50, 57, 51, 58, 47, 8, 54, 61, 67, 68, 69, 70, 71, 72, 73, or 74, wherein the GLP-2 is of the formula: R1-[Y]m-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu -Ala-aa3-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-[X]n-R2 (SEQ ID NO: 7) wherein: aa3 is Ala or Thr; X is Arg; Y is Arg; m is 0; n is 0; R1 is H or an N-terminal blocking group; and R2 is OH or a C-terminal blocking group. 80. A method according to any one of claims 4, 6-7, 9, 11, 13, 14, 17, 19-20, 22, 25, 27-28, 30, 33, 35, 36, 38, 41, 43, 44, 46, 48, 52, 53, 55, 59-60 or 62-66, wherein the patient is a human patient.