| 主权项 |
1. A combination of compounds for use in a method for preventing or reducing weight gain; promoting weight loss; improving circulating glucose levels, glucose tolerance or circulating cholesterol levels; lowering circulating LDL levels; increasing HDL/LDL ratio; or treating a condition caused or characterized by excess body weight, wherein said method comprises administering to a mammalian subject a combination of compounds comprising:
(a) a compound having the formula:
R1—Z—R2 wherein R1 is H, C1-4 alkyl, acetyl, formyl, benzoyl, or trifluoroacetyl; R2 is OH or NH2; and Z is a peptide having the formula I:His-X2-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-X12-Tyr-Leu-Asp-X16-X17-Ala-Ala-X20-X21-Phe-Val-X24-Trp-Leu-X27-X28-Ala-X30; (I) wherein X2 is selected from Aib and Ser; X12 is selected from Lys, Arg, or Leu; X16 is selected from Arg and X; X17 is selected from Arg and X; X20 is selected from Arg, His, and X; X21 is selected from Asp and Glu; X24 is selected from Ala and X; X27 is selected from Leu and X; X28 is selected from Arg and X; X30 is X or is absent; wherein at least one of X16, X17, X20, X24, X27, X28, and X30 is X; and wherein each residue X is independently selected from the group consisting of Glu, Lys, Ser, Cys, Dbu, Dpr, and Orn; wherein the side chain of at least one residue X is conjugated to a lipophilic substituent having the formula: (i) Z1, wherein Z1 is a lipophilic moiety conjugated directly to the side chain of X; or (ii) Z1Z2, wherein Z1 is a lipophilic moiety, Z2 is a spacer, and Z1 is conjugated to the side chain of X via Z2; and (b) an insulin analogue. |
