A fusion protein comprising or consisting of, a first polypeptide: glucagon-like peptide-1 (GLP-1) or an analogue thereof, a second polypeptide: a human IgG4 Fc portion and a third polypeptide: fibroblast growth factor 21 or a variant thereof, wherein the first polypeptide is linked to the second polypeptide via a first linker and the third polypeptide is linked to the second polypeptide via a second linker; and wherein the human IgG4 Fc portion comprises any one of the following combination of mutations: 1) S228P and R409K; 2) S228P, E233P and R409K; 3) S228P, N297A and R409K; 4) S228P, F234A, L235A and R409K; 5) S228P, F234V, L235E and R409K; and 6) S228P, F234A, L235A, R409K and K447, as compared to the wild-type human IgG4 Fc (EU Numbering System); the GLP-1 analogue comprises or consists of an amino acid sequence of SEQ ID NO: 7 (H X 1 EGTFTSDVSSYLE X 2 QAAKEFIAWL X 3 X 4 GX 5 X 6), wherein Xi is selected from G or V; X 2 is selected from E or G; X 3 is selected from V or K; X 4 is selected from K or N; X 5 is selected from G or E; and X 6 is selected from G, P or absent; and wherein the FGF21 comprises an amino acid sequence of SEQ ID NO: 15; wherein compared with SEQ ID NO: 15, the FGF21 variant comprises amino acid mutations at one or more sites of 98 or 171; wherein the amino acid mutation at position 98 is selected from the group consisting of L98D and L98R; and wherein the amino acid mutation at position 171 is selected from the group consisting of P171A and P171G; and wherein compared with SEQ ID NO: 15, the FGF21 variant further comprises one or more mutations at one or more sites selected from the group consisting of 167, 175 and 179; wherein the amino acid mutation at position 167 is selected from the group consisting of S167H and S167C; wherein the amino acid mutation at position 175 is selected from the group consisting of R175L, R175H and R175P; and wherein the amino acid mutation at position 179 is selected from the group consisting of Y 179S and Y179F. 1) S228P and R409K; 2) S228P, E233P and R409K; 3) S228P, N297A and R409K; 4) S228P, F234A, L235A and R409K; 5) S228P, F234V, L235E and R409K; and 6) S228P, F234A, L235A, R409K and K447, as compared to the wild-type human IgG4 Fc (EU Numbering System); the GLP-1 analogue comprises or consists of an amino acid sequence of SEQ ID NO: 7 (H X 1 EGTFTSDVSSYLE X 2 QAAKEFIAWL X 3 X 4 GX 5 X 6), wherein Xi is selected from G or V; X 2 is selected from E or G; X 3 is selected from V or K; X 4 is selected from K or N; X 5 is selected from G or E; and X 6 is selected from G, P or absent; and wherein the FGF21 comprises an amino acid sequence of SEQ ID NO: 15; wherein compared with SEQ ID NO: 15, the FGF21 variant comprises amino acid mutations at one or more sites of 98 or 171; wherein the amino acid mutation at position 98 is selected from the group consisting of L98D and L98R; and wherein the amino acid mutation at position 171 is selected from the group consisting of P171A and P171G; and wherein compared with SEQ ID NO: 15, the FGF21 variant further comprises one or more mutations at one or more sites selected from the group consisting of 167, 175 and 179; wherein the amino acid mutation at position 167 is selected from the group consisting of S167H and S167C; wherein the amino acid mutation at position 175 is selected from the group consisting of R175L, R175H and R175P; and wherein the amino acid mutation at position 179 is selected from the group consisting of Y 179S and Y179F.