An insulin prodrug comprising an A chain and a B chain wherein the A chain comprises the sequence Z-GIVEQCCX 1 SICSLYQLENX 2 CX 3 (SEQ ID NO: 3) and the B chain comprises the sequence of J-X 14 -X 4 LCGX 5 X 6 LVEALX 7 LVCGERGFX 8 (SEQ ID NO: 14), wherein Z and J are independently H or a dipeptide of the general structure: U-V; X 14 is a bond, or a 1 to 4 amino acid sequence selected from the group consisting of a FVNQ (SEQ ID NO: 11), VNQ, NQ and Q; X 1 is selected from the group consisting of threonine and histidine; X 2 is an amino acid of the general structure wherein X is selected from the group consisting of OH, NH 2, NHR 10 and OCH 3, wherein R 10 is a dipeptide of the general structure U-V; X 3 is selected from the group consisting of asparagine, ornithine, glycine, alanine, threonine, and serine; X 4 is selected from the group consisting of histidine and threonine; X 5 is selected from the group consisting of alanine, glycine and serine; X 6 is selected from the group consisting of histidine, aspartic acid, glutamic acid, homocysteic acid and cysteic acid; X 7 is an amino acid of the general structure wherein X 12 is selected from the group consisting of OH, NH 2, NHR 11 and OCH 3, wherein R 11 is a dipeptide of the general structure U-V; X 8 is histidine, asparagine or an amino acid of the general structure wherein X 13 is selected from the group consisting of H, OH, NH 2, NHR 12 and OCH 3, wherein R 12 is a dipeptide a dipeptide of the general structure U-V; wherein U is an amino acid selected from the group consisting of Aib, Gly, Ala, Leu, Met Asn, Glu, Asp, Gln, His, Lys, Arg, Ser, Cys, Pro, Phe, Tyr, Trp, Ile, Val, Thr, d-Ala, d-Leu, d-Met, d-Asn, d-Glu, d-Asp, d-Gln, d-His, d-Lys, d-Arg, d-Ser, d-Cys, d-Pro, d-Phe, d-Tyr, d-Trp, d-Ile, d-Val and d-Thr; and V is an amino acid selected from the group consisting of Gly(N-methyl), Ala(N-methyl), Leu(N-methyl), Met(N-methyl), Asn(N-methyl), Glu(N-methyl), Asp(N-niethyl), Gln(N-methyl), His(N-methyl), Lys(N-methyl), Arg(N-methyl), Ser(N-methyl), Cys(N-methyl), Phe(N-methyl), Tyr(N-methyl), Trp(N-methyl), Ile(N-methyl), Val(N-methyl), Thr(N-methyl), d-Ala(N-methyl), d-Leu(N-methyl), d-Met(N-methyl), d-Asn(N-methyl), d-Glu(N-methyl), d-Asp(N-methyl), d-Gln(N-methyl), d-His(N-methyl), d-Lys(N-methyl), d-Arg(N-methyl), d-Ser(N-methyl), d-Cys(N-methyl), d-Phe(N-methyl), d-Tyr(N-methyl), d-Trp(N-methyl), d-Ile(N-methyl), d-Val(N-methyl), d-Thr(N-methyl), Gly(N-hexyl), Ala(N-hexyl), Leu(N-hexyl), Met(N-hexyl), Asn(N-hexyl), Glu(N-hexyl), Asp(N-liexyl), Gln(N-hexyl), His(N-hexyl), Lys(N-hexyl), Arg(N-hexyl), Ser(N-hexyl), Cys(N-hexyl), Phe(N-hexyl), Tyr(N-hexyl), Trp(N-hexyl), Ile(N-hexyl), Val(N-hexyl), Thr(N-hexyl), d-Ala(N-hexyl), d-Leu(N-hexyl), d-Met(N-hexyl), d-Asn(N-hexyl), d-Glu(N-hexyl), d-Asp(N-hexyl), d-Gln(N-hexyl), d-His(N-hexyl), d-Lys(N-hexyl), d-Arg(N-hexyl), d-Ser(N-hexyl), d-Cys(N-hexyl), d-Phe(N-hexyl), d-Tyr(N-hexyl), d-Trp(N-hexyl), d-Ile(N-hexyl), d-Val(N-hexyl), d-Thr(N-hexyl), Tyr(N-C 1 -C 8 alkyl), Trp(N-C 1 -C 8 alkyl), Phe(N-C 1 -C 8 alkyl) and Gly(N-C 1 -C 8 alkyl); with the proviso that one and only one of X, X 12, X 13, J and Z comprises a dipeptide of the general structure: U-V.