A first aspect of the invention relates to a single chain insulin analog comprising: (A) the A-chain of human or animal insulin, or an analog or derivative thereof； (B) the B-chain of human or animal insulin, or an analog or derivative thereof； (C) one or more disulfide bonds between said A-chain and said B-chain； and (D) a further covalent link, L, between a functional group of an amino acid in the A-chain and a functional group of an amino acid in the B-chain, at least one of said functional groups being an amino acid side chain functional group. Further aspects of the invention relate to pharmaceutical compositions comprising said single chain insulin derivatives, and therapeutic uses thereof.
