Semaglutide

Semaglutide is chemically similar to liraglutide, with the inclusion of two structural modifications (Lau, Bloch, et al., 2015). The first is the replacement of Gly with the non-proteinogenic amino acid 2-aminoisobutyric acid (Aib) at position 2. The second is the attachment of octadecanoic diacid to the side chain of Lys-26 through a short polyethylene glycol (PEG) spacer and a γ-glutamic acid linker. The amino acid substitution renders the peptide more resistant to DPP-4 compared to liraglutide, and the presence of the 18-carbon fatty acid moiety results in a high binding affinity for serum albumin, which translates to a half-life of approximately 7 days in humans