| Liraglutide is a full agonist of the GLP-1 receptor and shares 97% of its amino acid sequence identity with human GLP-1. The Lys 34 in GLP-1 was substituted for by an arginine and an N-e(y- Glu[N-a-hexadecanoyl]) residue and was attached to Lys 26. This lipid anchor causes strong albumin binding, which protects the peptide against degradation. Semaglutide’s structure differs from liraglutide in two places. The Glycine at position 2 is substituted with Aib (U) and this modification provides significant protection against enzymatic degradation by DPP-4. In addition, a modified fatty acid chain and the two PEG2 spacers turned out to be optimal for both in vitro and in vivo prolonged duration of action. In June 2021, the US Food and Drug Administration (FDA) approved semaglutide injection sold under the brand name Wegovy for long-term weight management in adults. |