The discovery and development of liraglutide and semaglutide

Development history of two long-acting GLP-1 analogues from the developers' perspective. Describes the structural modifications (Aib8, Arg34, C18 diacid on Lys26) and their influence on half-life and receptor activity.

Key points

• Three targeted changes to GLP-1 extend the half-life from minutes to about a week.
• Fatty-acid albumin binding is described as the central principle of half-life extension.
• The paper summarises the preclinical and clinical programmes of the medicine.

Assessment

Evidence type: clinical, for the approved medicine. The authors are employees of the manufacturer. For peptide chemistry the paper is the best source on the design; the clinical data do not apply to research chemicals. Profile: Semaglutide.