Creating Glepaglutide: The First Long-Acting GLP-2 Analogue to enable a Ready-to-Use Subcutaneous Injection

Background: Human glucagon-like peptide-2 (hGLP-2) receptor agonists can be used for treatment of short bowel syndrome (SBS). Native GLP-2 is physically unstable in solution and is a so-called “difficult sequence”, resulting in low yields and complex mixtures in solid phase synthesis. We aimed in this work to resolve these challenges. This study describes the design and characterization of a long-acting GLP-2 analogue, glepaglutide, with physical and chemical properties enabling a ready-to-use formulation.