Ahmed Madny, Muzaffaruddin and Murthy, Aditya (2026) From Venom-to-Vial-to-Pill: The Translational Journey of GLP-1 Peptides and the Evolving Landscape of Biopharmaceutics Modeling. Journal of peptide science, 32. ISSN 1099-1387

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an important therapeutic option for metabolic disorders. Their development from the early identification of exendin-4 in Gila-monster venom to the creation of long-acting analogues and the first oral peptide marks a significant step in translational drug design. Each generation resolved issues of enzymatic instability, rapid clearance, and low permeability. These gains stemmed from improvements in acylation, fusion-protein engineering, and sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC) enabled absorption. This review integrates molecular evolution, formulation advances and biopharmaceutics modelling, including Physiologically based Biopharmaceutics Modeling (PBBM), to illustrate emerging strategies shaping next-generation oral peptide therapeutics

Item Type:	Article
Keywords:	GLP-1 receptor agonists; peptide engineering; oral semaglutide; SNAC; Physiologically based biopharmaceutics modelling; translational drug design
Date Deposited:	12 Mar 2026 00:45
Last Modified:	12 Mar 2026 00:45
URI:	https://oak.novartis.com/id/eprint/59461