Development of an orally delivered GLP-1 receptor agonist through peptide engineering and drug delivery to treat chronic disease.

ABSTRACT: Peptide therapeutics are increasingly used in the treatment of disease, but their administration by injection reduces patient compliance and convenience, especially for chronic diseases. Thus, oral administration of a peptide therapeutic represents a significant advance in medicine, but is challenged by gastrointestinal instability and ineffective uptake into the circulation. Here, we have used glucagon-like peptide-1 (GLP-1) as a model peptide therapeutic for treating obesity-linked type 2 diabetes, a common chronic disease. We describe a comprehensive multidisciplinary approach leading to the development of MEDI7219, a GLP-1 receptor agonist (GLP-1RA) specifically engineered for oral delivery. Sites of protease/peptidase vulnerabilities in GLP-1 were removed by amino acid substitution an

SUBMITTER: Pechenov S 

PROVIDER: S-EPMC8602401 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature