ArticleScientific reports2021
Development of an orally delivered GLP-1 receptor agonist through peptide engineering and drug delivery to treat chronic disease.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- The link between hyperuricemia and diabetes: insights from a quantitative analysis of scientific literature.Frontiers in endocrinology · 2024Pooled it
- Development and validation of a sensitive HPLC-MS/MS method for the analysis of semaglutide in human plasma.Bioanalysis · 2026Article
- Oral capsule administration of biomacromolecules that achieves bioavailability and pharmacokinetics comparable to subcutaneous injection in dogs - the BIONDDDrug delivery and translational research · 2026Article
- Advances in GLP-1 receptor agonists delivery systems for obesity and diabetes.Acta pharmaceutica Sinica. B · 2026Review
- Self-Assembly of a Therapeutic Peptide Surfactant: A Small-Angle X-ray Scattering Study.Langmuir : the ACS journal of surfaces and colloids · 2026Article
- Navigating the complexity of oral peptide delivery: challenges and strategies to enhance oral bioavailability.Frontiers in drug delivery · 2026Review
- Oral Treatment of Obesity by GLP-1 and Its Analogs.Pharmaceutics · 2025Review
- Artificial Intelligence Reveals Nature: Functional Parallels Between a Designed and a Natural Peptide.International journal of molecular sciences · 2025Article
- Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.Chemical reviews · 2025Review
- Design of potent and proteolytically stable double biaryl-stapled GLP-1R/GIPR peptide dual agonists.Bioorganic & medicinal chemistry · 2025Article
- Impact of Conjugation Chemistry on the Pharmacokinetics of Peptide-Polymer Conjugates in a Model of Traumatic Brain Injury.Bioconjugate chemistry · 2025Article
- In-vitro metabolite identification for MEDI7219, an oral GLP-1 analog, using LC-MS/MS with CID and EAD approaches.Bioanalysis · 2025Article
- Molecular Design of Unimolecular Tetra-Receptor Agonists.Journal of the American Chemical Society · 2025Article
- Metabolic resilience: liraglutide's potential in alleviating depressive symptoms.Molecular biology reports · 2025Review
- Pharmaceutical Analysis of Protein-Peptide Coformulations and the Influence of Polysorbates.Molecular pharmaceutics · 2025Article
- Design and Biosynthesis of Ornithine 8-Containing Semaglutide Variants with a Click Chemistry-Modifiable Position 26.ACS synthetic biology · 2025Article
- Investigations of Enteric-Coated Tablet Propyl Gallate-Induced Nephrotoxicity in Beagles as well as Human and Dog Renal Proximal Tubule Epithelial Cells.ACS pharmacology & translational science · 2025Article
- Advances in Oral Biomacromolecule Therapies for Metabolic Diseases.Pharmaceutics · 2025Review
- Central and peripheral neural circuits regulating glucose homeostasis.npj biomedical innovations · 2025Review
- Glucagon-like peptide-1 receptor: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2024 · on this mapReview
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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 and the peptide backbone was bis-lipidated to promote MEDI7219 reversible plasma protein binding without affecting potency. A combination of sodium chenodeoxycholate and propyl gallate was used to enhance bioavailability of MEDI7219 at the site of maximal gastrointestinal absorption, targeted by enteric-coated tablets. This synergistic approach resulted in MEDI7219 bioavailability of ~ 6% in dogs receiving oral tablets. In a dog model of obesity and insulin resistance, MEDI7219 oral tablets significantly decreased food intake, body weight and glucose excursions, validating the approach. This novel approach to the development of MEDI7219 provides a template for the development of other oral peptide therapeutics.
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