ArticlePharmaceutical research2022
Design and Development of a New Glucagon-Like Peptide-1 Receptor Agonist to Obtain High Oral Bioavailability.
Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Oral GLP-1-Based Therapeutics in the Obesity-Metabolic Syndrome-Diabetes Continuum: Translational Advances, Clinical Barriers, and Emerging Strategies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.Chemical reviews · 2025Review
- Advances in Oral Biomacromolecule Therapies for Metabolic Diseases.Pharmaceutics · 2025Review
- Oral absorption of semaglutide: pharmacokinetic modeling and molecular dynamics simulations.In silico pharmacology · 2025Article
- Gastrointestinal Permeation Enhancers for the Development of Oral Peptide Pharmaceuticals.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeSemaglutide is the only oral GLP-1 RA in the market, but oral bioavailability is generally limited in range of 0.4-1%. In this study, a new GLP-1RA named SHR-2042 was developed to gain higher oral bioavailability than semaglutide.
methodSelf-association of SHR-2042, semaglutide and liraglutide were assessed using SEC-MALS. The intestinal perfusion test in SD rats was used to select permeation enhancers (PEs) including SNAC, C10 and LCC. ITC, CD and DLS were used to explore the interaction between SHR-2042 and SNAC. Gastric administrated test in SD rats was used to screen SHR-2042 granules with different SHR-2042/SNAC ratios. The oral bioavailability of SHR-2042 was studied in rats and monkeys.
resultThe designed GLP-1RA, SHR-2042, gives a better solubility and lipophilicity than semaglutide. While it forms a similar oligomer with that of semaglutide. During the selection of PEs, SNAC shows better exposure than the other competing PEs including C10 and LCC. SHR-2042 and SNAC bind quickly and exhibit hydrophobic interaction. SNAC could promote monomerization of SHR-2042 and form micelles to trap the monomerized SHR-2042. The oral bioavailability of SHR-2042 paired with SNAC is 0.041% (1:0, w/w), 0.083% (1:10, w/w), 0.32% (1:30, w/w) and 2.83% (1:60, w/w) in rats. And the oral bioavailability of SHR-2042 matched with SNAC is 3.39% (1:30, w/w) in monkeys, which is over 10 times higher than that of semaglutide.
conclusionWe believe that the design and development of oral SHR-2042 will provide a new way to design more and more GLP-1RAs with high oral bioavailability in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.