{"doi":"10.1016/j.celrep.2020.107768","title":"Corrination of a GLP-1 Receptor Agonist for Glycemic Control without Emesis","abstract":"Glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat type 2 diabetes mellitus often produce nausea, vomiting, and in some patients, undesired anorexia. Notably, these behavioral effects are caused by direct central GLP-1R activation. Herein, we describe the creation of a GLP-1R agonist conjugate with modified brain penetrance that enhances GLP-1R-mediated glycemic control without inducing vomiting. Covalent attachment of the GLP-1R agonist exendin-4 (Ex4) to dicyanocobinamide (Cbi), a corrin ring containing precursor of vitamin B12, produces a \"corrinated\" Ex4 construct (Cbi-Ex4). Data collected in the musk shrew (Suncus murinus), an emetic mammal, reveal beneficial effects of Cbi-Ex4 relative to Ex4, as evidenced by improvements in glycemic responses in glucose tolerance tests and a profound reduction of emetic events. Our findings highlight the potential for clinical use of Cbi-Ex4 for millions of patients seeking improved glycemic control without common side effects (e.g., emesis) characteristic of current GLP-1 therapeutics.","journal":"Cell Reports","year":2020,"id":94810,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":472508,"name":"Jayme L. Workinger","orcid":null,"position":1,"is_corresponding":false},{"id":472509,"name":"Ian C. Tinsley","orcid":null,"position":2,"is_corresponding":false},{"id":449782,"name":"Samantha M. Fortin","orcid":"0000-0002-4640-6837","position":3,"is_corresponding":false},{"id":472510,"name":"Lauren M. Stein","orcid":null,"position":4,"is_corresponding":false},{"id":429774,"name":"Oleg G. Chepurny","orcid":"0009-0002-2003-0752","position":5,"is_corresponding":false},{"id":429775,"name":"George G. Holz","orcid":"0000-0002-1781-3580","position":6,"is_corresponding":false},{"id":471787,"name":"Aleksandra J. Wierzba","orcid":"0000-0001-8347-5498","position":7,"is_corresponding":false},{"id":471788,"name":"Dorota Gryko","orcid":"0000-0002-5197-4222","position":8,"is_corresponding":false},{"id":471789,"name":"Ebba Nexø","orcid":"0000-0001-9406-9081","position":9,"is_corresponding":false},{"id":240309,"name":"Evan D. Shaulson","orcid":"0000-0002-8770-3926","position":10,"is_corresponding":false},{"id":472511,"name":"Ankur Bamezai","orcid":null,"position":11,"is_corresponding":false},{"id":472512,"name":"Valentina A. Rodriguez Da Silva","orcid":null,"position":12,"is_corresponding":false},{"id":240314,"name":"Bart C. De Jonghe","orcid":"0000-0002-6980-5355","position":13,"is_corresponding":false},{"id":240313,"name":"Matthew R. Hayes","orcid":"0000-0001-9782-6551","position":14,"is_corresponding":false},{"id":240311,"name":"Robert P. Doyle","orcid":"0000-0001-6786-5656","position":15,"is_corresponding":false},{"id":240308,"name":"Tito Borner","orcid":"0000-0001-9438-695X","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T22:33:00.770265Z","pmid":"32553160","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}