{"id":"doi:10.1016/j.ejphar.2026.179406","kind":"review","title":"GLP-1 receptor biology and the therapeutic role of incretin-based agonists in metabolic diseases","authors":["Koceva E","Moll GN"],"author_count":2,"year":2026,"published":"2026-10-08","venue":"European journal of pharmacology","cited_by":0,"doi":"10.1016/j.ejphar.2026.179406","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.ejphar.2026.179406","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.ejphar.2026.179406","updated":null,"pmid":"42849689","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Type 2 diabetes (T2DM) and obesity represent a growing global health burden, sharing underlying pathophysiological mechanisms such as impaired insulin signalling and chronic low-grade inflammation. The discovery of the incretin effect opened the way for agonist therapies targeting the glucagon-like peptide-1 receptor (GLP-1R) as therapies capable of addressing the metabolic dysregulation common to both diseases simultaneously. This review examines the biology of GLP-1 and the incretin system, with a focus on the structure and signalling mechanisms of GLP-1R, including biased agonism and receptor trafficking. The clinical effectiveness of stable, long-acting GLP-1RAs is evaluated across three therapeutic domains: T2DM management, obesity treatment, and emerging cardiovascular protection. Current evidence demonstrates that GLP-1RAs, which induce insulin secretion and suppress appetite, achieve superior glycaemic control and significant weight reduction compared with conventional therapies, with emerging cardiovascular benefits now extending to non-diabetic patients as well. The shift towards dual and triple receptor agonists, such as tirzepatide and retatrutide, together with biased agonist design, is a promising development for further improvements in effectiveness. Progress in oral formulations of GLP-1RAs may also improve tolerability and patient adherence. Nevertheless, important challenges remain, including gastrointestinal side effects, weight regain upon discontinuation, loss of lean body mass, and unresolved questions regarding long-term safety. In conclusion, while GLP-1R-based therapies represent a major therapeutic advancement, particularly for T2DM patients, their broader application in obesity management requires careful patient selection, continued long-term safety monitoring, and integration with lifestyle interventions.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"GLP-1 receptor biology and the therapeutic role of incretin-based agonists in metabolic diseases\" by Koceva E, Moll GN, https://doi.org/10.1016/j.ejphar.2026.179406, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"glp1-metabolic","name":"GLP-1 & Incretin Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[]}