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Kahles, F.* ; Birkenfeld, A.L. ; Marx, N.*

GLP-1 and the cardiovascular system.

J. Clin. Invest. 136:e194748 (2026)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The incretin hormone glucagon-like peptide-1 (GLP-1) exerts potent effects on glucose metabolism, prompting the development of therapeutic strategies that enhance activity of the GLP-1 receptor (GLP-1R) pathway. Inhibitors of dipeptidyl peptidase 4 (DPP-4) prolong the half-life of endogenous GLP-1 and typically achieve reductions in HbA1c of 0.5%-0.8%. However, large-scale cardiovascular (CV) outcomes trials (CVOTs) with DPP-4 inhibitors demonstrated CV safety but did not show a reduction in CV events. A second incretin-based therapeutic approach was the development of GLP-1R agonists (GLP-1RAs). Various GLP-1RAs, including liraglutide, semaglutide, and dulaglutide, demonstrated a reduction in CV outcomes in large CVOTs. Initially, these medications were only available as injectable agents for subcutaneous administration, but recent technological advancements have enabled the development of orally available GLP-1RAs. A third incretin-based approach is tirzepatide, a dual agonist of GLP-1R and glucose-dependent insulinotropic polypeptide receptor (GIPR), which achieves greater HbA1c reduction and weight loss compared with GLP-1RAs alone. Ongoing large-scale CVOTs will determine its effects on hard cardiovascular endpoints. This Review summarizes the effects of GLP-1 and GLP-1RAs in the CV system as well as clinical data of GLP-1RAs in individuals with CV disease or high CV risk.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Peptide-1 Receptor Agonists; Myocardial Glucose-uptake; Chronic Heart-failure; Atherosclerotic Lesions; Ventricular-function; Clinical-outcomes; Cardiac-function; Conscious Dogs; Double-blind; Mouse Model
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Zeitschrift Journal of Clinical Investigation
Quellenangaben Band: 136, Heft: 4, Seiten: , Artikelnummer: e194748 Supplement: ,
Verlag American Society of Clinical Investigation
Verlagsort 2015 Manchester Rd, Ann Arbor, Mi 48104 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)
Förderungen Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (IZKF project)
German Research Foundation)
German Ministry of Education and Science (BMBF) via the German Center for Diabetes Research (DZD e.V.)
European Research Area Network on Cardiovascular Diseases (ERA-CVD)
BMBF
European Foundation for the Study of Diabetes (EFSD)/Novo Nordisk Foundation grant
Deutsche Forschungsgemeinschaft (DFG