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Article

Contractile Effects of Semaglutide in the Human Atrium

1
Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Magdeburger Straße 4, D-06112 Halle (Saale), Germany
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, SK-83232 Bratislava, Slovakia
3
Department of Cardiac Surgery, Mid-German Heart Center, University Hospital Halle, Ernst-Grube-Straße 40, D-06097 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2024, 16(9), 1139; https://doi.org/10.3390/pharmaceutics16091139
Submission received: 24 July 2024 / Revised: 22 August 2024 / Accepted: 27 August 2024 / Published: 28 August 2024
(This article belongs to the Section Biologics and Biosimilars)

Abstract

Semaglutide is a glucagon-like peptide 1 receptor (GLP-1R) agonist. GLP-1R agonists are used to treat type 2 diabetes and obesity. It is currently unknown whether semaglutide can directly increase force of contraction (FOC) in the human heart. We tested the hypothesis that semaglutide might increase the FOC in the isolated human atrium. To this end, we conducted contraction experiments in isolated human right atrial muscle preparations (HAP). HAP were obtained during open-heart surgery. We detected a concentration- and time-dependent positive inotropic effect (PIE) of semaglutide in HAP. These PIEs were accompanied by increases in the rates of tension development and tension relaxation and a reduction in muscle relaxation time. The PIE of semaglutide in HAP was attenuated by H89, an inhibitor of the cyclic AMP-dependent protein kinase and by ryanodine, an inhibitor of sarcoplasmic Ca2+ release. Semaglutide up to 100 nM failed to exert a PIE in isolated electrically paced (1 Hz) wild-type mouse left atrial preparations studied for comparison. Our data suggest that semaglutide can increase the FOC in the atria of patients at therapeutic drug concentrations.
Keywords: semaglutide; GLP-1 receptor; human atrium; inotropy semaglutide; GLP-1 receptor; human atrium; inotropy

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MDPI and ACS Style

Neumann, J.; Hadová, K.; Klimas, J.; Hofmann, B.; Gergs, U. Contractile Effects of Semaglutide in the Human Atrium. Pharmaceutics 2024, 16, 1139. https://doi.org/10.3390/pharmaceutics16091139

AMA Style

Neumann J, Hadová K, Klimas J, Hofmann B, Gergs U. Contractile Effects of Semaglutide in the Human Atrium. Pharmaceutics. 2024; 16(9):1139. https://doi.org/10.3390/pharmaceutics16091139

Chicago/Turabian Style

Neumann, Joachim, Katarína Hadová, Jan Klimas, Britt Hofmann, and Ulrich Gergs. 2024. "Contractile Effects of Semaglutide in the Human Atrium" Pharmaceutics 16, no. 9: 1139. https://doi.org/10.3390/pharmaceutics16091139

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