Hemodynamic and metabolomic responses to infusion of GLP-1 agonist exenatide in pulmonary arterial hypertension
File(s)
Author(s)
Type
Journal Article
Abstract
Preclinical studies suggest beneficial effects of GLP-1 agonists in pulmonary arterial hypertension (PAH). This first-in-disease study evaluated acute hemodynamic effects of GLP-1 agonist, exenatide administered i.v. in patients with idiopathic PAH and CTEPH as well as in a PAH rodent model. Seventeen patients (9 idiopathic PAH) received an exenatide infusion during right heart catheterization, which included multisite sampling for circulating metabolites. Acute effects of exenatide were also assessed by cardiac magnetic resonance imaging in monocrotaline (MCT) PAH and control rats. In the clinical study, exenatide was well tolerated, reduced mean pulmonary artery pressure (45 ± 15 mmHg versus 40 ± 18 mmHg), and improved cardiac index (2.1 ± 0.6 L/min versus 2.4 ± 0.9 L/min/m2) and pulmonary vascular resistance (7.8 ± 8.0 WU versus 5.9 ± 5.0 WU) across all patients. Right ventricular (RV) contractility and afterload improved in a subset of patients undergoing pressure-volume measurements. In an exploratory metabolomics analysis, 47 metabolite levels changed after exenatide infusion, predominantly in free fatty acid pathways. Six metabolites with prognostic relevance in PAH within myocardial glycolytic and lipid oxidation pathways were also altered after exenatide. In MCT rats, exenatide improved RV stroke-volume, RV ejection fraction, and RV-arterial coupling. These findings support the further evaluation of exenatide within chronic studies as a potentially novel pulmonary vasodilator therapy.
Date Issued
2026-05-22
Date Acceptance
2026-03-27
Citation
JCI Insight, 2026, 11 (10)
ISSN
2379-3708
Publisher
American Society for Clinical investigation
Journal / Book Title
JCI Insight
Volume
11
Issue
10
Copyright Statement
© 2026, Samaranayake et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/42171611
PII: 202660
Subjects
Cardiology
Cardiovascular disease
Metabolomics
Pulmonology
Exenatide
Animals
Rats
Male
Hemodynamics
Female
Humans
Metabolomics
Middle Aged
Disease Models, Animal
Glucagon-Like Peptide 1
Hypertension, Pulmonary
Pulmonary Arterial Hypertension
Cardiac Catheterization
Publication Status
Published
Coverage Spatial
United States
Article Number
e202660
Date Publish Online
2026-05-22