Effects of Acute GLP-1 Infusion on Pulmonary and Systemic Hemodynamics in Patients With Heart Failure: A Pilot Study Sophie J. Clarke, PhD 1 ; Stephen Pettit, MD 2 ; Joel P. Giblett, MD 2 ; Tian Zhao, MA 1 ; Anna C. Kydd, MD 2 ; Nicolai J.W. Albrechtsen, PhD 4 ; Carolyn F. Deacon, PhD 4 ; Jayan Parameshwar, MD 2 ; and Stephen P. Hoole, MA, DM, FRCP, FESC 3 1 Department of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom; 2 Department of Transplantation, Royal Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom; 3 Department of Interventional Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom; and 4 Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark ABSTRACT Purpose: Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms. Methods: In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15- minute continuous infusion of native GLP-1 (7-36) NH 2 . Findings: There was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P ¼ 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3% [6.8%]; P < 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P ¼ 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn $ s/cm 5 vs GLP-1, 1562 [247] dyn $ s/cm 5 ; P ¼ 0.001). Implications: Acute infusion of GLP-1 has a neutral hemodynamic effect, when assessed by thermodilution, in patients with heart failure. However, GLP-1 reduces mixed venous oxygen saturation. ClinicalTrials.gov identifier: NCT02129179. (Clin Ther. 2019;41:118e127) © 2018 Elsevier Inc. All rights reserved. Key words: GLP-1, heart failure, hemodynamics, right heart catheterization. INTRODUCTION An increasing proportion of patients survive an acute myocardial infarction due to timely and effective reperfusion, but many subsequently develop left ventricular (LV) dysfunction and congestive heart failure (CHF). 1 Ischemia reperfusion injury contributes significantly to the final infarct size. 2 Therapies that protect the heart against ischemia reperfusion injury and optimize ventricular myocardial performance and contractility may ameliorate the clinical effects of CHF. 3 Accepted for publication November 28, 2018 https://doi.org/10.1016/j.clinthera.2018.11.013 0149-2918/$ - see front matter © 2018 Elsevier Inc. All rights reserved. 118 Volume 41 Number 1 Clinical Therapeutics/Volume 41, Number 1, 2019