GLP-1 agonist, Semaglutide in acute pulmonary embolism recovery: a four week proof-of-concept study including proteomic profiling

Abstract Vasorelaxant and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) agonists support their potential role in aiding the recovery of patients with acute pulmonary embolism (PE) at risk of worse outcomes. In a four-week non-randomised, controlled open-label study examining proteomic changes and markers of vascular inflammation, GLP-1 agonist, Semaglutide (0.25mg weekly) added to standard of care anticoagulation in patients with intermediate high-risk PE downregulated forty-four proteins which were significantly enriched for glycoproteins (FDRq 0.01). Glycopeptide analysis of highly abundant glycoproteins between diagnosis and follow up demonstrated a reduction in glycopeptide abundance suggesting protein deglycosylation as the mechanism of glycoprotein downregulation. Downregulated proteins included regulators of metabolic stress and complement pathway intermediates which were at higher abundance in PE patients at diagnosis compared to age and sex-matched controls without PE (all p0.001). Exploratory evaluation of radiological markers of right ventricular dysfunction improved from baseline to follow up only in patients who received Semaglutide (p0.01).