Add-on GLP-1 agonists in the treatment of intermediate risk acute pulmonary embolism: a biomarker-driven proof-of-concept study

<bold>Background:</bold> Up to 50% of patients with acute pulmonary embolism (APE) demonstrate impaired pulmonary vascular recovery at follow-up. Multiple inflammatory and immune factors contribute to aberrant thrombus remodelling. <bold>Aims:</bold> Add-on Glucagon-like peptide-1 (GLP-1) agonists treatment, which have prominent anti-inflammatory and vasorelaxant properties, in APE was evaluated. <bold>Methods:</bold> 22 patients with intermediate high-risk APE were recruited and receive add-on Semaglutide to anticoagulation (0.25mcg s/c weekly for four weeks), (n=8) or anticoagulation alone (n=14). <bold>Results:</bold> Semaglutide was well tolerated. Plasma proteomics identified downregulation of 44 glycoproteins in response to GLP-1 which on enrichment testing predominated in complement and metabolic stress pathways. Reduction in complement mediators C3-C5 and plasma MMP-9 were confirmed by ELISA with glycopeptide analysis of candidate glycoproteins showing a reduced glycosylation profile in response to Semaglutide. Exploratory CT markers of right ventricular (RV) dysfunction between baseline and 4 weeks showed improvement in thrombus burden and RV function with semaglutide compared to anticoagulation alone. <bold>Conclusions:</bold> GLP-1 agonists downregulate complement pathway intermediaries in PE via perturbation in protein glycosylation. The therapeutic relevance of GLP-1 agonists in selected PE populations requires further evaluation. <fig><object-id>erj;64/suppl_68/OA5556/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>