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

TL;DR

A four-week study suggests that semaglutide, a GLP-1 agonist, may aid recovery in patients with acute pulmonary embolism by reducing inflammatory and metabolic stress proteins.

Contribution

This is the first study to explore GLP-1 agonists in acute pulmonary embolism recovery with proteomic profiling and imaging endpoints.

Findings

44 plasma proteins were downregulated with semaglutide, enriched for glycoproteins and linked to metabolic stress and complement pathways.

Glycopeptide analysis suggested protein deglycosylation as a mechanism for glycoprotein downregulation.

Radiological markers of right ventricular dysfunction improved only in semaglutide-treated patients.

Abstract

Vasorelaxant and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) agonists support their investigation in aiding the recovery of patients with acute pulmonary embolism (PE) at risk of worse outcomes.

We undertook a four week non-randomized, controlled open-label study examining proteomic changes, markers of vascular inflammation and exploratory imaging endpoints in response to GLP-1 agonist, semaglutide (0.25 mg weekly) added to standard of care anticoagulation in patients with intermediate high-risk PE.

44 plasma proteins were downregulated in response to semaglutide that were significantly enriched for glycoproteins (false discovery rate q < 0.01). Glycopeptide analysis of highly abundant glycoproteins between diagnosis and follow-up demonstrated a reduction in glycopeptide abundance suggesting protein deglycosylation as a possible mechanism of glycoprotein down-regulation. Down-regulated 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 P < 0.001). Exploratory evaluation of radiological markers of right ventricular dysfunction improved from baseline to follow-up only in patients who received semaglutide (P < 0.01).

These findings suggest merit in wider investigation of immunometabolic changes in the plasma proteome during acute PE recovery and their potential relevance to modulation using GLP-1 agonists.

The study was registered under clinicaltrials.org (NCT06118203).

Graphical Abstract

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