# 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.

## Key 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