Glepaglutide, a Novel Glucagon-like Peptide-2 Agonist, Has Anti-inflammatory and Mucosal Regenerative Effects in an Experimental Model of Inflammatory Bowel Disease in Rats

Overview

Journal BMC Gastroenterol

Publisher Biomed Central

Specialty Gastroenterology

Date 2023 Mar 22

PMID 36944922

Authors

Jolanta Skarbaliene

Jesper Mosolff Mathiesen

Bjarne Due Larsen

Christian Thorkildsen

Yvette Miata Petersen

Affiliations

Soon will be listed here.

Abstract

Background: Glucagon-like peptide-2 (GLP-2) enhances intestinal repair and attenuates inflammation in preclinical inflammatory bowel disease (IBD) models, making GLP-2 analogues attractive candidates for IBD therapy. Glepaglutide is a long-acting GLP-2 receptor agonist in clinical development for treatment of short bowel syndrome. Here, we investigated if glepaglutide is therapeutically beneficial in rats with small intestinal inflammation.

Methods: Small intestinal inflammation was induced with indomethacin in naive Wistar rats, followed by glepaglutide administration at different disease stages. Glepaglutide was administered in co-treatment and post-treatment regimens. Small intestinal length and concentrations of inflammatory markers α-1-acid glycoprotein and myeloperoxidase were used to assess anti-inflammatory effects. Small intestinal mass was evaluated to determine intestinotrophic effects.

Results: Glepaglutide co- and post-treatment significantly reduced severity of small intestinal inflammation, evidenced by reversed small intestinal shortening and decreased α-1-acid glycoprotein and/or myeloperoxidase concentration(s). Co- and post-treatment with glepaglutide also significantly increased small intestinal mass, indicating intestinal regenerative effects. Similar effects were observed in naive rats after glepaglutide treatment.

Conclusion: Glepaglutide has anti-inflammatory and intestinotrophic effects without the need for pre-treatment in a rat model of small intestinal inflammation. Thus, glepaglutide is of potential clinical interest for patients with IBD.

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