Attieh P, Dabboussi D, Meraabi W, Karam K, Al Bacha RR, Abboud B. Beyond intestinal failure: Expanding therapeutic frontiers of glucagon-like peptide-2 in gastrointestinal disease. World J Gastrointest Pharmacol Ther 2026; 17(2): 118861 [DOI: 10.4292/wjgpt.v17.i2.118861]
Corresponding Author of This Article
Bassam Abboud, Department of General Surgery, Geitaoui Hospital, Faculty of Medicine, Lebanese University, Rmeil, Beirut 16214, Lebanon. dbabboud@yahoo.fr
Research Domain of This Article
Medicine, General & Internal
Article-Type of This Article
Minireviews
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World J Gastrointest Pharmacol Ther. Jun 5, 2026; 17(2): 118861 Published online Jun 5, 2026. doi: 10.4292/wjgpt.v17.i2.118861
Beyond intestinal failure: Expanding therapeutic frontiers of glucagon-like peptide-2 in gastrointestinal disease
Philippe Attieh, Dana Dabboussi, Wael Meraabi, Karam Karam, Rose Raymond Al Bacha, Bassam Abboud
Philippe Attieh, Department of General Surgery, University of Balamand, Beirut 1100, Lebanon
Dana Dabboussi, Wael Meraabi, Karam Karam, Department of Gastroenterology, University of Balamand, Beirut 1100, Lebanon
Rose Raymond Al Bacha, Nini Hospital, University of Balamand, Tripoli 961, Lebanon
Bassam Abboud, Department of General Surgery, Geitaoui Hospital, Faculty of Medicine, Lebanese University, Beirut 16214, Lebanon
Author contributions: Attieh P, Dabboussi D, Meraabi W, Karam K, Al Bacha RR, and Abboud B contributed to writing of original draft preparation, review and editing; Abboud B contributed to conceptualization, supervision, and project administration. All authors have read and agreed to the published version of the manuscript.
AI contribution statement: We reconfirm that our manuscript was not generated by AI.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Bassam Abboud, Department of General Surgery, Geitaoui Hospital, Faculty of Medicine, Lebanese University, Rmeil, Beirut 16214, Lebanon. dbabboud@yahoo.fr
Received: January 13, 2026 Revised: February 3, 2026 Accepted: March 11, 2026 Published online: June 5, 2026 Processing time: 134 Days and 23 Hours
Abstract
Short bowel syndrome represents a severe form of intestinal failure characterized by malabsorption and dependence on parenteral nutrition (PN). Advances in gut hormone research have positioned glucagon-like peptide-2 (GLP-2) and its analogues as key pharmacologic agents promoting intestinal adaptation and reducing PN dependence. This minireview summarizes current evidence on the mechanisms, clinical efficacy, and expanding therapeutic applications of GLP-2 analogues, with emphasis on emerging agents such as glepaglutide and their safety profiles. GLP-2, a 33-amino acid peptide secreted by enteroendocrine L cells, enhances mucosal growth, nutrient absorption, and intestinal barrier integrity through activation of cyclic adenosine monophosphate-dependent and insulin-like growth factor-1-mediated pathways. Clinical trials have demonstrated that teduglutide and newer long-acting analogues such as glepaglutide significantly increase plasma citrulline levels, reduce fecal output, and decrease PN requirements while improving hepatic function and quality of life. Additionally, preclinical and clinical data support GLP-2’s anti-inflammatory effects in inflammatory bowel disease and its potential to mitigate intestinal failure-associated liver disease. Although current evidence indicates low neoplastic risk, long-term safety monitoring remains essential. GLP-2 analogues represent a paradigm shift in short bowel syndrome management, transforming care from supportive nutrition to regenerative therapy. Ongoing studies exploring novel formulations, broader indications, and precision medicine approaches will further refine their clinical integration and maximize therapeutic benefit.
Core Tip: Short bowel syndrome is a life-threatening cause of intestinal failure traditionally managed with long-term parenteral nutrition. Recent advances highlight glucagon-like peptide-2 analogues as disease-modifying therapies that enhance intestinal adaptation rather than merely providing nutritional support. By stimulating mucosal growth, improving absorptive capacity, and strengthening the intestinal barrier, agents such as teduglutide and emerging long-acting analogues like glepaglutide significantly reduce parenteral nutrition dependence and improve quality of life. Beyond short bowel syndrome, accumulating evidence suggests anti-inflammatory and hepatoprotective benefits, supporting broader therapeutic potential. Ongoing research and long-term safety surveillance will be crucial to optimizing their clinical application.
