GLP-2 analogues expand therapeutic frontiers beyond intestinal failure, transforming short bowel syndrome management

Patients with Short Bowel Syndrome (SBS) suffer from severe intestinal failure, leading to chronic malabsorption and critical dependence on parenteral nutrition (PN). Current standard-of-care often focuses on supportive nutrition, but a significant gap exists in therapies that actively promote intestinal adaptation and regeneration. Glucagon-like peptide-2 (GLP-2), a naturally occurring 33-amino acid peptide, has emerged as a key pharmacologic agent due to its ability to enhance mucosal growth, nutrient absorption, and intestinal barrier integrity, offering a regenerative approach to this debilitating condition.

This minireview synthesized current evidence on glucagon-like peptide-2 (GLP-2) analogues, including teduglutide and emerging agents like glepaglutide, focusing on their mechanisms, clinical efficacy, and safety profiles. It summarized findings from preclinical and clinical data to evaluate their expanding therapeutic applications in gastrointestinal diseases beyond Short Bowel Syndrome (SBS), such as inflammatory bowel disease and intestinal failure-associated liver disease. The review emphasized the shift from supportive nutrition to regenerative therapy in SBS management.

GLP-2, secreted by enteroendocrine L cells, enhances mucosal growth and nutrient absorption through activation of cyclic adenosine monophosphate-dependent and insulin-like growth factor-1-mediated pathways. Clinical trials have consistently demonstrated that teduglutide and newer long-acting analogues like glepaglutide significantly improve key markers of intestinal function. These improvements include increased plasma citrulline levels, reduced fecal output, and a substantial decrease in parenteral nutrition requirements. Patients also experienced improved hepatic function and enhanced quality of life. Preclinical and clinical data further support GLP-2's anti-inflammatory effects, showing potential in inflammatory bowel disease and mitigating intestinal failure-associated liver disease. > GLP-2 analogues represent a paradigm shift in short bowel syndrome management, transforming care from supportive nutrition to regenerative therapy. Although current evidence indicates low neoplastic risk, long-term safety monitoring remains essential for these agents.