Lee_2026_Front.Gastroenterol.(Lausanne)_5_1790420

Inflammatory bowel disease remains a chronic condition in which a substantial proportion of patients fail to achieve durable clinical remission despite advances in therapy. Although the treatment landscape has expanded to include biologics and small-molecule agents, contemporary management is increasingly focused on altering the course of the disease rather than relying on symptom control alone. Central to this shift is the recognition that intestinal reparative therapy, defined by objective endpoints such as endoscopic and histologic healing, is strongly associated with improved long-term outcomes. Emerging mechanistic data highlight epithelial repair pathways as actionable therapeutic targets. Among these, glucagon-like peptides secreted by intestinal enteroendocrine cells have gained attention for their roles in epithelial integrity and inflammation modulation. This review synthesizes basic science and translational evidence supporting glucagon-like peptide-1, glucagon-like peptide-2, and dipeptidyl peptidase-IV inhibition as emerging therapeutic concepts in inflammatory bowel disease. Furthermore, it provides a critical appraisal of recent human observational data, distinguishing metabolic benefits from intrinsic disease-modifying effects, and outlines the practical clinical friction points and prospective trials necessary to validate these pathways in future treatment paradigms.