GLP-1 and GLP-2 emerge as promising intestinal reparative therapies for inflammatory bowel disease

Despite advances in biologics and small-molecule agents, a substantial proportion of patients with inflammatory bowel disease (IBD) fail to achieve durable clinical remission. Current management is shifting from mere symptom control to disease course alteration, emphasizing intestinal reparative therapy defined by objective endpoints like endoscopic and histologic healing. This approach is strongly linked to improved long-term outcomes. Emerging mechanistic data point to epithelial repair pathways as actionable therapeutic targets, with glucagon-like peptides secreted by intestinal enteroendocrine cells gaining attention for their roles in maintaining epithelial integrity and modulating inflammation, addressing a critical gap in IBD treatment.

This comprehensive review synthesizes basic science and translational evidence regarding glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and dipeptidyl peptidase-IV (DPP-IV) inhibition as potential therapeutic concepts for inflammatory bowel disease. The authors critically appraised recent human observational data to differentiate between metabolic benefits and intrinsic disease-modifying effects. Furthermore, the review outlines practical clinical friction points and identifies necessary prospective trials to validate these pathways, providing a roadmap for future treatment paradigms in IBD.

The review highlights robust mechanistic data supporting the roles of GLP-1 and GLP-2 in promoting epithelial integrity and modulating inflammation within the gut. Both peptides, along with strategies to inhibit DPP-IV (which prolongs their half-life), are identified as emerging therapeutic concepts. The synthesis of evidence suggests that these peptides can directly influence intestinal repair pathways, which is crucial for achieving durable remission in IBD. Observational human data were carefully distinguished, indicating that while GLP-1 receptor agonists are known for metabolic benefits, their intrinsic disease-modifying effects in IBD are also gaining recognition. The review emphasizes the need for further clinical validation to confirm these findings. > The synthesis of evidence strongly supports GLP-1 and GLP-2 as key mediators of epithelial repair and inflammation modulation, positioning them as promising targets for IBD therapy.