Glepaglutide

Research-Grade

Glepaglutide is a long-acting analog of glucagon-like peptide-2 (GLP-2), the intestinotrophic hormone that stimulates growth of the gut lining. It belongs to the same therapeutic class as teduglutide but is designed with structural modifications that substantially extend its duration of action, with the goal of reducing dosing frequency from daily to once- or twice-weekly. This is a meaningful convenience improvement for a chronic, self-injected therapy in short bowel syndrome (SBS). Like other GLP-2 agonists, glepaglutide acts on the GLP-2 receptor to promote proliferation of intestinal crypt cells, increase villus height and mucosal surface area, improve intestinal blood flow, and enhance nutrient and fluid absorption. The therapeutic aim in short bowel syndrome is to reduce dependence on parenteral (intravenous) nutrition by improving the absorptive capacity of the remaining intestine. Glepaglutide has been evaluated in Phase 2 and Phase 3 clinical trials in adults with short bowel syndrome, with the EASE (Ending PArenteral Support Efficacy) program assessing its ability to reduce parenteral support volume. As of 2026 it is an investigational agent that is not yet broadly approved, and outside of clinical programs it is treated as a research compound. Like all intestinotrophic GLP-2 agents, its growth-promoting mechanism warrants surveillance for intestinal polyps.