Glepaglutid

Glepaglutide is a long-acting analogue of human GLP-2. GLP-2 is naturally secreted by the L cells of the intestine and promotes the growth and function of the intestinal mucosa. According to the assessment by the European Medicines Agency (EMA), glepaglutide increases blood flow to the intestine and portal vein, reduces gastric acid secretion and intestinal motility, and stimulates the growth of the intestinal mucosa. The goal is to support the adaptation of the remaining bowel and thereby improve the absorption of nutrients and fluids and reduce the need for parenteral nutrition. Endogenous GLP-2 has a duration of action of only a few minutes because it is rapidly broken down by the enzyme DPP-4; glepaglutide, as a long-acting analogue, is designed to act considerably longer and was tested in the studies on a twice-weekly schedule. GLP-2 belongs to the same proglucagon-derived hormone family as GLP-1 but acts via its own receptor and targets a different indication - it is expressly not a metabolic or weight-loss agent like the GLP-1 drugs semaglutide or tirzepatide.

The extended duration of action compared with endogenous GLP-2 is the basis for the studied, only twice-weekly administration. Specific dose amounts, concentrations, dose levels, or preparation and injection instructions are deliberately not stated here - this is an educational overview, not a usage guide. Such information belongs exclusively in the hands of treating physicians specialized in short bowel syndrome, within the context of treatment or a study.

Glepaglutide (development code ZP1848) was developed by Zealand Pharma A/S (Denmark) as a long-acting GLP-2 analogue for short bowel syndrome. The pivotal Phase 3 study EASE-1 (NCT03690206) started on 4 Oct 2018 and was completed on 26 Jul 2022; it enrolled 106 adults and compared a twice-weekly regimen, a once-weekly regimen and placebo (quadruple-masked). Based on the EASE program, Zealand submitted a New Drug Application to the US regulator FDA. On 19 Dec 2024, Zealand reported a Complete Response Letter from the FDA: in the regulator's view, the documentation did not fully demonstrate the efficacy and safety of the dosage to be marketed; the FDA recommended an additional clinical study. On 2 Jun 2025, Zealand announced the submission of the EU Marketing Authorization Application to the EMA, based on EASE-1 as the pivotal study, interim results of the extension studies EASE-2 and EASE-3, and the mechanistic study EASE-4 (Phase 3b). As a confirmatory study, the Phase 3 study EASE SBS 5 (NCT07197944) began, which according to the registry has been recruiting since 11 Feb 2026. On 17 Sep 2026, the EMA's Committee for Medicinal Products for Human Use (CHMP) issued a positive marketing authorization recommendation for the trade name Zeydovio; the final decision by the EU Commission was still pending as of October 2026. The full EASE-1 results were published peer-reviewed in the journal Gastroenterology (print edition April 2025, online ahead of print on 19 Dec 2024). Context: the established GLP-2 analogue for short bowel syndrome to date is teduglutide (Revestive/Gattex); another candidate in the same class in Phase 3 is apraglutide.