Glepaglutide: research in short bowel syndrome
Clinical review pending
Glepaglutide is intended to improve intestinal fluid and nutrient absorption. Its pivotal trial produced different results depending on the dosing schedule.
What is glepaglutide?
Glepaglutide is an investigational analogue of glucagon-like peptide-2 (GLP-2), a hormone that supports intestinal growth and nutrient absorption. Zealand Pharma is developing it under the code ZP1848 as a subcutaneous injection for short bowel syndrome with intestinal failure. People with this condition depend on intravenous nutrition. Glepaglutide belongs to the same drug class as apraglutide and the approved GLP-2 medicine teduglutide. According to the source article, glepaglutide is not yet approved. Source Source Source
How is glepaglutide intended to work?
Glepaglutide activates the GLP-2 receptor in the intestine 1. This is intended to increase growth and adaptation of the intestinal lining, as well as fluid and nutrient absorption. In short bowel syndrome, the aim is to reduce the need for intravenous nutrition. Whether that goal is achieved must be tested in clinical trials.
Is glepaglutide FDA-approved?
According to the source article, glepaglutide is not approved. Company statements report that the FDA issued a Complete Response Letter in December 2024, finding that the efficacy and safety of the proposed dosing regimen had not been adequately established. The once-weekly trial arm had not produced a positive result. Zealand therefore announced an additional phase 3 trial.
What do the studies show?
The main evidence comes from a phase 3 trial with mixed results. The source article also cites a smaller study; both are summarized in the table.
The pivotal evidence therefore rests on a single trial in which one of the two dosing schedules studied did not produce a positive result.
Studies at a glance
| Study | Study design | Result |
|---|---|---|
| EASE trial [1] | Phase 3: glepaglutide twice weekly, once weekly or placebo | Twice-weekly dosing met the primary endpoint: the weekly volume of intravenous support fell compared with placebo, and key secondary measures also improved. Once-weekly dosing did not reach statistical significance. |
| Smaller study [2] | Phase 3b | Greater energy absorption and a reduced need for parenteral support were reported over one year. |
References provided in the source article
Sources: the EASE Phase 3 trial (Jeppesen et al., Gastroenterology, 2025, DOI: 10.1053/j.gastro.2024.11.023 1 ) and a Phase 3b metabolic-balance study (Pinar et al., Clinical Nutrition ESPEN, 2025, DOI: 10.1016/j.clnesp.2025.08.006 2 ), both indexed on PubMed; and Zealand Pharma regulatory updates.
Provenance and editorial review status
Adapted for Nutrient Desk from the source article. The claims and source attributions in the original text still require clinical review. This draft has not been cleared for indexing.