- Evidence
- BSome human evidence
- FDA status
- In clinical trialsas of 2026-10-26
- Route
- Injection
- Studies cited
- 2 human0 animal or cell
It is a weekly injection being tested for short bowel syndrome, to cut the time spent on drip feeding. One trial of 106 people worked at one dosing schedule only, so the FDA asked for more.
Sold for
Glepaglutide is discussed as a long-acting GLP-2 analog that could reduce the hours patients with short bowel syndrome spend on intravenous nutrition.
Studies say
The phase 3 trial showed that glepaglutide at the trial dose cut parenteral support volume per week more than placebo, a real but single-trial result that regulators have not yet accepted, which is grade B.
Why grade B. One randomised placebo-controlled phase 3 trial in 106 patients with short bowel syndrome met its primary endpoint in the more frequent dosing arm but not the less frequent one, and the FDA judged that insufficient for approval. That is one positive trial with a split result, so the grade is B. 12
FDA. Glepaglutide is not approved by the FDA. Zealand Pharma filed a new drug application for short bowel syndrome and received a complete response letter in December 2024 asking for more evidence on the intended dose; a further phase 3 trial began enrolling in 2026. It is an investigational drug, not a research chemical. 1
Written from 2 cited sources. Fact-checked 2026-10-27: 16 claims checked, 3 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Short bowel syndrome, to need less drip feeding
- Can a US doctor prescribe it?
- Not yet; it is still in trials.
- Properly tested in people?
- Partly: one trial of 106 people with mixed results, so the FDA asked for another.
Evidence checklist
- Randomised controlled trial Placebo-controlled phase 3, EASE SBS 1yes
- Human study over 100 people 106 adults with short bowel syndromeyes
- More than one research group Sponsor trials; one extension reportno
- Clinical outcomes, not surrogate markers Weekly parenteral support volume cutyes
- Human safety data beyond case reports Small trials; long-term data lackingno
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Glepaglutide is a lab-made version of glucagon-like peptide 2 (GLP-2). GLP-2 is a gut hormone released after meals. It makes the intestinal lining grow and absorb more. The natural hormone lasts minutes in the blood. Glepaglutide was engineered to last days. That way, patients can inject it far less often. 1
It targets short bowel syndrome with intestinal failure. These patients have lost much of their small intestine. They depend on parenteral support, meaning nutrition and fluids given through a vein. The existing GLP-2 drug in this space is teduglutide. It needs far more frequent injections. 1
How it works
GLP-2 acts on receptors in the gut wall. It raises the height of the villi, the finger-like projections that absorb nutrients. It also slows stomach emptying. More absorbing surface means the body takes up more of what a patient eats. Then less has to be infused. Glepaglutide carries changes that protect it from the enzyme that normally breaks down GLP-2 within minutes. 1
What human research shows
EASE SBS 1 randomised 106 adults with short bowel syndrome. They needed parenteral support at least three days a week. They got glepaglutide at two dosing frequencies or placebo for 24 weeks. The group on the more frequent dosing cut its weekly parenteral support volume by 5.13 litres. The placebo group cut it by 2.85 litres. That gap was statistically significant. The group on less frequent dosing improved in number but not significantly. The FDA pointed to this gap. 1
A separate phase 3b study took place at one center and was open-label. It gave 10 patients glepaglutide once weekly. It measured absorption directly with metabolic balance studies. At 24 weeks, energy absorption rose by about 1,038 kJ a day. The rise in wet-weight absorption, the main measure, narrowly missed significance. By week 52, parenteral support volume had fallen by about 800 mL a day. Body weight stayed stable. Most of the authors work for or consult for Zealand Pharma. 2
| Study | Model | Finding |
|---|---|---|
| EASE SBS 1, phase 3 | Humans, n=106, randomised double-blind placebo-controlled, 24 weeks | At the more frequent trial dose glepaglutide reduced parenteral support by 5.13 L a week versus 2.85 L for placebo; the less frequent dose did not reach significance. 1 |
| Pinar 2025, metabolic balance study | Humans, n=10, single-centre open-label phase 3b, 52 weeks | Energy absorption rose at 24 weeks and parenteral support volume fell by about 800 mL a day by week 52. 2 |
Safety
In the phase 3 trial, the common side effects were injection-site reactions, stoma changes in patients with a stoma, belly pain and nausea. These fit the GLP-2 class. GLP-2 drugs stimulate intestinal growth. So the class carries a theoretical concern that they could speed up polyps or tumours in the bowel. That is why teduglutide's label includes colonoscopy checks, and they would be expected here. Long-term data beyond the extension studies do not yet exist. 1
Questions for your clinician
- Is glepaglutide available only through a trial, and could I join one?
- How does it compare with teduglutide, which is already approved?
- What bowel monitoring would be needed with a GLP-2 drug?
Questions people ask
Is glepaglutide FDA-approved?
No. The FDA issued a complete response letter in December 2024. It said the application did not establish how well and how safely the dose intended for marketing works. Only one of the two dosing arms in the main trial was positive. Zealand started another phase 3 trial in 2026 to answer that. 1
What is glepaglutide for?
Short bowel syndrome with intestinal failure. These patients depend on nutrition through a vein after losing much of their small intestine. The goal of treatment is fewer litres and fewer days of parenteral support. 1
How does glepaglutide differ from teduglutide?
Both are GLP-2 analogs. Teduglutide is approved, and patients must inject it far more often. Glepaglutide was built to last longer in the blood. The phase 3 result favoured the more frequent of its two tested schedules. 1
What did the phase 3 trial show?
In 106 patients, glepaglutide at the more frequent trial dose cut parenteral support volume by about 5 litres a week. Placebo cut it by about 3 litres, over 24 weeks. The less frequent arm did not separate from placebo statistically. 1