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Healing

Glepaglutide

Also known as: ZP1848, Zeydovio, Long-acting GLP-2 analog

Clinical Trials
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Key Facts: Glepaglutide

Category
Healing
FDA Status
Not FDA Approved
Clinical Status
Investigational in the US (FDA complete response letter December 2024; additional phase 3 EASE-5 underway). EU: positive CHMP opinion 17 September 2026 as Zeydovio for adults with SBS; European Commission decision pending as of October 2026. Not approved anywhere yet.
Banned in Sport (WADA)
Not named on the WADA list, but WADA's S0 catch-all (non-approved substances) covers any substance without current human therapeutic approval, which includes glepaglutide until it is approved. Prohibited at all times.
Administration
Subcutaneous injection (prefilled pen in the EU filing)
Typical Dose
10 mg twice weekly (trial dose)
Frequency
Twice weekly
Duration
24 weeks in EASE-1, with longer-term extension studies
Also Known As
ZP1848, Zeydovio, Long-acting GLP-2 analog

How does Glepaglutide work?

Glepaglutide activates the GLP-2 receptor in the intestine, the same target as teduglutide, which makes the gut lining grow and absorb more fluid and nutrients. What is different is the delivery. After a subcutaneous injection it forms a depot and is slowly released, mostly as two active metabolites rather than the parent molecule. In a healthy-volunteer study the effective half-life was roughly 88 to 124 hours, long enough to make weekly or twice-weekly dosing plausible. The flip side is the same as the rest of the GLP-2 class: anything that makes gut tissue grow raises questions about polyps and tumors over the long run.

What does the research show?

The main evidence is EASE-1, published in Gastroenterology in April 2025 (Jeppesen and colleagues). It randomized 106 adults with SBS and intestinal failure to glepaglutide 10 mg twice weekly, 10 mg once weekly, or placebo for 24 weeks. Twice weekly cut weekly parenteral support by 5.13 L versus 2.85 L on placebo (p=0.0039), and 65.7% were responders versus 38.9% on placebo. Once weekly (3.13 L) did not reach significance. A handful of patients came off IV support completely, none on placebo. On 19 December 2024 the FDA issued a complete response letter saying there was not enough evidence at the to-be-marketed dose and asked for another trial; Zealand is running EASE-5 to support a US resubmission. Zealand filed in Europe in June 2025 and the CHMP gave a positive opinion on 17 September 2026 for adults with SBS (10 mg prefilled pen). Common side effects listed by the EMA are injection site reactions, abdominal pain, nausea, and vomiting. Bottom line: real phase 3 data, but from a single trial with one of two doses positive, which is exactly why the two regulators disagreed.

Trial Progress:Phase III
Pre
I
II
III
IV
FDA

What doses have been studied?

Human Trials·One phase 3 trial positive at twice-weekly dosing; FDA rejected, EU committee recommended approval in 2026

Typical Dosingⓘ

Community experience

Common Dose

10 mg twice weekly (trial dose)

Range

10 mg once or twice weekly tested; only twice weekly was significant

Frequency

Twice weekly

These are phase 3 trial doses for SBS patients on IV support, given under specialist care with IV volume adjusted as absorption improves. Not a recommendation and not relevant to people without intestinal failure.

Research Dosingⓘ

Scientific studies

Trial doses only (no approved dose yet)

Duration

24 weeks in EASE-1, with longer-term extension studies

Administration

Subcutaneous injection (prefilled pen in the EU filing)

When and how is Glepaglutide taken?

Best Time to Take

Same days each week (trial schedule)

Twice weekly subcutaneous injection in EASE-1

Food Recommendation

With or without food

Why This Timing?

The depot releases slowly over days, so a steady twice-weekly schedule keeps levels even. Clock time was not a factor in the trials.

What are the side effects of Glepaglutide?

Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.

  • ●Injection site reactions
  • ●Abdominal pain
  • ●Nausea
  • ●Vomiting
  • ●Stoma changes and abdominal distension (GLP-2 class effect)
  • ●Fluid overload risk as absorption improves (class effect)
  • ●Theoretical acceleration of intestinal polyps or tumors (class concern, long-term data limited)

References

Research This Peptide Further

Frequently Asked Questions

What does Glepaglutide do?

Glepaglutide is Zealand Pharma's long-acting GLP-2 analog for short bowel syndrome, built to be injected once or twice a week instead of daily like teduglutide. Its path has been bumpy. The FDA rejected it in December 2024 because the single phase 3 trial only worked at the twice-weekly dose, but Europe went the other way: in September 2026 the EMA's CHMP recommended approval under the name Zeydovio. As of late October 2026 the final European Commission decision is still pending, and the US needs another trial.

How does Glepaglutide work?

Glepaglutide activates the GLP-2 receptor in the intestine, the same target as teduglutide, which makes the gut lining grow and absorb more fluid and nutrients. What is different is the delivery. After a subcutaneous injection it forms a depot and is slowly released, mostly as two active metabolites rather than the parent molecule. In a healthy-volunteer study the effective half-life was roughly 88 to 124 hours, long enough to make weekly or twice-weekly dosing plausible. The flip side is the same as the rest of the GLP-2 class: anything that makes gut tissue grow raises questions about polyps and tumors over the long run.

Is Glepaglutide FDA approved?

No, Glepaglutide is not currently FDA approved. Current status: Investigational in the US (FDA complete response letter December 2024; additional phase 3 EASE-5 underway). EU: positive CHMP opinion 17 September 2026 as Zeydovio for adults with SBS; European Commission decision pending as of October 2026. Not approved anywhere yet.

Is Glepaglutide banned in sport?

Not named on the WADA list, but WADA's S0 catch-all (non-approved substances) covers any substance without current human therapeutic approval, which includes glepaglutide until it is approved. Prohibited at all times.

What are the side effects of Glepaglutide?

Reported side effects include: Injection site reactions, Abdominal pain, Nausea, Vomiting, Stoma changes and abdominal distension (GLP-2 class effect). Individual responses vary based on dosage, duration, and personal health factors.

What is the typical dose of Glepaglutide?

Community-reported common dose: 10 mg twice weekly (trial dose) (Twice weekly). Range: 10 mg once or twice weekly tested; only twice weekly was significant. Administration: Subcutaneous injection (prefilled pen in the EU filing). Community-reported doses. Not medical advice. Consult healthcare provider.

Related Peptides

Peptides commonly compared with Glepaglutide or used in similar applications.

Thymosin Beta-4

Clinical Trials

Thymosin beta-4 (Tbeta4) is a small 43 amino acid peptide found in nearly every cell in the body, originally isolated from the thymus. Its main job is binding and sequestering G-actin, the building block of the cell's internal scaffolding, which lets it influence cell movement, wound repair, and tissue regeneration. It is researched heavily for healing of skin, cornea, and heart tissue, but it is not an FDA-approved drug. (The injectable sold as TB-500 is a synthetic fragment marketed as related to Tbeta4, not the full natural peptide.)

Healing

B7-33

Preclinical

B7-33 is a 27-amino-acid, single-chain peptide cut down from the B-chain of human relaxin-2, the hormone that loosens tissue during pregnancy. Relaxin itself has strong anti-scarring effects but is a complex two-chain molecule that is hard and expensive to make, so an Australian group (Hossain and colleagues, 2016) designed B7-33 as a simpler version. In rodent models it reduced heart and lung fibrosis about as well as full relaxin. It has never been tested in humans.

Healing

Apraglutide

Clinical Trials

Apraglutide is a once-weekly GLP-2 analog for short bowel syndrome, originally from VectivBio and now owned by Ironwood Pharmaceuticals. Its phase 3 STARS trial hit its main goal in 2024, but in April 2025 Ironwood said the FDA wanted a confirmatory trial, partly because patients in STARS got less drug exposure than planned due to how doses were prepared and given. That new trial, STARS-2, started in June 2026, so approval is years away (a submission before end of 2029 has been mentioned).

Healing

BPC-157

Preclinical

BPC-157 is a synthetic 15-amino-acid peptide (sequence Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) based on a fragment of a protective protein found in human gastric juice. It is studied almost entirely in animals for tendon, ligament, gut, and tissue healing, and it has racked up hundreds of preclinical papers. The catch: it is not approved by any regulator for any use, and the human evidence is a handful of small pilot studies, not real clinical proof.

Healing

TB-500

Preclinical

TB-500 is a synthetic peptide that copies the active region of thymosin beta-4, a natural protein that controls how cells build and move their internal skeleton. Most TB-500 products reproduce the short LKKTETQ sequence (residues 17 to 23) responsible for binding actin and driving cell migration, which is why it gets marketed for tendon, muscle, and wound repair. Here is the honest part: there are essentially no completed human trials of the TB-500 fragment itself, and almost all the human clinical data is for the full-length thymosin beta-4 molecule, which is related but not the same thing.

Healing

Pentadecapeptide

Preclinical

Pentadecapeptide almost always means BPC-157, a synthetic 15-amino-acid chain (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) derived from a protein found in human gastric juice. It is one of the most hyped 'healing' peptides online, marketed for tendon, gut, and muscle repair, but here is the catch: essentially all of the supporting evidence is from rats and mice. There is no FDA approval and no completed human clinical trial proving it does any of this.

Healing

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