Glepaglutide (Zeydovio)_Dosage, benefits & legal status
Also known as Zeydovio, ZP1848, ZP-1848, glepaglutide acetate
A GLP-2 with a six-lysine tail that is released slowly from a depot under the skin, so it can be given twice a week. Recommended for EU approval in September 2026; the FDA asked for another trial.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Glepaglutide (Zeydovio)?
Plain language first. The technical label stays, but it never stands alone.Overview
People with short bowel syndrome have lost so much intestine that many depend on fluids and nutrition through a vein several days a week. In the 106-person EASE SBS 1 trial, 10 mg twice weekly cut that intravenous support by 5.13 L a week against 2.85 L on placebo over 24 weeks, and 5 of 35 came off it entirely against none on placebo. The once-weekly dose did not beat placebo, the FDA asked for another trial in December 2024, and it is not yet approved anywhere.
Glepaglutide is a 39-residue GLP-2 analog: human GLP-2(1-33) with nine substitutions, including teduglutide's glycine at position 2, plus a tail of six lysines and a C-terminal amide. Under the skin it forms a depot where proteases trim the tail and slowly release active metabolites, giving an effective half-life of about 88 hours against about 2 hours for teduglutide (1.3 hours in short bowel syndrome). That supports twice-weekly dosing, against daily for teduglutide and once weekly for apraglutide; Zealand Pharma discovered and developed it.
What it's used for
An experimental twice-weekly injection for adults with short bowel syndrome who depend on intravenous nutrition or fluids. Recommended for EU approval in September 2026, but not approved anywhere yet.
How does Glepaglutide (Zeydovio) work?
What it does in the body, and where.Glepaglutide copies GLP-2, a gut hormone that tells the intestine to absorb more, and is built to release slowly from under the skin.
- 01A depot under the skinAfter injection most of the peptide stays in the tissue under the skin, where enzymes trim lysines off its tail. Two active forms, M1 and M2, leak slowly into the blood; at steady state M2 makes up about 91% of exposure and the intact peptide under 1%.
- 02The gut signalThese forms activate GLP-2 receptors in the gut wall. In lab tests at the human receptor, M2 (EC50 0.044 nanomolar) was more potent than the injected peptide (0.12 nanomolar), and native GLP-2 measured 0.025.
- 03Absorbing moreGLP-2 signaling grows the absorptive lining, with taller villi and deeper crypts, and slows transit. The remaining bowel takes up more fluid and nutrients, so less intravenous support is needed.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Phase 3, twice weekly (EASE SBS 1)
Investigational- Human trialSupport volume fell 5.13 L a week against 2.85 L on placebo at 24 weeks (difference -2.28 L, p=0.0039).
- Human trial5 of 35 came off intravenous support entirely against none of 36 on placebo (p=0.016), and 65.7% against 38.9% cut their volume by at least 20% (p=0.0243).
Phase 3, once weekly
tested-and-failed- Human trialSupport volume fell 3.76 L a week against 2.85 L on placebo (difference -0.91 L, 95% CI -2.52 to 0.71, p=0.27); the 20% responder and days-off endpoints were not significant (p=0.63 and p=0.17). Four of 35 came off support against none on placebo (nominal p=0.042), but that does not count as a finding once the primary endpoint failed.
- Human trialAt least a 20% cut in support volume: 45.7% on once weekly against 38.9% on placebo, not significant.
Absorption trial (EASE SBS 4)
Investigational- Human trialEnergy absorption rose 1,038 kJ a day at week 24 (p=0.0215), while wet weight absorption (+398 g a day, p=0.0585) was not significant; support volume fell 800 mL a day at week 52 (p=0.0106).
- No dataEASE SBS 4 figures are company-released and not yet peer reviewed.
How it is released
Investigational- human-earlyHealthy adults on 10 mg weekly: effective half-life 88 hours (95% CI 31 to 146) counting the parent and its active metabolites; the intact peptide given into a vein lasts 11.7 hours.
- human-earlyUnder 1% of the injected peptide reaches the blood intact; at steady state M2 accounts for about 91% of exposure and M1 about 7%.
Anti-drug antibodies
Investigational- No dataAnti-drug antibodies developed in 30 of 35 on twice weekly and 31 of 35 on once weekly against 0 of 36 on placebo; antibodies that neutralized the main active form, M2, were found in 10 of 35 and 14 of 35; whether they reduce the benefit is not established.
The once-weekly result is often quoted from Zealand's releases as -3.13 L a week against -2.85 L on placebo; the results posted on ClinicalTrials.gov give -3.76 L a week (95% CI -4.96 to -2.56), a difference of -0.91 L from placebo with p=0.27. Why the two figures differ is not explained, possibly a different analysis, but either way the weekly arm did not beat placebo and only twice weekly met the primary endpoint. Glepaglutide was tested once weekly, but that arm failed and its EU regimen is twice weekly; teduglutide is daily (half-life about 2 hours), glepaglutide twice weekly (about 88 hours effective) and apraglutide weekly. It is described as a 33-residue peptide, but that is the GLP-2 core: the molecule has 39 residues, with six added lysines and an amidated end. The CHMP opinion of September 17, 2026, is a recommendation, not an approval, and the US complete response letter of December 19, 2024, still stands; Zealand's CHMP release does not mention it. The 11.7-hour figure is the intact peptide given into a vein, not the 88-hour effective half-life after injection under the skin, and 'under 1% bioavailability' reflects conversion into active forms in the skin. The FDA orphan designation is sometimes dated October 24, 2017; the FDA database gives October 20, 2017. GSRS lists an estimated weight of 4310.0 Da and formula C197H327N53O56 that do not match the sequence; about 4.3 kDa is the safe figure. EASE SBS 3 interim results covered 43 and then 57 patients, different data cuts rather than a contradiction.
The published record
Papers and trials about Glepaglutide (Zeydovio)
31 papers tagged human · 14 not reviews or lab · 10 clinical trial publications
11 registered trials · 2 with posted results
Furthest stage reached: Phase 3, results posted
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Glepaglutide (Zeydovio)
Evidence
Investigational
Category
Healing and recovery
Common vial
Varies
Half-life
About 88 hours (effective, after injection under the skin)
How much, and do you cycle it?
The range, and whether you take breaks.10 mg twice weekly (phase 3 trial), twice weekly. Continuous in the trials Trial dose
Given twice weekly for 24 weeks in EASE SBS 1, then in extension trials of up to 104 weeks with no planned breaks; in interim company analyses of the extensions, reductions in intravenous support were generally maintained.
How long does it stay in the body?
The half-life, and where the figure comes from.About 88 hours (effective, after injection under the skin)Human study
Effective half-life 88 hours (95% CI 31 to 146) in healthy adults given 10 mg weekly for 6 weeks, counting the parent and its active metabolites M1 and M2. The intact peptide given into a vein lasts 11.7 hours, but under the skin it is released slowly from a depot, and total drug peaks at about 12 hours. Teduglutide lasts about 2 hours in healthy adults and 1.3 hours in short bowel syndrome.
Source: Agersnap MA et al., Clinical Drug Investigation 2022;42(12):1093-1100
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How do I dose and price it?
Enter your vial and your dose. Pick a mix. We show the draw and the cost.The vial holds a fixed amount of drug. Adding more water does not make more drug, it just spreads it thinner, so you draw a bigger number on the syringe for the same dose.
Choose your mix
Measuring the water1 mL = one full 100-unit syringe.
How do you store it?
Before mixing, and after.Dry powder in the freezer or fridge. Once mixed, fridge, and use within about a month.
Unmixed lyophilized Glepaglutide (Zeydovio) keeps for a long time cold. Once you add water the clock starts: most reconstituted vials hold up for roughly 28 to 30 days at fridge temperature. Keep it out of light, and do not freeze it after mixing.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 38% charged residues, 44% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- Not studied in children: the phase 3 enrolled adults aged 18 to 90
- Not studied in bowel obstruction, radiation damage to the bowel, or moderately to severely active inflammatory bowel disease
- Not studied in anyone with a history of colon cancer, or another cancer within the past 5 years
- Not studied in pregnancy or breastfeeding, decompensated heart failure, or severe liver impairment
- Use outside a clinical trial: it is not approved anywhere yet
Stop and get help
- Swelling of the legs, breathlessness or rapid weight gain: fluid retention or overload is among its most common side effects
- Severe abdominal pain, bloating or vomiting with little or no stool or stoma output, a possible bowel or stoma blockage
- Blood in the stool: the approved GLP-2 drug teduglutide carries a warning that it can speed the growth of tumors
Common effects
- Injection-site reactions, including redness, pain and hardening, in 25.7% on twice weekly and 42.9% on once weekly against 2.8% on placebo
- Nausea in 20.0% against 2.8%, abdominal pain in 14.3% against 5.6% and vomiting in 8.6% against none (twice weekly, 24 weeks)
- Swelling of the stoma in 23.5% of stoma patients on twice weekly against none on placebo
- Serious adverse events in 25.7% against 19.4% on placebo; 2 of 35 stopped for side effects, and no one died
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Glepaglutide (Zeydovio) approved?
And where the numbers on this page come from.No. Glepaglutide (Zeydovio) is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteUnder the skin (subcutaneous)
- Checked17 October 2026
- DoseFrom published clinical trials. Not approved by a regulator for this dose.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesFDA GSRS substance record, glepaglutide (UNII 4M3C1913N6)EMA, Zeydovio product pageZealand Pharma, positive CHMP opinion (GlobeNewswire, September 18, 2026)Zealand Pharma, complete response letter announcement (December 19, 2024)Zealand Pharma, EU marketing application (BioSpace, June 2, 2025)ClinicalTrials.gov, EASE SBS 1 results (NCT03690206)Jeppesen PB et al., Gastroenterology 2025;168(4):701-713.e6 (epub December 19, 2024)Agersnap MA et al., Clinical Drug Investigation 2022;42(12):1093-1100Agersnap MA et al., Clinical Pharmacokinetics 2023;62(4):645-651Larsen BD et al., Journal of Medicinal Chemistry 2025;68(3):3134-3145FDA orphan drug designation record, glepaglutideClinicalTrials.gov, EASE SBS 5 (NCT07197944)Hargrove et al., Journal of Pharmacology and Experimental Therapeutics 2020;373(2):193-203Gattex (teduglutide) US label, DailyMed
What has happened recently
Not approved anywhere. The FDA granted orphan drug designation for short bowel syndrome on October 20, 2017. Zealand Pharma's US application, filed at the end of 2023 and resting on the single EASE SBS 1 trial, received a complete response letter on December 19, 2024: the FDA said it did not provide substantial evidence of efficacy and safety for the dose to be marketed and recommended an additional clinical trial. That confirmatory trial, EASE SBS 5 (NCT07197944, 10 mg twice weekly against placebo, about 90 people), started on February 11, 2026, and is meant to support a new US application; its primary completion is estimated for October 2028, and no resubmission date has been given. In Europe, Zealand applied on June 2, 2025, for twice-weekly dosing, and on September 17, 2026, the EMA's CHMP adopted a positive opinion recommending Zeydovio for adults with short bowel syndrome. The European Commission decision is pending; Zealand expects it about 67 days after the opinion, valid across the EU, Iceland, Liechtenstein and Norway. As of September 2026, Zealand had no commercial partner and was in partnership talks.
You can compare this against the whole library, or read how to check a seller.
What else is like Glepaglutide (Zeydovio)?
Others in Healing and recovery, side by side.If you're weighing Glepaglutide (Zeydovio), it's worth reading Lacripep, Linaclotide (Linzess), and Nerinetide (NA-1) in the same class.
A GLP-2 with a six-lysine tail that is released slowly from a depot under the skin, so it can be given twice a week. Recommended for EU approval in September 2026; the FDA asked for another trial.
- Dose
- 10 mg twice weekly (phase 3 trial)
- How often
- Twice weekly
A short piece of a human tear protein, given as eye drops to help the cornea renew itself and its nerves regrow. Its first trial missed its main goal; a nerve-damage trial began in 2026.
- Dose
- One drop of 4 µM solution in both eyes three times a day (phase 2 trial)
- How often
- Three times a day
An approved oral peptide for constipation that works in the gut and barely reaches the blood.
- Dose
- 72, 145 or 290 mcg once daily (label)
- How often
- Once daily
A 20-residue peptide built to stop nerve cells dying during a stroke. Over 2,400 patients later, the main results are neutral.
- Dose
- 2.6 mg/kg once, up to 270 mg (trials)
- How often
- A single dose
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- FDA GSRS substance record, glepaglutide (UNII 4M3C1913N6)(2026)39-residue sequence with a C-terminal lysinamide; CAS 914009-86-2; INN and USAN; codes ZP1848 and ZP-1848.
- EMA, Zeydovio product page(2026)CHMP positive opinion September 17, 2026, European Commission decision pending; adults with short bowel syndrome; 10 mg pre-filled pen; ATC A16AX26; common side effects.
- Zealand Pharma, positive CHMP opinion (GlobeNewswire, September 18, 2026)(2026)Twice-weekly autoinjector; EC decision expected within about 67 days; EASE SBS 4 results; EASE SBS 5 meant to support a US application; partnership talks.
- Zealand Pharma, complete response letter announcement (December 19, 2024)(2024)FDA found the application did not meet the requirements for substantial evidence for the to-be-marketed dose and recommended an additional clinical trial.
- Zealand Pharma, EU marketing application (BioSpace, June 2, 2025)(2025)Application to the EMA for twice-weekly dosing in adults with short bowel syndrome.
- ClinicalTrials.gov, EASE SBS 1 results (NCT03690206)(2024)106 adults, 24 weeks: support volume down 5.13 L a week twice weekly, 3.76 L once weekly and 2.85 L on placebo (p=0.0039 and p=0.27); side-effect and antibody tables.
- Jeppesen PB et al., Gastroenterology 2025;168(4):701-713.e6 (epub December 19, 2024)(2025)Peer-reviewed EASE SBS 1 results: twice weekly reduced parenteral support against placebo.
- Agersnap MA et al., Clinical Drug Investigation 2022;42(12):1093-1100(2022)Healthy adults: effective half-life 88 hours; under 1% of the parent reaches the blood; M2 about 91% of exposure; receptor EC50 values.
- Agersnap MA et al., Clinical Pharmacokinetics 2023;62(4):645-651(2023)A single 10 mg dose in 8 people with severe kidney impairment or kidney failure and 8 controls: no clinically relevant change in exposure.
- Larsen BD et al., Journal of Medicinal Chemistry 2025;68(3):3134-3145(2025)Design paper: nine substitutions and a six-lysine structure-inducing probe that improved synthesis yields and liquid stability.
- FDA orphan drug designation record, glepaglutide(2017)Designated October 20, 2017, for short bowel syndrome; sponsor Zealand Pharma A/S.
- ClinicalTrials.gov, EASE SBS 5 (NCT07197944)(2026)Confirmatory phase 3 at 33 sites in 14 countries including the US, 10 mg twice weekly against placebo, about 90 people, started February 11, 2026; primary completion estimated October 2028.
- Hargrove et al., Journal of Pharmacology and Experimental Therapeutics 2020;373(2):193-203(2020)Ferring researchers: glepaglutide less potent than apraglutide at the GLP-2 receptor and less selective against the GLP-1 receptor (selectivity ratio 36).
- Gattex (teduglutide) US label, DailyMed(2025)Teduglutide comparison: 0.05 mg/kg once daily; half-life about 2 hours in healthy adults and 1.3 hours in short bowel syndrome; class warnings.
Beyond these, 43 records are indexed. Browse the records