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Larazotide

From PeptidePlaza, the free peptide reference · Entry #039 · Recovery · Hand-curated entry · Editorial standards

Research warning. Research chemical — not for human consumption. The phase 3 CedLara trial in celiac disease was discontinued for futility at interim analysis; claims of clinical efficacy for intestinal permeability disorders are not supported by definitive trial evidence.

Larazotide (also known as AT-1001, Larazotide acetate, INN-202) is a recovery research peptide. An eight-amino-acid peptide that acts locally in the gut lumen and is essentially not absorbed. Reached phase 3 for celiac disease — and failed at interim analysis.

Larazotide acetate is an orally administered octapeptide (Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) derived from the Vibrio cholerae zonula occludens toxin, developed as an antagonist of zonulin — the endogenous protein that reversibly opens intestinal tight junctions. In celiac disease, gliadin exposure triggers zonulin release, tight junctions loosen, and gluten peptides cross the epithelium to drive immune activation. Larazotide acts in the gut lumen to block this cascade, promoting redistribution of tight junction proteins and actin filaments to restore barrier integrity. Critically, it is not systemically absorbed — its pharmacology is confined to the intestinal surface, which gives it an unusually benign safety profile. Phase 2 trials suggested it limited gluten-induced symptom worsening in patients on a gluten-free diet, but the phase 3 CedLara trial was discontinued in 2022 after an interim analysis showed the sample size required for a significant clinical outcome had become impractically large. It remains the most extensively studied pharmacological approach to intestinal permeability, and the best-characterised "leaky gut" intervention in the peptide space — with the sobering result that the definitive trial did not succeed.

1 Mechanism of action

Antagonises zonulin-mediated tight junction disassembly at the intestinal epithelium. Promotes rearrangement of tight junction proteins (occludin, ZO-1) and actin filaments, reducing paracellular permeability to macromolecules including immunogenic gliadin fragments. Acts locally in the lumen with negligible systemic absorption.

Primary targets: Zonulin receptor pathway (PAR2/EGFR-mediated tight junction signalling)

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Restores intestinal tight junction integrity in preclinical and phase 2 data
  • Acts locally with negligible systemic absorption — very favourable safety profile
  • Reduced gluten-induced symptom worsening in phase 2 celiac trials
  • Preclinical evidence for barrier repair after ischaemic intestinal injury
  • Orally administered rather than injected

2.2 Side effects

  • Headache
  • Nausea
  • Abdominal discomfort and flatulence
  • Urinary tract infection reported in trials
  • Inverted dose-response — higher doses performed worse than lower ones

3 Chemical and physical properties

Molar mass725.8 g/mol
Purity (typical)>98%
Half-lifeNot systemically absorbed — acts locally in the intestinal lumen
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsZonulin receptor pathway (PAR2/EGFR-mediated tight junction signalling)

3.1 Amino acid sequence

Gly-Gly-Val-Leu-Val-Gln-Pro-Gly

4 Research dosages

Phase 2/3 protocols: 0.5 mg orally three times daily before meals (the 0.5 mg dose outperformed 1 mg and 2 mg).

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet
    Gastroenterology (2015) · RCT · N=342
    Phase 2b randomised placebo-controlled trial of larazotide acetate in celiac patients with persistent symptoms on a gluten-free diet.
    Key finding: 0.5 mg three times daily reduced symptom scores versus placebo; higher doses were not more effective, an inverted dose-response later seen as a warning sign.
  2. Larazotide acetate: a pharmacological peptide approach to tight junction regulation
    American Journal of Physiology - Gastrointestinal and Liver Physiology (2021) · Review · N/A (review)
    Mechanistic review of tight junction pharmacology and larazotide's mode of action.
    Key finding: Larazotide restores barrier function through tight junction protein and actin redistribution rather than systemic immunomodulation.
  3. Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment.
    Journal of controlled release : official journal of the Controlled Release Society (2025) · Preclinical
    Gut barrier loss exacerbated gut microbiota dysbiosis by permitting pathogenic blooms, while gut microbiota dysbiosis caused the development of gut mucosal wounds by reducing mucus and breaking down epithelial...
  4. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide.
    Science translational medicine (2025) · RCT
    Multisystem inflammatory syndrome (MIS) is a severe disease that occurs weeks to months after acute infection with SARS-CoV-2, often occurring in children (MISC).
  5. Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials.
    Clinics and research in hepatology and gastroenterology (2022) · Meta-Analysis
    AT-1001 is largely well-endured and seems somehow superior to placebo in alleviating gastrointestinal symptoms among CD patients undergoing gluten challenge.
  6. Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series.
    Critical care explorations (2022) · Preclinical
    Larazotide appears safe and well-tolerated and may offer potential benefit as an adjuvant to immune-targeted therapies.
  7. Larazotide acetate: a pharmacological peptide approach to tight junction regulation.
    American journal of physiology. Gastrointestinal and liver physiology (2021) · Review
    Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function.
  8. Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions.
    PloS one (2021) · Preclinical
    Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions.

6 Safety and risk profile

6.1 Regulatory status

Larazotide is currently classified as Not approved. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 88/100 — low concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Pregnancy or lactation (insufficient data)
  • Known hypersensitivity to the peptide

6.3 Drug interactions

Drug or classInteractionRisk
Oral medicationsTheoretical reduction in paracellular absorption of drugs that cross via tight junctions; clinically uncharacterised.Low
NSAIDsNSAIDs increase intestinal permeability, working against larazotide's mechanism.Low

6.4 Long-term risks

  • No long-term exposure data beyond trial durations
  • Unknown consequences of chronic tight junction modulation

6.5 Research best practices

  • Store lyophilised at −20 °C, protected from moisture
  • Administer before meals in protocols — the mechanism is prophylactic against a gliadin challenge, not therapeutic afterwards
  • Note the inverted dose-response: more is demonstrably not better
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

Did larazotide work for celiac disease?
Not definitively. Phase 2 results were promising at the 0.5 mg dose, but the phase 3 CedLara trial was discontinued in 2022 after interim analysis indicated the trial would need an impractically large sample to demonstrate a significant clinical outcome.
Is larazotide the "leaky gut" drug?
It is the most rigorously studied intervention aimed at intestinal permeability, which makes it the reference compound for that concept — but the honest reading of the phase 3 outcome is that reducing measured permeability did not translate into a clear clinical benefit in celiac disease.
Why is its safety profile so clean?
Because it is not systemically absorbed. The peptide acts on the luminal surface of the intestinal epithelium and is degraded in the gut, so systemic exposure — and therefore systemic toxicity — is minimal.

8 References

  1. Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment. PubMed (2025). Yu F, et al.. View source
  2. Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide. PubMed (2025). Yonker LM, et al.. View source
  3. Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials. PubMed (2022). Hoilat GJ, et al.. View source
  4. Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series. PubMed (2022). Yonker LM, et al.. View source

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9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.