Larazotide

AT-1001, INN-202, larazotide acetate

Recovery, repair & tissue

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Synthetic octapeptide (8 amino acids), derived from a fragment of the Vibrio cholerae zonula occludens toxin
Mechanism: Acts locally in the gut lining to stop tight junctions between cells from loosening, so fewer gluten fragments and other large molecules slip through
Routes studied: Oral, delayed-release capsule, before meals (all human trials)
Dose range reported: Trials: 0.5 mg, 1 mg, 2 mg, 4 mg and 8 mg three times daily before meals; the 0.5 mg dose performed best and higher doses did not. No approved dose
Half-life: Not meaningful systemically — the peptide is designed to stay in the gut, is broken down by intestinal enzymes and is barely detectable in blood
Storage: Capsules: room temperature per trial supply. Raw peptide powder, where encountered: refrigerate, dry, protect from light
Regulatory status: Not approved anywhere. Development stopped in 2022 after a Phase 3 interim analysis

Doses are as reported in studies or by the community — never recommendations.

1What it is

Larazotide is a small synthetic peptide built from part of a bacterial toxin that cholera uses to open the gut barrier. The peptide does the opposite: it blocks the opening signal. It was developed first by Alba Therapeutics, later by Innovate Biopharmaceuticals and 9 Meters Biopharma, as the first drug candidate aimed at coeliac disease itself rather than at avoiding gluten. The idea was an add-on for people who still have symptoms despite a gluten-free diet.

After a decade of mostly encouraging mid-stage trials, the Phase 3 CeDLara trial was halted in 2022 when an interim look suggested it was unlikely to hit its endpoint, and the sponsor later ceased operations. Larazotide is therefore a well-studied but failed drug candidate. It surfaces in peptide circles because of interest in "leaky gut", a popular term for increased intestinal permeability.

2How it's thought to work

The cells lining the small intestine are sealed together by tight junctions. A protein called zonulin (pre-haptoglobin-2) can signal those junctions to open. In coeliac disease, gluten fragments trigger zonulin release, the junctions loosen, more gluten reaches the immune cells under the lining, and inflammation follows.

Larazotide is thought to:

Block the zonulin receptor pathway, preventing the actin-filament rearrangement that pulls junctions apart (Gopalakrishnan 2012, Peptides).

Promote re-assembly of tight-junction proteins such as ZO-1 and occludin after they have been disturbed.

Reduce the passage of gluten peptides across cell layers in culture.

Proposed: an eight-amino-acid peptide that acts in the gut lumen to hold tight junctions shut rather than being absorbed. The intent is to keep gluten fragments from crossing in coeliac disease; its phase III trial did not meet its primary endpoint.Schematic — not to scale

It is not absorbed in meaningful amounts, so any effect is local to the gut lining.

3What the research shows

Graded A (positive Phase 2b, failed Phase 3)

Coeliac disease on a gluten-free diet with persistent symptoms

In a 342-patient randomised, double-blind, placebo-controlled Phase 2b trial, 0.5 mg three times daily reduced coeliac symptom scores versus placebo over 12 weeks; 1 mg and 2 mg did not separate from placebo, an inverse dose response that was never fully explained (Leffler 2015, Gastroenterology). The Phase 3 CeDLara trial using similar low doses was stopped for futility at interim analysis in 2022; full results have not been published in a peer-reviewed journal †. [4]

Graded A (mixed)

Gluten-challenge studies

In earlier controlled gluten-challenge trials, larazotide reduced gluten-induced symptoms and, in some analyses, blunted the rise in anti-tTG antibodies, but did not consistently change the primary permeability measure (lactulose-mannitol ratio) (Paterson 2007, Aliment Pharmacol Ther; Leffler 2012, Am J Gastroenterol; Kelly 2013, Aliment Pharmacol Ther). [1][2][3]

Multisystem inflammatory syndrome in children (MIS-C) after COVID-19

A small case series of children treated with larazotide alongside standard care reported faster symptom resolution and a drop in circulating spike antigen, consistent with a gut-barrier mechanism (Yonker 2022, Crit Care Explor). Uncontrolled, four patients. [7]

Type 1 diabetes, necrotising enterocolitis, other barrier conditions

Larazotide or its parent fragment reduced disease in a diabetes-prone rat model and in animal barrier-injury models (Watts 2005, PNAS). No human trials. [6]

Not gradedno data

"Leaky gut" in healthy people, athletes or non-coeliac gut complaints

No published study. Community use for general permeability rests on extrapolation from coeliac trials.

4Reported side effects and interactions

Literature-reported

across trials, adverse events were similar in frequency to placebo; the most common were headache, gastrointestinal upset and urinary tract infection, none clearly drug-related. No serious safety signal emerged in roughly 1,000 trial participants.

Community-reported

few reports; occasional bloating or nausea. Many products described online as larazotide are of unknown identity and purity, which is the main practical risk.

Theoretical. tightening the gut barrier could, in principle, reduce absorption of some nutrients or drugs that rely on paracellular passage; this has not been observed in trials.

Interactions. none identified. Because the peptide stays in the gut, systemic drug interactions are unlikely.

Markers researchers commonly monitor

Drawn from the trial endpoints and from standard coeliac follow-up:

Marker	Why it's watched
Anti-tissue transglutaminase (tTG-IgA) and deamidated gliadin antibodies	the standard blood markers of ongoing gluten exposure in coeliac disease; used as secondary endpoints in larazotide trials.
Lactulose/mannitol ratio	the research measure of intestinal permeability; available in some labs, variable, and not changed consistently by larazotide in trials.
Faecal calprotectin	a gut-inflammation marker, useful context for anyone studying gut-lining compounds.
Serum zonulin	commercially offered but assays are poorly validated and the test is not recommended for decisions; worth knowing why it is unreliable before paying for it.
Ferritin, B12, folate, vitamin D	nutrient markers that track mucosal recovery in coeliac disease.
Symptom diary (e.g. CeD-GSRS or similar)	the primary endpoint in every larazotide trial was patient-reported symptoms.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Larazotide was studied as an oral delayed-release capsule, not as an injectable, and there is no rationale for injecting it. Trial dosing was 15 minutes before meals. Raw powder, if encountered, is sometimes put into capsules by the community; stability in acid and gut enzymes was engineered into the formulation, not the bare peptide, so a home-filled capsule may not deliver the same amount to the small intestine. No calculator entry applies.

Open in calculator, pre-loaded →

6Commonly studied alongside

In trials, only a gluten-free diet. Community discussion pairs it with KPV (see set 2), BPC-157 (profile 1) and glutamine for gut-lining support; no combined study exists.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. Held Fast Track designation for coeliac disease during development; programme discontinued 2022
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not listed by WADA; not a performance substance †

8Open questions

Why did 0.5 mg work in Phase 2b while higher doses did not, and did that oddity predict the Phase 3 failure?
Does the compound change permeability in any population, given lactulose/mannitol results were flat?
Any role outside coeliac disease — MIS-C, IBS, non-coeliac gluten sensitivity — remains untested in controlled trials.

9References

1Paterson BM et al. (2007). The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Aliment Pharmacol Ther. PubMed · DOI
2Leffler DA et al. (2012). A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol. PubMed · DOI
3Kelly CP et al. (2013). Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther. PubMed · DOI
4Leffler DA et al. (2015). Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology. PubMed · DOI
5Gopalakrishnan S et al. (2012). Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides. PubMed · DOI
6Watts T et al. (2005). Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci USA. PubMed · DOI
7Yonker LM et al. (2022). Zonulin antagonist, larazotide (AT1001), as an adjuvant treatment for multisystem inflammatory syndrome in children: a case series. Crit Care Explor. PubMed · DOI
8Fasano A (2011). Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. PubMed · DOI

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

26 Oct 2026Profile published — awaiting medical review

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