Larazotide acetate

Origin and structure

Larazotide is a synthetic chain of eight amino acids, Gly-Gly-Val-Leu-Val-Gln-Pro-Gly (GGVLVQPG; C32H55N9O10, 725.8 g/mol, CAS 258818-34-7), developed as its acetate salt. It grew out of Alessio Fasano's research at the University of Maryland on zonula occludens toxin (Zot), a toxin of the cholera bacterium Vibrio cholerae that loosens the tight junctions sealing the gaps between gut cells. In 2000 his group described zonulin, a human protein they saw as the body's own counterpart of Zot, and reported raised levels in the gut during active coeliac disease (Fasano et al., Lancet 2000). Larazotide was designed to block that signal; its developer described its structure as derived from a protein secreted by V. cholerae.

Alba Therapeutics in Baltimore, which Fasano co-founded, began testing it in people in 2005 under the code AT-1001. In February 2016 Alba licensed it to Innovate Biopharmaceuticals in Raleigh, North Carolina, which developed it as INN-202 and renamed itself 9 Meters Biopharma after a merger in 2020. The trial product is a capsule of small enteric-coated beads, built to pass the stomach intact and release the peptide in two steps in the upper small intestine, where coeliac disease does its damage.

How it is thought to work

In coeliac disease, fragments of gluten that cross the lining of the small intestine set off an immune reaction in the tissue beneath it. The idea behind larazotide is that gliadin, one of the gluten proteins, makes gut cells release zonulin, which opens the tight junctions and lets more gluten fragments through. Larazotide was meant to keep those junctions shut. In cultured gut cells it stopped gliadin fragments and a Zot-derived peptide from rearranging the junction protein ZO-1 and the cells' actin skeleton, kept the electrical resistance across the cell layer from falling and reduced the passage of a gliadin peptide. In gliadin-sensitised mice carrying the coeliac-risk gene HLA-DQ8 it limited the build-up of immune cells in the gut wall and preserved normal junctions (Gopalakrishnan et al., Peptides 2012). This laboratory work came from the developer itself.

How it does this is not settled. A 2021 review by researchers with financial ties to the developer still describes it as 'thought to' act as a zonulin antagonist and links it to inhibition of myosin light chain kinase, an enzyme that puts tension on the junctions (Slifer et al., Am J Physiol 2021). In 2009 Fasano's group identified zonulin as prehaptoglobin-2, the precursor of a common blood protein, but larazotide's sequence occurs in neither Zot nor haptoglobin as published in the UniProt protein database. In a 2021 letter in Gut titled 'Lack of relationship of AT1001 to zonulin and prehaptoglobin-2', the coeliac immunologists Ludvig Sollid (University of Oslo) and Frits Koning (Leiden University Medical Center) disputed the link.

As far as is known, larazotide acts only inside the gut. In the human trials that measured it, every blood level stayed below the assay's lowest quantifiable concentration of 0.5 ng/ml (Paterson et al. 2007; Leffler et al. 2012), so its pharmacokinetics in people have never been described. In a study in three pigs, an oral dose of the trial formulation reached measurable concentrations in the duodenum and upper jejunum, peaking after about an hour and still detectable up to four hours later (Enomoto et al., PLoS One 2021).

Is larazotide approved?

No. No medicines regulator anywhere has approved larazotide. It has never been authorised in the EU, the EMA's medicines database lists no application for it, and in the Netherlands it is not a registered medicine; none of its trials had a Dutch site. No medicine is authorised for coeliac disease in the EU or approved for it by the FDA, so a strict, lifelong gluten-free diet remains the treatment.

In the United States the FDA gave larazotide Fast Track designation for coeliac disease, a status meant to speed up drugs for serious conditions with an unmet need. It did not get past phase 3. On 21 June 2022, 9 Meters announced that an interim analysis of its CedLara trial had shown that the number of extra patients needed to prove a difference from placebo was too large to justify continuing. In August 2022 it ended development in coeliac disease, and on 17 July 2023 it ceased operations and filed for liquidation under Chapter 7 of the US Bankruptcy Code. No new coeliac trial has been registered on ClinicalTrials.gov since; researchers at Massachusetts General Hospital have run small trials in post-COVID conditions.

In sport larazotide is not named on the WADA Prohibited List, but class S0 prohibits at all times any pharmacological substance without current approval for human therapeutic use, including drugs whose development was discontinued. The Dopingautoriteit applies the same list in the Netherlands.

What the research shows

Larazotide went through seven controlled trials in people with coeliac disease, together enrolling more than 1,000 participants, plus a phase 1 study in 24 healthy volunteers. All were sponsored by its developers. Four were published, and a 2022 meta-analysis pooled four randomised trials; two phase 2 trials and the phase 3 trial have no published results. Every coeliac trial added larazotide to a gluten-free diet, and none tested it as a replacement. The main findings:

• Phase 1b (Paterson et al., Aliment Pharmacol Ther 2007): 21 adults with controlled coeliac disease, given larazotide or placebo during an in-patient gluten challenge. Adverse events were no more frequent than on placebo. Gut permeability rose 70% in the placebo group and not in the larazotide group, and gastrointestinal symptoms were less frequent (P = 0.018); the study was small and exploratory.
• Gluten challenge, two weeks (Leffler et al., Am J Gastroenterol 2012): 86 patients. The permeability test varied too much outside hospital to judge, and larazotide and placebo did not differ significantly on it. Some lower doses limited the worsening of symptoms caused by gluten; the highest dose did not.
• Gluten challenge, six weeks (Kelly et al., Aliment Pharmacol Ther 2013): 184 patients. No difference in the permeability test. The lowest dose limited gluten-induced symptoms (P = 0.002), and coeliac antibodies (anti-tTG IgA) rose less at all three doses: on average to 19.0 times baseline on placebo against 3.9 to 7.7 times on larazotide.
• Persistent symptoms on a gluten-free diet (Leffler et al., Gastroenterology 2015): 342 adults treated for 12 weeks. The lowest of three doses met the primary endpoint, fewer coeliac symptoms than placebo (P = 0.022), with 26% fewer symptomatic days; the two higher doses were no better than placebo on any endpoint. The authors called it unclear why higher doses did worse and suggested the peptide may clump together at higher doses.
• Meta-analysis (Hoilat et al., Clin Res Hepatol Gastroenterol 2022): four randomised trials, 626 patients. No significant effect on the lactulose-mannitol permeability ratio, with or without gluten. Symptom scores improved in the gluten-challenge trials but not in patients on a gluten-free diet alone; gluten-related diarrhoea was less frequent and other adverse events were similar.
• Never published: a phase 2b trial in active coeliac disease (105 people, sites in the US, Canada and Spain; NCT00620451) and a 42-person gluten-challenge trial (NCT00889473) finished in 2009 and 2010 without published results.
• Phase 3, CedLara (NCT03569007): adults with persistent symptoms on a gluten-free diet, randomised to one of two low doses or placebo for 12 weeks at 160 US sites. Of 525 planned, 307 were enrolled from May 2019; the trial was stopped in June 2022 after the interim analysis, and its results were never published.
• MIS-C (Yonker et al., Sci Transl Med 2025): a randomised, placebo-controlled phase 2a trial in 12 children (median age 5.7 years) with multisystem inflammatory syndrome after COVID-19, given larazotide or placebo on top of standard care for three weeks. No larazotide-related adverse events were reported, and treated children had faster resolution of gut symptoms, faster clearance of viral spike protein from the blood and a faster return to normal activities. The trial was stopped early as MIS-C cases declined; it followed an open case series of four children (2022).
• Long COVID (NCT05747534): a placebo-controlled phase 2a trial at Massachusetts General Hospital enrolled 107 people aged 7 to 50 for a 21-day course. It was completed on 18 June 2026; no results had been posted by October 2026.
• Animal studies: in mice larazotide reduced the onset of arthritis (Tajik et al., Nat Commun 2020), and in pieces of pig small intestine injured by ischaemia and kept alive in the lab it sped up repair of the gut barrier (Slifer et al., PLoS One 2021). Neither use has been tested in people.

Zonulin and the 'leaky gut' question

Larazotide is often described online as a 'leaky gut' peptide. The trial data do not back that up. In the controlled trials the lactulose-mannitol test, the standard measure of small-intestinal permeability, did not differ significantly between larazotide and placebo, and no trial has tested it in people with 'leaky gut' as a diagnosis. The zonulin measurements behind much of the leaky-gut literature are themselves in doubt: in 2019 researchers at Monash University found that two widely used commercial zonulin blood tests detected other proteins, such as complement C3, rather than prehaptoglobin-2 (Ajamian et al., PLoS One 2019).

Next to the other gut peptides on this wiki, larazotide is both the best tested and the clearest disappointment. BPC-157 and KPV rest mainly on rat and mouse studies, with five small human studies for BPC-157 and none for KPV. Larazotide went through controlled trials in more than 1,000 people with coeliac disease and was well tolerated in them, but its benefit was small, inconsistent across doses and not confirmed in phase 3.

Frequently asked questions

Is larazotide approved or available in the Netherlands?

No. No regulator anywhere has approved larazotide, the EMA has no record of an application, and in the Netherlands it is not a registered medicine, so it cannot be prescribed as one. None of its trials ran in the Netherlands. Larazotide offered online is research material, not the enteric-coated capsule used in the trials.

Why was the larazotide phase 3 trial stopped?

In June 2022 an independent statistician used data from roughly the first half of the planned 525 participants to re-estimate how many patients the CedLara trial would need to show a difference from placebo in abdominal symptoms. The number was too large to be feasible, so 9 Meters stopped the trial, ended its coeliac programme that August and filed for liquidation in July 2023. The results have never been published.

Does larazotide help with leaky gut?

That has not been shown. In controlled trials the standard permeability test, the lactulose-mannitol ratio, did not differ significantly between larazotide and placebo, either during gluten challenges or on a gluten-free diet. No trial has tested it in people with 'leaky gut' as a diagnosis, and two widely used commercial zonulin blood tests, often used in that context, turned out to detect other proteins.

Can larazotide replace a gluten-free diet?

No. It was only ever tested as an add-on to a gluten-free diet. In gluten-challenge trials it limited symptoms at some low doses, but gut permeability did not change significantly and coeliac antibodies still rose, if less than on placebo. Its best result, fewer symptoms at one low dose in a 342-person trial, was not confirmed in phase 3.

Is larazotide banned in sport?

Yes, at all times. It is not named on the WADA list, but class S0 covers any pharmacological substance without current approval for human therapeutic use, including drugs whose development was stopped. The Dopingautoriteit applies the same list in the Netherlands.

Is AT-1001 the same as migalastat?

No. Three unrelated compounds have carried the code AT-1001 or AT1001: larazotide from Alba Therapeutics; migalastat from Amicus Therapeutics, authorised in the EU as Galafold for Fabry disease since May 2016; and a nicotinic-receptor compound studied in rats for nicotine addiction. Trial registries and search results mix them up, so check the compound name.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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