Larazotide
An oral eight-amino-acid peptide designed to keep the gut's tight junctions closed, tested in coeliac disease until its phase 3 trial was terminated
Larazotide acetate is an oral peptide designed to stop the tight junctions between gut cells from opening, so less gluten crosses the intestinal lining. In coeliac disease trials it eased symptoms at some doses but never changed the permeability marker it targeted, and its phase 3 trial was terminated by the sponsor in 2022. It is not approved in the US.
What is it?
In coeliac disease, gluten fragments cross the intestinal lining and trigger an immune reaction, and the opening of tight junctions, the seals between gut cells, is thought to help them through. Larazotide acetate, derived from a cholera-bacterium protein, was designed to keep those junctions shut.
In the laboratory it does what it was built for. In intestinal cells it blocked junction opening caused by gliadin, cytokines and a zonulin-derived peptide, stopped a gliadin fragment crossing, and helped junctions reassemble. In pigs, a delayed-release formulation delivered it to the duodenum and upper jejunum, where coeliac disease does its damage, and in injured pig gut it worked best at a modest dose because its own breakdown fragments interfered at higher ones.
Its trials told a mixed story. In the first safety study, 12 mg doses were tolerated and blunted the rise in gut permeability after gluten. In gluten-challenge trials of 86 and 184 patients, it did not change the lactulose-mannitol permeability ratio, though some lower doses limited symptoms. In 342 adults with symptoms despite a gluten-free diet, only 0.5 mg three times a day met the primary end point, the lowest dose tested, and a pooled analysis found no effect on the permeability ratio.
ClinicalTrials.gov lists its phase 3 coeliac trial (NCT03569007) as terminated by the sponsor in 2022. Since then, the barrier idea has moved elsewhere: in children with post-COVID multisystem inflammatory syndrome, those given larazotide cleared viral spike protein and recovered faster, in two small reports, and rat studies in pancreatitis and liver failure found less gut damage. Drugs@FDA holds no application for it.
One caution for readers searching the literature: the code AT-1001 is also used for an unrelated nicotinic receptor drug studied in addiction; those papers are not about larazotide.
Mechanism of Action
Larazotide acetate is an 8-amino-acid peptide that acts on the tight junctions between intestinal cells, keeping them closed against gluten, cytokines and zonulin signalling.
Junctions kept shut
Blocks tight-junction opening triggered by gliadin, inflammatory cytokines and a zonulin-derived peptide in intestinal cells.
Junctions rebuilt
Promotes assembly of ZO-1, occludin and claudins at the junctions and reduces leakiness; reduces MLC-2 phosphorylation, likely via ROCK.
Acts locally
Taken by mouth in a delayed-release formulation that releases it in the duodenum and upper jejunum.
Published Research
These are the studies that describe larazotide, read from their PubMed abstracts: five human trials and a meta-analysis.
Symptoms despite a gluten-free diet: 342 adults
0.5, 1 or 2 mg three times a day for 12 weeks. Only 0.5 mg met the primary end point, with fewer symptoms than placebo and 26% fewer symptomatic days; 1 and 2 mg were no different from placebo. Safety was comparable with placebo.
Gluten challenge: 184 patients, 6 weeks
1, 4 or 8 mg three times a day with 2.7 g of gluten daily. The permeability ratio did not differ from placebo; 1 mg limited symptoms, and all doses blunted the rise in anti-transglutaminase antibodies.
Gluten challenge: 86 patients, 14 days
0.25 to 8 mg three times a day, with or without 2.4 g of gluten daily. The permeability measure was too variable to show an effect; some lower doses limited symptom worsening.
First safety study with gluten
12 mg doses caused no more adverse events than placebo. After gluten, intestinal permeability rose 70% on placebo and not at all on larazotide, and gastrointestinal symptoms were less frequent.
Children with post-COVID inflammatory syndrome: 12 patients
Added to treatment four times a day for 3 weeks: faster resolution of gastrointestinal symptoms, faster spike-antigen clearance and a faster return to usual activities, with no larazotide-related adverse events.
First children with MIS-C
Four children with post-COVID multisystem inflammatory syndrome took oral larazotide four times a day for 21 days without adverse effects; spike antigen became undetectable and gastrointestinal symptoms resolved faster than in 22 children on standard therapy alone.
Meta-analysis: 4 trials, 626 patients
The permeability ratio did not differ from placebo. During gluten challenge, larazotide improved symptom scores and reduced gluten-related diarrhoea; on a gluten-free diet it did not. Other adverse events were similar to placebo.
Keeping junctions closed
In intestinal cell lines, larazotide blocked tight-junction opening caused by a zonulin-derived peptide, by cytokines and by gliadin, and stopped a gliadin fragment crossing the cell layer; in gliadin-sensitised transgenic mice it preserved junction structure.
Helping junctions assemble
The 8-amino-acid peptide promoted tight-junction assembly, actin rearrangement and the junctional placement of ZO-1, occludin and claudins, and reduced leakiness in Caco-2 cells.
Protection from oxygen deprivation
Pre-treatment preserved barrier resistance and junction proteins in intestinal cells through anoxia and reoxygenation, reduced MLC-2 phosphorylation, likely via the ROCK pathway, and increased cell proliferation.
Ischaemic pig gut
In ischaemia-injured pig jejunum, 1 µM larazotide stimulated barrier repair at the tight junctions; higher doses worked less well because its own fragments inhibited it, which a D-amino-acid analogue avoided.
Where the delayed-release form releases
In fasted pigs given 1 mg of a delayed-release formulation, larazotide peaked at 0.32 to 1.76 µM in the duodenum and proximal jejunum at one hour, the region coeliac disease affects.
Acute pancreatitis in rats
In rats with acute pancreatitis, larazotide reduced intestinal damage and permeability and halved bacterial translocation (50% against 100%).
Acute liver failure in rats
In rats with drug-induced liver failure, larazotide in drinking water reduced intestinal damage and ALT but did not change liver damage scores.
Dosing Data
There is no approved dose. Coeliac trials gave it by mouth three times a day, from 0.25 to 8 mg; only 0.5 mg met its primary endpoint.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
Larazotide has no label. These cautions follow from its record.
Legal Status
Larazotide is an investigational drug with no approval.
Frequently Asked Questions
?What is larazotide?
An oral eight-amino-acid peptide designed to keep the gut's tight junctions from opening, tested mainly in coeliac disease.
?Does larazotide work for coeliac disease?
Mixed: it never changed the permeability marker it targeted, and only 0.5 mg eased symptoms in the largest trial. Its phase 3 trial was terminated in 2022.
?Is larazotide approved?
No. Drugs@FDA holds no application for it, as of September 30, 2026.
?Is it studied for anything else?
A 2025 trial in 12 children with post-COVID multisystem inflammatory syndrome reported faster recovery on larazotide; it was small.
References
- [fda] FDA. Drugs@FDA (openFDA): no application for larazotide. Read September 30, 2026.
- [other] ClinicalTrials.gov. NCT03569007: Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms. Status: Terminated (trial terminated by sponsor); record updated July 26, 2022. Read September 30, 2026.
- [pubmed] Leffler DA, et al. "Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial." Gastroenterology, 2015;148(7):1311-9.e6. PMID: 25683116.
- [pubmed] Kelly CP, et al. "Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study." Aliment Pharmacol Ther, 2013;37(2):252-62. PMID: 23163616.
- [pubmed] Leffler DA, et al. "A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge." Am J Gastroenterol, 2012;107(10):1554-62. PMID: 22825365.
- [pubmed] Paterson BM, et al. "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, 2007;26(5):757-66. PMID: 17697209.
- [pubmed] Yonker LM, et al. "Viral spike antigen clearance and augmented recovery in children with post-COVID multisystem inflammatory syndrome treated with larazotide." Sci Transl Med, 2025;17(809):eadu4284. PMID: 40737433.
- [pubmed] Hoilat GJ, et al. "Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials." Clin Res Hepatol Gastroenterol, 2022;46(1):101782. PMID: 34339872.
- [other] 9 Meters Biopharma, press release (SEC 8-K exhibit 99.1), June 21, 2022: an interim analysis of the phase 3 CedLara trial does not support continuing it. Read September 30, 2026.
- [pubmed] Yonker LM, et al. "Zonulin Antagonist, Larazotide (AT1001), As an Adjuvant Treatment for Multisystem Inflammatory Syndrome in Children: A Case Series." Crit Care Explor, 2022;10(2):e0641. PMID: 35211683.
- [pubmed] Gopalakrishnan S, et al. "Larazotide acetate regulates epithelial tight junctions in vitro and in vivo." Peptides, 2012;35(1):86-94. PMID: 22401908.
- [pubmed] Gopalakrishnan S, et al. "Larazotide acetate promotes tight junction assembly in epithelial cells." Peptides, 2012;35(1):95-101. PMID: 22401910.
- [pubmed] Kim J, et al. "Larazotide Acetate Protects the Intestinal Mucosal Barrier from Anoxia/Reoxygenation Injury via Various Cellular Mechanisms." Biomedicines, 2025;13(10). PMID: 41153766.
- [pubmed] Slifer ZM, et al. "Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions." PLoS One, 2021;16(4):e0250165. PMID: 33886649.
- [pubmed] Enomoto H, et al. "In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model." PLoS One, 2021;16(4):e0249179. PMID: 33844694.
- [pubmed] Karahan D, et al. "Ameliorative Effects of Larazotide Acetate on Intestinal Permeability and Bacterial Translocation in Acute Pancreatitis Model in Rats." Dig Dis Sci, 2024;69(4):1242-1252. PMID: 38441784.
- [pubmed] Caliskan AR, et al. "Effects of larazotide acetate, a tight junction regulator, on the liver and intestinal damage in acute liver failure in rats." Hum Exp Toxicol, 2021;40(12_suppl):S693-S701. PMID: 34791921.
Sources & Citations
Studies were read from their PubMed abstracts; no label exists. Read October 6, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.