Larazotide is an eight-amino-acid peptide (sequence Gly-Gly-Val-Leu-Val-Gln-Pro-Gly) that was designed to do one narrow thing: tighten the junctions between cells lining the small intestine. It is usually handled as larazotide acetate, and you will see it under several research labels, including AT-1001, AT-2347, and the CAS number 258818-34-7. It came out of work on zonulin, a human protein that loosens the gut barrier, and the peptide is derived from a fetal zonulin sequence (Khaleghi et al., review in *Am J Physiol Gastrointest Liver Physiol*, 2021).
What it was meant to do
In celiac disease, gluten triggers the release of zonulin in the small intestine. Zonulin binds receptors on the gut lining and sets off a cascade that pulls apart tight-junction protein complexes, making the barrier more permeable. Larazotide is proposed to act as a zonulin antagonist: it competitively blocks zonulin from binding its receptor, and has been linked to inhibition of myosin light chain kinase, which reduces tension on the actin filaments that hold junctions open. The net effect studied was redistribution of tight-junction proteins back into place and a restored barrier (review, *AJP-GI*, 2021).
One design feature matters here. Larazotide is taken orally and acts locally in the gut. It is minimally absorbed into the bloodstream, so its effect is meant to stay in the intestine. That was the rationale for using it as an add-on to a gluten-free diet rather than a systemic drug.
The clinical record
Larazotide went further in human testing than any other non-dietary celiac therapy. It originated at Alba Therapeutics and was later developed by 9 Meters Biopharma.
The most cited trial is a phase 2b study published in Gastroenterology in 2015. It was a multicenter, randomized, double-blind, placebo-controlled study testing larazotide acetate at 0.5, 1, or 2 mg three times daily in 342 adults who still had symptoms despite a gluten-free diet for a year or more. The 0.5 mg dose performed best on the symptom endpoint; oddly, higher doses did not (Leffler et al., *Gastroenterology* 2015).
The FDA granted larazotide fast track designation, and a phase 3 trial (the CeDLara study, NCT03569007) opened across more than 100 sites in the US and Canada. In June 2022, 9 Meters discontinued it. An interim analysis concluded the trial would need an impractically large number of patients to show a significant difference from placebo, so the study was stopped for likely futility, not for a safety problem. Across roughly 800 patients in earlier studies, larazotide had been comparable to placebo on safety (Celiac Disease Foundation, 2022).
The same barrier rationale led to a smaller pandemic-era project: a phase 2a study (NCT05022303) and a published four-child case series looking at larazotide in multisystem inflammatory syndrome in children (MIS-C) linked to COVID-19, on the idea that a leaky gut lets viral particles drive inflammation. That work is early and far smaller than the celiac program (9 Meters Biopharma announcement, BioSpace).
Regulatory and quality notes
Larazotide is not an approved drug anywhere. Its lead indication, celiac disease, lost its pivotal trial, and the compound has no marketing authorization from the FDA, EMA, or other regulators. Any material sold under this name is research-use-only, not a medicine, and nothing here is medical or dosing advice.
Because it is an unapproved peptide, there is no pharmaceutical-grade supply chain behind the larazotide sold to researchers. Identity and purity rest entirely on the seller's own documentation. If you are sourcing it for lab work, the things worth checking are the same ones this site tracks across vendors: a recent certificate of analysis tied to the specific lot, a mass-spec or HPLC identity and purity readout, and independent third-party testing rather than the vendor's word alone.