Larazotide

Tight junction regulator · Also known as Larazotide acetate, AT-1001, INN-202

What is larazotide?

A synthetic eight-amino-acid peptide that regulates intestinal tight junctions by antagonizing zonulin. Developed as an adjunct to a gluten-free diet for people with celiac disease who continue to experience symptoms despite dietary compliance.

Larazotide was originally developed by Alba Therapeutics, then licensed to Innovate Biopharmaceuticals (later 9 Metres Biopharma). It is the first tight junction regulator to reach advanced clinical trials. While phase 2 results at the 0.5 mg dose showed significant symptom improvement in celiac patients, the phase 3 trial was discontinued in 2023 after an interim analysis suggested an impractically large sample size would be needed to demonstrate significance.

Key takeaway: Larazotide is the first-in-class tight junction regulator with phase 2 evidence of symptom reduction in celiac disease, though its phase 3 trial was discontinued due to insufficient effect size.

Benefits & evidence

Reduced celiac symptoms on GFD Moderate confidence
Intestinal barrier support Moderate confidence
Reduced gluten-induced permeability Moderate confidence
GI symptom relief Moderate confidence
Leaky gut support (non-celiac) Preliminary confidence

How it works

When gluten fragments reach the intestinal lining in people with celiac disease, they trigger the release of zonulin, a protein that opens the tight junctions between intestinal epithelial cells. This increased permeability allows gluten peptides to cross into the submucosa, where they activate an immune response that damages the intestinal villi.

Larazotide works by antagonizing zonulin and promoting tight junction assembly. It inhibits myosin light chain kinase, reducing tension on the actin filaments that anchor tight junctions. This helps keep the intestinal barrier intact, preventing gluten fragments from crossing into immune-active tissue. Because it acts locally in the gut lumen and has minimal systemic absorption, its safety profile has been consistently favorable across clinical trials.

Dosing information

Typical dosing protocol
Starting dose

0.5 mg three times daily

Taken 15 min before meals
Maintenance dose

0.5 mg three times daily

12 weeks (trial duration)

The 0.5 mg TID dose was the only dose to show significant benefit over placebo in phase 2b. Higher doses (1 mg and 2 mg TID) did not show improvement, suggesting an inverted dose-response. Taken orally before meals. Development currently paused.

Side effects

Most side effects tend to improve as your body adjusts.

Headache Common
Bloating Common
Flatulence Common
Nausea Uncommon
Soft stools Uncommon

Research (10 studies)

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
Celiac disease: Hope for new treatments beyond a gluten-free diet. Clinical nutrition (Edinburgh, Scotland) · 2024