What it is
Larazotide acetate is an oral peptide investigated as a tight-junction regulator for celiac disease and "leaky gut". Tight junctions are the seals between neighboring cells lining the intestine. Larazotide acts locally in the gut rather than systemically.
In the PeptidesAI encyclopedia it is categorized under healing. It was studied as an add-on to a gluten-free diet, which is the standard management for celiac disease.
How it's thought to work
Larazotide is a zonulin antagonist, meaning it opposes zonulin, a protein linked to opening the gaps between intestinal cells. It is described as promoting tight-junction assembly in the intestinal epithelium, reducing paracellular permeability (the passage of material between cells, or "leaky gut") and limiting antigen passage. In a randomized gluten-challenge study, however, a measure of intestinal permeability, the lactulose-to-mannitol ratio, did not differ significantly between larazotide and placebo.
What the research says
Larazotide reached phase 3 for celiac disease as an adjunct to a gluten-free diet. A randomized, placebo-controlled study of 342 adults with ongoing symptoms despite a gluten-free diet met its primary endpoint at one of the three dose levels tested, while the other two did not differ from placebo. A 184-patient gluten-challenge study reported limited gluten-induced symptoms in one dose group. A meta-analysis of four randomized trials (626 patients) found a symptom benefit in people undergoing gluten challenge but not in people on a gluten-free diet. The authors of the larger study described their own results as mixed.
In June 2022 the company announced that an interim analysis of its phase 3 trial did not support trial continuation, because the number of additional patients needed was too large. Larazotide is not FDA-approved.
Reported side effects
In trials, mild gastrointestinal symptoms, headache and urinary tract symptoms were reported at rates similar to placebo.
Form
Larazotide is taken by mouth as capsules and acts locally in the gut, so it is not reconstituted.
Important notes
Larazotide is not FDA-approved. It is an oral, locally acting compound, and its phase 3 trial was discontinued in 2022.
Sources
- Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Leffler DA et al. Gastroenterology, 2015. Human trial
- Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Kelly CP et al. Aliment Pharmacol Ther, 2013. Human trial
- Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials. Hoilat GJ et al. Clin Res Hepatol Gastroenterol, 2022. Review
- 9 Meters Biopharma announces interim analysis of Phase 3 study of larazotide for celiac disease does not support trial continuation. 9 Meters Biopharma, 2022. Announcement
Frequently asked questions
These questions cover the same ground as the sections above, in a shorter format.
What is larazotide?
Larazotide acetate is an oral peptide investigated as a tight-junction regulator for celiac disease and "leaky gut", acting locally in the gut rather than systemically.
How is larazotide thought to work?
It is a zonulin antagonist described as promoting tight-junction assembly in the intestinal lining, reducing paracellular permeability and limiting antigen passage.
What does the research on larazotide say?
It reached phase 3 for celiac disease as an adjunct to a gluten-free diet with mixed results; the phase 3 trial was stopped in 2022 and larazotide is not FDA-approved.
What are the reported side effects of larazotide?
In trials, mild gastrointestinal symptoms, headache and urinary tract symptoms were reported at rates similar to placebo.
The full entry, plus the calculator
The PeptidesAI app has the complete encyclopedia entry for Larazotide — one of 70 compounds covered — plus the reconstitution calculator, a dose log and reminders. Free to download on iPhone.
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