Larazotide

PEPTIDES+ MEMBERS ONLY

INDICATIONS FOR USE

Larazotide is used off-label and experimentally to support gut barrier integrity and reduce intestinal permeability, particularly in individuals with suspected or confirmed “leaky gut” or autoimmune-related gastrointestinal disorders. It has been investigated as a supportive treatment in celiac disease and other inflammatory bowel conditions where tight junction dysfunction contributes to symptoms.

ROUTE OF ADMINISTRATION

  • Oral capsule

COMMON INITIAL DOSING REGIMENS

  • Typical dosing ranges from 0.5 mg to 1 mg orally, taken up to three times daily before meals. Duration of treatment may vary depending on clinical response and underlying condition, with courses often lasting 4–12 weeks or longer.

MECHANISM OF ACTION

  • Larazotide acetate is a synthetic peptide that modulates the function of tight junctions between intestinal epithelial cells. By inhibiting the signaling cascade that leads to tight junction disassembly, Larazotide helps maintain intestinal barrier integrity and prevent the translocation of pro-inflammatory substances (e.g., gluten peptides, bacterial endotoxins) from the gut lumen into the bloodstream.

  • This barrier-supportive mechanism may reduce systemic inflammation, autoimmunity, and gastrointestinal symptoms in patients with increased intestinal permeability.

COMMON SIDE EFFECTS

  • Gastrointestinal: Bloating, flatulence, nausea, or soft stools.

  • General: Mild fatigue or headache.

  • Allergic: Rash or itching.

  • Rare: Constipation, abdominal cramping, or transient appetite changes.

CONTRAINDICATIONS

  • Absolute: Known hypersensitivity to Larazotide or any inactive ingredients.

  • Relative: Use with caution in individuals with severe gastrointestinal motility disorders, small bowel obstructions, or concurrent use of medications that may alter gut permeability or motility.

COMPARISON WITH OTHER AGENTS

  • Zonulin Modulators: Larazotide is one of the few agents shown to directly inhibit zonulin-induced tight junction opening, making it unique in its class.

  • Probiotics or L-glutamine: These may support gut health indirectly through microbiome modulation or mucosal healing, whereas Larazotide acts directly at the cellular junction level.

  • Anti-inflammatory agents: Drugs like mesalamine or corticosteroids reduce GI inflammation but do not specifically target barrier function. Larazotide may complement these agents in barrier dysfunction cases.

EXPERIMENTAL TREATMENT DISCLAIMER:

  • Larazotide is not FDA-approved for the treatment of any disease or condition. Its use is considered experimental. While promising clinical trial results exist for certain conditions, such as celiac disease, the long-term safety and effectiveness of Larazotide in broader applications remain unproven. The patient acknowledges the investigational nature of this therapy and agrees to proceed with full understanding of the associated risks and uncertainties.

MORE INFORMATION

  • FDA Safety Data Sheet not available (experimental peptide).

  • Slifer ZM. Larazotide acetate: a pharmacological peptide approach to tight junction regulation. Am J Physiol Gastrointest Liver Physiol. 2021 [PubMed Link]

  • Kulkarni A. Current pharmacological approaches and potential future therapies for Celiac disease. Eur J Pharmacol. 2021 [PubMed Link]

  • Troisi J. The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases. Curr Med Chem. 2021 [PubMed Link]

  • Hoilat GJ. Larazotide acetate for treatment of celiac disease: A systematic review and meta-analysis of randomized controlled trials. Clin Res Hepatol Gastroenterol. 2022 [PubMed Link]

  • Glinka DM. The PAR2 Antagonist Larazotide Can Mitigate Acute Histamine-Stimulated Epithelial Barrier Disruption in Keratinocytes: A Potential Adjunct Treatment for Atopic Dermatitis. JID Innov. 2025 [PubMed Link]

  • Slifer ZM. Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions. PLoS One. 2021 [PubMed Link]

  • Armandi A. Tight junction regulation in celiac disease: role of larazotide acetate. Minerva Gastroenterol (Torino). 2022 [PubMed Link]

  • Enomoto H. In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model. PLoS One. 2021 [PubMed Link]

  • D'heedene M. Celiac disease: Hope for new treatments beyond a gluten-free diet. Clin Nutr. 2024 [PubMed Link]