Overview
Larazotide is a synthetic 8-amino-acid octapeptide developed initially by Alba Therapeutics, then by Innovate Biopharmaceuticals / 9 Meters Biopharma, as a zonulin-pathway antagonist that tightens intestinal epithelial tight junctions. Its target indication has been celiac disease — specifically, the ~30% of celiac patients on a strict gluten-free diet who continue to experience symptoms from inadvertent gluten exposure. Phase 2b data (Leffler 2015) was mildly encouraging. The two pivotal Phase 3 trials (CeDLara, completed 2022) did not meet their primary endpoints, and 9 Meters wound down the program. Community / functional-medicine use of larazotide for general 'leaky gut' or non-celiac gut permeability runs far past what the evidence supports — the trials were designed for active gluten exposure in celiac, not for a syndromic 'leaky gut' diagnosis.
Mechanism
Antagonizes zonulin signaling at the apical surface of intestinal epithelial cells. Zonulin (haptoglobin precursor 2) loosens tight junctions in response to gluten and certain bacteria; larazotide blocks this loosening, maintaining tight-junction integrity and reducing paracellular permeability. Active locally in the small intestine; minimal systemic absorption is expected given the route and design.
Evidence by indication
We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.
Symptom relief in celiac patients on gluten-free diet (residual symptoms)
Phase 2b trial (Leffler 2015, n=342) reported improved symptom scores at 0.5 mg TID. The pivotal Phase 3 CeDLara trial (n=525) did not meet its primary endpoint of celiac symptom-free days when read out in 2022, leading 9 Meters to wind down the program. Tier 2 reflects strong RCT-grade trials with mixed/null primary outcomes — better evidence than most peptides in this library, but not a positive Phase 3.
Non-celiac 'leaky gut' / general intestinal permeability
Functional-medicine and community marketing extends larazotide use to non-celiac gut-permeability syndromes, IBS, and food-intolerance presentations. There is no RCT supporting any of these indications — the entire clinical development program targeted celiac.
No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.
Inflammatory and autoimmune conditions linked to gut permeability
The 'leaky gut as a driver of autoimmunity' hypothesis is mechanistically coherent but underpowered as a therapeutic rationale. Some preclinical work in NOD mice and other models exists; no human RCT in non-celiac autoimmune disease.
No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.
Studied dose ranges
The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.
Phase 2b/3 trials in celiac used 0.5 mg or 1 mg three times daily before meals (so 1.5–3 mg/day total). Note the unit math: 500–2000 mcg per dose, 3× daily. Higher doses in Phase 2b unexpectedly performed worse, suggesting an inverted U dose-response.
Contraindications
- Known hypersensitivity to larazotide
- Pregnancy and breastfeeding (no human safety data outside clinical trials)
- Pediatric use outside formal trials
- Active GI malignancy (no data on tight-junction modulation in this context)
Reported side effects
- Generally well tolerated in trials — adverse-event profile similar to placebo
- Headache
- Upper-respiratory-tract symptoms
- Urinary tract infection (modest excess vs placebo in Phase 2b)
- Nausea
Reconstitution & storage
Oral capsule formulation — no reconstitution. Taken approximately 15 minutes before meals.
Storage. Manufacturer instructions; typically room temperature, dry, protect from light.
Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.
Editorial note
DRAFT — pending Wayne's review. Larazotide is the most clinically-developed peptide in the gut/permeability space, and that clinical development is the story: Phase 2b mixed-positive, Phase 3 negative, program wound down. The 'leaky gut' community marketing is not supported by trials. Hold the editorial line on Tier 2 for celiac residual-symptom evidence; Tier 4 for any non-celiac indication.
Citations
- [1]Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trialLeffler DA, Kelly CP, Green PH, et al. · Gastroenterology · 2015 · PMID 26060847Phase 2b RCT (n=342) — best published evidence for larazotide in residual celiac symptoms. Anchor for Tier 2 indication.View source