Larazotide Acetate
Larazotide acetate (AT-1001) is an oral 8-amino-acid tight-junction regulator investigated for celiac disease. Unlike most peptides in this list it reached phase 3 trials, giving it comparatively more human data — though the pivotal trial was halted and it remains unapproved.
01 Overview
Larazotide acetate is a synthetic octapeptide that tightens intestinal epithelial tight junctions by antagonising zonulin-driven permeability. It was developed as an oral adjunct to the gluten-free diet in celiac disease and progressed through phase 2 trials showing symptom benefit, then into a phase 3 program.\n\nThe phase 3 trial was discontinued after an interim futility analysis, so larazotide is not approved. In the gut-health peptide market it is nonetheless sold for 'leaky gut,' an indication without controlled support.
02 Mechanism
Acts locally in the gut lumen as a zonulin antagonist, promoting tight-junction assembly and reducing paracellular permeability and antigen passage.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Trial dose | 500 mcg | Oral | 0.5 mg three times daily before meals in celiac trials. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced intestinal permeabilityTightens tight junctions and reduced gluten-induced permeability in celiac trials. | n/a | Clinical | |
| Symptom reduction in celiac diseasePhase 2 trials showed reduced GI/extraintestinal symptoms vs placebo; phase 3 did not confirm at interim. | modest | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal symptomsAbdominal discomfort, nausea and headache were reported, though generally similar to placebo. | Mild | Common | Clinical | |
| Lack of proven benefit outside celiacMarketed 'leaky gut' uses have no controlled human evidence; the pivotal celiac trial failed at interim. | Mild | Situational | Unconfirmed |