Larazotide acetate

The intestinal lining is held together by tight junctions, protein seals that control what slips between cells. In celiac disease, the immune reaction to gluten loosens these seals, and zonulin is thought to be one of the signals that does so. Larazotide is thought to act as a zonulin antagonist, helping tight-junction proteins and the cell's actin scaffolding rearrange; more recent work also links it to inhibition of myosin light chain kinase, which would ease tension on the junctions and help them close¹. It is taken by mouth, and trial records describe it as acting locally in the gut rather than being absorbed into the body⁶. Much of this mechanistic picture comes from laboratory and animal work, including rodent and pig models, rather than from people¹.

Human trials have been mixed. In 342 adults who still had symptoms despite a gluten-free diet, a 12-week randomized trial met its main symptom endpoint only at the lowest dose studied; the higher doses did no better than placebo².

A 2022 meta-analysis of four randomized trials (626 patients) found no effect on the lactulose-mannitol gut-permeability test, and a symptom benefit only in people deliberately eating gluten during the study, not in those on a gluten-free diet³. The Phase 3 celiac trial, which enrolled 307 people, was terminated by its sponsor in 2022⁴. Separately, a small Phase 2a placebo-controlled trial in 12 children with post-COVID multisystem inflammatory syndrome reported faster resolution of gut symptoms and faster clearance of viral spike protein from the blood⁵.

A Phase 2a trial in children and adults with long COVID (107 enrolled) was completed in June 2026; no results had been posted to its registry record as of this writing⁶.

Larazotide is not approved by the FDA, and no approval by another regulator was found; it remains investigational.

Across the published celiac trials, side effects occurred at rates similar to placebo^2,3; among people eating gluten during the studies, gluten-related diarrhea was actually less frequent on larazotide³. The pediatric pilot reported no adverse events attributed to larazotide⁵. The published trials were short, lasting weeks rather than years, so long-term effects in people are unknown.

1. Slifer et al., Am J Physiol Gastrointest Liver Physiol 2021PubMed
2. Leffler et al., Gastroenterology 2015PubMed
3. Hoilat et al., Clin Res Hepatol Gastroenterol 2022PubMed
4. ClinicalTrials.gov: NCT03569007ClinicalTrials.gov
5. Yonker et al., Sci Transl Med 2025PubMed
6. ClinicalTrials.gov: NCT05747534ClinicalTrials.gov