Immune

Larazotide

A synthetic peptide designed to tighten the gut lining in coeliac disease. Promising in mid-stage trials, then failed its phase 3 primary endpoint.

Moderate evidenceNot approvedAdd to compare

What it is

Larazotide acetate is an eight-amino-acid synthetic peptide developed as a tight-junction regulator for coeliac disease, meant to be taken alongside a gluten-free diet rather than replacing it. It was never approved, and development was halted after the phase 3 programme missed its main endpoint.

How it works

1
Acts on the protein zonulin, which opens the tight junctions between intestinal lining cells.
2
By opposing zonulin, it keeps those junctions closed and reduces paracellular permeability — the gaps through which larger fragments cross the gut wall.
3
In coeliac disease, gluten fragments crossing that barrier trigger the immune reaction that damages the intestine.
4
The peptide works upstream of the immune response; it does not suppress the immune system or repair existing damage.

What it's studied for

Coeliac disease in people already on a gluten-free diet

Persistent symptoms despite a gluten-free diet

Intestinal permeability in healthy volunteers

Irritable bowel syndrome (early-stage only)

Reported and studied effects

Reduced intestinal permeability markers in early studies
Some improvement in gastrointestinal symptom scores in a phase 2b trial
Phase 3 trial did not meet its primary endpoint, which ended the development programme
No meaningful change in intestinal villous architecture

Research protocol notes

Research context only

Research context only — there is no approved product. Trials used oral capsules of 0.125–1 mg taken three times daily before meals for 12–52 weeks. It was always investigated as an add-on to a gluten-free diet, never as a replacement.

These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.

Possible side effects and contraindications

Safety profile

Possible side effects

Adverse events were similar to placebo in the published trials
Mild gastrointestinal symptoms
Headache
Long-term safety was never established because development stopped

Contraindications and cautions

Not established — no approved product exists
Never a substitute for a strict gluten-free diet in coeliac disease
Pregnancy and breastfeeding data are absent
Persistent coeliac symptoms require gastroenterology assessment, not supplements

A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.

Evidence assessment

Moderate evidenceSeveral human trials, some inconsistencies

Several human trials, some inconsistencies

Several randomised controlled trials were completed, so the human data are comparatively substantial — but the results were inconsistent and the definitive phase 3 trial was negative.

References

References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.

Compare Larazotide with another peptide →

Related peptides

Other entries in Immune.

All Immune peptides →

Immune

ARA-290 (cibinetide)

An erythropoietin-derived peptide that targets tissue repair rather than red blood cells; small trials, mixed results, no approval.

Limited evidenceInvestigational

Immune

Ecallantide

A recombinant plasma kallikrein inhibitor for acute hereditary angioedema attacks, given under medical supervision.

Moderate evidenceApproved drug

Immune

Enfuvirtide

The first HIV fusion inhibitor, an injected peptide that blocks the virus from entering cells.

Strong evidenceApproved drug