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Gut & neuroendocrine

Linaclotide

A 14-amino-acid peptide swallowed as a capsule that works locally on the gut lining — approved oral proof that not every peptide is digested into uselessness.

L5Practice-changingApproved medicineApprovedHigh confidenceLast reviewed 2026-08-23
Oral

Also known as: Linzess, Constella

Evidence passport

Last reviewed 2026-08-23

Evidence level
L5Practice-changing
Confidence
High confidence
Human efficacy
82/100
Human safety
78/100
Regulatory status
Approved medicine
Development
Approved
Routes
Oral
Evidence base
Includes human data
Furthest stage
Approved
Source curation
Sources fully curated
Clinical maturity
Established oral gut peptide

Overview

Human evidence82/100
Preclinical evidence70/100
Human safety evidence78/100

Clinical maturity: Established oral gut peptide

Routes & formulations

Studied / approved routes

Oral

Taken by mouth and acts locally in the intestine with minimal systemic absorption — the route is the mechanism, not a workaround.

Route availability is not evidence of efficacy, and evidence from one route does not transfer to another. The Registry never provides dosing or sourcing information.

Peptide lifecycle

  1. Discovery

  2. Preclinical

  3. Phase I

  4. Phase II

  5. Phase III

  6. Approved

Approved

What it is

A synthetic peptide agonist of guanylate cyclase-C on intestinal cells, increasing fluid secretion and transit; structurally related to the natural gut hormone uroguanylin.

What people claim

  • Relieves constipation and abdominal symptoms in IBS-C and chronic idiopathic constipation

What the evidence actually says

Multiple pivotal randomised trials support its labelled constipation indications. Because it acts locally with minimal absorption, it is the standard counter-example to the claim that oral peptides cannot work.

Human evidence

  • Pivotal randomised placebo-controlled trials in IBS-C and CIC populations.

Preclinical evidence

  • GC-C pharmacology and intestinal-fluid models.

Animal and cell findings are Level 1–2 evidence.

Mechanism and pathways

  • GC-C activation raises intracellular cGMP in intestinal cells, driving chloride and water secretion and accelerating transit.

Safety and unknowns

  • Diarrhoea is the most common labelled adverse effect.
  • Labelled age restrictions reflect a risk identified in juvenile animal studies; use follows the current label.

Cancer relevance

No concern identified

No established human cancer signal within approved use.

Regulatory status

FDA-approved (Linzess) for irritable bowel syndrome with constipation and chronic idiopathic constipation, with age-specific labelled populations that have evolved over time. Approved in other regions under other brand names.

Evidence grade

L5Practice-changingHigh confidence

Replicated large randomised trials, pivotal Phase 3 programmes, or a major regulatory decision.

What would change our rating?

  • Not applicable at this evidence tier.

References and sources

Sources fully curated

Source hierarchy: regulatory documents and trial registries first, peer-reviewed work next, sponsor material flagged as non-independent. We never use supplier or clinic marketing as evidence, and where a verified source has not yet been curated we say so rather than inventing one.

Evidence change history

No recorded changes yet. Baseline position set on 2026-08-23.

Related claims we’ve checked

MisleadingL5Practice-changingRoutes & formulations

“Peptides can't be taken orally — stomach acid destroys them all.”

Misleading — approved oral peptide medicines exist.

  • Linaclotide and plecanatide are orally administered peptide medicines, FDA-approved for constipation indications, that act locally on the gut lining with minimal systemic absorption.
  • Oral semaglutide (Rybelsus) reaches the bloodstream using an absorption-enhancer formulation — oral systemic peptide delivery is difficult, not impossible.
  • The reverse error matters too: an oral formulation existing for one peptide says nothing about whether some other peptide works orally.
Last reviewed 2026-08-23Compound profile