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Peptide Evidence Registry

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.

L5Repeated human trialsApproved medicine (jurisdiction-specific) · FDA (US)Approved
How settled this rating is:
high confidence in the current evidence rating
Routes studied:
Oral
Also known as:
Linzess, Constella
Last reviewed:
2026-08-23
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Evidence passport

Linaclotide

A one-screen evidence identity for this compound. These fields describe research maturity, confidence and legal status. They are not a safety guarantee, efficacy percentage or recommendation.

Reviewed 2026-08-23
Evidence level
L5Repeated human trials
Confidence
High confidence in rating
Regulatory status
Approved medicine (jurisdiction-specific) · See jurisdiction details
Development status
Approved

Evidence strength

Human efficacy evidence82 of 100 evidence strength

Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.

Human safety evidence78 of 100 evidence strength

Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.

The 0-100 values rate the strength and maturity of evidence, not how effective or safe the compound is.

Evidence base
Includes human studies
Furthest established stage
Approved
Human research maturity
Established oral gut peptide
Source curation
Sources fully curated

Routes recorded

Oral

Overview

Human efficacy evidence strength82 of 100 evidence strength

Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.

Preclinical (animal / lab) evidence strength70 of 100 evidence strength

Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.

Human safety evidence strength78 of 100 evidence strength

Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number.

How to read these scores

Every number here rates the evidence, not the compound. They are editorial 0-100 strength ratings, not percentages, and not a rating out of five stars.

  • Human efficacy evidence strength — Higher = more and better-quality human evidence. It does not mean the effect is bigger or that the compound works for you.
  • Preclinical evidence strength — Higher = more animal, tissue or cell research. Preclinical results are a starting point, not proof of a human benefit.
  • Human safety evidence strength — Higher = more mature, better-documented human safety data. It does not mean the compound is safer than one with a lower number. A score of 80 does not mean “80% safe”.
  • Evidence level (L0-L5) — the strongest type of study behind the compound, from anecdote (L0) to large replicated human trials (L5). It is a description of the study evidence, not a quality, safety or recommendation rating.
  • Confidence — how likely we think it is that this rating changes as new research lands. Low confidence means the picture is unsettled, not that the compound is bad.

None of these ratings is medical advice, a safety guarantee, or a recommendation to use anything. How we grade evidence.

How far human research has progressed: 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.

Related evidence

Useful next reads based on this compound — not recommendations.

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

This section covers questions raised by how the compound works in the body, plus anything regulators and trial teams keep an eye on. It is not a statement that this compound causes cancer — for most compounds here, no human data exist in either direction.

No concern identified

No established human cancer signal within approved use.

Regulatory status

Regulatory decisions apply to specific jurisdictions, products, formulations and indications. An approval elsewhere is not automatically an approval in your country.

Named regulators: FDA (US)

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

L5Repeated human trialsHigh confidence in rating

Substantial, consistent controlled human evidence supporting a specified outcome, preferably independently replicated. Approval is reported separately.

What would change our rating?

  • Not applicable at this evidence tier.

References and sources

Source transparency

A provenance snapshot of this profile. Counts show what kinds of sources are cited, not how much scientific weight each source deserves.

Sources fully curated
Last editorial review
2026-08-23
Recently reviewed · 54 days ago
Linked curated sources
1
Sources still pending
0
External specialist reviews
0
None recorded for this profile
Regulatory / label: 1

Review provenance

Registry editorial review: Colin Jackson-White, creator and editor, who is not a doctor or clinician. External specialist review is credited only when a named reviewer has completed a review of this exact profile.

Literature-discovery and AI tools may help locate or challenge candidate evidence, but they are not counted as evidence sources here. Registry judgements are tied to the underlying papers, trial records, regulator documents and official study records.

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

These entries record changes to our assessment of the published evidence — not changes to the compound itself.

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

Related claims we’ve checked — in full

Claim verdict

Routes & formulations

MisleadingL5Repeated human trials

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

This verdict applies to the exact claim above. It is not a verdict on the compound overall, a safety guarantee, or a recommendation to use it.

Registry verdict

Misleading — approved oral peptide medicines exist.

Why this verdict

  • 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.