Gastrointestinal

Linaclotide

An oral peptide that stimulates fluid secretion in the gut, approved for irritable bowel syndrome with constipation.

Strong evidenceApproved drugAdd to compare

What it is

Linaclotide is a 14-amino-acid peptide that mimics the gut hormones guanylin and uroguanylin. It is taken by mouth, acts on the intestine, and is barely absorbed into the bloodstream, which is why its effects are almost entirely local. It is licensed for irritable bowel syndrome with constipation and for chronic idiopathic constipation.

How it works

1
Binds guanylate cyclase-C on the intestinal lining.
2
Raises intracellular cGMP, which opens the CFTR chloride channel.
3
Chloride and water flow into the gut lumen, softening stool and speeding transit.
4
cGMP also dampens pain-sensing nerve endings, which explains effects on abdominal pain.
5
Minimal systemic absorption, so systemic exposure is very low.

What it's studied for

Irritable bowel syndrome with constipation (two phase 3 trials)

Chronic idiopathic constipation

Abdominal pain reduction as a co-primary endpoint

Reported and studied effects

Increased complete spontaneous bowel movements per week
Reduced abdominal pain scores, a co-primary endpoint in the IBS trials
Diarrhoea, the main reason people stop treatment
Effects begin within the first week in most responders

Research protocol notes

Research context only

Research context only - prescription medicine. Licensed adult dosing is 290 micrograms once daily for irritable bowel syndrome with constipation and 145 micrograms once daily for chronic constipation, taken about 30 minutes before the first meal; phase 3 trials ran 12 to 26 weeks and counted complete spontaneous bowel movements and worst abdominal pain over 24-hour recall.

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

Diarrhoea, sometimes severe
Abdominal distension and flatulence
Nausea
Dehydration if diarrhoea is heavy
Rare reports of severe dehydration in older patients

Contraindications and cautions

Children and adolescents under 18 - animal data showed fatal dehydration
Known or suspected mechanical gastrointestinal obstruction
Prior hypersensitivity
Diarrhoea should prompt review

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

Strong evidenceReplicated, large human trials

Replicated, large human trials

Two large randomised placebo-controlled phase 3 trials for each indication with co-primary symptom endpoints, and regulatory approval in the EU and US.

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.

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