Adverse effect · Linaclotide

How common is diarrhoea with Linaclotide?

A
Grade A — established in humans1 phase 3 RCT (n=804); approval programme · effect size: moderate · adverse
Short answerEstablished in humans. 1 phase 3 RCT (n=804); approval programme point the same way: a moderate effect. The mechanism's own side effect and the reason people stop. Otherwise the adverse-event profile matched placebo. The label carries a contraindication in patients under 2 years of age on the basis of deaths in juvenile animal studies.

What the studies show

The mechanism's own side effect and the reason people stop. Otherwise the adverse-event profile matched placebo. The label carries a contraindication in patients under 2 years of age on the basis of deaths in juvenile animal studies.

“AE incidence was similar between treatment groups, except for diarrhea, which caused discontinuation in 4.5 % of linaclotide patients vs. 0.2 % of placebo patients.”

Verbatim, from the abstractChey WD, Lembo AJ, Lavins BJ, et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. Am J Gastroenterol, 2012;107:1702–1712

Several well-run randomised trials in people, pointing the same way. You can plan around this. It still says nothing about whether the effect is worth the side effects for you.

  1. 1
  2. 2
    Linzess (linaclotide) prescribing information.DailyMed, read 29 Oct 2026Oral route, negligible systemic availability, indications and the contraindication under 2 years of age.

In context

Linaclotide is a 14-amino-acid peptide with three disulfide bonds, approved since 2012 as Linzess and Constella for irritable bowel syndrome with constipation and for chronic idiopathic constipation. It is taken as a capsule and is minimally absorbed — it acts on guanylate cyclase-C receptors on the luminal surface of the intestine. In a 26-week phase 3 trial, 33.7% of treated patients met the FDA responder endpoint against 13.9% on placebo. Diarrhoea is the dose-limiting effect.

Linaclotide is approved (rx). Legal status differs by country — see the regulation section or the jurisdiction pages.

Questions

Is Linaclotide proven to cause diarrhoea?
Yes, as far as human trials can show it: 1 phase 3 RCT (n=804); approval programme. LYO grades this outcome A.
What studies are behind the grade?
The mechanism's own side effect and the reason people stop. Otherwise the adverse-event profile matched placebo. The label carries a contraindication in patients under 2 years of age on the basis of deaths in juvenile animal studies.
Is Linaclotide approved for this?
Linaclotide is an approved medicine (Approved (Rx)); whether this particular outcome is a licensed indication is stated on the compound page's regulation section.

Other outcomes for Linaclotide

Written and maintained by LYO Research — how pages are written and checked. Reviewed 29 October 2026. Grades count human evidence only; see how LYO grades. Not medical advice. Correct this page →