Linaclotide and Plecanatide: Medicine Overviews
Linaclotide (Linzess) and plecanatide (Trulance) are oral guanylate cyclase-C agonist peptides approved for constipation conditions; this page covers labels, trial results and the pediatric dehydration warning.
Content last updated . This page has not been medically reviewed.
Quick overview
Linaclotide and plecanatide are the two guanylate cyclase-C (GC-C) agonists discussed here. They are prescription peptide medicines taken by mouth for constipation-related gut conditions. This page explains what official labels say. It is education only: no dosing, no advice on starting or stopping, and no comparison to pick a product.Evidence label used here: approved medicine. Please also see Gastrointestinal Peptide Medicines for the wider class and Constipation for general guidance.
Linaclotide
Active ingredient and brands. Linaclotide is sold in the US as Linzess (Allergan/AbbVie), with initial US approval in 2012. The DailyMed version read was dated 2026-10-09. [1] In the EU the EMA lists linaclotide as Constella. [2]Approved uses, United States. Irritable bowel syndrome with constipation (IBS-C) in adults and in children 7 years and older; chronic idiopathic constipation (CIC) in adults; and functional constipation (FC) in children 2 years and older. [1]
Approved use, European Union. The EMA says Constella is indicated for symptomatic treatment of moderate to severe IBS-C in adults, authorized 26 November 2012. [2]
How it works. The label says linaclotide is structurally related to the natural gut hormones guanylin and uroguanylin and acts on GC-C receptors on the inner surface of the intestine. That raises cGMP, leading to more fluid in the gut and faster transit. In an animal model it also reduced pain-nerve activity; that finding is from animals. [1]
It stays in the gut. Linaclotide is minimally absorbed. Blood levels after oral doses were below the limit of measurement. [1]
Trial results. In two 12-week adult IBS-C trials (about 800 people each), the share who met the combined responder definition (a 30% pain reduction plus improved bowel movements) at least 9 of 12 weeks was 12% versus 5% and 13% versus 3% for linaclotide versus placebo. In two adult CIC trials, a bowel-movement responder rate of 20% versus 3% and 15% versus 6% was reported. [1] Label responder definitions are specific, so these are not "percent of people cured."
Plecanatide
Active ingredient and brand. Plecanatide is sold in the US as Trulance (Salix). The DailyMed version read was dated 2024-04-04. [3] Approval in the EU was not verified for this page.Approved uses, United States. In adults, chronic idiopathic constipation and irritable bowel syndrome with constipation. [3]
How it works. The label says plecanatide is a structural analog of human uroguanylin that acts as a GC-C agonist locally in the intestine, with the same cGMP-driven fluid secretion and faster transit described above. [3] It is also minimally absorbed. [3]
Trial results. In two 12-week adult CIC studies, the responder rate was 21% versus 10% in the first study and 21% versus 13% in the second for plecanatide versus placebo. In two IBS-C studies the overall responder rates were 30% versus 18% and 21% versus 14%. [3]
Side by side
| Linaclotide (Linzess) | Plecanatide (Trulance) | |
|---|---|---|
| Natural molecule it resembles | Guanylin and uroguanylin | Uroguanylin |
| US adult uses | IBS-C, CIC | CIC, IBS-C |
| US pediatric label | IBS-C from age 7, functional constipation from age 2 | Not established under 18; contraindicated under 6 |
| Most common side effect | Diarrhea | Diarrhea |
[1][3] The trials used different designs and endpoints, so their numbers cannot be directly compared. No head-to-head trial is in these labels.
Monitoring and professional care
Constipation can have many causes, and new or severe symptoms, bleeding or weight loss should be evaluated by a clinician. See Digestive Symptoms: When to Get Help and Irritable Bowel Syndrome for general information.Off-label and investigational questions
Uses beyond the labeled conditions were not reviewed. Proper evidence not found in the labels and EMA page read. They are not a general "gut peptide" supplement category: see Approved, Investigational and Unapproved Peptides.Frequently asked questions
Are linaclotide and plecanatide the same drug?
No. They are two GC-C agonists with different molecules, brands and slightly different US labels. [1][3]
Do they get into the bloodstream?
The labels say both are minimally absorbed and not measurable in blood after oral doses. [1][3]
Why are children a concern?
Young mice given a single oral dose died of dehydration, and the labels set age limits. [1][3]
Are they approved in Europe?
Linaclotide is authorized as Constella for IBS-C in adults. Plecanatide in the EU was not verified. [2]
Should I stop or change a constipation medicine?
This page cannot advise that. Talk with your prescriber.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
Major safety information
- Boxed warning, children. Both drugs carry a boxed warning on serious dehydration. Linzess is contraindicated under 2 years, and Trulance under 6 years, after deaths from dehydration in young mice given single doses. Trulance also advises avoiding use at 6 to under 18 years. [1][3] Animal results prompted the warnings; the labels note insufficient human data in the youngest children.
- Diarrhea. It was the most common reaction. In pooled IBS-C trials, 20% on linaclotide reported diarrhea versus 3% on placebo; severe diarrhea occurred in 2%, and 5% stopped treatment because of diarrhea. For plecanatide, severe diarrhea was reported in 0.6% of patients in the CIC trials and in the IBS-C trials. [1][3]
- Blockage. Both are contraindicated in people with known or suspected mechanical gastrointestinal obstruction. [1][3]
- Other common effects with linaclotide: abdominal pain, gas and bloating. [1]
References
- LINZESS (linaclotide) capsules, prescribing information (DailyMed label version dated 2026-10-09). Read 2026-10-22.
- EMA, Constella: European public assessment report overview. Read 2026-10-22.
- TRULANCE (plecanatide) tablets, prescribing information (DailyMed label version dated 2024-04-04). Read 2026-10-22.