Peptides / Gut and digestion

Synthetic analog · 14 amino acids · 1,526.8 Da

Linaclotide

ApprovedNot banned in sport

Linaclotide (Linzess, Constella) is a guanylate cyclase-C agonist approved in the US and EU for IBS with constipation, and in the US for chronic constipation. Studies in people tested it on bowel movements, belly pain and colonoscopy prep, and tracked stomach side effects. PepBank shows 294 results on linaclotide from 47 studies in people, and 95 from animal and lab studies. The strongest evidence is a randomized trial in people. Data as of 2026-10-30.

Also known as Constella, Linzess

14 amino acids, from first to lastCCEYCCNPACTGCY

Evidence level: Large trials in people294 of 389 results come from studies in people, including randomized trials.

Results in people

294

76% of 389 results

Results in animals

70

18% of 389 results

Results in lab cells

25

6% of 389 results

From computer models

0

0% of 389 results

Overview

Linaclotide at a glance

What it is	Synthetic analog, 14 amino acids
Approval	Approved in the US and EU (Linzess, 2012)
In sport	Not listed as banned by WADA
Studies	66 studies with results. 65 of them gave linaclotide, with 389 results. 294 in people70 in animals25 in lab cells
Best study in people	Randomized controlled trial with 1,464 people (2025)
Clinical trials	52 registered: 7 active or planned, 24 with posted results
Community use	Adults with irritable bowel syndrome with constipation

The science

What is linaclotide?

Linaclotide is a 14-residue peptide with three disulfide bridges.

14

Amino acids in one chain

The history of linaclotide

2007
The oldest paper on linaclotide in PepBank is from 2007.
2008August
A registered trial of linaclotide started (NCT00730015).
2012August
FDA approved Linzess for iBS-C in adults and pediatric patients aged 7 years and older. CIC in adults. Functional constipation in pediatric patients aged 2 years and older.

Linaclotide structure and chemistry

The key facts about the molecule. Long codes are in the closed section below.

Sequence, 14 amino acidsFrom the first amino acid to the last

C1C−EYC5CNPAC10TGCY

Darker means more water-repelling+ and − show charge in the body

Structure

Linaclotide is a synthetic analog of 14 amino acids, with a ring, 3 disulfide bonds, no changed amino acids.

Formula

C₅₉H₇₉N₁₅O₂₁S₆

Molecular weight

1,526.8 g/mol

CAS number

851199-59-2

Target

Guanylate cyclase C (gene GUCY2C): agonistEvidence: Official prescribing information, mechanism of action

Development

Highest phase: past the trial stage (see status).

Identifiers

PubChem 16158208, ChEMBL CHEMBL3301675, UNII N0TXR0XR5X, DrugBank DB08890

Full sequence, SMILES and InChIKey

InChIKey
KXGCNMMJRFDFNR-WDRJZQOASA-N

SMILES
C[C@H]1C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)CNC(=O)[C@@H](NC2=O)[C@@H](C)O)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)O)C(=O)N[C@@H](CSSC[C@@H](C(=O)N3)N)C(=O)N[C@H](C(=O)N5CCC[C@H]5C(=O)N1)CC(=O)N)CC6=CC=C(C=C6)O)CCC(=O)O

See charge, composition and 3D structure on the Scientific page

The evidence

What linaclotide studies show

Results grouped by what the studies measured. Each card shows where its results come from.

Large trials in people294 of 389 results come from studies in people, including randomized trials.

Stomach and gut

189 results · 162 in people · 20 animal · 7 lab

In IBS-C patients, IBS relief response was higher with linaclotide than placebo. Journal of gastroenterology and hepatology, 2018

Top results

In IBS-C patients, IBS relief response was higher with linaclotide than placebo. (Journal of gastroenterology and hepatology, 2018)
In IBS-C Trial 302, linaclotide increased abdominal pain/discomfort response versus placebo. (Alimentary pharmacology & therapeutics, 2013)
In Japanese patients with IBS-C, linaclotide increased global improvement responder rates versus placebo. (Neurogastroenterology and motility, 2018)

Surgery and procedures

23 results · 23 in people

In colonoscopy outpatients, linaclotide produced higher adequate preparation rates than senna with the same PEG-Asc background. The American journal of gastroenterology, 2025

Top results

In colonoscopy outpatients, linaclotide produced higher adequate preparation rates than senna with the same PEG-Asc background. (The American journal of gastroenterology, 2025)
In at-risk patients, adequate bowel preparation did not differ significantly between linaclotide and placebo with PEG. (Digestive and liver disease, 2026)
In colonoscopy patients, adding linaclotide to 2 L PEG increased adequate bowel preparation compared with 2 L PEG alone. (European journal of gastroenterology & hepatology, 2021)

Pain

44 results · 22 in people · 20 animal · 2 lab

In IBS-C patients, pain and discomfort response was higher with linaclotide than placebo. Journal of gastroenterology and hepatology, 2018

Top results

In IBS-C patients, pain and discomfort response was higher with linaclotide than placebo. (Journal of gastroenterology and hepatology, 2018)
Tolerance was similar between the higher and lower linaclotide regimens with the same PEG background. (International journal of colorectal disease, 2024)
In rats with endometriosis, linaclotide increased vaginal pain thresholds compared with vehicle. (Pain, 2019)

Daily life and fitness

15 results · 15 in people

In adults with IBS-C, linaclotide reduced daily activity impairment by 4.7% versus placebo at week 12. American health & drug benefits, 2014

Top results

In adults with IBS-C, linaclotide reduced daily activity impairment by 4.7% versus placebo at week 12. (American health & drug benefits, 2014)
In IBS-C patients, linaclotide improved quality of life compared with placebo. (Alimentary pharmacology & therapeutics, 2020)
In adults with opioid-induced constipation, linaclotide improved treatment satisfaction more than placebo. (Pain, 2020)

Overall treatment results

2 results · 2 in people

In linaclotide-treated Spanish IBS-C patients, baseline characteristics were not linked to response at week 12. Therapeutic advances in gastroenterology, 2019

Top results

In linaclotide-treated Spanish IBS-C patients, baseline characteristics were not linked to response at week 12. (Therapeutic advances in gastroenterology, 2019)
In linaclotide-treated Spanish IBS-C patients, response at week 4 was linked to response at week 12. (Therapeutic advances in gastroenterology, 2019)

Sleep

2 results · 2 in people

In colonoscopy patients, sleep quality was similar with 2LPEG plus linaclotide and 2LPEG alone. JGH open, 2023

Top results

In colonoscopy patients, sleep quality was similar with 2LPEG plus linaclotide and 2LPEG alone. (JGH open, 2023)
Sleep quality was similar between the higher and lower linaclotide regimens with the same PEG background. (International journal of colorectal disease, 2024)

Linaclotide has 251 linked papers. PepBank read up to 120 of the most-cited studies that gave it to people, up to 20 other studies, and the main trials.

All 66 linaclotide studies by area Open the Scientific page

Key linaclotide studies

Studies in people come first, then studies in animals and in the lab.

People
Efficacy of 1 L Polyethylene Glycol Plus Ascorbic Acid With Linaclotide Versus Senna for Bowel Preparation: A Multicenter, Endoscopist-Blinded, Randomized Controlled Trial (Apple Trial)
Maeda et al. 2025 · The American journal of gastroenterology · 1,464 people · cited by 6
5 results
People
Two randomized trials of linaclotide for chronic constipation
Lembo et al. 2011 · The New England journal of medicine · 1,276 people · cited by 272
9 results
People
Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions
Yang et al. 2018 · Journal of gastroenterology and hepatology · 839 people · cited by 39
5 results
People
Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints
Quigley et al. 2013 · Alimentary pharmacology & therapeutics · 805 people · cited by 97
8 results
People
Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety
Chey et al. 2012 · The American journal of gastroenterology · 804 people · cited by 357
8 results

All 66 Linaclotide studies

Linaclotide clinical trials

ClinicalTrials.gov lists 52 trials of linaclotide. 7 are active or planned, and 24 have posted results. PepBank does not show trial results.

Solid bars are dates that happened. Hatched bars are planned dates. Data from ClinicalTrials.gov.

An Open-label, Long-term Safety Study of Linaclotide in Patients With Chronic Constipation or Irritable Bowel Syndrome With Constipation

Phase 3completed1,743 people

A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C)

Phase 3completed1,722 people

An Open-Label, Long-Term Safety Study of Linaclotide in Patients With Chronic Constipation or Irritable Bowel Syndrome With Constipation

Phase 3completed1,559 people

All 31 Linaclotide trials

Status and safety

Is linaclotide approved?

FDA

United States

Approved

An approved medicine contains it.

EMA

European Union

Approved

An approved medicine contains it.

WADA

Sport

Not banned

Not on the 2026 Prohibited List.

Yes. Approved in the US and EU (Linzess, 2012). The FDA label for Linzess says: “IBS-C in adults and pediatric patients aged 7 years and older” Not listed as banned by WADA.

Laws and labels change, so check the regulator for the current status.

Linaclotide side effects and safety

PepBank has 57 safety results from studies of linaclotide. 57 of them come from studies in people.

Safety results from studies (57)

Adding one-day linaclotide to 4L PEG reduced mild adverse events compared with 4L PEG alone. (Clinical and translational gastroenterology, 2024)
In colonoscopy patients, adverse reaction rates were similar with 2LPEG plus linaclotide and 2LPEG alone. (JGH open, 2023)
Adverse reactions were similar between the higher and lower linaclotide regimens with the same PEG background. (International journal of colorectal disease, 2024)
In colonoscopy outpatients, adverse events were similar with linaclotide and senna with the same PEG-Asc background. (The American journal of gastroenterology, 2025)
In chronic constipation patients, side effect frequency was similar across linaclotide and placebo groups, except for diarrhea. (The New England journal of medicine, 2011)
In IBS-C patients, diarrhea was more frequent with linaclotide than placebo. (Journal of gastroenterology and hepatology, 2018)
In IBS-C patients, side effect frequency was similar with linaclotide and placebo, except for diarrhea. (The American journal of gastroenterology, 2012)
In IBS-C patients, more people stopped linaclotide because of diarrhea than stopped placebo. (The American journal of gastroenterology, 2012)
In Chinese IBS-C patients, diarrhea was more frequent with linaclotide than placebo. (Journal of digestive diseases, 2022)
In IBS-C patients, diarrhea was more frequent with linaclotide than placebo. (The American journal of gastroenterology, 2021)
In IBS-C patients, side effect frequency was similar with linaclotide and placebo, except for diarrhea. (Gastroenterology, 2010)
Diarrhoea occurred in more children receiving linaclotide than placebo. (The lancet. Gastroenterology & hepatology, 2024)
In adults with opioid-induced constipation, neither linaclotide nor placebo groups reported serious diarrhea-related adverse events. (Pain, 2020)
In constipation patients with bloating, diarrhea occurred in 6% with linaclotide 145 μg versus 2% with placebo. (PloS one, 2015)
In constipation patients, diarrhea discontinuations were more frequent with linaclotide 72 μg than placebo. (The American journal of gastroenterology, 2018)
In IBS-C patients, MD-7246 and placebo had similar diarrhea rates. (The American journal of gastroenterology, 2021)
In pooled trials, diarrhea occurred more often with linaclotide than placebo. (Expert review of gastroenterology & hepatology, 2019)
In children with constipation and neurodevelopmental disorders, linaclotide was well tolerated, consistent with previous safety reports. (Journal of pediatric gastroenterology and nutrition, 2026)
In women with constipation-predominant irritable bowel syndrome treated with linaclotide, researchers identified no safety issues. (Gastroenterology, 2007)
In chronic constipation patients, diarrhea was the most common side effect and the only one related to linaclotide dose. (Gastroenterology, 2010)
In patients with chronic constipation receiving linaclotide, diarrhea was the most common adverse event. (The American journal of gastroenterology, 2009)
In IBS-C patients with severe abdominal symptoms, diarrhea was the most common linaclotide adverse event, reported in 18.8%-21.0%. (Clinical gastroenterology and hepatology, 2014)
In Japanese constipation patients, diarrhea was the most common drug-related event during linaclotide treatment. (Neurogastroenterology and motility, 2019)
In the Japanese IBS-C study, diarrhea occurred in 14.5% of patients and was mild or moderate. (Neurogastroenterology and motility, 2018)

See every safety result on the Scientific page

Doses studied (40 shown)

The doses that these studies used. They are not recommendations.

Dose as reported	Class	Species	Route	Duration	Design	Source
0.5 mg	Human	human	Not reported	Not reported	Randomized trial in people · n = 1,464	Maeda 2025
290 μg once daily	Human	human	oral	Not reported	Randomized trial in people · n = 839	Yang 2018
290 μg once daily	Human	human	Not reported	12 weeks	Randomized trial in people · n = 805	Quigley 2013
290 μg once daily	Human	human	oral	12 weeks	Randomized trial in people · n = 804	Chey 2012
290 μg once daily	Human	human	oral	12 weeks	Randomized trial in people · n = 800	Rao 2012
290 μg/d	Human	human	Not reported	12 weeks	Randomized trial in people · n = 659	Peng 2022
290 μg daily	Human	human	Not reported	12 weeks	Randomized trial in people · n = 614	Chang 2021
0.5 mg daily	Human	human	Not reported	12 weeks	Randomized trial in people · n = 500	Fukudo 2018
72 μg once daily	Human	human	oral	12 weeks	Randomized trial in people · n = 328	Di 2024
0.5 mg	Human	human	Not reported	Not reported	Randomized trial in people · n = 186	Fukudo 2019
290 µg once daily	Human	human	Not reported	8 weeks	Randomized trial in people · n = 167	Brenner 2020
145 µg once daily	Human	human	Not reported	8 weeks	Randomized trial in people · n = 166	Brenner 2020
290 μg daily	Human	human	Not reported	4 weeks	Randomized trial in people · n = 71	Cheng 2025
72 µg once daily	Human	human	oral	12 weeks	Randomized trial in people · n = 57	Person 2026
290 µg	Human	human	Not reported	10 weeks	Randomized trial in people · n = 39	Rao 2020
145 μg once daily	Human	human	Not reported	12 weeks	Randomized trial in people	Lembo 2011
290 μg once daily	Human	human	Not reported	12 weeks	Randomized trial in people	Lembo 2011
75 microg once daily	Human	human	oral	4 weeks	Randomized trial in people	Lembo 2010
150 microg once daily	Human	human	oral	4 weeks	Randomized trial in people	Lembo 2010
300 microg once daily	Human	human	oral	4 weeks	Randomized trial in people	Lembo 2010
600 microg once daily	Human	human	oral	4 weeks	Randomized trial in people	Lembo 2010
145 μg once daily	Human	human	oral	12 weeks	Randomized trial in people	Lacy 2015
72 μg once daily	Human	human	Not reported	12 weeks	Randomized trial in people	Schoenfeld 2018
145 μg once daily	Human	human	Not reported	12 weeks	Randomized trial in people	Schoenfeld 2018
290 µg	Human	human	Not reported	Not reported	Randomized trial in people	Zhang 2021
0.0625 mg	Human	human	Not reported	12 weeks	Randomized trial in people	Fukudo 2018
0.125 mg	Human	human	Not reported	12 weeks	Randomized trial in people	Fukudo 2018
0.25 mg	Human	human	Not reported	12 weeks	Randomized trial in people	Fukudo 2018
0.5 mg	Human	human	Not reported	12 weeks	Randomized trial in people	Fukudo 2018
0.0625 mg	Human	human	Not reported	Not reported	Randomized trial in people	Fukudo 2018
0.125 mg	Human	human	Not reported	Not reported	Randomized trial in people	Fukudo 2018
0.25 mg	Human	human	Not reported	Not reported	Randomized trial in people	Fukudo 2018
0.5 mg	Human	human	Not reported	Not reported	Randomized trial in people	Fukudo 2018
Dose A: 18 or 36 µg once daily	Human	human	Not reported	4 weeks	Randomized trial in people	Di 2024
Dose B: 36 or 72 µg once daily	Human	human	Not reported	4 weeks	Randomized trial in people	Di 2024
Dose C: 72 or 145 µg once daily	Human	human	Not reported	4 weeks	Randomized trial in people	Di 2024
290 µg once daily	Human	human	Not reported	4 weeks	Randomized trial in people	Di 2024
290 μg once daily	Human	human	oral	12 weeks	Randomized trial in people	Lacy 2015
145 and 290 µg once daily	Human	human	Not reported	8 weeks	Randomized trial in people	Brenner 2020
100 microg/day	Human	human	oral	2 weeks	Randomized trial in people	Johnston 2009

From the community

How people use it

What people report online. It comes from forums and guides, not from studies.

Community-reported. Not tested in trials.

The official US label reports prescription use. The regimen below is label information.

Reported routines and cautions

What people use it for

Adults with irritable bowel syndrome with constipationS1

Reported regimens

Regimens that community sources report for Linaclotide. Community-reported, not tested in trials.
Context	Route	Amount	How often	How long	Agreement	Sources
Adults with irritable bowel syndrome with constipation. LINZESS linaclotide-coated beads in hard gelatin capsules.Official label dosing of an approved product	oralThis selected regimen describes swallowing the capsule whole.	290 mcg per dose	once daily	Not stated	Single official US label source.	S1

Cautions

The label contraindicates use in patients younger than 2 years because of serious dehydration risk. It also contraindicates known or suspected mechanical gastrointestinal obstruction. Severe diarrhea requires suspended dosing and rehydration.S1

Status notes

The EMA authorises Constella for symptomatic treatment of moderate to severe IBS-C in adults.S2

Community sources

S1Linzess US prescribing information (opens in a new tab)dailymed.nlm.nih.gov
S2EMA regulatory information (opens in a new tab)ema.europa.eu

Gaps

No separate community regimen is verified in this record. This record covers one adult IBS-C label regimen for intact LINZESS capsules. The full label contains other patient groups and instructions for opened capsules and feeding tubes. The dosage instructions do not specify a fixed duration.

Questions and more

Ask a question about linaclotide

The answer links to every study it uses.

What does the evidence say about linaclotide?Is linaclotide tested in people?Compare with Teduglutide Compare with Plecanatide

Sources

Database: PepBank data for linaclotide (data version 308560)
Regulator: FDA status record
Regulator: EMA status record
Regulator: WADA status record
Trial registry: ClinicalTrials.gov
Community: community sources (forums and guides), as summarized in the PepBank community file

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

PepBank is a research reference. Talk to a doctor before you use any peptide.

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