Reviewed & approved by Dr. Nova Reyes · Last checked 2026-10-25. ← Back to Evidence Library

title: "Linaclotide: What the evidence says" slug: linaclotide status: Draft (v1), pending review by Dr. Nova Reyes (Batch F #65) last_checked: 2026-10-25 evidence_verdict: "IBS-C and chronic constipation (labeled): Strong · Gray-market use: No human data" card_verdict: "Strong (IBS with constipation, chronic constipation) · Gray-market: No human data" related: [larazotide]

Draft (v1), pending review. Not public. · ← Library · DRAFT · not published · last checked 2026-10-25

Linaclotide: what the evidence says

At a glance

What it is: a 14-amino-acid peptide taken by mouth that acts inside the gut (guanylate cyclase-C agonist), sold as Linzess for irritable bowel syndrome with constipation (IBS-C), chronic idiopathic constipation and pediatric functional constipation. ^{R1, R2} Generics have been approved. ^R2

What the evidence says: in phase 3 trials it beat placebo: 33.7% vs 13.9% met FDA's combined pain-and-bowel responder goal in IBS-C ^R3, and 16–21% vs 3–6% met the main goal in chronic constipation. ^R4

Biggest risks: boxed warning: contraindicated under age 2 because of fatal dehydration in newborn mice. ^R1 Diarrhea is the main side effect and led 4.2% to stop in the constipation trials. ^R4

Rating


Human Human evidence	Strong for IBS-C and chronic idiopathic constipation ^{R3, R4}; No human data on gray-market products
Animal Animal / lab evidence	Neonatal mouse deaths from dehydration (label) ^R1
Regulatory	FDA-approved: Linzess NDA 202811 (Aug 30, 2012); generic ANDAs approved ^R2 · boxed warning ^R1 · WADA: not named on the 2026 List ^R5
Established human dose	For labeled use: on the FDA label ^R1. Study details lists what trials used

Evidence verdict: IBS-C and chronic constipation (labeled): Strong · Gray-market use: No human data Card verdict: Strong (IBS with constipation, chronic constipation) · Gray-market: No human data Card note: Never for children under 2, see page.

This page reports what studies used. It is not dosing advice.

Legend: HUMAN data · ANIMAL / LAB data · UNKNOWN · UNVERIFIED: not yet confirmed against a primary source

About the evidence: both trials were funded by the developers, Ironwood Pharmaceuticals and Forest Laboratories. ^{R3, R4}

What is it?

Linaclotide binds guanylate cyclase-C on gut lining cells, which pulls fluid into the bowel and speeds transit; it is barely absorbed into the blood. ^{R1, R4} It is a pill, not an injection. Related page: Larazotide.

Does it work?

Human IBS-C (phase 3): 804 patients: FDA responder 33.7% vs 13.9%; number needed to treat about 5. ^R3
Human Chronic constipation (two trials): 1,276 patients, 12 weeks: primary goal 16.0–21.3% vs 3.3–6.0%. ^R4

Is it safe?

Human Boxed warning: serious dehydration risk; contraindicated in children under 2. ^R1
Human Diarrhea: can be severe; stopping for diarrhea 4.2% in trials. ^R4

Gray-market "research use only" Linaclotide: extra risks

Not the approved product. Linaclotide is an oral prescription capsule rather than an injectable research peptide; any unapproved or "research" product sold online has unknown identity and strength.

What we don't know

Unknown Long-term risks beyond the trials (the 2011 authors called for more study) ^R4

Is it legal?

US: FDA-approved as Linzess (NDA 202811) for IBS-C in adults and children 7 and older, chronic idiopathic constipation in adults, and functional constipation in children 2 and older. Generic linaclotide ANDAs are approved (for example Mylan ANDA 209564). ^{R1, R2} EU, UK and others: UNVERIFIED. WADA: not named on the 2026 Prohibited List. ^R5

Study details

These are amounts researchers used, not recommendations. ### R3 Human RCT: IBS-C phase 3 (Chey 2012) | Study | People / model | Route | Amount used | Follow-up | Reported | Side effects / limitations | Citation | |---|---|---|---|---|---|---|---| | Chey 2012 | 804 adults with IBS-C | Oral | 290 mcg once daily | 26 weeks | FDA responder 33.7% vs 13.9% | Diarrhea | [PMID 22986437](https://pubmed.ncbi.nlm.nih.gov/22986437/) | ### R4 Human RCTs: chronic constipation (Lembo 2011) | Study | People / model | Route | Amount used | Follow-up | Reported | Side effects / limitations | Citation | |---|---|---|---|---|---|---|---| | Lembo 2011 | 1,276 adults with chronic constipation | Oral | 145 or 290 mcg once daily | 12 weeks | Primary end point 16–21% vs 3–6% | Diarrhea led 4.2% to stop | [PMID 21830967](https://pubmed.ncbi.nlm.nih.gov/21830967/) · [NCT00765882](https://clinicaltrials.gov/study/NCT00765882) · [NCT00730015](https://clinicaltrials.gov/study/NCT00730015) |

Full reference list (PubMed, ClinicalTrials.gov, openFDA and DailyMed entries checked Oct 25, 2026)

^R1 DailyMed. LINZESS (linaclotide) capsule label, Allergan/AbbVie, published Oct 19, 2026. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3
^R2 FDA. Drugs@FDA data (openFDA drugsfda): NDA 202811 (Linzess, AbbVie), original approval 2012-08-30; ANDA 209564 (Mylan), ANDA 209611 (Aurobindo), ANDA 211255 (Actavis); checked Oct 25, 2026. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=202811
^R3 Chey WD, 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. PMID 22986437
^R4 Lembo AJ, et al. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011. PMID 21830967
^R5 WADA. The 2026 Prohibited List (in force 1 January 2026). https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf

Disclaimer

This page is for education and harm reduction, not medical advice or a recommendation to use Linaclotide. Talk to a clinician you trust before using any drug, and report problems to FDA MedWatch (https://www.fda.gov/safety/medwatch).

Approved for Adam Greene by Dr. Nova Reyes, 2026-10-25.