Linaclotide

Linaclotide (brand names Linzess and Constella) is a prescription medicine for three long-term gut conditions: irritable bowel syndrome with constipation, chronic constipation with no identified cause, and functional constipation in children. It is a peptide you swallow rather than inject — it stays in the gut and switches on a receptor in the intestinal lining that draws fluid into the bowel and changes how gut pain signals are carried. It is FDA-approved and taken as a once-daily capsule. It also carries the most serious warning label US regulators issue: it must never be given to a child under 2 years old, because in newborn mice it caused deaths from dehydration.

Linaclotide has been studied in large trials in people with constipation- predominant IBS and with chronic constipation. Across two Phase 3 IBS trials totalling about 1,600 people, it improved abdominal pain, bloating, discomfort, fullness and cramping more than placebo — including in the people who started with the most severe symptoms. In chronic constipation with bad bloating, more people met the study's bowel-movement target on linaclotide than on placebo, though the numbers on both sides were modest. The honest part: diarrhea is the common side effect, reported by up to about one in five people in the IBS trials, and it rose with the higher dose — which makes sense, since drawing fluid into the bowel is exactly how the drug works. The other honest part sits outside the adult trials: the drug carries the most serious warning label US regulators issue, because it must never be given to a child under 2 — newborn mice given a single adult-sized dose died of dehydration.

FDA-approved prescription drug (Linzess in the US; Constella in the EU). Boxed warning — risk of serious dehydration in pediatric patients less than 2 years of age. Linzess is contraindicated in patients less than 2 years of age; in neonatal mice, linaclotide caused deaths due to dehydration. This is the FDA's most serious warning class, it applies to the currently-marketed capsule rather than to a discontinued formulation, and it is molecule-wide here — there is only one marketed product. Three approved indications, with different age ranges — this is not an adults-only drug: irritable bowel syndrome with constipation (IBS-C) in adults and pediatric patients 7 years of age and older; chronic idiopathic constipation (CIC) in adults; and functional constipation (FC) in pediatric patients 2 years of age and older. Only CIC is adults-only. Verified against DailyMed SPL 09beda19-56d6-4a56-afdc-9a77b70b2ef3 version 39 (label revised 5/2026), checked 2026-09-08. ⭐ Notable as a peptide you swallow — a 14-amino-acid peptide taken as an oral capsule acting on receptors in the intestinal lining, rather than an injectable. WADA status: linaclotide is not named on the 2026 or 2027 WADA Prohibited List[⁴], and no guanylate cyclase-C drug class appears on that list. Because it holds regulatory approval for human therapeutic use, S0 (Non-Approved Substances) does not capture it. Athletes should still verify with their anti-doping organization. Not DEA-scheduled (prescription, non-controlled).

Linaclotide carries a boxed warning, the most serious warning label US regulators issue: it must never be given to a child under 2 years old, because in newborn mice a single adult-sized dose caused deaths from dehydration. It must also not be used by anyone with a known or suspected mechanical blockage of the gut. Beyond those two, it is a prescription drug for diagnosed gut conditions — and it is approved for children as well as adults, at ages that differ by condition. Its most common side effect is diarrhea, reported by roughly one in five people in the IBS trials and clearly dose-related in the constipation trials — 6% at the lower dose and 17% at the higher, against 2% on placebo. That is the drug's own mechanism overshooting rather than an unrelated effect. It is not named on the WADA Prohibited List and, being an approved medicine, is not captured by the S0 non-approved-substances category — though athletes should verify with their anti-doping organization. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ boxed warning — risk of serious dehydration in children under 2. Linzess is contraindicated in patients less than 2 years of age; in neonatal mice, a single clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. This is the FDA's most serious warning class. It is also contraindicated in anyone with known or suspected mechanical gastrointestinal obstruction. Verified against DailyMed SPL 09beda19-56d6-4a56-afdc-9a77b70b2ef3 version 39 (label revised 5/2026), checked 2026-09-08.

⚠️ This is an approved prescription medicine, not a research peptide. Linaclotide is dispensed by a pharmacy for diagnosed conditions. The reconstitution and self-dosing workflows used elsewhere in this library do not apply. Information here is informational, not medical advice.

⚠️ A peptide you swallow. Almost every compound in this library is injected, because the digestive tract destroys peptides. Linaclotide is a 14-amino-acid peptide taken as an oral capsule — it works because it stays in the gut, acting on receptors in the intestinal lining. Alongside oral octreotide and orforglipron, it is one of this library's worked examples of peptide-class pharmacology in a swallowed dose.

⚠️ It is not a general "gut health" supplement. Linaclotide's evidence base is in diagnosed conditions — IBS-C, chronic idiopathic constipation, and functional constipation in children — in trials where participants met formal diagnostic criteria.[¹][²][³] Nothing in this entry supports using it for general digestion, bloating without a diagnosis, or gut-lining "repair," none of which it was tested for.

Linaclotide is a synthetic 14-amino-acid peptide agonist of guanylate cyclase-C (GC-C), marketed as Linzess and Constella.

Mechanism. GC-C sits on the surface of the intestinal lining. Activating it increases fluid secretion into the bowel lumen, which softens stool and speeds transit. The trials also consistently measured abdominal symptoms — pain, bloating, discomfort, fullness, cramping — separately from bowel symptoms, and reported improvement in both.[¹] That the abdominal symptom improvement is a distinct effect rather than a downstream consequence of easier stooling is a mechanistic claim this entry's sources describe but do not settle.

Why the trials separate abdominal from bowel symptoms. One of the pooled analyses makes an interesting structural point: in patients with more severe abdominal pain, abdominal symptoms — not bowel symptoms — correlated more strongly with how the patient rated their overall constipation severity, quality of life and treatment satisfaction.[³] In other words, for a substantial subgroup the pain is the complaint, and stool frequency is a poor proxy for whether the patient feels better.

Evidence quality. Large, randomized, placebo-controlled, and pre-registered:

- Two Phase 3 IBS-C trials, pooled: intent-to-treat population 1,602 patients (797 placebo, 805 linaclotide), 12 weeks, meeting modified Rome II criteria.[¹] At baseline, severe symptoms were common — bloating 44%, fullness 44%, discomfort 32%, pain 23%, cramping 22%.[¹] In patients with severe symptoms, mean changes from baseline ranged −2.7 to −3.4 on linaclotide versus −1.4 to −1.9 on placebo (P <.0001), with global measures and IBS quality-of-life scores also improved.[¹] Diarrhea was the most common adverse event, at 18.8%–21.0% in these severe-symptom subgroups.[¹] - A Phase 3b trial in chronic idiopathic constipation with moderate-to-severe bloating, 483 patients randomized to linaclotide or placebo for 12 weeks.[²] The primary responder endpoint — at least 3 complete spontaneous bowel movements per week with an increase of at least 1 from baseline, for at least 9 of 12 weeks — was met by 15.7% on linaclotide versus 7.6% on placebo (P <.05).[²] Both doses significantly improved abdominal bloating.[²] ⚠️ Note the absolute numbers: roughly double the placebo rate, but 15.7% still means most patients did not meet that bar. Responder endpoints are deliberately strict — read them as a high hurdle, not as "the drug failed 84% of people." - A pooled analysis of two Phase 3 CIC trials, 1,271 patients on or placebo.[³] Source for the finding that abdominal symptoms drive patients' global assessments when pain is severe.[³]

Dose-related diarrhea. The bloating trial reports it cleanly: diarrhea in 6%, 17%, and 2% on placebo.[²] Discontinuations due to adverse events were 5% and 9% versus 6% on placebo.[²] The dose-response is exactly what the mechanism predicts.

Regulatory status (US). FDA-approved as Linzess for three indications, and the age ranges differ between them: IBS-C in adults and pediatric patients 7 years of age and older; chronic idiopathic constipation (CIC) in adults; and functional constipation (FC) in pediatric patients 2 years of age and older. So the entry's older "in adults" framing was incomplete — only CIC is adults-only. The label carries a boxed warning — the FDA's most serious warning class — for risk of serious dehydration in pediatric patients less than 2 years of age: Linzess is contraindicated under 2, because in neonatal mice a single clinically relevant adult oral dose caused deaths due to dehydration. The label also contraindicates it in known or suspected mechanical gastrointestinal obstruction. Verified against DailyMed SPL 09beda19-56d6-4a56-afdc-9a77b70b2ef3 version 39 (label revised 5/2026), checked 2026-09-08. Not DEA-scheduled.

Regulatory status (sport — WADA). Linaclotide is not named on the 2026 or 2027 WADA Prohibited List[⁴], and no guanylate cyclase-C class appears anywhere on it. S0 captures only substances with no current approval by any regulatory health authority — linaclotide is approved, so S0 does not reach it. Verify current status with your National Anti-Doping Organization.

Commonly reported

• Diarrhea — the most common adverse event throughout. 18.8%–21.0% in the severe-symptom IBS-C subgroups;[¹] clearly dose-related in chronic constipation at 6%, 17% versus 2% (placebo).[²]
• Discontinuation due to adverse events: 5% and 9%, versus 6% on placebo.[²] Note the lower dose discontinued less than placebo.

This is a prescription medicine for diagnosed conditions. Use outside that context is outside everything the evidence base covers.

Contraindicated under 2 years of age — this is the label's boxed warning. In neonatal mice, a single clinically relevant adult oral dose of linaclotide caused deaths due to dehydration. The FDA states this as its most serious warning class, not as a precaution. Verified against DailyMed SPL 09beda19-56d6-4a56-afdc-9a77b70b2ef3 version 39 (label revised 5/2026), checked 2026-09-08.

Known or suspected mechanical gastrointestinal obstruction — a labeled contraindication, not merely a caution. Verified against DailyMed SPL 09beda19-56d6-4a56-afdc-9a77b70b2ef3 version 39 (label revised 5/2026), checked 2026-09-08.

Age ranges differ by indication and are part of the approval, not a general restriction. IBS-C is approved from 7 years, functional constipation from 2 years, and CIC in adults only. The trials cited in this entry enrolled adults and adolescents.[¹][²]

Existing diarrhea, or conditions where fluid loss is dangerous — the dominant, dose-related adverse effect is diarrhea.[²]

General "gut health" or undiagnosed bloating — not studied, not approved, not supported by any source in this entry.

Pregnancy and lactation — not addressed by the sources here. Refer to current labeling.

Regulatory note (sport): not named on the 2026 or 2027 WADA Prohibited List[⁴] and not captured by S0 (approved medicine). Verify with your anti-doping organization.

Not DEA-scheduled.

Peptide

A short chain of amino acids, the building blocks of proteins. Most peptides are injected because the gut breaks them down — linaclotide is unusual in being taken by mouth, because the gut is where it works.

Guanylate cyclase-C (GC-C)

A receptor on the surface of the intestinal lining. Activating it increases fluid secretion into the bowel and has been studied for its effect on gut pain signaling.

IBS-C

Irritable bowel syndrome with constipation — a long-term condition combining abdominal pain and discomfort with infrequent, hard stools.

Chronic idiopathic constipation (CIC)

Long-lasting constipation with no identified underlying cause. "Idiopathic" simply means the cause is not known.

Responder endpoint

A pass/fail bar a trial sets in advance — for example, a set number of bowel movements per week for a set number of weeks. It is stricter than "did the average improve", so responder rates often look low even when a drug works.

1. Rao SSC, Quigley EMM, Shiff SJ, Lavins BJ, Kurtz CB, MacDougall JE, Currie MG, Johnston JM. (2014). Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. Clinical Gastroenterology and Hepatology, 12(4):616–623.(PMID 24075889 · NCT00938717)
2. Lacy BE, Schey R, Shiff SJ, Lavins BJ, Fox SM, Jia XD, Blakesley RE, Hao X, Cronin JA, Currie MG, Kurtz CB, Johnston JM, Lembo AJ. (2015). Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial. PLoS One, 10(7):e0134349.(PMID 26222318 · NCT01642914)
3. Chang L, Lembo AJ, Lavins BJ, Shiff SJ, Hao X, Chickering JG, Jia XD, Currie MG, Kurtz CB, Johnston JM. (2014). The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials. Alimentary Pharmacology & Therapeutics, 40(11-12):1302–1312.(PMID 25312449 · NCT00765882)
4. World Anti-Doping Agency. World Anti-Doping Code International Standard Prohibited List 2027 (effective 1 January 2027). PDF: wada-ama.org/sites/default/files/2026-09/2027list_en_final_clean_26_august_2026_2.pdf. Linaclotide is not named. S0 (Non-Approved Substances) keeps its 2026 wording and adds "peptides" to its examples.

• Teduglutide — same mechanism class