Gastrointestinal Peptides
Linaclotide
Commonly used for
Constipation ReliefIBS-CMetabolic Health
What is it?
Linaclotide is a 14-amino acid synthetic peptide that activates guanylate cyclase-C receptors within the intestinal epithelium. It was the first GC-C agonist developed for chronic constipation disorders. Unlike plecanatide, linaclotide is structurally derived from the bacterial heat-stable enterotoxin peptide but is modified for therapeutic use.
Brand names: Linzess® (US), Constella® (Europe)
Mechanism of action: Guanylate cyclase-C receptor agonist; Increases intracellular cGMP; Activates CFTR chloride channels; Increases intestinal fluid secretion; Accelerates gastrointestinal transit; Reduces visceral pain through extracellular cGMP signaling
What do people use it for?
Approved indications: Irritable Bowel Syndrome with Constipation (IBS-C); Chronic Idiopathic Constipation (CIC); Functional constipation in selected pediatric populations (age-specific approvals)
Proposed indications: Opioid-induced constipation; Functional bowel disorders; Chronic abdominal pain; Pelvic floor dysfunction (adjunct); Radiation-induced constipation
How is it used? / Dosing
Administration: Oral capsule, taken on an empty stomach at least 30 minutes before the first meal of the day — Once daily
How does it compare?
Compare with:
How well does it work? / Evidence
✓ Well-established
Evidence rating: Grade A — Extensively studied with numerous randomized controlled trials and long-term safety data.
Landmark trials: Multiple Phase III trials — Consistently demonstrated increased complete spontaneous bowel movements, reduced abdominal pain, improved quality of life in IBS-C, and sustained efficacy with long-term treatment.
Safety & side effects
Common side effects: Diarrhea, Abdominal pain, Flatulence, Abdominal distension, Urgency
Serious risks: Severe diarrhea leading to dehydration; Pediatric toxicity (boxed warning)
Drug interactions: No clinically meaningful systemic drug interactions are expected because of negligible systemic absorption.
Monitoring: Stool frequency, Stool consistency, Symptom improvement, Hydration status, Diarrhea severity
Legal & regulatory status
Legal status: Prescription required. This is an FDA-approved medication available only through a licensed prescriber — dosing is determined by your prescriber based on your medical history and is not provided here.
Regulatory status: FDA Approved • EMA Approved
Who should avoid it?
Contraindications: Known or suspected mechanical gastrointestinal obstruction; Children under 2 years of age (boxed warning due to dehydration risk); Hypersensitivity
Pregnancy & breastfeeding: Limited human data. Given minimal systemic absorption, fetal exposure is expected to be low, but use should be based on clinical need.
Research & references
Chey WD et al. (2012). Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. American Journal of Gastroenterology. Lembo AJ, et al. (2011). Two Randomized Trials of Linaclotide for Chronic Constipation. New England Journal of Medicine, 365(6), 527–536. https://doi.org/10.1056/NEJMoa1010863