Guanylate cyclase-C (GC-C) agonist peptide (14 amino acids)
Linaclotide
Approvedaka MD-1100, Linzess, Constella
Linaclotide is a minimally absorbed 14-amino-acid peptide taken by mouth for IBS-C and chronic idiopathic constipation. Two Phase 3 trials published in 2012 (Chey et al. and Rao et al.) reported improvements in bowel and abdominal symptom endpoints versus placebo, with diarrhea the most common adverse effect. It is approved by the FDA, EMA, and TGA.
Mechanism
In plain terms, linaclotide draws fluid into the intestine and speeds the movement of stool, easing constipation and reducing abdominal pain. Technically, it is a 14-amino-acid peptide agonist of guanylate cyclase-C on the luminal surface of intestinal epithelial cells; receptor activation raises intracellular and extracellular cyclic GMP, which stimulates CFTR-mediated chloride and bicarbonate secretion into the intestinal lumen to accelerate transit, while extracellular cyclic GMP is associated with reduced activity of pain-sensing afferent nerves.
Regulatory Status by Region
- United States (FDA)Approved. Linzess (linaclotide) for adults with irritable bowel syndrome with constipation and with chronic idiopathic constipation, August 2012.
- Australia (TGA)Registered on the ARTG as Constella (linaclotide) for adults with IBS-C and chronic idiopathic constipation; prescription medicine.
- European Union (EMA)Authorized. Constella (linaclotide) received an EU-wide marketing authorisation in November 2012 for irritable bowel syndrome with constipation in adults.
- WADANot listed on the WADA Prohibited List.
Key Studies
- Phase 3 IBS-C trial (26-week); Chey WD et al. (opens in a new tab) (Am J Gastroenterol 2012;107(11):1702-1712; DOI 10.1038/ajg.2012.254; PMID 22986437; NCT00938717)
- Phase 3 IBS-C trial (12-week with randomized withdrawal); Rao S et al. (opens in a new tab) (Am J Gastroenterol 2012;107(11):1714-1724; DOI 10.1038/ajg.2012.255; PMID 22986440; NCT00948818)
Related Clinical Trials
- Proof of Principle Study for an Efficacy Trial of Linaclotide for Cystic FibrosisEARLY_Phase 1 · Recruiting
- "Efficacy and Safety of Linaclotide in Chronic Constipation"Phase 4 · Not Yet Recruiting
- Linaclotide for Colonoscopy Bowel PrepPhase 1/Phase 2 · Recruiting
- Clinical Study on the Application of Lactulose Combined with Linaclotide in Bowel Preparation for ColonoscopyPhase 4 · Enrolling By Invitation
- A Study of Virtual Reality and Linaclotide for IBS-CN/A · Recruiting
- Clinical Study of Bowel Preparation Before ColonoscopyN/A · Completed
- A Study to Assess Adverse Events and Change in Disease Activity in Pediatric Participants (Age 6 Months to <2 Years) With Functional Constipation Who Are Treated With LinaclotidePhase 2 · Completed
- A Study to Assess Adverse Events and Change in Symptoms With Linaclotide Versus Placebo in Pediatric Subjects, Ages 2 to 5 Years, With Functional ConstipationPhase 3 · Completed
Latest research
- Post-marketing safety assessment of constipation drugs: a real-world pharmacovigilance study based on FAERS database. (opens in a new tab)
Expert opinion on drug safety · Jul 1, 2026
Common Questions
- What is Linaclotide?
- Linaclotide is an oral guanylate cyclase-C (GC-C) agonist peptide approved for irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation in adults. The FDA approved it as Linzess in August 2012 and the EMA authorized it as Constella in November 2012.
- Is Linaclotide approved for medical use?
- Linaclotide is approved for one or more medical uses in at least one major jurisdiction. United States (FDA): Approved. Linzess (linaclotide) for adults with irritable bowel syndrome with constipation and with chronic idiopathic constipation, August 2012. European Union (EMA): Authorized. Constella (linaclotide) received an EU-wide marketing authorisation in November 2012 for irritable bowel syndrome with constipation in adults. Australia (TGA): Registered on the ARTG as Constella (linaclotide) for adults with IBS-C and chronic idiopathic constipation; prescription medicine.
- How does Linaclotide work?
- In plain terms, linaclotide draws fluid into the intestine and speeds the movement of stool, easing constipation and reducing abdominal pain. Technically, it is a 14-amino-acid peptide agonist of guanylate cyclase-C on the luminal surface of intestinal epithelial cells; receptor activation raises intracellular and extracellular cyclic GMP, which stimulates CFTR-mediated chloride and bicarbonate secretion into the intestinal lumen to accelerate transit, while extracellular cyclic GMP is associated with reduced activity of pain-sensing afferent nerves.
- Is Linaclotide legal in Australia?
- Linaclotide in Australia (TGA): Registered on the ARTG as Constella (linaclotide) for adults with IBS-C and chronic idiopathic constipation; prescription medicine.
- Is Linaclotide banned in sport?
- Linaclotide under the World Anti-Doping Agency (WADA) code: Not listed on the WADA Prohibited List.