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Peptide

Linaclotide (Linzess)

Linaclotide is a 14-amino acid peptide guanylate cyclase-C (GC-C) agonist. FDA-approved 2012 for chronic idiopathic constipation (CIC) and IBS-C. Phase 3: 33.7% FDA responder rate vs 13.9% placebo in IBS-C. Improves bowel frequency, stool consistency, and abdominal pain. Doses: 72-145 mcg (CIC), 290 mcg (IBS-C) once daily.

Research notice. This page is for education and research. Peptides may not be FDA-approved for human use and may only be legally available for research. Talk to a qualified clinician before considering any peptide.

Best evidence
Grade A
Conditions studied
2
Outcomes
8
Graded outcomes
4211

Evidence by condition

  • Strong
  • Moderate
  • Limited
  • Very limited

2 conditions, plus general outcomes

Constipation

Constipation: outcomes studied for Linaclotide (Linzess)
GradeOutcomeEffectSizeStudiesPeopleStudies list
Abdominal Bloating

Phase 3b: Significant reduction in moderate-to-severe bloating. Improved quality of life and global assessment. Both 145 and 290 mcg doses effective for bloating symptom relief.

Improves (the measure goes down)Large effect23 studies

Studies that measured abdominal bloating

and 13 more in the citations list

Complete Spontaneous BM

Significant increase in CSBMs/week vs placebo. Phase 3 CIC: ≥3 CSBMs/week with ≥1 increase from baseline achieved in significantly more patients. Improved stool consistency and reduced straining.

Improves (the measure goes up)Large effect22 studies

Studies that measured complete spontaneous bm

and 12 more in the citations list

Constipation-Predominant Irritable Bowel Syndrome (IBS-C)

Constipation-Predominant Irritable Bowel Syndrome (IBS-C): outcomes studied for Linaclotide (Linzess)
GradeOutcomeEffectSizeStudiesPeopleStudies list
FDA Responder Rate IBS-C

Phase 3: 33.6-33.7% FDA responders vs 13.9-21.0% placebo (P<0.0001). Dual endpoint: ≥30% pain improvement + ≥1 CSBM increase for ≥50% of weeks. Effect maintained over 26 weeks.

Improves (the measure goes up)Large effect20 studies

Studies that measured fda responder rate ibs-c

and 10 more in the citations list

Abdominal Pain Relief

Significant improvement in worst abdominal pain scores vs placebo. Pain relief observed within first week. cGMP-mediated visceral analgesia independent of bowel effects. No rebound worsening on discontinuation.

Improves (the measure goes down)Large effect15 studies

Studies that measured abdominal pain relief

and 5 more in the citations list

General

General: outcomes studied for Linaclotide (Linzess)
GradeOutcomeEffectSizeStudiesPeopleStudies list
GI Protection

10 human trials support this finding. Human clinical trial data available.

Improves (the measure goes up)Moderate effect22 studies

Studies that measured gi protection

and 12 more in the citations list

Safety/Tolerability

8 human trials and systematic reviews support this finding. Evidence includes systematic reviews/meta-analyses. Human clinical trial data available.

Improves (the measure goes up)Moderate effect20 studies

Studies that measured safety/tolerability

and 10 more in the citations list

Anti-Cancer Activity

3 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect15 studies

Studies that measured anti-cancer activity

and 5 more in the citations list

Liver Protection

2 preclinical studies support this finding. Primarily preclinical evidence.

Improves (the measure goes up)Small effect14 studies

Studies that measured liver protection

and 4 more in the citations list

Key findings

  • Abdominal BloatingConstipationImproves (the measure goes down)
  • Complete Spontaneous BMConstipationImproves (the measure goes up)
  • FDA Responder Rate IBS-CConstipation-Predominant Irritable Bowel Syndrome (IBS-C)Improves (the measure goes up)

Studies cited

49 studies from PubMed

  1. Linaclotide combined with polyethylene glycol for bowel preparation in colonoscopy: a systematic review and meta-analysis of randomized controlled trials.Surgical endoscopy, 2026 · PMID 41168471
  2. Efficacy and Safety of Linaclotide as an Adjunct to Polyethylene Glycol in Bowel Preparation: A Meta-Analysis.Journal of digestive diseases, 2025 · PMID 40955723
  3. Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis.The Lancet. Child & adolescent health, 2025 · PMID 41101321
  4. Safety and efficacy of linaclotide as an adjuvant for bowel preparation: A systematic review and meta-analysis.Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, 2025 · PMID 41203453
  5. ESPGHAN/NASPGHAN guidelines for treatment of irritable bowel syndrome and functional abdominal pain-not otherwise specified in children aged 4-18 years.Journal of pediatric gastroenterology and nutrition, 2025 · PMID 40444524
  6. Management of Chronic Constipation: A Comprehensive Review.Internal medicine (Tokyo, Japan), 2025 · PMID 37952945
  7. Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials.International journal of colorectal disease, 2025 · PMID 40528061
  8. Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trialLancet Gastroenterol Hepatol, 2024 · PMID 38211604
  9. Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label studyJ Gastroenterol Hepatol, 2024 · PMID 39370607
  10. Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.Journal of pediatric gastroenterology and nutrition, 2024 · PMID 38504394
  11. Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study.Journal of pediatric gastroenterology and nutrition, 2024 · PMID 38962910
  12. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm.BMC gastroenterology, 2024 · PMID 38166671
  13. Bowel preparation efficacy and safety of compound polyethylene glycol electrolyte powder combined with linaclotide for colonoscopy: A randomized controlled trial.JGH open : an open access journal of gastroenterology and hepatology, 2023 · PMID 37744708
  14. Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation, 2023 · PMID 36548082
  15. Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience, 2023 · PMID 38027512
  16. Editorial: repurposed linaclotide and the quest for abdominal pain management in irritable bowel syndrome.Alimentary pharmacology & therapeutics, 2023 · PMID 36565004
  17. Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub-cohort analysis of a phase III, randomized, double-blind, placebo-controlled trialJ Gastroenterol Hepatol, 2022 · PMID 35019221
  18. Chronic Constipation: Gastroenterohepatologist's Approach.Digestive diseases (Basel, Switzerland), 2022 · PMID 33946065
  19. Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis.Zeitschrift fur Gastroenterologie, 2022 · PMID 34215016
  20. Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring SystemAm J Gastroenterol, 2021 · PMID 34465695
  21. [Efficacy and Safety of Linaclotide in Elderly Patients].Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 2021 · PMID 33518646
  22. Improving the Gastrointestinal Stability of Linaclotide.Journal of medicinal chemistry, 2021 · PMID 33979161
  23. Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation.Neurogastroenterology and motility, 2021 · PMID 33751780
  24. Systematic review and network meta-analysis: efficacy of licensed drugs for abdominal bloating in irritable bowel syndrome with constipation.Alimentary pharmacology & therapeutics, 2021 · PMID 34114657
  25. Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis.Alimentary pharmacology & therapeutics, 2020 · PMID 32406112
  26. Tadalafil versus linaclotide in gastrointestinal dysfunction and depressive behavior in constipation-predominant irritable bowel syndrome.Life sciences, 2020 · PMID 32534033
  27. Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysisExpert Rev Gastroenterol Hepatol, 2019 · PMID 30791771
  28. Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis.The lancet. Gastroenterology & hepatology, 2019 · PMID 31474542
  29. Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-AnalysisAm J Gastroenterol, 2018 · PMID 29380823
  30. Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3.American journal of physiology. Gastrointestinal and liver physiology, 2018 · PMID 30118317
  31. Gastrointestinal Pharmacology.Handbook of experimental pharmacology, 2017 · PMID 28236087
  32. Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine.Physiological reports, 2017 · PMID 28592587
  33. GUCY2C ligand replacement to prevent colorectal cancer.Cancer biology & therapy, 2016 · PMID 27104761
  34. Guanylyl cyclase C signaling axis and colon cancer prevention.World journal of gastroenterology, 2016 · PMID 27688649
  35. Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled TrialPLoS One, 2015 · PMID 26222318
  36. Linaclotide: a novel therapy for chronic constipation and constipation-predominant irritable bowel syndromeUnited European Gastroenterol J, 2014 · PMID 24683372
  37. Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation.Drugs, 2014 · PMID 24293117
  38. Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis.Neurogastroenterology and motility, 2014 · PMID 24351035
  39. Review article: Linaclotide for the management of irritable bowel syndrome with constipation.Alimentary pharmacology & therapeutics, 2014 · PMID 24433216
  40. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpointsAliment Pharmacol Ther, 2013 · PMID 23116208
  41. Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndromeAdv Ther, 2013 · PMID 23436110
  42. Translating colorectal cancer prevention through the guanylyl cyclase C signaling axis.Expert review of clinical pharmacology, 2013 · PMID 23971873
  43. A review of the clinical efficacy of linaclotide in irritable bowel syndrome with constipation.Current medical research and opinion, 2013 · PMID 23198977
  44. Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2013 · PMID 23644388
  45. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safetyAm J Gastroenterol, 2012 · PMID 22986437
  46. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipationAm J Gastroenterol, 2012 · PMID 22986440
  47. Linaclotide in the management of gastrointestinal tract disorders.Drugs of today (Barcelona, Spain : 1998), 2012 · PMID 22462039
  48. The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide.Expert opinion on drug metabolism & toxicology, 2011 · PMID 21446888
  49. Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation.Expert review of gastroenterology & hepatology, 2011 · PMID 21651347