Linaclotide

Overview

Linaclotide is a guanylate cyclase-C agonist peptide studied for gastrointestinal symptoms. Constipation-related conditions, age groups, and bowel-preparation studies are distinct settings and should be interpreted separately.

Evidence quality

WPF’s atlas lists work in chronic constipation and pediatric functional constipation, plus trials and reviews of linaclotide as an adjunct in colonoscopy preparation. Bowel-cleansing outcomes do not automatically establish relief of a chronic condition, and subgroup or post hoc findings need their own limits.

Safety concerns

The Directory has no published source-linked citations or jurisdiction-specific regulatory record here. Efficacy, adverse events, pediatric applicability, and approved indications require primary and official sources rather than a pooled screening list.

Citations as of this version

• A post hoc analysis of linaclotide in pediatric patients with functional constipation and neurodevelopmental disorders. (2026)
• The Efficacy of Single Dose Linaclotide in Polyethylene Glycol-Based Bowel Preparation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (2026)
• Linaclotide for irritable bowel syndrome with constipation: integrating realworld evidence into the therapeutic puzzle. (2026)
• Effect of Age and Age-Defined Menopausal Status on Linaclotide Efficacy and Safety in Adults With Irritable Bowel Syndrome With Constipation or Chronic Idiopathic Constipation: Post Hoc Analyses of Phase 2b/3 Studies. (2026)
• Effect of Linaclotide on Colonic Motility Assessed With Intraluminal Colonic High-Resolution Manometry in Healthy Subjects. An Acute, Open Label, Randomized, Crossover, Reader-Blinded Study. (2026)
• Efficacy safety of linaclotide combined with polyethylene glycol for bowel preparation in patients with constipation: a meta-analysis. (2026)
• Evaluating linaclotide for the treatment of functional constipation in children and adolescents. (2026)
• Identification and Quantification of Structurally Related Peptide Impurity in Linaclotide by Liquid Chromatography-High Resolution Mass Spectrometry. (2026)
• Short-term linaclotide plus polyethylene glycol in patients at increased risk of inadequate bowel preparation: A randomized, double-blind, multicenter trial. (2026)
• Adjunctive linaclotide improves bowel cleansing and patient experience in polyethylene glycol-based bowel preparation. (2026)
• Evaluating linaclotide for the treatment of irritable bowel syndrome with constipation in children and adolescents. (2026)
• Linaclotide in combination with compound polyethylene glycol powder enhances bowel preparation for colonoscopy in patients aged over 60 years: a multi-center, endoscopist-blind, randomized controlled trial. (2026)
• Effect of linaclotide combined with polyethylene glycol on bowel preparation before colonoscopy in patients with constipation. (2026)
• Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation: A Meta-analysis of Randomized Controlled Trials. (2026)
• Linaclotide combined with polyethylene glycol for bowel preparation in colonoscopy: a systematic review and meta-analysis of randomized controlled trials. (2026)
• Effect of 3-Day Linaclotide Administration to Reduce the Polyethylene Glycol Volume for Colonoscopy Bowel Preparation: A Multicenter, Noninferiority, Randomized Controlled Trial. (2026)
• Linaclotide Use for the Treatment of Constipation and Gastrointestinal Symptoms in People With Cystic Fibrosis. (2025)
• Safety and efficacy of linaclotide as an adjuvant for bowel preparation: A systematic review and meta-analysis. (2025)
• Efficacy and Safety of Linaclotide as an Adjunct to Polyethylene Glycol in Bowel Preparation: A Meta-Analysis. (2025)
• Real-world safety of linaclotide in Chinese patients with irritable bowel syndrome with constipation: a multicenter, single-arm, prospective observational study. (2025)
• Characterization of disulfide bridges containing cyclic peptide Linaclotide and its degradation products by using LC-HRMS/MS. (2025)
• Efficacy of 1 L Polyethylene Glycol Plus Ascorbic Acid With Linaclotide Versus Senna for Bowel Preparation: A Multicenter, Endoscopist-Blinded, Randomized Controlled Trial (Apple Trial). (2025)
• Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials. (2025)
• Cost-Effectiveness of Vibrant System vs. Linaclotide in Chronic Idiopathic Constipation. (2025)
• Efficacy of Linaclotide in Functional Dyspepsia and Constipation-Predominant Irritable Bowel Syndrome Overlap: A Randomized Trial. (2025)
• Effects of the combined use of linaclotide and oral sulfate solution in bowel preparation for patients with chronic constipation undergoing colonoscopy: protocol of a prospective, randomised, controlled, single-blind clinical trial from a single centre in China. (2025)
• Efficacy of linaclotide in combination with polyethylene glycol for bowel preparation in Chinese patients undergoing colonoscopy polypectomy: protocol for a randomised controlled trial. (2024)
• Application of linaclotide in bowel preparation for colonoscopy in patients with constipation: A prospective randomized controlled study. (2024)
• The Effects of Combined Use of Linaclotide and Polyethylene Glycol Electrolyte Powder in Colonoscopy Preparation for Patients With Chronic Constipation. (2024)
• Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm. (2024)
• Linaclotide for paediatric functional constipation. (2024)
• Renoprotective effects of laxative linaclotide: Inhibition of acute kidney injury and fibrosis in a rat model of renal ischemia-reperfusion. (2024)
• Ten years of successful linaclotide treatment in a patient with intestinal pseudo-obstruction due to Ehlers-Danlos syndrome. (2024)
• Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. (2024)
• Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation. (2024)
• Efficacy of Polyethylene Glycol Electrolyte Powder Combined With Linaclotide for Colon Cleansing in Patients With Chronic Constipation Undergoing Colonoscopy: A Multicenter, Single-Blinded, Randomized Controlled Trial. (2024)
• Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study. (2024)
• Linaclotide (2024)
• Linaclotide for functional constipation in paediatric patients: phase III results. (2024)
• Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation. (2024)
• Examining linaclotide for the treatment of chronic idiopathic constipation. (2024)
• Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study. (2024)
• Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients. (2024)
• DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function. (2024)
• Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study. (2024)
• The gut microbiota participates in the effect of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C): a multicenter, prospective, pre-post study. (2024)
• Editorial: repurposed linaclotide and the quest for abdominal pain management in irritable bowel syndrome. (2023)
• Linaclotide (Linzess) for functional constipation. (2023)
• A novel ultra-low-volume regimen combining 1 L polyethylene glycol and linaclotide versus 2 L polyethylene glycol for colonoscopy cleansing in low-risk individuals: a randomized controlled trial. (2023)
• A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide. (2023)
• Linaclotide Reduced Response Time for Irritable Bowel Syndrome With Constipation Symptoms: Analysis of 4 Randomized Controlled Trials. (2023)
• Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids. (2023)
• Cost impact of incorporating linaclotide into low-volume colonoscopy preparation. (2023)
• Linaclotide for treating patients with irritable bowel syndrome with predominant constipation: a multicentre study of real-world data in China. (2022)
• Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis. (2022)
• 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 trial. (2022)
• Linaclotide utilization and potential for off-label use and misuse in three European countries. (2022)
• Cost-Effectiveness of Linaclotide Compared to Osmotic Laxatives in the Treatment of Irritable Bowel Syndrome with Constipation in China. (2022)
• Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial. (2021)
• Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis. (2021)
• Improving the Gastrointestinal Stability of Linaclotide. (2021)
• Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. (2021)
• [Efficacy and Safety of Linaclotide in Elderly Patients]. (2021)
• The Use of Linaclotide in Children with Functional Constipation or Irritable Bowel Syndrome: A Retrospective Chart Review. (2021)
• Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. (2021)
• Tadalafil versus linaclotide in gastrointestinal dysfunction and depressive behavior in constipation-predominant irritable bowel syndrome. (2020)
• The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. (2020)
• Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study. (2020)
• Randomised clinical trial: linaclotide vs placebo-a study of bi-directional gut and brain axis. (2020)
• Clinical response to linaclotide at week 4 predicts sustained response in irritable bowel syndrome with constipation and improvements in digestive and extra-digestive symptoms. (2019)
• High-dose linaclotide is effective and safe in patients with chronic constipation: A phase III randomized, double-blind, placebo-controlled study with a long-term open-label extension study in Japan. (2019)
• Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysis. (2019)
• Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk. (2019)
• Long-term treatment with linaclotide of intestinal pseudo-obstruction secondary to Ehlers-Danlos syndrome. (2019)
• Single-Dose Linaclotide Is Equal in Efficacy to Polyethylene Glycol for Bowel Preparation Prior to Capsule Endoscopy. (2019)
• Effectiveness and tolerability of linaclotide in the treatment of IBS-C in a "real-life" setting: Results from a Portuguese single-center study. (2019)
• [Pharmacological and clinical profile of linaclotide (Linzess^®), a novel therapeutic agent for irritable bowel syndrome with constipation and chronic constipation]. (2019)
• The Impact of Stool Consistency on Bowel Movement Satisfaction in Patients With IBS-C or CIC Treated With Linaclotide or Other Medications: Real-World Evidence From the CONTOR Study. (2019)
• Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation. (2019)
• Multicentre, non-interventional study of the efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in primary, secondary and tertiary centres: the Alpine study. (2019)
• Determining an optimal dose of linaclotide for use in Japanese patients with irritable bowel syndrome with constipation: A phase II randomized, double-blind, placebo-controlled study. (2018)
• Linaclotide for the treatment of chronic constipation. (2018)
• Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions. (2018)
• Linaclotide inhibits colonic and urinary bladder hypersensitivity in adult female rats following unpredictable neonatal stress. (2018)
• Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization. (2018)
• Linaclotide improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3. (2018)
• Low-Dose Linaclotide (72 μg) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. (2018)
• Long-term results of linaclotide in the treatment of constipation-type irritable bowel syndrome. (2018)
• Dose-finding study of linaclotide in Japanese patients with chronic constipation: A phase II randomized, double-blind, and placebo-controlled study. (2018)
• Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction. (2018)
• Efficacy of linaclotide in irritable bowel syndrome with constipation: Real-world data. (2018)
• Efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in a real‑world setting - results from a German noninterventional study. (2018)
• A randomized controlled and long-term linaclotide study of irritable bowel syndrome with constipation patients in Japan. (2018)
• Health Care Resource Use and Costs Pre- and Post-Treatment Initiation With Linaclotide: Retrospective Analyses of a U.S. Insured Population. (2018)
• Randomized, double-blind, placebo-controlled study vs data in the daily practice using linaclotide in patients with irritable bowel syndrome with constipation. (2018)
• Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine. (2017)
• Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report. (2017)
• Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention. (2017)
• Cost-effectiveness of linaclotide compared to antidepressants in the treatment of irritable bowel syndrome with constipation in Scotland. (2016)
• Economic Evaluation of Linaclotide for the Treatment of Adult Patients With Chronic Idiopathic Constipation in the United States. (2016)
• A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa. (2015)
• Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States. (2015)
• Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial. (2015)
• MRP4 Modulation of the Guanylate Cyclase-C/cGMP Pathway: Effects on Linaclotide-Induced Electrolyte Secretion and cGMP Efflux. (2015)
• Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. (2014)
• Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. (2014)
• Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. (2014)
• Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. (2014)
• Clarification of linaclotide pharmacology presented in a recent clinical study of plecanatide. (2014)
• Review article: Linaclotide for the management of irritable bowel syndrome with constipation. (2014)
• Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C. (2014)
• Impact of linaclotide treatment on work productivity and activity impairment in adults with irritable bowel syndrome with constipation: results from 2 randomized, double-blind, placebo-controlled phase 3 trials. (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. (2014)
• Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis. (2014)
• Linaclotide for treatment of irritable bowel syndrome--the view of European regulators. (2013)
• Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. (2013)
• Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. (2013)
• Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. (2013)
• [Joint Statement of the German Society for Digestive and Metabolic Diseases (DGVS), the German Society for Neurogastroenterology and motility (DGNM) and the German Society for Internal Medicine (DGIM) for linaclotide-benefit assessment of the Institute for Quality and Efficiency in Health Care (IQWiG) in accordance with § 35a SGB V (dossier evaluation)]. (2013)
• Constella™(EU)-Linzess™(USA): the last milestone in the long journey of the peptide linaclotide and its implications for the future of peptide drugs. (2013)
• Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. (2013)
• Linaclotide: a novel compound for the treatment of irritable bowel syndrome with constipation. (2013)
• Linaclotide for constipation-predominant IBS. (2013)
• An evaluation of the FDA responder endpoint for IBS-C clinical trials: analysis of data from linaclotide Phase 3 clinical trials. (2013)
• A review of the clinical efficacy of linaclotide in irritable bowel syndrome with constipation. (2013)
• Linaclotide: a new option for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation in adults. (2013)
• Linaclotide-a novel secretagogue in the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. (2013)
• Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate. (2013)
• Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. (2013)
• Pharmacologic properties, metabolism, and disposition of linaclotide, a novel therapeutic peptide approved for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. (2013)
• Challenges of managing pain in constipation-predominant IBS: clinical perspectives on antinociceptive actions of linaclotide. (2013)
• Linaclotide (2012)
• Linaclotide: promising IBS-C efficacy in an era of provisional study endpoints. (2012)
• Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. (2012)
• Linaclotide: first global approval. (2012)
• 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 constipation. (2012)
• Linaclotide in the management of gastrointestinal tract disorders. (2012)
• Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors. (2012)
• Linaclotide (Linzess) for constipation. (2012)
• Elvitegravir/cobicistat, mirabegron, and linaclotide. (2012)
• The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. (2011)
• Two randomized trials of linaclotide for chronic constipation. (2011)
• Linaclotide: a novel approach to the treatment of irritable bowel syndrome. (2011)
• Optimized Fmoc solid-phase synthesis of the cysteine-rich peptide linaclotide. (2011)
• Linaclotide, a synthetic guanylate cyclase C agonist, for the treatment of functional gastrointestinal disorders associated with constipation. (2011)
• Molecule of the month. Linaclotide acetate. (2010)
• Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. (2010)
• Linaclotide - a secretagogue and antihyperalgesic agent - what next? (2010)
• Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. (2010)
• Constipation: Linaclotide--a stimulating new drug for chronic constipation. (2010)
• Efficacy of linaclotide for patients with chronic constipation. (2010)
• Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. (2010)
• Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. (2010)
• Pilot study on the effect of linaclotide in patients with chronic constipation. (2009)
• Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. (2007)
• Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. (2007)
• Linaclotide (2006)

Regulatory status as of this version

• European Union — EMA: approved — Constella (linaclotide) is centrally authorized for the symptomatic treatment of moderate to severe irritable bowel syndrome with constipation (IBS-C) in adults.
• United States — FDA: approved — LINZESS (linaclotide) is indicated for the treatment of: 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 6 years of age and older. Contraindicated in patients less than 2 years of age (boxed warning: risk of serious dehydration).