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

Efficacy, adverse events, pediatric applicability, and approved indications require primary and official sources rather than a pooled screening list.

Citations as of this version

• Linaclotide for Bowel Preparation: Is "Afterload Reduction" Not Just for Heart Failure Anymore?
• Application of oral sulfate solution combined with linaclotide in bowel preparation for colonoscopy.
• Efficacy of Polyethylene Glycol Electrolyte Powder Combined with Linaclotide for Bowel Preparation for Colonoscopy in Children with Functional Constipation.
• Efficacy and safety of linaclotide plus polyethylene glycol for bowel preparation before colonoscopy in elderly Chinese patients: a systematic review and meta-analysis.
• Efficacy and safety of Guanylyl cyclase C agonists (linaclotide and plecanatide) in patients with irritable bowel syndrome with constipation: a systematic review and meta-analysis of randomized controlled trials.
• Efficacy of linaclotide as adjunct for bowel preparation in patients with chronic constipation: a pre-specified analysis of the APPLE trial.
• Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy
• Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, Plecanatide, and Tenapanor: analysis of the FDA Adverse Event Reporting System (FAERS) database.
• A pharmacovigilance study of the association between linaclotide/plecanatide and muscle spasms based on food and drug administration adverse event reporting system.
• Partially differentiated enterocytes in ileal and distal-colonic human F508del-CF-enteroids secrete fluid in response to forskolin and linaclotide
• Effect of 3-Day Linaclotide Administration to Reduce the Polyethylene Glycol Volume for Colonoscopy Bowel Preparation: A Multicenter, Noninferiority, Randomized Controlled Trial. (2026)
• Short-term linaclotide plus polyethylene glycol in patients at increased risk of inadequate bowel preparation: A randomized, double-blind, multicenter trial. (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)
• Efficacy safety of linaclotide combined with polyethylene glycol for bowel preparation in patients with constipation: a meta-analysis. (2026)
• A post hoc analysis of linaclotide in pediatric patients with functional constipation and neurodevelopmental disorders. (2026)
• Evaluating linaclotide for the treatment of functional constipation in children and adolescents. (2026)
• Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation: A Meta-analysis of Randomized Controlled Trials. (2026)
• Identification and Quantification of Structurally Related Peptide Impurity in Linaclotide by Liquid Chromatography-High Resolution Mass Spectrometry. (2026)
• Linaclotide for irritable bowel syndrome with constipation: integrating realworld evidence into the therapeutic puzzle. (2026)
• Adjunctive linaclotide improves bowel cleansing and patient experience in polyethylene glycol-based bowel preparation. (2026)
• The Efficacy of Single Dose Linaclotide in Polyethylene Glycol-Based Bowel Preparation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (2026)
• Effect of linaclotide combined with polyethylene glycol on bowel preparation before colonoscopy in patients with constipation. (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)
• Linaclotide combined with polyethylene glycol for bowel preparation in colonoscopy: a systematic review and meta-analysis of randomized controlled trials. (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)
• 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)
• Cost-Effectiveness of Vibrant System vs. Linaclotide in Chronic Idiopathic Constipation. (2025)
• Safety and efficacy of linaclotide as an adjuvant for bowel preparation: A systematic review and meta-analysis. (2025)
• Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials. (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 and Safety of Linaclotide as an Adjunct to Polyethylene Glycol in Bowel Preparation: A Meta-Analysis. (2025)
• Linaclotide Use for the Treatment of Constipation and Gastrointestinal Symptoms in People With Cystic Fibrosis. (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 Linaclotide in Functional Dyspepsia and Constipation-Predominant Irritable Bowel Syndrome Overlap: A Randomized Trial. (2025)
• Linaclotide for paediatric functional 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)
• Safety and efficacy of linaclotide in children aged 2-5 years with functional constipation: Phase 2, randomized study. (2024)
• DRA involvement in linaclotide-stimulated bicarbonate secretion during loss of CFTR function. (2024)
• Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients. (2024)
• Renoprotective effects of laxative linaclotide: Inhibition of acute kidney injury and fibrosis in a rat model of renal ischemia-reperfusion. (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)
• Linaclotide (2024)
• Examining linaclotide for the treatment of chronic idiopathic constipation. (2024)
• Efficacy and safety of linaclotide in treating functional constipation in paediatric patients: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. (2024)
• Application of linaclotide in bowel preparation for colonoscopy in patients with constipation: A prospective randomized controlled study. (2024)
• Efficacy of linaclotide in combination with polyethylene glycol for bowel preparation in Chinese patients undergoing colonoscopy polypectomy: protocol for a randomised controlled trial. (2024)
• Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study. (2024)
• Linaclotide for functional constipation in paediatric patients: phase III results. (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)
• Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation. (2024)
• Ten years of successful linaclotide treatment in a patient with intestinal pseudo-obstruction due to Ehlers-Danlos syndrome. (2024)
• The Effects of Combined Use of Linaclotide and Polyethylene Glycol Electrolyte Powder in Colonoscopy Preparation for Patients With Chronic Constipation. (2024)
• Randomized controlled trial of linaclotide in children aged 6-17 years with functional 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)
• Editorial: repurposed linaclotide and the quest for abdominal pain management in irritable bowel syndrome. (2023)
• A New Regioselective Synthesis of the Cysteine-Rich Peptide Linaclotide. (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)
• Linaclotide Reduced Response Time for Irritable Bowel Syndrome With Constipation Symptoms: Analysis of 4 Randomized Controlled Trials. (2023)
• Cost impact of incorporating linaclotide into low-volume colonoscopy preparation. (2023)
• Microbiota-derived butyrate dampens linaclotide stimulation of the guanylate cyclase C pathway in patient-derived colonoids. (2023)
• Linaclotide for treating patients with irritable bowel syndrome with predominant constipation: a multicentre study of real-world data in China. (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)
• 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)
• Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis. (2022)
• Efficacy of Linaclotide in Reducing Abdominal Symptoms of Bloating, Discomfort, and Pain: A Phase 3B Trial Using a Novel Abdominal Scoring System. (2021)
• Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial. (2021)
• [Efficacy and Safety of Linaclotide in Elderly Patients]. (2021)
• Linaclotide for the treatment of refractory lower bowel manifestations of systemic sclerosis. (2021)
• The Use of Linaclotide in Children with Functional Constipation or Irritable Bowel Syndrome: A Retrospective Chart Review. (2021)
• Randomized Trial of 2 Delayed-Release Formulations of Linaclotide in Patients With Irritable Bowel Syndrome With Constipation. (2021)
• Improving the Gastrointestinal Stability of Linaclotide. (2021)
• Tadalafil versus linaclotide in gastrointestinal dysfunction and depressive behavior in constipation-predominant irritable bowel syndrome. (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)
• The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. (2020)
• Linaclotide increases cecal pH, accelerates colonic transit, and increases colonic motility in irritable bowel syndrome with constipation. (2019)
• 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)
• Effectiveness and tolerability of linaclotide in the treatment of IBS-C in a "real-life" setting: Results from a Portuguese single-center study. (2019)
• Single-Dose Linaclotide Is Equal in Efficacy to Polyethylene Glycol for Bowel Preparation Prior to Capsule Endoscopy. (2019)
• Long-term treatment with linaclotide of intestinal pseudo-obstruction secondary to Ehlers-Danlos syndrome. (2019)
• [Pharmacological and clinical profile of linaclotide (Linzess^®), a novel therapeutic agent for irritable bowel syndrome with constipation and chronic constipation]. (2019)
• Linaclotide treatment reduces endometriosis-associated vaginal hyperalgesia and mechanical allodynia through viscerovisceral cross-talk. (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)
• Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysis. (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)
• 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 for the treatment of chronic constipation. (2018)
• Randomized, double-blind, placebo-controlled study vs data in the daily practice using linaclotide in patients with irritable bowel syndrome with constipation. (2018)
• 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 improves gastrointestinal transit in cystic fibrosis mice by inhibiting sodium/hydrogen exchanger 3. (2018)
• Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization. (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)
• Linaclotide inhibits colonic and urinary bladder hypersensitivity in adult female rats following unpredictable neonatal stress. (2018)
• Low-Dose Linaclotide (72 μg) for Chronic Idiopathic Constipation: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Trial. (2018)
• Health Care Resource Use and Costs Pre- and Post-Treatment Initiation With Linaclotide: Retrospective Analyses of a U.S. Insured Population. (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)
• Chronic linaclotide treatment reduces colitis-induced neuroplasticity and reverses persistent bladder dysfunction. (2018)
• Linaclotide in irritable bowel syndrome with constipation: A Phase 3 randomized trial in China and other regions. (2018)
• Efficacy of linaclotide in irritable bowel syndrome with constipation: Real-world data. (2018)
• 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)
• Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine. (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)
• Linaclotide in Chronic Idiopathic Constipation Patients with Moderate to Severe Abdominal Bloating: A Randomized, Controlled Trial. (2015)
• A comparison of linaclotide and lubiprostone dosing regimens on ion transport responses in human colonic mucosa. (2015)
• MRP4 Modulation of the Guanylate Cyclase-C/cGMP Pathway: Effects on Linaclotide-Induced Electrolyte Secretion and cGMP Efflux. (2015)
• Economic evaluation of linaclotide for the treatment of adult patients with irritable bowel syndrome with constipation in the United States. (2015)
• Linaclotide: a review of its use in the treatment of irritable bowel syndrome with constipation. (2014)
• Linaclotide. A bacterial enterotoxin derivative with a laxative action, nothing more. (2014)
• Linaclotide: a novel agent for chronic constipation and irritable bowel syndrome. (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)
• Clarification of linaclotide pharmacology presented in a recent clinical study of plecanatide. (2014)
• Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C. (2014)
• Review article: Linaclotide for the management of irritable bowel syndrome with constipation. (2014)
• Effect of linaclotide in irritable bowel syndrome with constipation (IBS-C): a systematic review and meta-analysis. (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)
• Effect of linaclotide on severe abdominal symptoms in patients with irritable bowel syndrome with constipation. (2014)
• [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)
• Linaclotide for constipation-predominant IBS. (2013)
• Linaclotide for treatment of irritable bowel syndrome--the view of European regulators. (2013)
• Challenges of managing pain in constipation-predominant IBS: clinical perspectives on antinociceptive actions of linaclotide. (2013)
• Linaclotide, novel therapy for the treatment of chronic idiopathic constipation and constipation-predominant irritable bowel syndrome. (2013)
• Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate. (2013)
• Linaclotide-a novel secretagogue in the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation. (2013)
• Linaclotide: a new option for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation in adults. (2013)
• Linaclotide in the treatment of patients with irritable bowel syndrome and constipation - analysis of an opportunity. (2013)
• Linaclotide: A new drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. (2013)
• Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis. (2013)
• Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints. (2013)
• A review of the clinical efficacy of linaclotide in irritable bowel syndrome with constipation. (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)
• 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)
• An evaluation of the FDA responder endpoint for IBS-C clinical trials: analysis of data from linaclotide Phase 3 clinical trials. (2013)
• Linaclotide: a novel compound for the treatment of irritable bowel syndrome with constipation. (2013)
• Linaclotide: first global approval. (2012)
• Linaclotide in the management of gastrointestinal tract disorders. (2012)
• Elvitegravir/cobicistat, mirabegron, and linaclotide. (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)
• 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 (2012)
• Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety. (2012)
• Linaclotide: promising IBS-C efficacy in an era of provisional study endpoints. (2012)
• 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)
• The pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of linaclotide. (2011)
• Two randomized trials of linaclotide for chronic constipation. (2011)
• Efficacy of linaclotide for patients with chronic constipation. (2010)
• Linaclotide is a potent and selective guanylate cyclase C agonist that elicits pharmacological effects locally in the gastrointestinal tract. (2010)
• Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. (2010)
• Linaclotide - a secretagogue and antihyperalgesic agent - what next? (2010)
• Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation. (2010)
• Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. (2010)
• Constipation: Linaclotide--a stimulating new drug for chronic constipation. (2010)
• Molecule of the month. Linaclotide acetate. (2010)
• Pilot study on the effect of linaclotide in patients with chronic constipation. (2009)
• Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. (2007)
• Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. (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).