Linzess (linaclotide) / AstraZeneca, Astellas, Ironwood Pharma, AbbVie - LARVOL DELTA

Current Treatment Options for Children with Functional Constipation-What Is in the Pipeline? (PubMed, Children (Basel)) - "New agents such as lubiprostone, prucalopride, linaclotide, and plecanatide have demonstrated improved outcomes compared to placebo or conventional therapies, particularly in increasing spontaneous bowel movements. Therapy-resistant FC in children is a complex and impactful condition. An individualized, stepwise approach is essential, with surgical options such as colonic resection reserved as a last resort."

Journal • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Seoul Consensus on Clinical Practice Guidelines for Functional Constipation (PubMed, Korean J Gastroenterol) - "The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding management. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding managing functional constipation."

Clinical guideline • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Linaclotide for Colonoscopy Bowel Prep (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: University of Florida | Initiation date: Jun 2025 ➔ Sep 2025

Trial initiation date

EFFICACY OF POLYETHYLENE GLYCOL (PEG) IN COMBINATION WITH LINACLOTIDE FOR BOWEL PREPARATION: A SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2025) - No abstract available

Combination therapy • Retrospective data • Review

UNITY VCS Vitreoretinal Surgery: Randomized Comparative Clinical Trial (clinicaltrials.gov) - P=N/A | N=260 | Not yet recruiting | Sponsor: Alcon Research

New trial • Cataract • Diabetic Retinopathy • Hematological Disorders • Retinal Disorders

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 Linaclotide (clinicaltrials.gov) - P2 | N=19 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Long-term Safety of Linaclotide in Pediatric Participants With FC or IBS-C (clinicaltrials.gov) - P3 | N=389 | Completed | Sponsor: AbbVie | Active, not recruiting ➔ Completed

Trial completion • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

Evaluation of the combined use of linaclotide and probiotics on clinical treatment efficacy and quality of life in patients with constipation-predominant irritable bowel syndrome. (PubMed, Am J Transl Res) - "The combined use of linaclotide and Bifid Triple Viable Capsules significantly enhances bowel movement frequency, reduces constipation severity, and improves QoL and psychological well-being in IBS-C patients. This approach offers a promising strategy for the comprehensive management of IBS-C."

HEOR • Journal • CNS Disorders • Constipation • Depression • Gastroenterology • Gastrointestinal Disorder • Mood Disorders • Psychiatry

Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials. (PubMed, Int J Colorectal Dis) - "Combining PEG with Lin improves bowel cleanliness compared to 3L-PEG, with 2L PEG + 2Lin being the most effective and well-tolerated. Despite some heterogeneity, the findings suggest that adding Lin may enhance bowel preparation with comparable safety, warranting consideration of individual patient factors."

Clinical • Journal • Retrospective data • Review • Colorectal Cancer • Oncology • Pain • Solid Tumor

PROVISIONAL EXPERT RECOMMENDATIONS FOR THE MANAGEMENT OF FECAL INCONTINENCE IN SYSTEMIC SCLEROSIS: A REPORT FROM WORLD SCLERODERMA FOUNDATION (WSF) GASTROINTESTINAL "AD HOC COMMITTEE" (EULAR 2025) - "(100%) Consider and prioritize pelvic physical therapy upfront for SSc-FI attributable to pelvic floor weakness before testing, as patients often improve and risk is minimal (if any) (100%) If overflow diarrhea is the issue and slow colonic transit is present, consider a trial of prokinetics (e.g., prucalopride or pyridostigmine). (83.3%) If slow colonic transit is not an issue, consider a trial of other medications (e.g., secretagogues, such as linaclotide, lubiprostone, plecanatide) to help alleviate stool burden... We present provisional recommendations for the evaluation and management of fecal incontinence in SSc. Only minimal refinement and voting is required to finalize these practical recommendations. Our collegiate approach will provide guidance for clinical practice and also inform a future research agenda."

Gastroenterology • Immunology • Rheumatology • Scleroderma • Systemic Sclerosis

Constipation-predominant irritable bowel syndrome treatment options Linaclotide, Lubiprostone, plecanatide, and Tenapanor: analysis of the FDA adverse event reporting system (FAERS) database. (PubMed, Expert Opin Drug Saf) - "This post-marketing analysis of the FAERS database revealed diarrhea, abdominal pain, bloating, and nausea/vomiting were the most frequently reported AEs across all medications. Novel findings include the potential for clinically significant dehydration from Linaclotide-induced diarrhea and Lubiprostone-associated dyspnea and chest pain."

Adverse events • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pulmonary Disease

Linaclotide for Colonoscopy Bowel Prep (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: University of Florida | Initiation date: Mar 2025 ➔ Jun 2025 | Trial primary completion date: Aug 2025 ➔ Nov 2025

Trial initiation date • Trial primary completion date

Real-world study on the safety and efficacy of Linaclotide combined with Ultra-low-volume Polyethylene Glycol for bowel preparation in Low-Risk Patients (ChiCTR) - P4 | N=8364 | Not yet recruiting | Sponsor: The Third People's Hospital of Chengdu; The Third People's Hospital of Chengdu

New P4 trial • Real-world evidence

The Safety of Pharmacotherapy for Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. (PubMed, Am J Gastroenterol) - "Among pharmacotherapies for IBS, tricyclics (especially at elevated doses), tenapanor, and alosetron have the highest absolute risk of discontinuation due to an AE when compared to rifaximin, the safest pharmacotherapy studied."

Journal • Retrospective data • Gastrointestinal Disorder

Unlocking the Enigmas of Plasmodium Aspartyl Protease in Antimalarial Therapy: Flap Region Dynamics and Enzyme Repression of Non-Food Vacuole Using Molecular Dynamics Simulations. (PubMed, Curr Pharm Des) - "Finally, we developed a pharmacophore model based on UCB7362 to offer recommendations for rational drug design of optimized antimalarial drug candidates."

Journal • Infectious Disease • Malaria

Effect of 3-day linaclotide administration to reduce the PEG volume for colonoscopy bowel preparation: A multicenter, noninferiority, randomized controlled trial. (PubMed, Am J Gastroenterol) - "The adequate bowel preparation rate of the combination of 3-day linaclotide and 2 L PEG was neither inferior to the combination of 3-day linaclotide and 3 L PEG nor 3 L PEG alone in the average-risk population."

Head-to-Head • Journal

Effect to Linaclotide on Colonic Motility (clinicaltrials.gov) - P4 | N=10 | Completed | Sponsor: Universitaire Ziekenhuizen KU Leuven

New P4 trial • Constipation • Gastroenterology • Gastrointestinal Disorder

EFFICACY OF LINACLOTIDE AS A BOWEL CLEANSING AGENT IN PATIENTS WITH CHRONIC CONSTIPATION: A SEVERITY-BASED ANALYSIS OF THE APPLE TRIAL (DDW 2025) - No abstract available

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

LONG-TERM SAFETY OF LINACLOTIDE IN TREATING PEDIATRIC PATIENTS AGED 7–17 YEARS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C): INTERIM RESULTS FROM A PHASE 3 STUDY (DDW 2025) - P2, P3 | "Conclusions In pediatric patients aged 7–17 years with IBS-C, linaclotide was well tolerated, with findings consistent with the known safety profile. The incidence of diarrhea was low (6.1%) and was less than the reported rates from adult IBS-C clinical studies with linaclotide."

Clinical • P3 data • P3 data: top line • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

EFFICACY AND SAFETY OF LINACLOTIDE IN TREATING PEDIATRIC PATIENTS AGED 7–17 YEARS WITH IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C): RESULTS FROM A PHASE 3 STUDY (DDW 2025) - P3 | No abstract available

Clinical • P3 data • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

THE CLINICAL EFFICACY OF LINACLOTIDE AND PLECANATIDE IN IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (IBS-C) AND CHRONIC IDIOPATHIC CONSTIPATION (CIC): A POTENTIAL BENEFIT TO SWITCHING GUANYLATE CYCLASE C (GCC) AGONISTS? (DDW 2025) - "GCC agonist switch strategies in the setting of patients' non-response or intolerance to initial regimens may yield improvements in global CIC/IBS-C symptoms. This observation does not appear to be associated with DGBI diagnosis or baseline symptom severity. Further prospective study in larger, more diverse populations is needed to better understand the potential benefits of GCC switch approaches to bowel disorders."

Clinical • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Mood Disorders • Pain • Psychiatry

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 Linaclotide (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting | N=30 ➔ 19

Adverse events • Enrollment change • Enrollment closed • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

ANALYSES OF THE SOCIOECONOMIC VALUES OF TREATMENTS FOR CHRONIC CONSTIPATION IN JAPAN (DDW 2025) - "Methods Using data from clinical trials of Lubiprostone, Linaclotide, and Elobixibat conducted in Japan, changes in the number of spontaneous bowel movements (SBM) were synthesized using network meta-analysis (NMA), with placebo results set at zero for comparison. Sensitivity Analysis: The results were sensitive to the effectiveness of Elobixibat, but the trend remained consistent with the base case analysis for the other costs. Conclusions When selecting constipation treatment drugs, it is essential to consider not only their efficacy and cost but also their potential to reduce the socioeconomic burden associated with chronic constipation."

Constipation • Gastroenterology • Gastrointestinal Disorder

Brain-derived uroguanylin as a regulator of postprandial brown adipose tissue activation: a potential therapeutic approach for metabolic disorders. (PubMed, Front Pharmacol) - "In mice, centrally applied UGN and its analog linaclotide, affecting the hypothalamus, induced both acute and chronic activation of BAT, which decreases the plasma glucose concentration. Similarly, centrally applied analog of glucagon-like peptide 1 (GLP-1-liraglutide) affected proUGN expression and was associated with increased basal BAT activity but reduced BAT activation after a meal in patients with T2D receiving GLP-1 therapy. Postprandial BAT activation is regulated by brain-derived UGN, which could serve as a novel therapeutic approach to enhance BAT activity in patients with obesity and T2D to improve postprandial glucose regulation."

Journal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

GCC Agonist Signal in the Small Intestine (clinicaltrials.gov) - P1 | N=43 | Recruiting | Sponsor: University of Wisconsin, Madison | Trial completion date: Feb 2025 ➔ Jun 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2025

Trial completion date • Trial primary completion date • Barrett Esophagus • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology