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

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

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

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

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. (PubMed, BMJ Open) - P4 | "Study findings will be published in peer-reviewed journals. ChiCTR2500096394."

Clinical • Clinical protocol • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Partially differentiated ileal and distal-colonic human F508del-cystic fibrosis-enteroids secrete fluid in response to forskolin and linaclotide. (PubMed, iScience) - "Also, linaclotide and a general phosphodiesterase (PDE) inhibitor independently enhanced the combined CFTR-modulator-induced FIS response from partially differentiated F508del-CF enteroids. These findings demonstrate that partially differentiated ileal and distal colonic F508del-CFTR enteroids can be stimulated to secrete fluid by cAMP and cGMP."

Journal • Constipation • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

EVALUATING THE SAFETY OF PHARMACOTHERAPY FOR IRRITABLE BOWEL SYNDROME: A META-ANALYSIS (DDW 2025) - "AEs were more varied for tricyclics (indicated for IBS global symptoms); for example, compared to placebo the three most common AEs with associated risk increases were drowsiness (14%), dry mouth (12%), and weight gain (9%) for amitriptyline, dry mouth (22%), flushing (18%), and constipation (17%) for desipramine, and fatigue (15%), dry mouth (3%) and blurry vision (1.5%) for doxepin...The NNH for linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor (indicated for IBS-C) was 27 (p < 0.01), 53 (p = 0.59), 58 (p < 0.01), 59 (p = 0.03), and 17 (p <0.01) respectively. The NNH for alosetron and eluxadoline (indicated for IBS-D) was 16 (p < 0.01) and 32 (p < 0.01). Ramosetron and rifaximin (indicated for IBS-D) had a negative risk difference, with the rate of withdrawal due to AEs higher in the placebo arm, so NNH was a negative, although statistically insignificant, value... Tricyclics, alosetron, and tenapanor are associated with a higher..."

Retrospective data • Constipation • Fatigue • Gastrointestinal Disorder • Xerostomia

IBS-C PATIENT EXPERIENCES WITH PHARMACOLOGIC THERAPIES: QUALITATIVE ANALYSIS OF ONLINE POSTS FROM (TWITTER) AND E-HEALTH FORUMS (DDW 2025) - "To find relevant posts from IBS-specific subforums, we applied filters targeting FDA-approved IBS-C medications (linaclotide, lubiprostone, plecanatide, tegaserod, tenapanor). Discussions : Our study highlights the diverse real-world experiences of IBS-C patients with FDA-approved therapies, revealing variability in both efficacy and the biopsychosocial impacts associated with each medication. These findings highlight the importance of shared decision making in selecting an IBS-C treatment, including evaluating the need to switch medications or classes, as well as addressing barriers such as cost and side effects to improve adherence and patient outcomes."

Clinical • CNS Disorders • Constipation • Gastrointestinal Disorder • Mood Disorders • Psychiatry

Linaclotide As a SingleAgent Bowel Preparation Regimen Before Colonoscopy. (ASCRS 2025) - "C: Transverse Colon. D: Descending Colon."

Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Obesity • Pain

GCC Agonist Signal in the Small Intestine (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: University of Wisconsin, Madison | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2025 ➔ Oct 2025 | Trial primary completion date: Jun 2025 ➔ Oct 2025

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

ADDING LINACLOTIDE TO 1-L PEG-ASC REGIMEN: EFFICACY ACROSS AGE GROUPS IN A SUBGROUP ANALYSIS OF THE APPLE TRIAL (DDW 2025) - No abstract available

Clinical

LINACLOTIDE COMBINED WITH POLYETHYLENE GLYCOL FOR BOWEL PREPARATION IN OUTPATIENT COLONOSCOPY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (DDW 2025) - "PEG combined with linaclotide improved bowel preparation quality, reduced the risk of common AEs, and increased the willingness to repeat the preparation compared to standard bowel preparation. Noteworthy, reduced-volume PEG combined with linaclotide minimized AEs and improved patient acceptance, while conventional-volume PEG combined with linaclotide provided superior preparation quality and improved key colonoscopy outcomes, including PDR and ADR."

Retrospective data • Review • Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Oncology • Solid Tumor

COMPARATIVE EFFICACY AND SAFETY OF LINACLOTIDE AND POLYETHYLENE GLYCOL COMBINATIONS FOR COLONOSCOPY BOWEL PREPARATION: A NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. (DDW 2025) - "Conclusion Combining PEG with Lin improves bowel cleanliness compared to 3L-PEG, with 2L PEG + 2Lin being the most effective and maintaining a favorable safety profile. Despite heterogeneity in Efficacy outcomes, the findings suggest linaclotide enhances bowel preparation, warranting consideration of individual patient factors."

Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain

Pharmacologic treatment of irritable bowel syndrome. Position statement of the Asociación Mexicana de Gastroenterología, 2024. (PubMed, Rev Gastroenterol Mex (Engl Ed)) - "Overall, these recommendations provide a solid framework for personalizing treatment, based on the clinical characteristics of the Mexican patient with IBS."

Clinical guideline • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain