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

Impact of Comorbid Conditions on Linaclotide Treatment Outcomes in Adults With CIC or IBS-C and Pediatric Patients With FC: A Post Hoc Analysis of Phase 3 Clinical Trial Data (ACG 2026) - P3, P3b | "In adult (n=5193) and pediatric (6â17 years; n=328) pts, 56.0% and 13.7% had â¥1 comorbidity, respectively: those with (vs without) comorbidities were slightly older and more often female; other BL characteristics were comparable ( Table ). Treatment with LIN (vs PBO) improved SBM/week and CSBM/week across all comorbidity subgroups . In adults, i mprovements were seen in stool consistency, abdominal pain and bloating, regardless of BL comorbidity status ( Figure )."

Clinical • P3 data • Retrospective data • CNS Disorders • Constipation • Depression • Discoid Lupus Erythematosus • Dyspepsia • Endometriosis • Fibromyalgia • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Gynecology • Immunology • Inflammatory Arthritis • Lupus • Migraine • Mood Disorders • Musculoskeletal Pain • Myositis • Pediatrics • Rheumatoid Arthritis • Systemic Lupus Erythematosus • Women's Health

Efficacy, Safety, and Tolerability of Bowel Preparation Regimens in Elderly Adults: A Systematic Review and Network Meta-Analysis (ACG 2026) - "Eighteen RCTs (13 regimens) were included from 6,028 records. The only significant comparison, 1L PEG-Asc + linaclotide versus 2L PEG-Asc (OR 3.82, 95% CI 1.22-11.93), was an indirect estimate whose linaclotide node rests on a single low-certainty trial. I²=0% with no inconsistency detected, though sparse data limit power to detect either."

Retrospective data • Review

First Reported Case of MRI Performed on a Patient With Multiple Vibrant Vibrating Capsules In Situ (ACG 2026) - "She experienced ineffective responses or side-effects to multiple pharmacologic therapies including polyethylene glycol, senna, bisacodyl (oral and rectal), glycerin suppositories, magnesium salts, linaclotide, plecanatide, lubiprostone, prucalopride, and tenapanor. This report also highlights the need for improved screening for ingestible electronic devices prior to MRI. Figure: X-ray Showing 5 Vibrant Vibrating Capsules In Situ 1 Day After MRI"

Clinical • Constipation • Endocrine Disorders • Fibromyalgia • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics

Multidimensional Symptom Improvement in Adults With Severe Irritable Bowel Syndrome With Constipation (IBS-C) Treated With Linaclotide: A Post Hoc Analysis of Phase 3 Trials (ACG 2026) - P3, P3b | "A total of 1651 patients met criteria for severe IBS-C at BL. Demographics and BL symptoms were similar between LIN (n=838) and PBO (n=813) groups ( Table ). LIN vs PBO, respectively, had greater least-squares mean (standard error) improvements from BL in CSBMs/week 2.3 (0.09) vs 0.73 (0.09) and SBMs/week 3.9 (0.12) vs 1.3 (0.12) over 12 weeks ( P < 0.0001)."

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

A Rare Cause of Sigmoid Volvulus: Giant Fecaloma from Buprenorphine-Induced Constipation (ACG 2026) - "He was started on linaclotide as an inpatient but left against medical advice prior to colonoscopy...Figure: Axial CT of the abdomen and pelvis demonstrating the mesenteric whirl sign (arrow) with adjacent swirling of mesenteric vessels and fat, consistent with sigmoid volvulus in the setting of a giant fecaloma. Figure: Sagittal CT of the abdomen and pelvis demonstrating a giant fecaloma occupying the rectum and sigmoid colon with significant colonic distension, illustrating the extensive fecal burden that served as the nidus for sigmoid volvulus."

CNS Disorders • Constipation • Epilepsy • Gastroenterology • Gastrointestinal Disorder • Immunology • Substance Abuse

Linaclotide Plus Extended Clear Liquid Diet Achieves 100% Gastric Visualization During Upper Endoscopy in GLP-1 Receptor Agonist Users: A Case Series (ACG 2026) - "Figure: Table 1. Patient demographics and procedure characteristics."

Clinical

Comparative Real-World Safety of Linaclotide, Plecanatide, and Lubiprostone: Risks of AKI and Hemodynamic Events (ACG 2026) - "After matching, 40,131 linaclotide-plecanatide and 115,091 linaclotide-lubiprostone pairs were identified. Compared with plecanatide, linaclotide users had higher 30-day risks of AKI (0.47% vs 0.24%; RR 1.95, 95% CI 1.53-2.49, p< 0.0001), volume depletion (0.53% vs 0.40%; RR 1.32, 95% CI 1.07-1.61, p=0.008), hypotension (0.70% vs 0.59%; RR 1.20, 95% CI 1.01-1.42, p=0.04), and diarrhea (1.32% vs 1.04%; RR 1.27, 95% CI 1.11-1.44, p=0.0003). When compared with lubiprostone, linaclotide users experienced lower risks of AKI (0.59% vs 0.74%; RR 0.80, 95% CI 0.73-0.89, p< 0.0001), volume depletion (0.61% vs 0.76%; RR 0.81, 95% CI 0.73-0.89, p< 0.0001), and hypotension (0.83% vs 0.95%; RR 0.88, 95% CI 0.80-0.95, p=0.002), with similar rates of diarrhea (1.30% vs 1.30%; RR 1.00, 95% CI 0.93-1.07, p=0.94)."

Clinical • Real-world • Real-world evidence • Acute Kidney Injury • Chronic Kidney Disease • Constipation • Gastroenterology • Gastrointestinal Disorder • Hepatology • Hypotension • Nephrology • Renal Disease

Clinical Characteristics Associated With Achieving â¥3 CSBMs/Week During Linaclotide Treatment in Adults With Chronic Idiopathic Constipation (ACG 2026) - P3, P3b | "In the primary analysis, higher BL weekly CSBM rate showed the strongest association with achieving â¥3 CSBMs/week. Age and higher BMI demonstrated small positive associations with response, whereas other selected variables including antidepressant use GI history, treatment dose, BL pain, BL BSFS, and ethnicity were not significantly associated with response ( Table 2 ). In the female population, similar variables and associations were identified except use of antidepressants."

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

Adjunctive Use of Vibrating Capsule for Refractory Constipation in Autosomal Dominant Polycystic Kidney Disease With Severe Organomegaly (ACG 2026) - "He had failed or inadequately responded to lactulose, polyethylene glycol, magnesium citrate, bisacodyl, senna, mineral oil, enemas, suppositories, lubiprostone, prucalopride, fiber, linaclotide alone, plecanatide alone, and pelvic floor physical therapy. Figure: Figure 1b. Sagittal T2-weighted MRI demonstrates renomegaly along with stool-filled colon."

Autism Spectrum Disorder • Autosomal Dominant Polycystic Kidney Disease • Chronic Kidney Disease • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Muscular Dystrophy • Myotonic Dystrophy • Nephrology • Pancreatic Cancer • Polycystic Kidney Disease • Renal Disease

Efficacy and Safety of Linaclotide Versus Placebo in Irritable Bowel Syndrome With Constipation: A Systematic Review and Meta-Analysis (ACG 2026) - "Seven randomized, double-blind, placebo-controlled trials comprising 4,513 participants were included. Linaclotide significantly improved FDA composite responder rates compared with placebo (RR 1.78, 95% CI 1.41â2.23; I² = 38%; NNT 7). Significant improvements were also observed for abdominal pain responders (RR 1.41, 95% CI 1.22â1.63; NNT 7) and CSBM responders (RR 3.01, 95% CI 2.44â3.72; NNT 7)."

Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder

Staying Ahead of Distal Intestinal Obstructive Syndrome in Cystic Fibrosis (ACG 2026) - "Home bowel regimen included polyethylene glycol 3350 (PEG) 34 g BID, linaclotide 290 g daily and PEG-electrolyte solution (PEG-ELS) weekly...Given her refractory obstruction, prucalopride and metoclopramide were trialed...Presence of thickened distal/terminal ileum. Large stool burden."

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

When Colitis Looks Like Cancer: Constipation-Predominant Ulcerative Colitis Mimicking Large Bowel Obstruction and Colorectal Malignancy (ACG 2026) - "Case Description/ A 70-year-old woman with UC on infliximab presented with two months of progressive constipation, hematochezia, abdominal pain, nausea, and vomiting refractory to six outpatient therapies including polyethylene glycol, linaclotide, tenapanor, laxatives, and enemas. Figure: CT abdomen/pelvis demonstrating left-sided colonic narrowing with proximal colonic dilation and fecal loading. Figure: Abdominal radiograph demonstrating persistent large colonic stool burden."

Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Mucositis • Oncology • Ulcerative Colitis

Early Physiologic Motility Testing Versus Empiric Medical Management in IBS-C: A Propensity-Matched Real-World Analysis (ACG 2026) - "Cohort 2 received empiric management (lubiprostone, linaclotide, plecanatide, tegaserod, lactulose, or PEG 3350) without motility testing. Cohorts were well-balanced post-matching (83.5% female each). Functional symptom persistence was similar (74.9% vs. 77.3%; RR 0.97, 95% CI 0.90â1.05; p=0.42; HR 0.88, 95% CI 0.76â1.03; log-rank p=0.12)."

Clinical • Real-world • Real-world evidence • CNS Disorders • Colorectal Cancer • Diabetes • Gastrointestinal Disorder • Metabolic Disorders • Mood Disorders • Type 2 Diabetes Mellitus

Pharmacotherapy of Irritable Bowel Syndrome with Constipation in Children: An Update on Clinical Progress and Successes. (PubMed, Drugs) - "Particular attention is given to newer agents approved for adults with irritable bowel syndrome with constipation, including secretagogues (linaclotide, plecanatide, and lubiprostone) and the retainagogue tenapanor, with a detailed discussion of their pharmacological properties and clinical trial data. While other novel agents have shown promise in adults, pediatric data remain limited or unavailable. Overall, although pharmacological treatment options for pediatric irritable bowel syndrome with constipation are expanding, high-quality, pediatric specific clinical trials are still needed to guide safe and effective management."

Journal • Review • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pediatrics

Trends in linaclotide use in patients age 6-25 with cystic fibrosis and constipation: Data analysis from a multicenter database (NACFC 2026) - "Linaclotide use in pwCF aged 6–25 years has increased more than 20-fold over the past decade, with the most notable rise occurring in the post-CFTR modulator era. In our cohort, use was more prevalent among young adults, likely reflecting more severe cystic fibrosis phenotypes as suggested by PERT use. These findings suggest that providers are more frequently prescribing linaclotide and reinforce prior evidence that constipation remains a burden in the post-modulator era."

Clinical • Constipation • Cystic Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Gynecology • Immunology • Musculoskeletal Pain • Respiratory Diseases • CFTR

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. (PubMed, Neurogastroenterol Motil) - "In this exploratory post hoc analysis, linaclotide was associated with improvements in bowel and abdominal symptoms across age and age-defined menopausal subgroups, with a safety profile consistent with previous studies, suggesting that age and menopausal status did not meaningfully influence treatment outcomes."

Journal • P2/3 data • P2b data • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder

Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation: A Meta-analysis of Randomized Controlled Trials. (PubMed, Ann Pharmacother) - "Linaclotide improves stool consistency and reduces straining in pediatric FC but does not consistently improve bowel frequency or global symptom resolution. Its safety profile is generally acceptable, although diarrhea is a notable adverse effect. Further long-term, independently funded trials are needed to define its optimal role in clinical practice."

Journal • Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Pediatrics

Patients' Real-World Experiences With Pharmacologic Therapies for Irritable Bowel Syndrome With Constipation: A Mixed-Methods Analysis and Classification of Social Media and E-Forum Posts. (PubMed, Neurogastroenterol Motil) - "Social media provides unique insights into IBS-C patients' real-world experiences with FDA-approved therapies. Findings highlight variability in efficacy, biopsychosocial impacts, and adherence challenges, underscoring the need for shared decision making and proactive management of barriers to optimize outcomes."

Journal • Real-world evidence • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Mood Disorders • Psychiatry

Resolving conformational polymorphism in disulfide-rich peptide drugs. (PubMed, Front Chem) - "Here, cyclic ion mobility-mass spectrometry (cIM-MS), combined with accelerated thermal stress testing, was applied to a manufacturing batch of ziconotide and linaclotide under native and thermally stressed conditions. The high-resolution separation achieved by cIM-MS enabled detailed mapping of coexisting conformers and their stress-induced transitions. These results demonstrate that cIM-MS provides a spatially resolved analytical platform for interrogating higher-order structural heterogeneity in disulfide-rich peptide therapeutics, extending the capabilities of conventional mass spectrometry and offering a generalizable approach for structural characterization and quality assessment."

Journal

Efficacy of linaclotide as adjunct for bowel preparation in patients with chronic constipation: a pre-specified analysis of the APPLE trial. (PubMed, Clin Endosc) - No abstract available

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

EFFICACY OF LINACLOTIDE AS ADJUNCT FOR BOWEL PREPARATION IN PATIENTS WITH CHRONIC CONSTIPATION: A PRE-SPECIFIED ANALYSIS OF THE APPLE TRIAL (UEGW 2026) - No abstract available

Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

LINACLOTIDE IMPROVES TOLERABILITY AND ACCEPTANCE OF POLYETHYLENE GLYCOL BOWEL PREPARATION BEFORE COLONOSCOPY: A SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2026) - No abstract available

Retrospective data • Review

MRI Parameters as Biomarkers in Cystic Fibrosis (FEMPTO) (clinicaltrials.gov) - P=N/A | N=12 | Not yet recruiting | Sponsor: University of Nottingham

Biomarker • New trial • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

CTV678-H003: Surgical Procedure Efficiency Evaluation stuDy (clinicaltrials.gov) - P=N/A | N=180 | Recruiting | Sponsor: Alcon Research | Trial completion date: Aug 2026 ➔ Mar 2027 | Trial primary completion date: Aug 2026 ➔ Mar 2027

Real-world evidence • Trial completion date • Trial primary completion date • Cataract • Hematological Disorders • Ophthalmology • Retinal Disorders

Rapid and comprehensive identification of the metabolic soft spots of peptide drugs with highly cross-linked disulfide bonds by integrating established proteomic workflow with a product ion filtering strategy. (PubMed, Drug Metab Dispos) - "Linaclotide, insulin glargine, and insulin degludec were selected as representative peptide drugs. Reduction and alkylation eliminate analytical complexity from cross-linked disulfide architectures, enabling comprehensive peptide metabolite characterization. This study provides a transferable, integrated analytical strategy for the comprehensive identification of metabolic soft spots and metabolites in other peptides with highly cross-linked disulfide bonds."

Journal