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

The Efficacy of Single Dose Linaclotide in Polyethylene Glycol-Based Bowel Preparation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, J Clin Gastroenterol) - "Linaclotide used as a single dose adjunct to bowel prep before colonoscopy increased ADR and PDR. Adequate prep was higher with linaclotide in patients with diagnosed constipation. Linaclotide also decreased the odds of abdominal pain, bloating, and sleep disturbances."

Journal • Retrospective data • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Pain • Sleep Disorder

Socioeconomic value of treatments for chronic idiopathic constipation in Japan. (PubMed, BMC Gastroenterol) - "Considering CIC-related medical costs, QoL, productivity loss, and caregiver burden, elobixibat 10 mg is associated with better QoL and lower costs than linaclotide 0.5 mg and lubiprostone 48 μg."

Clinical • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Survey of Latin American gastroenterologists, specialists in disorders of gut-brain interaction, on the diagnosis and treatment of irritable bowel syndrome in clinical practice. (PubMed, Rev Gastroenterol Mex (Engl Ed)) - "Even though most of the specialists diagnose and treat IBS in accordance with guidelines, there are differences regarding local availability, and abdominopelvic CT appears to be overused. Knowing how general practitioners and internists manage this entity would be useful for establishing practical guidelines on the diagnosis and treatment of IBS that are adjusted by country."

Journal • CNS Disorders • Depression • Gastrointestinal Disorder • Psychiatry

Efficacy and safety of pharmacological therapies for functional constipation in children: a systematic review and meta-analysis. (PubMed, Lancet Child Adolesc Health) - "Polyethylene glycol is probably more effective than placebo and key comparator therapies and should be considered the standard of first-line care. Future studies should consider polyethylene glycol as an index therapy, and clearly describe methods, patient characteristics, and previous therapeutics."

Journal • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder

Linaclotide in Treating Patients With Stages 0-3 Colorectal Cancer (clinicaltrials.gov) - P2 | N=230 | Active, not recruiting | Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

Based on the FDA Adverse Event Reporting System Database, a Study on Signal Mining of Adverse Events for Guanylate Cyclase-C Receptor Agonists. (PubMed, Hosp Pharm) - "To analyze and evaluate adverse drug event (ADE) signals for two GC-C receptor agonists, Linaclotide and Plecanatide, thereby enhancing understanding of their clinical safety. Clinical utilization of GC-C receptor agonists should take into account not only the prevalent gastrointestinal ADEs but also emerging signals associated with the urinary system, metabolic and nutritional disorders, and the nervous system. A comprehensive understanding of these signals is essential for evaluating medication risks and ensuring appropriate drug administration."

Adverse events • Journal • CNS Disorders • Pain • Sleep Disorder

WHEN THE GUT STRUGGLES: ACUTE EXACERBATION OF CHRONIC INTESTINAL PSEUDO-OBSTRUCTION (CHEST 2025) - "He required an aggressive bowel regimen with miralax four times a day, senna and linaclotide to have regular bowel movements along with erythromycin and metoclopramide. Acute exacerbations of CIPO can be life-threatening and cause compromise to multiple organs. Optimal care depends on a multidisciplinary approach with critical care, gastroenterology and colorectal surgery."

Celiac Disease • Dermatomyositis • Genito-urinary Cancer • Immunology • Inflammatory Arthritis • Lung Cancer • Lupus • Myositis • Prostate Cancer • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Scleroderma • Small Cell Lung Cancer • Solid Tumor • Systemic Sclerosis • Thymoma • Thymus Cancer

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

Combination therapy • Retrospective data • Review

Sustained Efficacy and Tolerability of Vibrant Capsule Therapy in a 77-Year-Old Female With Chronic Constipation: A 24-Month Case Study (ACG 2025) - "Previous treatments included linaclotide, plecanatide, and magnesium-based products, which provided only partial relief and were associated with adverse effects including bloating and diarrhea. The patient reported sustained symptom relief, reduced treatment burden, and high satisfaction over 24 months of use. Vibrant may offer a well-tolerated, non-pharmacologic alternative in elderly patients with refractory constipation.Figure: Patient Assessment (Table 1)Figure: The Vibrant System (Fig 1)"

Case study • Clinical • Constipation • Gastroenterology • Gastrointestinal Disorder

Linaclotide's Time to Response for Chronic Idiopathic Constipation Symptom Relief: A Post Hoc Analysis of Randomized Controlled Studies (ACG 2025) - P3, P3b | "Overall, 2400 patients were included: LIN 72 µg, n = 411, mean age: 45.8 years, female: 75.9%; LIN 145 µg, n = 994, 47.5 years, 84.3%; PBO, n = 995, 46.7 years, 85.4%. Median (95% CI) time to achieving ≥ 3 CSBMs/week was 11 (8, 12) and 5 (4, 6) weeks for patients treated with LIN 72 µg and 145 µg, respectively (not reached [NR] for PBO; Figure). Median time to first SBM after initial dose of LIN (72 µg or 145 µg) was 2 days vs 3 days with PBO."

Clinical • Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder

Real-World Safety Analysis of the Constipation-Predominant Irritable Bowel Syndrome Treatment Options Linaclotide, Lubiprostone, Plecanatide, and Tenapanor (ACG 2025) - "Linaclotide was suspected of frequently inducing diarrhea (n=2,082, 24.1%), abdominal pain (n=815, 9.4%), abdominal bloating (n=795, 9.2%), and nausea/vomiting (n=266, 3.1%). Plecanatide was suspected of frequently inducing diarrhea (n=137, 20.4%), abdominal pain (n=76, 11.3%), abdominal bloating (n=62, 9.2%), and nausea/vomiting (n=34, 5.1%). Tenapanor was suspected of frequently inducing diarrhea (n=51, 32.9%), abdominal pain (n=13, 8.4%), and abdominal bloating and nausea/vomiting (n=11 each, 7.1%)."

Clinical • Real-world • Real-world evidence • Constipation • Gastroenterology • Gastrointestinal Disorder • Pulmonary Disease

Comparing Safety and Efficacy of Different Bowel Preparation Regimens in Constipated Patients Undergoing Colonoscopy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Fifteen RCTs were included in this network meta-analysis. Compared to 4L PEG (polyethylene glycol), 3L PEG + 3d-Lin (3 days-Linaclotide) (RR=1.29; 95%CI:[1.12,1.47], p=0.0002), 4L PEG + 1d-Lin (RR=1.25; 95%CI:[1.04,1.51], p=0.02), NaP (sodium phosphate) + bisacodyl (RR=1.52; 95%CI:[1.09,2.10], p=0.01) and Probiotic 14d + NaP (RR= 3.59; 95%CI:[1.83,7.04], p=0.0002) arms significantly increased the adequate bowel preparation with Probiotic 14d + NaP group ranked highest and Senna + MgSO4 (Magnesium sulphate) ranked lowest regarding this outcome. The risk of all other adverse effects, including nausea, vomiting, and bloating, was comparable between different regimens, except abdominal pain, which was significantly reduced in the 3L PEG + 3d-Lin arm (RR=0.18; 95%CI:[0.04,0.88], p=0.03) compared to 4L PEG. In constipated patients, Probiotic 14d + NaP showed the highest efficacy for adequate bowel preparation, while Senna + MgSO4 was least effective."

Retrospective data • Review • Constipation • Gastroenterology • Gastrointestinal Disorder

Efficacy and Safety of Linaclotide-Enhanced Polyethylene Glycol Regimens for Bowel Preparation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ACG 2025) - "Six randomized controlled trials (RCTs), comprising 1,876 participants, met the inclusion criteria. Regimens combining linaclotide and polyethylene glycol (PEG) resulted in significantly higher rates of adequate bowel preparation compared to PEG alone (RR = 1.14, 95% CI: 1.06–1.22; p < 0.001; I² = moderate). The polyp detection rate was also higher in the linaclotide group (RR = 1.24, 95% CI: 1.08–1.43; p = 0.002)."

Retrospective data • Review

Safety and Efficacy of Polyethylene Glycol and Linaclotide in Improving Bowel Preparation During Colonoscopy in Constipated Patients: A Systematic Review and Meta-Analysis (ACG 2025) - "Seven RCTs including 4851 patients were included in our study. Three studies used the Ottawa scale for bowel preparation with results favoring PEG plus Linaclotide group (WMD= 0.35; 95% CI= 0.01 - 0.69; p= 0.04; I2= 48%) and 5 studies used the Boston score showing similar results (WMD= 0.38; 95% CI= 0.09 - 0.67; p= 0.01; I2=77%). Comparable results were found between both groups for adenoma detection rate (RR= 1.09; 95% CI= 0.98 to 1.22; p= 0.11; I2= 0%) and polyp detection rate (RR= 1.06; 95% CI= 0.97 - 1.15; p= 0.16, I2= 32%)."

Retrospective data • Review • Constipation

Outpatient Management of Partial Small Bowel Obstruction Using an Oral Palatable Elemental Diet (ACG 2025) - "Given her prior postoperative complications, she has been understandably hesitant to undergo surgical lysis of adhesions.Episodes of pSBO would occur despite multiple gut-directed treatments including lubiprostone, linaclotide, plecanatide, pyridostigmine, and rifaximin daily. Elemental diets provide complete nutrition with high absorptive efficiency in the proximal small bowel. Being fiber- and residue-free, they present an intriguing option for the conservative management of partial bowel obstruction.Figure: Figure 1) Serial abdominal radiographs demonstrating the progression and resolution of partial small bowel obstruction in response to outpatient exclusive elemental diet consumption in 2024.Figure: Figure 2) Serial abdominal radiographs demonstrating the progression and resolution of partial small bowel obstruction in response to outpatient elemental diet consumption in 2025."

Clinical

Collagenous Gastritis as a Presentation of Iron Deficiency Anemia: A Case Report (ACG 2025) - "He had previously used linaclotide and sertraline. Endoscopic evidence of diffuse nodular mucosa in the gastric body (A and B). Gastric biopsy with increased chronic inflammatory infiltrate of the lamina propria associated with patchy increased subepithelial collagen with a thickness of up to 0.1 cm (C)."

Case report • Clinical • Anemia • CNS Disorders • Crohn's disease • Depression • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Inflammatory Bowel Disease • Lymphoma • Mood Disorders • Psychiatry • Rare Diseases • Sarcoidosis

Chronic Constipation and Small Bowel Obstruction as a Complication of Uterine Fibroids (ACG 2025) - "Trials of lubiprostone and linaclotide did not provide relief. UAE was successfully performed, leading to symptomatic relief and resolution of the obstruction without the need for surgical resection. This case underscores the importance of considering pelvic pathology in the differential diagnosis of bowel obstruction and chronic constipation in women and demonstrates the utility of UAE as a minimally invasive, fertility-sparing therapeutic option in select patients.Figure: Uterine Fibroids Causing Sigmoid NarrowingFigure: CT Coronal View Uterine Fibroids"

Constipation • Gastroenterology • Gastrointestinal Disorder • Gynecology • Solid Tumor • Uterine Leiomyoma • Women's Health

Exploring the Efficacy and Safety of Linaclotide in Pediatric Patients of Functional Constipation and Irritable Bowel Syndrome With Constipation: A Meta-Analysis of Randomized Control Trials (ACG 2025) - "Out of 1,653 identified records, three RCTs (309 patients) met the inclusion criteria. Linaclotide showed no statistically significant improvement over placebo in overall CSBMs (SMD = 0.01 [-0.19, 0.20], P = 0.94), abdominal pain (SMD = 0.12 [-0.07, 0.32], P = 0.21), or bloating (SMD = 0.14 [-0.05, 0.34], P = 0.14). However, it significantly improved stool consistency (SMD = 0.52 [0.31, 0.72], P < 0.00001) and reduced straining severity (SMD = -0.29 [-0.49, -0.09], P = 0.004), particularly with higher doses."

Retrospective data • Constipation • Gastroenterology • Gastrointestinal Disorder • Pediatrics

New Kid on the Block: Could Suzetrigine's Promise of Pain Relief Improve Outcomes in Management of DGBI? (ACG 2025) - "He tried linaclotide, plecanatide, lubiprostone, prucalopride, and tenapanor...Adjunct pharmacological neuromodulators like nortriptyline, duloxetine and gabapentin were not helpful...She responded partially to duloxetine, buspirone, mirtazapine, and cognitive behavioral therapy...Studies have directly and indirectly established the importance of NaV1.8 to visceral pain perception (Table 1). Additional trials are needed to evaluate the impact of this medicine on visceral pain perception especially in conditions associated with acute and/or chronic abdominal pain, including DGBIs.Figure: Summary of Studies Supporting the Role of Nav1.8 in Visceral Pain Perception"

Cardiovascular • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Mood Disorders • Novel Coronavirus Disease • Pain • Psychiatry • NAV1

Comparative Effectiveness of Bowel Preparation Agents in Colonoscopy: A Network Meta-Analysis (ACG 2025) - "Among 13,192 pooled patients from 35 RCTs, 3L PEG+3D-LINACLOTIDE (3-litre PEG with 3-day linaclotide) showed comparatively superior cleansing success (Relative Risk (RR) 1.27, 95% Confidence Interval (CI) [1.13, 1.43]) with P-score= 0.98 and I2= 58.3%, followed by 4L PEG+1D-LINACLOTIDE (4-litre PEG with 1-day linaclotide) with RR: 1.24; [CI 1.05, 1.45], P-score= 0.95 and SENNA with RR: 1.13; [CI 1.01, 1.27], P-score= 0.87, with all the three regimens being statistically significant. Regarding ADR, magnesium sulfate solution had the highest rate with RR: 1.41; [CI 0.88, 2.27], P-score= 0.79 and I2= 29.3%, followed by 4L PEG+1D-LINACLOTIDE with RR: 1.42; [CI 0.85, 2.3], P-score= 0.79.In respect to nausea, the lowest incidence rate of nausea was seen in 1L PEG+LINACLOTIDE with RR: 0.19; [CI 0.06, 0.59], P-score= 0.97 and I2= 73.5%, followed by 2L PEG with RR: 0.42; [CI 0.21, 0.86], P-score= 0.81, and 2L PEG+LINACLOTIDE with RR: 0.45; [CI 0.21, 0.93], P-score= 0.78. However,..."

HEOR • Retrospective data • Gastrointestinal Disorder

The membrane excitability properties of GUCY2C-high neuropod cells in the gut-brain axis (Neuroscience 2025) - "Overall, these results demonstrate that GUCY2C-high NPCs display neuron-like excitability and the expected Na and K membrane conductance. Supporting the importance of GUCY2C-high NPCs’ membrane excitability, preliminary experiments also showed the optogenetic hyperpolarization of the GUCY2C-high NPCs membrane potential with archaerhodopsin recapitulates the silencing effect of linaclotide on DRG neurons."

CNS Disorders • GUCY2C

Zinc inhibits cAMP-induced Cl- secretion in intestinal epithelial cells via calcium-sensing receptor (CaSR). (PubMed, Am J Physiol Cell Physiol) - "In human intestinal T84 cells expressing CaSR, zinc (100 μM) inhibited forskolin-induced secretory Isc by 60% and its effect was comparable to CaSR activator cinacalcet...Interestingly, zinc had no effect on cGMP agonists (heat-stable E. coli enterotoxin and linaclotide)-induced secretory Isc, suggesting its antisecretory effects are specific to cAMP...Our findings suggest that CaSR activation is a major mechanism for the antidiarrheal effects of zinc which specifically reduces cAMP levels. In addition to its use in cholera, zinc can be effective in other cAMP-mediated secretory diarrheas."

Journal • Cholera • CASR • VIL1

Zinc inhibits CFTR in the intestinal epithelia via activating calcium-sensing receptor (CaSR) (NACFC 2025) - " In human intestinal T84 cells natively expressing CaSR and CFTR, 100 mM zinc inhibited forskolin-induced secretory short-circuit current (Isc) and CFTR activity by 60%, which was comparable to the effect of CaSR activator drug cinacalcet...Interestingly, zinc had no effect on cGMP agonists (heat-stable E. coli enterotoxin and linaclotide)-induced secretory Isc or CFTR activity, suggesting that its antisecretory effects are specific to cAMP agonists... These findings suggest that zinc has prominent CFTR inhibitory effects in intestinal epithelial cells. Zinc effect on CFTR appears to be due to reduced cAMP levels via CaSR activation. Although zinc deficiency has detrimental effects on epithelial health and immune system, these results suggest that zinc supplementation can potentially worsen gastrointestinal problems in CF which warrants investigation in the clinical setting."

Cholera • Constipation • Gastroenterology • Gastrointestinal Disorder • CASR • VIL1

Application effect of linaclotide capsules combined with compound polyethylene glycol in colonoscopy bowel preparation. (PubMed, World J Gastrointest Surg) - "Linaclotide capsules show a trend in improving bowel preparation quality and reducing the dosage of SF-PEG."

Journal

Laxative logic: when lifestyle is not enough. (PubMed, Curr Opin Gastroenterol) - "Patients with constipation now have access to a wide range of medications, from over-the-counter osmotic and stimulant agents to prescription laxative combination strategies. This breadth allows clinicians to tailor therapy to diverse pathophysiology and symptom profiles. Yet despite this choice, real-world adherence remains poor and many patients are dissatisfied, reflecting the complexity of treating constipation and frequent mismatches between therapy and patients' most bothersome symptoms. Management should emphasize careful symptom assessment, shared decision-making, and clear expectation setting, while leveraging the available armamentarium."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder