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

Differential segment-specific signalling pathways for guanylate cyclase C-activated anion secretion in murine ileocolon. (PubMed, Br J Pharmacol) - "GC-C activation leads to CFTR-mediated ASR in all segments of the intestine. In the mid and distal colon ASR is strongly reduced by the low cGKII and high PDE9 expression, with the CFTR channel being activated via cAMP-mediated phosphorylation."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor

Image-guided therapy of colorectal cancer using a zirconium coordinated nanosensitizer. (PubMed, J Nanobiotechnology) - "In this study, a tumor-targeting nanosonosensitizer, Zr-HMME-PEG-Linaclotide (HP-LNC), was designed by coordinating the sonosensitizer hematoporphyrin monomethyl ether (HMME) with zirconium (Zr) to form a Zr-HMME complex...PET and fluorescence imaging results revealed efficient accumulation of HP-LNC at the tumor site, excellent in vivo stability for HP-LNC, and effective monitoring of therapeutic progress. Overall, this nanoplatform successfully integrates dual-modal imaging with ROS-mediated therapy, highlighting its substantial potential in multimodal cancer treatment, particularly for colorectal cancer therapy."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CALR • HMGB1

Bali Chronic Constipation Roundtable Report: Chronic Constipation Management in Asia. (PubMed, J Neurogastroenterol Motil) - "First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. The Bali Chronic Constipation Roundtable highlighted Asia's need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia."

Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

CTV678-H003: Surgical Procedure Efficiency Evaluation stuDy (clinicaltrials.gov) - P=N/A | N=180 | Not yet recruiting | Sponsor: Alcon Research

New trial • Real-world evidence • Cataract • Hematological Disorders • Ophthalmology • Retinal Disorders

Oxalate nephropathy precipitated by linaclotide in a high-risk patient. (PubMed, Clin Nephrol Case Stud) - "Linaclotide can contribute to ON in predisposed patients. Clinicians should consider medication history and risk factors in unexplained AKI and pursuing kidney biopsy for diagnosis."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Constipation • Fatigue • Gastroenterology • Gastrointestinal Disorder • Nephrology • Pain • Renal Disease

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

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. (PubMed, Scand J Gastroenterol) - "The bowel preparation efficacy of Lina + 2 L-PEG is comparable to that of 3 L-PEG, yet superior to that of 2 L-PEG. Moreover, Lina + 2 L-PEG is associated with fewer adverse reactions, a lower cost, and a higher willingness to repeat the colonoscopy among patients aged over 60 years."

Journal

Safety and efficacy of linaclotide as an adjuvant for bowel preparation: A systematic review and meta-analysis. (PubMed, Arab J Gastroenterol) - "Linaclotide demonstrates superior efficacy compared to the control group with equal PEG doses and shows no statistically significant difference when compared to the group with double the PEG dosage, all while resulting in fewer adverse events."

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

U.S. Food and Drug Administration (FDA) approved the company’s Linzess (linaclotide) capsules for pediatric patients 7 years and older with irritable bowel syndrome with constipation (IBS-C). (Investing.com) - "The FDA’s decision was supported by efficacy data extrapolated from adult studies and a 12-week clinical trial in pediatric patients aged 7 to 17 years."

FDA approval • Constipation • Gastrointestinal Disorder

Effect of linaclotide combined with Simethicone and polyethylene glycol electrolyte powder on cleansing effect of bowel in patients with constipation (ChiCTR) - P=N/A | N=390 | Completed | Sponsor: The People's Hospital of Jianyang City; The People's Hospital of Jianyang City

New trial • Constipation • Gastroenterology • Gastrointestinal Disorder

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

Linaclotide combined with polyethylene glycol for bowel preparation in colonoscopy: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Surg Endosc) - "Linaclotide with PEG improved preparation quality, willingness to repeat the preparation, and reduced AEs compared to PEG alone. Subgroup analyses findings are particularly relevant for patients with a history of inadequate bowel preparation, especially those with low tolerance to high-volume PEG or difficulty achieving effective colonic cleansing. Future studies should further explore the cost-effectiveness and the applicability across diverse regimens and patient characteristics."

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

Cost-utility analysis of treatment strategies for chronic constipation in Japan. (PubMed, J Gastroenterol) - "The lubiprostone-elobixibat-PEG formulation strategy showed the most favorable cost-effectiveness profile. In addition, novel treatment options, including lubiprostone, linaclotide, elobixibat, and PEG formulation, were found to be cost-effective compared to MgO. Further research is warranted to confirm these findings and support their application in clinical practice."

HEOR • Journal • Constipation • Gastroenterology • Gastrointestinal Disorder

Choosing and switching biologics for patients with severe asthma–real-world evidence from the GAN severe asthma registry (OGP-OGTC 2025) - "The most frequent switch constella tions were anti-IL5 to anti-IL5R (n=64), anti-IL5R to anti-IL4R (n=55) and anti-IL5 to anti-IL4R (n=42). Phenotyping patients with severe asthma is important for the initial choice of biologic therapy in real world practice. Additionally, choice and switch of biologic have evolved over time influenced by availability of different drugs."

Clinical • HEOR • Real-world • Real-world evidence • Asthma • Immunology • Respiratory Diseases • IL5