Cited by 119Gastrointestinal motility and disordersPelvic floor disorders treatmentsCongenital gastrointestinal and neural anomalies

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.

Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis

Open access

Shah, Eric D, Kim, Hyungjin Myra, Schoenfeld, Philip·2018·American Journal of Gastroenterology

DOI 10.1038/ajg.2017.495PMC PMC7213047

Open this paper in CoChat — free account

Abstract

OBJECTIVES: Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs). METHODS: We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and United States Securities and Exchange Commission filings of drug sponsors to identify RCTs of CIC or IBS-C patients. We assessed efficacy based on FDA-approved composite responder endpoints, diarrhea as an adverse event, and study withdrawal owing to diarrhea for each therapy. Trial results were pooled using DerSimonian and Laird random effects model of meta-analysis and exact logistic regression when appropriate with 95% confidence intervals. Meta-regression was performed to compare outcomes between therapies adjusting for placebo event rate. RESULTS: Eight linaclotide trials (five CIC; three IBS-C) and seven plecanatide trials (four CIC; three IBS-C) evaluating 10,369 patients met inclusion criteria. FDA publications documented that different definitions for diarrhea were used in linaclotide vs. plecanatide trials. Both drugs were efficacious in treating CIC (linaclotide 72 μg (Odds ratio (OR)=3.11, 95% CI 1.81-5.34); linaclotide 145 μg (OR=3.25, 2.15-4.91); plecanatide 3 mg (OR=1.99, 1.57-2.51)) and IBS-C (linaclotide 290 μg (OR=2.43, 1.48-3.98); plecanatide 3 mg (OR=1.87, 1.47-2.38); plecanatide 6 mg (OR=1.92, 1.48-2.48)). Diarrhea occurred in excess of placebo in treating CIC (linaclotide 72 μg (OR=3.07, 1.97-4.77); linaclotide 145 μg (OR=3.70, 2.69-5.10); plecanatide 3 mg (OR=3.86, 1.83-8.12)) and IBS-C (linaclotide 290 μg (OR=8.02, 5.20-12.37); plecanatide 3 mg (OR=5.55, 1.62-19.00); plecanatide 6 mg (OR=4.13, 1.57-10.83)). Based on meta-regression, there were no statistically significant differences between therapies in odds ratios for efficacy, diarrhea, or diarrhea-related study withdrawals. CONCLUSIONS: Both linaclotide and plecanatide demonstrate similar efficacy and tolerability in treating IBS-C and CIC. No differences in odds of diarrhea were seen between linaclotide and plecanatide.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/ajg.2017.495

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817
The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants
Dermyshi, E., Wang, Y., Yan, C., Hong, W., Qiu, G., Gong, X., & Zhang, T. (2017) · Neonatology · doi:10.1159/000454668 · Cited by 24,586
Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis
Lovell, R. M., & Ford, A. C. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.02.029 · Cited by 2,155
What to add to nothing? Use and avoidance of continuity corrections in meta‐analysis of sparse data
J. Sweeting, M., J. Sutton, A., & C. Lambert, P. (2004) · Statistics in Medicine · doi:10.1002/sim.1761 · Cited by 1,734
Linaclotide for Irritable Bowel Syndrome With Constipation: A 26-Week, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety
Chey, W. D., Lembo, A. J., Lavins, B. J., Shiff, S. J., Kurtz, C. B., Currie, M. G., MacDougall, J. E., Jia, X. D., Shao, J. Z., Fitch, D. A., et al. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.254 · Cited by 463
A 12-Week, Randomized, Controlled Trial With a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Linaclotide in Irritable Bowel Syndrome With Constipation
Rao, S. S. C., Lembo, A., Shiff, S., Lavins, B., Currie, M., Jia, X., Shi, K., Macdougall, J. E., Shao, J. Z., Eng, P., et al. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2012.255 · Cited by 394
Two randomized trials of linaclotide for chronic constipation
Lembo, A. J., Schneier, H. A., Shiff, S. J., Kurtz, C. B., MacDougall, J. E., Jia, X. D., Shao, J. Z., Lavins, B. J., Currie, M. G., Fitch, D. A., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1010863 · Cited by 373
Health‐related quality of life among persons with irritable bowel syndrome: a systematic review
El‐Serag, H. B., Olden, K. W., & Bjorkman, D. J. (2002) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.2002.01290.x · Cited by 305
Efficacy of Linaclotide for Patients With Chronic Constipation
Lembo, A. J., Kurtz, C. B., MacDougall, J. E., Lavins, B. J., Currie, M. G., Fitch, D. A., Jeglinski, B. I., & Johnston, J. M. (2010) · Gastroenterology · doi:10.1053/j.gastro.2009.12.050 · Cited by 237
Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit
Busby, R. W., Bryant, A. P., Bartolini, W. P., Cordero, E. A., Hannig, G., Kessler, M. M., Mahajan‐Miklos, S., Pierce, C. M., Solinga, R. M., Sun, L. J., et al. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.09.019 · Cited by 236

Show all 28 references

Research works printed but not linked: 3

2012, Med Lett Drugs T, her, 54, 91
Hanes, 2016, Clinical review (Application Number 208745Orig1s000)., US Food Drug Adm, 140, 140
Wynn, 2012, Clinical review (Application Number 202811Orig1s000)., US Food Drug Adm, 169, 169

Sorted by citations

ACG Clinical Guideline: Management of Irritable Bowel Syndrome
Lacy, B. E., Pimentel, M., Brenner, D. M., Chey, W. D., Keefer, L. A., Long, M. D., & Moshiree, B. (2021) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001036 · Cited by 893
Mechanisms, evaluation, and management of chronic constipation
Bharucha, A. E., & Lacy, B. E. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.034 · Cited by 655
American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome
Ford, A. C., Moayyedi, P., Chey, W. D., Harris, L. A., Lacy, B. E., Saito, Y. A., & Quigley, E. M. M. (2018) · American Journal of Gastroenterology · doi:10.1038/s41395-018-0084-x · Cited by 388
The Microbiome and Irritable Bowel Syndrome – A Review on the Pathophysiology, Current Research and Future Therapy
Chong, P. P., Chin, V. K., Looi, C. Y., Wong, W. F., Madhavan, P., & Yong, P. V. C. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01136 · Cited by 353
Chronic constipation
Bharucha, A. E., & Wald, A. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.01.031 · Cited by 238
Evidence-based clinical practice guidelines for irritable bowel syndrome 2020
Fukudo, S., Okumura, T., Inamori, M., Okuyama, Y., Kanazawa, M., Kamiya, T., Sato, K., Shiotani, A., Naito, Y., Fujikawa, Y., et al. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-020-01746-z · Cited by 201
American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
Chang, L., Chey, W. D., Imdad, A., Almario, C. V., Bharucha, A. E., Diem, S., Greer, K. B., Hanson, B., Harris, L. A., Ko, C., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.03.214 · Cited by 185
Self-citation
Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis
Black, C. J., Burr, N. E., Quigley, E. M. M., Moayyedi, P., Houghton, L. A., & Ford, A. C. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.08.021 · Cited by 166
The gut Microbiome in adult and pediatric functional gastrointestinal disorders
Shin, A., Preidis, G. A., Shulman, R., & Kashyap, P. C. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.08.054 · Cited by 163
AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with constipation
Chang, L., Sultan, S., Lembo, A., Verne, G. N., Smalley, W., & Heidelbaugh, J. J. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.04.016 · Cited by 163
Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders
Narayanan, S. P., Anderson, B., & Bharucha, A. E. (2021) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.10.004 · Cited by 131
Second Asian Consensus on Irritable Bowel Syndrome
Gwee, K., Gonlachanvit, S., Ghoshal, U. C., Chua, A. S. B., Miwa, H., Wu, J. C. Y., Bak, Y., Lee, O. Y., Lu, C., Park, H., et al. (2019) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm19041 · Cited by 112
Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders
Waldman, S. A., & Camilleri, M. (2018) · Gut · doi:10.1136/gutjnl-2018-316029 · Cited by 110
The effect of microbial composition and proteomic on improvement of functional constipation by Chrysanthemum morifolium polysaccharide
Wang, J., Liang, Q., Zhao, Q., Tang, Q., Ahmed, A. F., Zhang, Y., & Kang, W. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112305 · Cited by 96
Action Mode of Gut Motility, Fluid and Electrolyte Transport in Chronic Constipation
Zhao, Q., Chen, Y., Xu, D., Yue, S., Fu, R., Yang, J., Xing, L.-M., & Tang, Y. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.630249 · Cited by 87
Chronic constipation: new insights, better outcomes?
Schiller, L. R. (2019) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30199-2 · Cited by 78
Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016
Layer, P., Andresen, V., Allescher, H. ‐., Bischoff, S. C., Claßen, M., Elsenbruch, S., Freitag, M., Frieling, T., Gebhard, M., Goebel‐Stengel, M., et al. (2021) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1591-4794 · Cited by 81
Italian guidelines for the management of irritable bowel syndrome
Barbara, G., Cremon, C., Bellini, M., Corsetti, M., di Nardo, G., Falangone, F., Fuccio, L., Galeazzi, F., Iovino, P., Sarnelli, G., et al. (2022) · Digestive and Liver Disease · doi:10.1016/j.dld.2022.11.015 · Cited by 69
The Guanylate Cyclase C—cGMP Signaling Axis Opposes Intestinal Epithelial Injury and Neoplasia
Rappaport, J. A., & Waldman, S. A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00299 · Cited by 58
Bifidobacterium pseudolongum ‐Derived Bile Acid from Dietary Carvacrol and Thymol Supplementation Attenuates Colitis via cGMP‐PKG‐mTORC1 Pathway
Zhang, K., Xu, Y., Zheng, Y., Zhang, T., Wu, Y., Yan, Y., Yu, L., Cao, X., Wang, X., Yan, F., et al. (2024) · Advanced Science · doi:10.1002/advs.202406917 · Cited by 59
New advances in the treatment of paediatric functional abdominal pain disorders
Santucci, N. R., Saps, M., & van Tilburg, M. A. L. (2019) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(19)30256-0 · Cited by 50
Functional Constipation: Individualising Assessment and Treatment
Pannemans, J., Masuy, I., & Tack, J. (2020) · Drugs · doi:10.1007/s40265-020-01305-z · Cited by 46
American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation
Chang, L., Chey, W. D., Imdad, A., Almario, C. V., Bharucha, A. E., Diem, S. J., Greer, K. B., Hanson, B., Harris, L. A., Ko, C. W., et al. (2023) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002227 · Cited by 48
Self-citation
Irritable bowel syndrome: diagnosis and management
Masuy, I., Pannemans, J., & Tack, J. F. (2020) · Minerva Gastroenterologica e Dietologica · doi:10.23736/s1121-421x.19.02640-0 · Cited by 45
2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation
Cho, Y. S., Lee, Y. J., Shin, J. E., Jung, H., Park, S., Kang, S. J., Song, K. H., Kim, J., Lim, H. C., Park, H. S., et al. (2023) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm23066 · Cited by 47
Comparative study on alleviating effect of kiwi berry (Actinidia arguta) polysaccharide and polyphenol extracts on constipated mice
Zhang, J., Gao, N., Jiang, H., Li, H., Cui, X., Tang, S., Jin, C., Tian, J., & Li, B. (2022) · Food Research International · doi:10.1016/j.foodres.2022.112037 · Cited by 39
Real-World Treatment Strategies to Improve Outcomes in Patients With Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation
Brenner, D. M., Harris, L. A., Chang, C. H., Waldman, S. A., Poppers, D. M., Kassebaum-Ladewski, A., & Sayuk, G. S. (2022) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001709 · Cited by 34
Aktualisierte S2k-Leitlinie chronische Obstipation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie & Motilität (DGNM) – April 2022 – AWMF-Registriernummer: 021–019
Andresen, V., Pehl, C., Becker, G., Frieling, T., Goebel‐Stengel, M., Gundling, F., Herold, A., Karaus, M., Keller, J., Kim, M., et al. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1880-1928 · Cited by 32
Tegaserod for Irritable Bowel Syndrome With Constipation in Women Younger Than 65 Years Without Cardiovascular Disease: Pooled Analyses of 4 Controlled Trials
Shah, E. D., Lacy, B. E., Chey, W. D., Chang, L., & Brenner, D. M. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001313 · Cited by 31
Self-citation
Mechanisms of Action of Current Pharmacologic Options for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation
Sayuk, G. S., Waldman, S. A., & Brenner, D. M. (2022) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001687 · Cited by 29
Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis
Shah, E. D., Chang, L., Salwen‐Deremer, J. K., Gibson, P. R., Keefer, L., Muir, J. G., Eswaran, S. L., & Chey, W. D. (2020) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000989 · Cited by 28
Self-citation
2025 Seoul Consensus on Clinical Practice Guidelines for Irritable Bowel Syndrome
Choi, Y., Youn, Y. H., Kang, S. J., Shin, J. E., Cho, Y. S., Jung, Y. S., Shin, S. Y., Huh, C. W., Lee, Y. J., Koo, H. S., et al. (2025) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm25007 · Cited by 36
Plecanatide: a new guanylate cyclase agonist for the treatment of chronic idiopathic constipation
Rao, S. S. C. (2018) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756284818777945 · Cited by 27
Evaluating the Impact of Cost on the Treatment Algorithm for Chronic Idiopathic Constipation: Cost-Effectiveness Analysis
Shah, E. D., Staller, K. D., Nee, J. W., Ahuja, N. K., Chan, W. W., Lembo, A. J., Brenner, D. M., Siegel, C. A., & Chey, W. D. (2021) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001403 · Cited by 27
Self-citation
Gut-associated cGMP mediates colitis and dysbiosis in a mouse model of an activating mutation in GUCY2C
Mishra, V., Bose, A., Kiran, S., Banerjee, S., Shah, I. A., Chaukimath, P., Reshi, M. M., Srinivas, S., Barman, A., & Visweswariah, S. S. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20210479 · Cited by 27
A therapeutic guide on pediatric irritable bowel syndrome and functional abdominal pain-not otherwise specified
Rexwinkel, R., Vlieger, A. M., Saps, M., Tabbers, M. M., & Benninga, M. A. (2022) · European Journal of Pediatrics · doi:10.1007/s00431-022-04459-y · Cited by 29
Evaluating when and why patients discontinue chronic therapy for irritable bowel syndrome with constipation and chronic idiopathic constipation
Shah, E. D., Suresh, S., Jou, J., Chey, W. D., & Stidham, R. W. (2020) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000530 · Cited by 23
Self-citation
Update S3-Leitlinie Intestinale Motilitätsstörungen: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM)
Keller, J., Wedel, T., Seidl, H., Kreis, M. E., van der Voort, I., Gebhard, M., Langhorst, J., Jansen, P. L., Schwandner, O., Storr, M., et al. (2022) · Zeitschrift für Gastroenterologie · doi:10.1055/a-1646-1279 · Cited by 22
Heterogeneity of cGMP signalling in tumour cells and the tumour microenvironment: Challenges and chances for cancer pharmacology and therapeutics
Stehle, D., Barresi, M., Schulz, J., & Feil, R. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108337 · Cited by 22
Constipation in Patients With Chronic Kidney Disease
Cha, R. R., Park, S., & Camilleri, M. (2023) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm23133 · Cited by 28
Medical Therapy of Constipation: Current Standards and Beyond
Andresen, V., & Layer, P. (2018) · Visceral Medicine · doi:10.1159/000488695 · Cited by 24
Pharmacologic, Dietary, and Psychological Treatments for Irritable Bowel Syndrome With Constipation: Cost Utility Analysis
Shah, E., Salwen-Deremer, J., Gibson, P., Muir, J., Eswaran, S., & Chey, W. (2021) · MDM Policy & Practice · doi:10.1177/2381468320978417 · Cited by 17
Self-citation
Management of Chronic Multisymptom Illness: Synopsis of the 2021 US Department of Veterans Affairs and US Department of Defense Clinical Practice Guideline
Robbins, R. C., Helmer, D. A., Monahan, P., Hunt, S. C., McAndrew, L. M., Nazario, M., Brown, W. J., Chao, W., Navarro, A., & Sall, J. (2022) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2022.01.031 · Cited by 20
Irritable Bowel Syndrome
Greer, K. B., & Sultan, S. (2025) · Annals of Internal Medicine · doi:10.7326/annals-25-01965 · Cited by 22
Deglycosylated Azithromycin Targets Transgelin to Enhance Intestinal Smooth Muscle Function
Zhong, W., Sun, B., Ruan, H., Yang, G., Qian, B., Cao, H., He, L., Fan, Y., Roberts, A. G., Liu, X., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101464 · Cited by 19
Value-based Pricing for Rifaximin Increases Access of Patients With Irritable Bowel Syndrome With Diarrhea to Therapy
Shah, E. D., Saini, S. D., & Chey, W. D. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.02.039 · Cited by 19
Self-citation
Refractory Constipation
Camilleri, M., & Brandler, J. (2020) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2020.05.002 · Cited by 15
Tenapanor for the treatment of irritable bowel syndrome with constipation
Sinagra, E., Rossi, F., Raimondo, D., Conoscenti, G., Anderloni, A. A., Guarnotta, V., & Maida, M. F. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2020.1762570 · Cited by 12
Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options
Wechsler, E. V., & Shah, E. (2021) · Drugs · doi:10.1007/s40265-021-01634-7 · Cited by 16
Self-citation
Profile of plecanatide in the treatment of chronic idiopathic constipation: design, development, and place in therapy
Sharma, A., Herekar, A., Bhagatwala, J., & Rao, S. S. C. (2019) · Clinical and Experimental Gastroenterology · doi:10.2147/ceg.s145668 · Cited by 14
Deciphering ion transporters, kinases and PDZ-adaptor molecules that mediate guanylate cyclase C agonist-dependent intestinal fluid loss in vivo
Liu, Y., Tan, Q., Riederer, B., Stefano, G. D., Römermann, D., Qian, J., Reiner, J., & Seidler, U. E. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.114040 · Cited by 14
Plecanatide for Treatment of Chronic Constipation and Irritable Bowel Syndrome
Love, B. L. (2018) · The American Journal of Medicine · doi:10.1016/j.amjmed.2018.11.027 · Cited by 13
Preventive effect of kiwi berry ( Actinidia arguta ) on loperamide-induced constipation
Zhang, J., Li, B., Gao, N., Li, H., Cui, X., Jiang, H., Tang, S., Jin, C., & Tian, J. (2023) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250119 · Cited by 12
What’s in the pipeline for lower functional gastrointestinal disorders in the next 5 years?
Camilleri, M. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00205.2019 · Cited by 12
Therapeutic effects of saffron (Crocus sativus) versus fluoxetine on Irritable Bowel Syndrome: A double-blind randomized clinical trial
Najafabadi, B. T., Ghamari, K., Ranjabari, T. K., Noorbala, A. A., Daryani, N. E., Vanaki, E., & Akhondzadeh, S. (2019) · Advances in Integrative Medicine · doi:10.1016/j.aimed.2019.01.001 · Cited by 12
An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer
Rappaport, J. A., & Waldman, S. A. (2020) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2020.1826304 · Cited by 12
Clinical utility of plecanatide in the treatment of chronic idiopathic constipation
Islam, B. N., Sharman, S. K., & Browning, D. D. (2018) · International Journal of General Medicine · doi:10.2147/ijgm.s125051 · Cited by 11
Chronic constipation
Lembo, A. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-13911-6.00009-8 · Cited by 10
Fundamental Neurochemistry Review: The role of enteroendocrine cells in visceral pain
Londregan, A., Alexander, T. D., Covarrubias, M., & Waldman, S. A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16022 · Cited by 12
Targeted pharmacotherapy of irritable bowel syndrome.
Arokiadoss, A., & Weber, H. (2021) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0000000000000618 · Cited by 9
Phosphodiesterase-5 inhibitors for colon cancer chemoprevention
Islam, B. N., & Browning, D. D. (2018) · Aging · doi:10.18632/aging.101545 · Cited by 9
Managing pain in irritable bowel syndrome: current perspectives and best practice
Algera, J. P., Lövdahl, J., Sjölund, J., Tornkvist, N. T., & Törnblom, H. (2023) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2023.2242775 · Cited by 10
Optimizing the Management Algorithm for Adults With Functional Constipation Failing a Fiber/Laxative Trial in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis
Shah, E. D., Ahuja, N. K., Brenner, D. M., Chan, W. W., Curley, M. A., Nee, J. W., Iturrino-Moreda, J., Staller, K. D., Saini, S. D., & Chey, W. D. (2023) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000002515 · Cited by 8
Self-citation
Identification of the multiple bioactive derivatives and their endogenous molecular targets that may mediate the laxative effect of rhubarb in rats
Xie, L., Wang, Y., Luo, G., Zhou, W., Miao, J., Tang, S., Jiang, Q., Guan, Y., & Gao, X. (2020) · Journal of Traditional Chinese Medical Sciences · doi:10.1016/j.jtcms.2020.04.004 · Cited by 8
Pharmacologic Treatments for Irritable Bowel Syndrome: an Umbrella Systematic Review
Chen, M., Tang, T., Qin, D., Yue, L., & Zheng, H. (2020) · Journal of Gastrointestinal and Liver Diseases · doi:10.15403/jgld-817 · Cited by 8
DIAGNOSIS AND MANAGEMENT OF CHRONIC IDIOPATHIC CONSTIPATION: A NARRATIVE REVIEW FROM A BRAZILIAN EXPERT TASK FORCE
Passos, M. D. C. F., Alvariz, R. C., ANDRÉ, E. A., Barbuti, R. C., Fillmann, H. S., MURAD-REGADAS, S. M., Filho, J. R., Perrotti, M., & GUEDES, L. S. (2022) · Arquivos de Gastroenterologia · doi:10.1590/s0004-2803.202200001-23 · Cited by 10
Effects of Functional Red Pine Seed Direct-Drinking Oil on Constipation and Intestinal Barrier Function in Mice
Li, J., Zheng, H., Liu, J., Ding, J., Guo, Q., & Zhang, N. (2024) · Antioxidants · doi:10.3390/antiox14010014 · Cited by 9
Decoding Abdominal Pain in Constipation-predominant Irritable Bowel Syndrome and Functional Constipation: Mechanisms and Managements
Luo, J., Xu, Q., Xu, S., Zhai, L., Yuan, C., & Bian, Z. (2025) · Current Gastroenterology Reports · doi:10.1007/s11894-025-00967-7 · Cited by 8
Navigating through 65 years of insights: lessons learned on functional abdominal pain in children
Rajindrajith, S., Boey, C., Devanarayana, N., Niriella, M., Thapar, N., & Benninga, M. (2024) · European Journal of Pediatrics · doi:10.1007/s00431-024-05667-4 · Cited by 8
Comparative Efficacy of Drugs for the Treatment of Chronic Constipation
Zhang, Y., Yin, F., Xu, L., Li, Y.-F., Chen, J., Liu, H., Zheng, Q., & Li, L. (2020) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001303 · Cited by 7
Multicentre, non-interventional study of the efficacy and tolerability of linaclotide in the treatment of irritable bowel syndrome with constipation in primary, secondary and tertiary centres: the Alpine study
Pohl, D., Fried, M., Lawrance, D., Beck, E., & Hammer, H. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-025627 · Cited by 6
Pharmacologic Treatment of Irritable Bowel Syndrome with Predominant Constipation
Kim, D.-H., Song, H. Y., Nam, K., & the Korean Society of Neurogastroenterology and Motility (2025) · Korean Journal of Gastroenterology · doi:10.4166/kjg.2025.002 · Cited by 8
Price Is Right: Exploring Prescription Drug Coverage Barriers for Irritable Bowel Syndrome Using Threshold Pricing Analysis
Shah, E. D., Chang, L., Lembo, A. J., Staller, K. D., Curley, M. A., & Chey, W. D. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06806-1 · Cited by 6
Self-citation
The effect of kiwi berry (Actinidia arguta) on preventing and alleviating loperamide-induced constipation
Zhang, J., Li, D., Tian, Q., Ding, Y., Jiang, H., Xin, G., Cheng, S., Tang, S., Jin, C., Tian, J., et al. (2023) · Food Innovation and Advances · doi:10.48130/fia-2023-0001 · Cited by 6
The enduring promise of phosphodiesterase 5 inhibitors for colon cancer prevention
Browning, D. D. (2019) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.12.10 · Cited by 6
Die neue Leitlinie zum Reizdarmsyndrom: Was ändert sich?
von Schassen, H., Andresen, V., & Layer, P. (2021) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-1331-6478 · Cited by 5
Review article: current and future treatment approaches for IBS with constipation
Liu, J. J., & Brenner, D. M. (2021) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.16607 · Cited by 5
Baseline Predictors of Discontinuation of Prescription Drug Therapy for IBS-C: Cohort Analysis at an Integrated Healthcare System
Shah, E. D., Brenner, D. M., & Chen, V. L. (2021) · Digestive Diseases and Sciences · doi:10.1007/s10620-021-06963-x · Cited by 5
Self-citation
Mechanistic Prediction of Chinese Herb Compound (Zhi Zhu Ma Ren Pill) in the Treatment of Constipation Using Network Pharmacology and Molecular Docking
Wen, Y., Zhan, Y., Tang, S., Kang, J., Wu, R., & Tang, X. (2022) · Natural Product Communications · doi:10.1177/1934578x221124780 · Cited by 5
Focus on Pharmacotherapy for Irritable Bowel Syndrome with Constipation
Liu, J. J., & Brenner, D. M. (2021) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2021.04.004 · Cited by 4
Comparison of the Efficacy and Safety of Different Doses of Linaclotide for Patients with Chronic Constipation: A Meta-Analysis and Bayesian Analysis
Yang, J., & Lei, Y.-C. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/9923879 · Cited by 4
Efficacy and safety of linaclotide in treatment‐resistant chronic constipation: A multicenter, open‐label study
Yoshihara, T., Kessoku, T., Takatsu, T., Misawa, N., Ashikari, K., Fuyuki, A., Ohkubo, H., Higurashi, T., Iwaki, M., Kurihashi, T., et al. (2024) · Neurogastroenterology & Motility · doi:10.1111/nmo.14938 · Cited by 4
Treatment and Management of Gastrointestinal Disorders
Montgomery, G., Patel, A., & Pfeil, S. A. (2024) · Medical Clinics of North America · doi:10.1016/j.mcna.2024.03.010 · Cited by 4
Modern aspects of the management of patients with irritable bowel syndrome
Tsukanov, V. V., Vasyutin, A. V., & Tonkikh, Y. L. (2021) · Meditsinskiy sovet = Medical Council · doi:10.21518/2079-701x-2021-5-22-28 · Cited by 5
Barley Leaves Improves Loperamide-Induced Constipation via Gut Barrier and Microbiota Modulation in Mice
Xu, Y., Wu, Z., Cohoon, M. L., Ma, M., Sui, Z., & Corke, H. (2025) · Foods · doi:10.3390/foods15010095 · Cited by 3
From leptin to lasers: the past and present of mouse models of obesity
Barton, J. R., Snook, A. E., & Waldman, S. A. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1877654 · Cited by 4
Evaluation of Constipation and Treatment of Abdominal Component
Garrett, K. A., & Ogilvie, J. W. (2021) · Springer eBooks · doi:10.1007/978-3-030-66049-9_58 · Cited by 3
Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases
Yin, Q., Zheng, X., Song, Y., Wu, L., Li, L., Tong, R., Han, L., & Bian, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1272073 · Cited by 3
Gastrointestinal drugs
Coppiano, L. S., & May, D. W. (2019) · Side effects of drugs annual · doi:10.1016/bs.seda.2019.08.009 · Cited by 3
Comment on Meta Analysis by Shah et al.
Griffin, P. H. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0114-8 · Cited by 3
Seoul Consensus on Clinical Practice Guidelines for Functional Constipation
Song, K. H., Cho, Y. S., Shin, J. E., Jung, H., Park, S., Kang, S. J., Kim, J., Lee, Y. J., Lim, H. C., Park, H. S., et al. (2025) · Korean Journal of Gastroenterology · doi:10.4166/kjg.2024.156 · Cited by 2
Real-World Evidence of the Long-Term Clinical Utility of a Vibrating Capsule in the Management of Chronic Idiopathic Constipation
Brenner, D. M., Rao, S. S. C., Curtin, B. F., & Quigley, E. M. M. (2025) · Clinical and Translational Gastroenterology · doi:10.14309/ctg.0000000000000918 · Cited by 2
Guanylyl Cyclase C As A Biomarker for Immunotherapies for the Treatment of Gastrointestinal Malignancies
Flickinger, J. C., Rappaport, J. A., Barton, J. R., Baybutt, T. R., Pattison, A. M., Snook, A. E., & Waldman, S. A. (2021) · Biomarkers in Medicine · doi:10.2217/bmm-2020-0359 · Cited by 2
The Burden and Treatment of Chronic Constipation Among US Nursing Home Residents
Zhang, T., Zullo, A. R., James, H. O., Lee, Y., Taylor, D. C. A., & Daiello, L. A. (2023) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2023.05.006 · Cited by 2
The Role of the Nurse in the Management of Irritable Bowel Syndrome: a narrative review
Ruggiero, L., Andretta, V., Soldaini, C., Fricano, I., Mancusi, M., Sellitti, A., Vastarella, J., & Santonicola, A. (2023) · Translational Medicine UniSa · doi:10.37825/2239-9747.1043 · Cited by 2
Combining symptoms and biomarkers: The future diagnostic approach for disorders of gut‐brain interaction?
Simrén, M., & Tack, J. F. (2020) · Neurogastroenterology & Motility · doi:10.1111/nmo.14019 · Cited by 2
Abdominal Pain-Related Functional Gastrointestinal Disorder and Disorders of Brain–Gut Interactions
Febo‐Rodriguez, L., & Saps, M. (2022) · Springer eBooks · doi:10.1007/978-3-031-15229-0_37 · Cited by 2
Constipation
Dharmarajan, T. S., Widjaja, D., & Pitchumoni, C. S. (2021) · Springer eBooks · doi:10.1007/978-3-030-30192-7_45 · Cited by 2
Excretory Functions of the Gastrointestinal Tract. Defecation
Welcome, M. O. (2018) · Springer eBooks · doi:10.1007/978-3-319-91056-7_13 · Cited by 1
Laxative logic: when lifestyle is not enough
Colbran, R., & Neshatian, L. (2025) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000001137 · Cited by 1

Authors: Shah, E. D., Kim, H. M., & Schoenfeld, P.
Affiliations: University of Michigan (US)
Corresponding author: Schoenfeld, Philip
ORCID: Shah, Eric D
Kim, Hyungjin Myra
Schoenfeld, Philip
Venue: American Journal of Gastroenterology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2018-03
Volume: 113
Issue: 3
Pages: 329-338
ISSN: 0002-9270 (ISSN-L)
DOI: 10.1038/ajg.2017.495
PMC: PMC7213047
OpenAlex: W2789261715
Cited by: 119
References: 28
Citations by year: 2026: 3 · 2025: 10 · 2024: 8 · 2023: 17 · 2022: 13 · 2021: 26 · 2020: 16 · 2019: 12 · 2018: 14
FWCI: 3.03
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The American Journal of Gastroenterology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Ironwood Pharmaceuticals, Incorporated
National Institute of Diabetes and Digestive and Kidney Diseases (K24DK084208, T32DK062708)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Health Sciences › Medicine › Urology › Pelvic floor disorders treatments
Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Keywords: guanylate cyclase-C agonist, linaclotide, plecanatide, irritable bowel syndrome with constipation, chronic idiopathic constipation, diarrhea, drug tolerability, drug efficacy, meta-regression
MeSH terms: Guanylyl Cyclase C Agonists, Chronic Disease, Constipation, Diarrhea, Humans, Peptides, Randomized Controlled Trials as Topic, Irritable Bowel Syndrome, Natriuretic Peptides

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks