Effects of linaclotide: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major Findings

Linaclotide is a guanylate cyclase-C (GCC) agonist found in intestinal epithelial cells and is used to treat chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C). 20 Several randomized controlled trials (RCTs) have been conducted to evaluate its efficacy and safety. 20 Linaclotide has been proposed as a treatment for the same gastrointestinal indications for which lubiprostone has been approved, chronic idiopathic constipation and irritable bowel syndrome with constipation. 17 Linaclotide is an FDA-approved drug for the treatment of adult patients with Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation. 1 Linaclotide activates guanylate cyclase-C/cGMP/protein kinase-II-dependent trafficking of CFTR in the intestine, which is the major pathway of linaclotide-mediated intestinal fluid secretion. 1 Linaclotide has very limited systemic absorption and appears safe in patients with CKD. 16 Linaclotide is effective and safe for use in elderly patients. 8 However, the incidence of diarrhea may increase when linaclotide is administered alone or concurrently used with medications that cause constipation. 8

Benefits and Risks

Benefit Summary

Linaclotide has many benefits, including improving constipation symptoms, reducing abdominal pain and bloating, and effectiveness and safety in the elderly. 20 , 11 , 8

Risk Summary

Linaclotide can cause side effects such as diarrhea. 20

Study Comparison

Study Commonalities

Many studies have shown that linaclotide is effective in improving constipation symptoms. 20 , 11 , 8 Linaclotide acts as a GCC agonist, promoting intestinal motility and increasing stool water content, thus alleviating constipation. 23 , 11

Study Differences

There may be differences in the efficacy and side effect profiles of linaclotide across studies. 20 , 11 , 8 This may be due to differences in the study population or design. 20 , 11 , 8

Consistency and Contradictions

Many studies have shown that linaclotide is effective in improving constipation symptoms. 20 , 11 , 8 However, there may be differences in the efficacy and side effect profiles of linaclotide across studies, and these discrepancies require further investigation. 20 , 11 , 8

Practical Application

Linaclotide is a promising drug for the treatment of chronic constipation and irritable bowel syndrome with constipation. 20 , 11 , 8 However, linaclotide can cause side effects such as diarrhea, so it is important to take it as directed by your doctor. 20 Linaclotide may not be effective for all patients with constipation. 20

Limitations

It can be difficult to compare the results of linaclotide studies because of variations in the study population and design. 20 , 11 , 8 Further research is needed to assess the long-term efficacy and safety of linaclotide. 20 , 11 , 8

Future Research

Further research is needed to assess the long-term efficacy and safety of linaclotide. 20 , 11 , 8 More research is needed to determine which types of constipation patients benefit from linaclotide. 20 , 11 , 8

Conclusion

Linaclotide shows promise as a medication for the treatment of chronic constipation and irritable bowel syndrome with constipation. 20 , 11 , 8 However, it is important to take linaclotide as directed by your doctor because it can cause side effects such as diarrhea. 20 Linaclotide may not be effective for all patients with constipation. 20 Further research is needed to assess the long-term efficacy and safety of linaclotide. 20 , 11 , 8

Literature analysis of 23 papers
Positive Content
23
Neutral Content
0
Negative Content
0
Article Type
1
5
4
9
23
2.

Management of Opioid-induced Constipation in Older Adults.

Author: HorriganJamie, BhumiSriya, MillerDavid, JafriMikram, TadrosMicheal

OIC treatment
None reported

This review provides guidance on managing opioid-induced constipation (OIC) in older adults. It recommends considering nonpharmacologic interventions and over-the-counter laxatives before moving to prescription opioid receptor antagonists. The review emphasizes the importance of individualizing treatment based on the complex pharmacokinetic profile of aging individuals.

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Systematic review with meta-analysis: efficacy and safety of treatments for opioid-induced constipation.

Author: VijayvargiyaPriya, CamilleriMichael, VijayvargiyaPooja, ErwinPatricia, MuradM Hassan

Constipation treatment
Opioid withdrawal

Peripherally acting μ-opioid receptor antagonists (PAMORAs) were more effective than other treatments in relieving opioid-induced constipation. Methylnaltrexone, naloxegol, and naldemidine were the most effective PAMORAs and were associated with a low risk of serious adverse events.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

4.

Recent Updates on the Treatment of Constipation.

Author: RyuHan Seung, ChoiSuck Chei

Constipation treatment

This abstract reviews various treatments for constipation, including pharmacologic, non-pharmacologic, biofeedback, and surgical treatments. While conventional laxatives have less adverse effects and are inexpensive, they often have limited efficacy. Recently developed enterokinetic agents and intestinal secretagogues have high efficacies and low incidences of adverse events.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

American Gastroenterological Association-American College of Gastroenterology Clinical Practice Guideline: Pharmacological Management of Chronic Idiopathic Constipation.

Author: ChangLin, CheyWilliam D, ImdadAamer, AlmarioChristopher V, BharuchaAdil E, DiemSusan, GreerKatarina B, HansonBrian, HarrisLucinda A, KoCynthia, MuradM Hassan, PatelAmit, ShahEric D, LemboAnthony J, SultanShahnaz

CIC treatment

This clinical practice guideline provides evidence-based practice recommendations for the pharmacological treatment of chronic idiopathic constipation (CIC) in adults.

Practice GuidelineGuidelines and recommendations for the diagnosis and treatment of specific medical conditions in medical practice.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis.

Author: BlackChristopher J, BurrNicholas E, QuigleyEamonn M M, MoayyediPaul, HoughtonLesley A, FordAlexander C

IBS-C treatment

This network meta-analysis compares the efficacy of various secretagogues approved for irritable bowel syndrome with constipation (IBS-C). The relative efficacy of these drugs is unclear due to the lack of head-to-head randomized controlled trials.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

8.

[Efficacy and Safety of Linaclotide in Elderly Patients].

Author: IshigoTomoyuki, ShimotsuboTatsuto, TakadaRyo, NakanoKeita, FujiiSatoshi, KitagawaManabu, KimyoTomoko, NakataHiromasa, FukudoMasahide

Constipation treatment
Diarrhea

Linaclotide is a drug for constipation. This study investigated the efficacy and safety of linaclotide in elderly patients. It found that linaclotide was effective and safe in elderly patients, and the incidence of diarrhea increased with linaclotide monotherapy or concurrent use with constipation-inducing medications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Japanese

9.

Recommendations for the management of opioid-induced constipation - how to improve usability in clinical practice.

Author: OkdahlTina, EmmanuelAnton, MorlionBart, FarmerAdam, VarrassiGiustino, DrewesAsbjørn Mohr

Opioid constipation treatment

This review discusses the challenges of treating opioid-induced constipation and the need for simplified and behaviorally-oriented guidelines to improve management.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Recent advances in understanding and managing chronic constipation.

Author: PrichardDavid O, BharuchaAdil E

Constipation treatment
Undesirable side effects

Constipation is a common condition that can affect physical, mental, and social functioning. Current guidelines recommend empiric therapy, but limited surveys suggest that fewer than half of treated individuals are satisfied with treatment. Newer therapeutic agents, such as secretagogues and pro-kinetics, may offer more effective treatment options.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

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

Author: ShahEric D, KimHyungjin Myra, SchoenfeldPhilip

Constipation treatment

This review evaluates the efficacy and tolerability of guanylate cyclase-C (GCC) agonists linaclotide and plecanatide for treating chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

12.

Management of Constipation in Older Adults.

Author: MounseyAnne, RaleighMeghan, WilsonAnthony

Constipation treatment
Toxicity

Chronic constipation is common in older adults, with up to 50% of nursing home residents affected. Treatment begins with lifestyle modifications such as scheduled toileting, increased fluids, and dietary fiber. Further options include osmotic laxatives, stool softeners, stimulant laxatives, and linaclotide or lubiprostone. Peripherally acting mu-opioid antagonists are effective for opioid-induced constipation but are expensive.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Patient Education HandoutA document or pamphlet that provides information to educate patients about specific medical conditions or treatment methods.

Language : English

13.

EFFICACY AND SAFETY OF INTESTINAL SECRETAGOGUES FOR CHRONIC CONSTIPATION: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Author: LasaJuan Sebastian, AltamiranoMaría Josefina, BrachoLuis Florez, PazSilvina, ZubiaurreIgnacio

Improved bowel movement frequency

Intestinal secretagogues were effective and safe for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. Compared to placebo, these medications significantly increased the number of spontaneous bowel movements and improved constipation-related symptoms.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

15.

Single-Dose Linaclotide Is Equal in Efficacy to Polyethylene Glycol for Bowel Preparation Prior to Capsule Endoscopy.

Author: SteinDaniel J, CoplandAndrew, McDanielDeborah, HaysR Ann

Small bowel visualization
Recorder failure

Linaclotide, a single-dose given 1 hour before capsule endoscopy, was equally effective as polyethylene glycol (PEG) in improving visualization and transit time in patients undergoing small bowel capsule endoscopy. Both regimens were well-tolerated.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

16.

Constipation in Patients With Chronic Kidney Disease.

Author: ChaRa Ri, ParkSeon-Young, CamilleriMichael,

Improved bowel function
Reduced phosphate absorption
Reno-protective effects
Adverse effects
Insufficient efficacy

This review outlines the mechanisms and management of constipation in patients with chronic kidney disease (CKD). It discusses common causes, impact on overall health, and available treatment options, including lactulose, lubiprostone, linaclotide, plecanatide, tenapanor, and prucalopride.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

17.

Contrasting effects of linaclotide and lubiprostone on restitution of epithelial cell barrier properties and cellular homeostasis after exposure to cell stressors.

Author: CuppolettiJohn, BlikslagerAnthony T, ChakrabartiJayati, NighotPrashant K, MalinowskaDanuta H

Barrier repair
Constipation treatment

This study examined the effects of linaclotide on the repair of barrier and cell function after ischemia in pig jejunum and after treatment with proinflammatory cytokines in T84 cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Effects of linaclotide in the treatment of chronic constipation and irritable bowel syndrome with constipation: a meta-analysis.

Author: ZhaoQi, FangYongkun, YanCheng, GaoJing, LiuZhuangzhuang, ZhuHanjian, TangDong, WangDaorong

Treat IBS-C
Treat constipation

This study reviews randomized controlled trials (RCTs) evaluating the efficacy and safety of linaclotide, a guanylate cyclase-C (GCC) agonist, in treating chronic constipation (CC) and irritable bowel syndrome with constipation (IBS-C).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

21.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article.

Author: ChenLongtu, IlhamSheikh J, FengBin

IBS pain relief

Irritable bowel syndrome (IBS) is a common condition that causes abdominal pain. This study discusses current and investigational treatments for IBS pain.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

New Options in Constipation Management.

Author: DavisMellar, GamierPamela

Constipation management

Constipation is a common problem in the general population, particularly for those on opioids or suffering from advanced cancer. While self-management with dietary changes, exercise, and laxatives is often insufficient, there are multiple new anti-constipating medications available.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

23.

Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.

Author: EntezariAriana A, SnookAdam E, WaldmanScott A

Chemoprevention potential
Promising GI cancer target

This abstract highlights the potential of targeting guanylyl cyclase C (GUCY2C) for the treatment and prevention of gastrointestinal cancers. GUCY2C plays a crucial role in intestinal signaling and homeostasis, and its aberrant expression is linked to the development of GI malignancies. Targeting this pathway holds promise for developing novel therapies for GI cancers.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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