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HOME > Clin Endosc > Volume 58(5); 2025 > Article
Systematic Review and Meta-analysis Efficacy and safety of polyethylene glycol in combination with linaclotide versus polyethylene glycol alone for colonoscopy: a grade-assessed systematic review and meta-analysis
Umar Akram1orcid, Eeman Ahmad2orcid, Shahzaib Ahmed2orcid, Zain Ali Nadeem1orcid, Muhammad Ahmed Raza1orcid, Eeshal Fatima3orcid, Syed Adeel Hassan4orcid, Ahtshamullah Chaudhry5orcid, Hareesha Rishab Bharadwaj6orcid, Muhammad Arslan Tariq1orcid, Faryal Altaf7orcid, Zaheer Qureshi8orcid
Clinical Endoscopy 2025;58(5):670-683.
DOI: https://doi.org/10.5946/ce.2025.073
Published online: September 1, 2025

1Department of Medicine, Allama Iqbal Medical College, Lahore, Pakistan

2Department of Medicine, Fatima Memorial Hospital College of Medicine and Dentistry, Lahore, Pakistan

3Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan

4Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY, USA

5Department of Internal Medicine, St. Dominic’s Hospital, Jackson, MS, USA

6Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK

7Department of Internal Medicine, Icahn School of Medicine at Mount Sinai/BronxCare Health System, New York, NY, USA

8The Frank H. Netter M.D. School of Medicine at Quinnipiac University, Bridgeport, CT, USA

Correspondence: Umar Akram Allama Iqbal Medical College, Allama Shabbir Ahmed Usmani Road, Lahore, Pakistan E-mail: umar.akram2025@gmail.com
• Received: March 8, 2025   • Revised: April 21, 2025   • Accepted: April 25, 2025

© 2025 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background/Aims
    The effectiveness of colonoscopy largely depends on the quality of bowel preparation. Polyethylene glycol (PEG) is commonly used but has certain limitations. This review evaluates whether combining PEG with linaclotide improves preparation efficacy and safety compared with PEG alone.
  • Methods
    A search was conducted in Medline, Embase, and ClinicalTrials.gov up to October 2024. Only randomized controlled trials comparing PEG combined with linaclotide versus PEG alone and reporting adenoma detection rates (ADR) or polyp detection rates (PDR) were included. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were reported.
  • Results
    A total of eight studies, including 3,071 participants, were included. Pooled analysis indicated that PEG combined with linaclotide was significantly associated with a higher ADR (RR, 1.15; 95% CI, 1.03–1.28), higher Boston bowel preparation scale score (MD, 0.31; 95% CI, 0.02–0.61), and greater willingness to repeat colonoscopy (RR, 1.16; 95% CI, 1.08–1.24). Although PDR (RR, 1.05; 95% CI, 0.89–1.24) was numerically higher in the intervention group, the difference was not statistically significant. Additionally, the intervention significantly reduced the incidence of nausea, vomiting, bloating, and abdominal pain.
  • Conclusions
    PEG combined with linaclotide is a safe alternative to PEG alone, improving ADR, bowel preparation quality, and patient comfort.
  • Keywords: Colonoscopy; Linaclotide; Meta-analysis; Polyethylene glycols
Colorectal cancer (CRC) is a major health concern both globally and in the United States. The incidence of CRC increased from 842,098 cases in 1990 to 2.17 million cases in 2019.1 The rising incidence among adults under 50 years of age has led to updated guidelines recommending screening starting at age 45.1-3 Screening methods include direct colonoscopy and a two-step process involving stool tests followed by colonoscopy.4
Colonoscopy is preferred over stool-based tests and other direct visualization methods due to its superior specificity and sensitivity. It has also contributed to a significant reduction in CRC-related mortality compared to other screening techniques.5 The efficacy of colonoscopy depends on a variety of factors, including the type and dosage of the bowel preparation regimen, comorbidities, concomitant medication use, clinical setting, and patient age.6,7 Inadequate bowel preparation can lead to numerous adverse outcomes, including incomplete visualization, reduced efficacy and safety, longer procedural times, shorter intervals between colonoscopies, and increased healthcare costs.8,9
Current guidelines recommend the use of polyethylene glycol (PEG),10,11 a laxative that forms hydrogen bonds with water to inhibit reabsorption, thereby increasing osmotic pressure and producing softer stools.12 However, PEG use is associated with several adverse effects, including diarrhea, nausea, flatulence, and abdominal cramping.13,14 Moreover, patient compliance can be reduced due to sleep disturbances, unpleasant taste, and the need for large-volume regimens.15,16
Efforts have been made to identify alternative regimens that are both effective and better tolerated by patients.17,18 One such agent is linaclotide, a guanylate cyclase C receptor agonist commonly used in the management of chronic constipation and irritable bowel syndrome.19 It has been hypothesized that linaclotide may not only offer a more tolerable alternative but also enhance the efficacy of low-dose PEG, resulting in improved bowel preparation.20 The objective of this systematic review and meta-analysis is to synthesize available evidence comparing the use of PEG combined with linaclotide versus PEG alone for bowel preparation before colonoscopy. This review aims to provide clinicians with updated evidence on this regimen and to assess its efficacy and safety compared to PEG, the most widely used purgative for bowel preparation.21
This systematic review and meta-analysis was conducted according to the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).22 The review was registered with PROSPERO (CRD42024556506). Ethical approval was not required, as the study used previously published, publicly available data.
Data sources and search strategy
We searched three electronic databases—Medline (via PubMed), Embase (via Ovid), and the Cochrane CENTRAL Library—from inception to October 2024. The clinical trial registration database (clinicaltrials.gov) was also searched for relevant trials. Additionally, reference lists of review articles identified during the search, as well as those of the final included articles, were screened to identify other potentially eligible studies.
The search strategy was developed using the following Medical Subject Headings (MeSH) terms: “Polyethylene Glycol”, “Polyethylene”, “Colonoscopy”, and “Linaclotide”. Detailed search strategies are provided in Supplementary Table 1.
Study selection
Two investigators independently assessed all potentially relevant studies. Based on the Population/Intervention/Comparator/Outcome (PICO) framework, the following inclusion criteria were used to screen eligible studies: Population, patients undergoing colonoscopy; Intervention, using PEG combined with linaclotide for bowel preparation; Comparator, PEG solution alone; and Outcome, polyp detection rate (PDR), adenoma detection rate (ADR), cecal insertion time (CIT), cecal intubation rate (CIR), or bowel preparation scores. Only randomized controlled trials (RCTs) and studies published in English were considered. Bowel preparation scores were assessed using the Boston bowel preparation scale (BBPS). Review articles, commentaries, conference abstracts, studies lacking sufficient data, animal studies, and non-randomized trials were excluded. Any discrepancy between the two investigators was resolved by consulting a third investigator. Definitions of clinical outcomes reported by included studies are detailed in Supplementary Table 2.
Data extraction
Two investigators independently extracted the following data from the finalized studies: first author’s surname, year of publication, study location, type of colonoscopy, clinical setting of colonoscopy, type of intervention, preparation regimen, sample size, mean age, body mass index (BMI), PDR, ADR, CIT, CIR, BBPS score, rate of adequate bowel preparation, willingness to repeat colonoscopy, and adverse events (AEs). Any discrepancies between the two investigators were resolved through consultation with a third investigator.
Quality assessment
Two reviewers independently assessed the quality of the included studies using the revised version of the Cochrane Risk of Bias tool for randomized trials (RoB 2). This tool evaluates five domains of a randomized study to reach an overall risk-of-bias judgment: bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in the measurement of the outcome, and bias in the selection of the reported result. Any disagreements were resolved by a third investigator.
Statistical analysis
Statistical analysis was performed using R ver. 4.4.0 (R Foundation for Statistical Computing) with the “meta” and “metasens” packages. For continuous outcomes, including BBPS scores and CIT, mean differences (MDs) with 95% confidence intervals (CIs) were calculated and pooled using the inverse variance method. For dichotomous outcomes—including ADR, PDR, CIR, willingness to repeat colonoscopy, and AEs—risk ratios (RRs) with 95% CIs were calculated and pooled using the Mantel-Haenszel method within a random-effects model.23 The Knapp-Hartung adjustment was applied to the CIs to account for potential statistical heterogeneity.24 Variance was calculated using the Paule-Mandel estimator25 for dichotomous outcomes and the restricted maximum likelihood estimator26 for continuous outcomes. Heterogeneity was assessed using the cutoff values in accordance with the Cochrane Handbook of Systematic Reviews of Interventions for the Higgins I2 statistic, keeping in view the results of the chi-squared test—0% to 40%, low heterogeneity; 30% to 60%, moderate heterogeneity; 50% to 90%, substantial heterogeneity; and 75% to 100%, considerable heterogeneity.27 Where more than two studies were included, sensitivity analysis was conducted by sequentially omitting one study at a time. A two-tailed p-value <0.05 was considered statistically significant throughout. Publication bias was not assessed because fewer than ten studies were included.
To avoid unit-of-analysis errors, when multiple arms from the same study were compared to a shared control group, we combined the intervention groups as recommended.27
Since our meta-analysis included both constipated and non-constipated patients undergoing colonoscopy, subgroup analyses were performed based on patient population (constipated vs. non-constipated) for the outcomes ADR, PDR, and BBPS scores. Additionally, a separate analysis was conducted based on the volume of bowel preparation consumed to assess the efficacy of low-volume preparations (≤2 liters protocol) for the same outcomes.
Certainty of evidence
The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.28 A summary of effects table was generated using the GRADEpro Guideline Development Tool (Supplementary Table 3).29
Study selection and study characteristics
A total of 3,584 records were identified through a comprehensive literature search. After removing duplicates, 2,389 articles underwent primary screening, with eight RCTs ultimately included in the systematic review and meta-analysis. Results of the full-text screening, along with reasons for exclusion, are provided in Supplementary Table 4. The screening process is detailed in the PRISMA flow diagram (Fig. 1).
This systematic review and meta-analysis included 3,579 participants from eight RCTs,30-37 with 1,952 participants (54.5%) receiving PEG in combination with linaclotide and 1,627 participants (45.5%) receiving PEG alone. The mean age of participants was 48.8±11.8 years in the intervention group and 50.0±11.7 years in the control group. All included studies were conducted in China. A split-dose regimen was used for colonoscopy preparation in all studies, with one study employing both split-dose and same-day regimens. The mean BMI was reported as 23.1 kg/m2 in the intervention group and 23.4 kg/m2 in the control group. Baseline characteristics of the included studies are summarized in Table 1.30-37
Risk of bias and Certainty of evidence assessment
Our quality assessment revealed a low risk of bias in all included studies, except for Yang et al.,33 which was rated as having some concerns. Detailed results of the risk of bias assessment are presented in Supplementary Figures 1 and 2.
We also evaluated the certainty of the evidence based on parameters including risk of bias, inconsistency, indirectness, imprecision, and publication bias. The findings are summarized in Supplementary Table 2.30-37
Meta-analysis results

1) Adenoma detection rate

In the meta-analysis of seven RCTs30-32,34-37 involving 3,239 participants that reported ADR, pooled analysis revealed a significantly higher ADR in patients receiving PEG combined with linaclotide compared to those receiving PEG alone (RR, 1.15; 95% CI, 1.03–1.28; p=0.02; I2=0%; Fig. 2).
Subgroup analysis showed that PEG+linaclotide significantly increased ADR in non-constipated patients compared to PEG alone (RR, 1.23; 95% CI, 1.13–1.34; p<0.01; I2=0%; Fig. 3). For constipated patients, the pooled ADR was numerically higher in the PEG+linaclotide group but was not statistically significant (RR, 1.10; 95% CI, 0.88–1.37, p=0.28; I2=0%; Fig. 3).
Additionally, pooled ADR from five RCTs using a low-volume protocol revealed no significant difference between the two groups (RR, 1.14; 95% CI, 0.95–1.35; p=0.11; I2=0%; Supplementary Fig. 3).

2) Polyp detection rate

Seven RCTs30-35,37 including 3,250 participants reported PDR. Pooled analysis revealed a slightly higher PDR in patients receiving PEG combined with linaclotide, though the difference was not statistically significant (RR, 1.05; 95% CI, 0.92–1.19; p=0.43; I2=28%; Fig. 4).
Leave-one-out sensitivity analysis, conducted by removing Zhang et al.,31 reduced the heterogeneity to zero; however, the overall results remained non-significant (RR, 1.08; 95% CI, 0.99–1.18, p=0.08; I2=0%; Supplementary Fig. 4).
Subgroup analysis indicated that PEG+linaclotide did not significantly increase PDR compared to PEG alone in either constipated (RR, 1.10; 95% CI, 0.97–1.24; p=0.09; I2=0%; Fig. 5) or non-constipated patients (RR, 0.91; 95% CI, 0.73–1.13; p=0.20; I2=0%; Fig. 5).
Furthermore, pooled PDR from five RCTs using a low-volume protocol showed no significant difference between the two groups (RR, 1.03; 95% CI, 0.89–1.19; p=0.57; I2=19%; Supplementary Fig. 5).

3) Boston bowel preparation scale score

BBPS was reported by six RCTs31-36 including 2,310 participants. Pooled analysis showed a significant increase in BBPS scores among patients receiving linaclotide in combination with PEG compared to those receiving PEG alone (MD, 0.31; 95% CI, 0.02–0.61; p=0.04; I2=76%; Fig. 6).
Omitting Zhang et al.31 in the sensitivity analysis significantly reduced heterogeneity while maintaining the significance of the overall results, as shown in Supplementary Figure 6.
Subgroup analysis revealed that PEG+linaclotide significantly increased BBPS scores in constipated patients compared to PEG alone (MD, 0.43; 95% CI, 0.05–0.80; p=0.04; I2 = 53%; Fig. 7). In non-constipated patients, the pooled BBPS score was not significantly different between the two groups (MD, 0.09; 95% CI, –2.34 to 2.52; p=0.73; I2=60%; Fig. 7).
Furthermore, pooled analysis from four RCTs using a low-volume protocol revealed no significant difference in BBPS scores between patients receiving PEG+linaclotide and those receiving PEG alone (MD, 1.37; 95% CI, –1.96 to 4.71; p=0.28; I2=99%; Supplementary Fig. 7).
Secondary outcomes
Adequate bowel preparation rates were reported by five RCTs30-32,34,35 including 2,247 participants. Pooled analysis suggested a numerically higher rate in patients receiving linaclotide in combination with PEG, although the difference was not statistically significant (RR, 1.08; 95% CI, 0.94–1.23; p=0.21; I2=82%; Supplementary Fig. 8). Sensitivity analysis did not alter the results.
Pooled analyses for CIT (MD, 0.11; 95% CI, –0.90 to 1.11; p=0.76; I²=79%; Supplementary Fig. 9), CIR (RR, 1.00; 95% CI, 0.99–1.01; p=0.64; I²=0%; Supplementary Fig. 10), and withdrawal time (MD, –0.10; 95% CI, –0.84 to 0.64; p=0.69; I2=80%; Fig. 4C) showed no significant differences between the two groups. Removing Wang et al.35 from the CIT analysis significantly reduced heterogeneity; however, the overall effect remained non-significant, as shown in Supplementary Figure 11. Willingness to repeat colonoscopy was reported by seven studies including 3,205 participants. Pooled analysis revealed a significantly higher willingness among patients receiving PEG combined with linaclotide compared to those receiving PEG alone (RR, 1.16; 95% CI, 1.08–1.24; p<0.01; I2=66%; Fig. 8). Sensitivity analysis, conducted by removing Liu et al.37 reduced heterogeneity to 0% while maintaining the significance of the overall results (Supplementary Fig. 12).
Several AEs were reported across the included studies. The incidences of nausea (RR, 0.61; 95% CI, 0.46–0.81; p<0.01, I2=50%), vomiting (RR, 0.48; 95% CI, 0.32–0.74; p<0.01; I2=20%), bloating (RR, 0.76; 95% CI, 0.67–0.85; p<0.01; I2=9%), and abdominal pain (RR, 0.61; 95% CI, 0.41–0.89; p=0.02; I2=50%) were significantly reduced with the use of PEG combined with linaclotide compared to PEG alone. However, other AEs, including headache (RR, 0.83; 95% CI, 0.06–10.62; p=0.52; I2=0%) and dizziness (RR, 0.73; 95% CI, 0.11–5.0; p=0.28; I2=0%), were not significantly associated with either preparation. Sensitivity analyses conducted by removing Zhang et al.,32 Wang et al.35 and Wu et al.30 (abdominal pain) reduced heterogeneity to 0% while maintaining the significance of the overall results, as shown in Supplementary Figures 13–15. Pooled AEs are summarized in Table 2.30,32,34,35
Publication bias
Publication bias was not assessed because fewer than ten studies were included in the meta-analysis.
In this systematic review and meta-analysis, we observed a significantly higher ADR, BBPS score, and willingness to repeat colonoscopy with the use of PEG combined with linaclotide for colonoscopy preparation compared to PEG alone. However, no significant differences were observed for other outcomes such as PDR, CIR, CIT, and withdrawal time. In terms of AEs, PEG combined with linaclotide reduced the incidence of nausea, vomiting, bloating, and abdominal pain, while no differences were observed for headache and dizziness compared to PEG alone. Subgroup analysis revealed that PEG combined with linaclotide increased ADR in non-constipated patients and improved BBPS scores in constipated patients.
ADR is the primary indicator for determining the effectiveness of colonoscopies, demonstrating an inverse relationship with the future risk of CRC.38 Several factors influence ADR, including the experience and training of the endoscopist, as well as patient age and sex, with lower detection rates generally observed in females.39 Our results showed higher ADR rates with the use of PEG combined with linaclotide. As a guanylate cyclase-2C (GC-2C) agonist, linaclotide increases intestinal fluid secretion and transit, potentially improving bowel cleansing for colonoscopy preparation. Poor or suboptimal colonoscopy preparation often necessitates repeat procedures, and patients may be reluctant to undergo another preparation process, leading to missed follow-up appointments. Ultimately, suboptimal bowel preparation is associated with an increased risk of interval CRC, likely due to missed early detection opportunities.40 Because ADR requires histopathological evaluation of polyps, PDR is often used as a surrogate marker due to its strong positive correlation with ADR.41,42 In our analysis, we observed an improvement in ADR but not in PDR with PEG combined with linaclotide. According to Murphy et al.,41 while the difference between ADR and PDR may seem subtle, it carries important clinical implications. ADR specifically reflects the detection of adenomatous (precancerous) polyps, which are directly linked to CRC risk, whereas PDR includes all polyp types, including non-neoplastic lesions such as hyperplastic polyps, which have minimal or no malignant potential.41 Our results suggest that the addition of linaclotide may specifically improve the detection of precancerous polyps. Since the risk of cancer is more strongly associated with larger polyps,43 we hypothesize that PEG combined with linaclotide facilitates better bowel cleansing, thereby enhancing the detection of adenomas within size ranges that could otherwise be missed with inadequate preparation. We also observed a greater BBPS score with PEG combined with linaclotide, directly indicating better bowel preparation and a cleaner colon, which facilitates the detection of polyps and other pathological features.44 Achieving optimal colonoscopy preparation during the first procedure is crucial for ensuring the best patient outcomes. However, it is important to note that the high heterogeneity observed in the BBPS score analysis was largely attributable to variations in dosing regimens, colonoscopy settings, and patient demographic characteristics reported in Zhang et al.31 After omitting this study, heterogeneity was significantly reduced.
Our subgroup analysis compared outcomes between constipated and non-constipated patients. Constipation often complicates colonoscopy due to two main factors: difficulty with cecal intubation and poor bowel preparation.45 Our results showed better BBPS scores in constipated patients, which may ease colonoscopic procedures in this population. Linaclotide has been shown to be effective in treating chronic constipation and irritable bowel syndrome with constipation by increasing intestinal fluid secretion and accelerating intestinal transit,46 which likely explains its benefits in improving BBPS among constipated patients.47 However, ADR was not significantly increased in this subgroup. Besides poor bowel preparation, constipation is associated with elongation and looping of bowel segments, such as the sigmoid colon, which can also impair polyp detection.45 A cohort study48 conducted in Israel in 2024 similarly reported that constipation does not increase the risk of CRC or PDR. Nevertheless, although linaclotide improved BBPS scores—indicating enhanced bowel cleansing in constipated patients—no significant improvement was observed in clinical outcomes related to the detection of precancerous lesions. Several constipation-related factors, such as prolonged colonic transit time compared to non-constipated patients, could potentially affect polyp visibility or formation.49
In patients at risk of CRC, repeated colonoscopies are required for screening purposes.50 Our results revealed greater willingness to undergo repeat colonoscopy with PEG combined with linaclotide compared to PEG alone. Linaclotide is known to inhibit pain receptors in the colon,51 which may lead to a better overall patient experience and contribute to greater willingness to undergo repeat procedures. Furthermore, we observed a lower incidence of nausea, vomiting, bloating, and abdominal pain with the PEG and linaclotide combination. This may be attributed to decrease in the required dose of PEG when combined with linaclotide, as reduced PEG volume has been associated with a lower incidence of nausea.36 This reduction may further improve patient perceptions and increase adherence to recommended screening guidelines. It is pertinent to note that one of the reasons for suboptimal preparation is patients' inability to tolerate the unpleasant taste of PEG, which can induce vomiting.52 Vomiting is one of the most important adverse effects during colonoscopy preparation,53 and mitigating this factor may directly lead to higher success rates. This is further evidenced by the non-inferiority of the PEG and linaclotide combination compared to PEG alone regarding other AEs. We did not find any significant associations with other predictors of colonoscopy preparation. This lack of association likely reflects imprecision in effect estimates and highlights the need for further research to confirm these findings.
This is the first meta-analysis to evaluate the efficacy and safety of PEG combined with linaclotide in participants undergoing colonoscopy. The major strength of our meta-analysis lies in its restriction to RCTs, complemented by robust subgroup and sensitivity analyses, which helped address heterogeneity. Additionally, all included studies had a low risk of bias. However, several limitations should be considered when interpreting our results. Some outcomes may be subject to small-study effects, potentially representing publication bias due to unpublished studies. Moreover, we could not analyze the size of detected lesions, as this information was not reported by the included studies. Another limitation is that all the included studies originated from China. This may be explained by the current approval status of linaclotide, which is approved by the US Food and Drug Administration only for the treatment of irritable bowel syndrome with predominant constipation and chronic idiopathic constipation. A trial underway at the University of Florida, expected to conclude in 2025, is anticipated to provide new insights into the use of linaclotide as a bowel preparation agent in Western populations.54 Until robust data from diverse populations become available, clinicians should exercise caution in applying our findings to broader populations. Significant differences in bowel preparation practices and outcomes have been reported between Western and Asian countries due to various risk factors,55 underscoring the need for region-specific evidence before widespread adoption of linaclotide for colonoscopy preparation.
Traditionally, 4-liter PEG has been considered the gold standard for colonoscopy preparation,56 with strong evidence suggesting that split-dose preparation is more effective.57 Despite its good efficacy, the high volume required with 4 L PEG is associated with several adverse effects, which can negatively impact patient compliance. Various alternatives have been explored, but currently, the only approved low-volume PEG preparation is 2 L PEG combined with ascorbate.58 Given that colonoscopy preparation is often an uncomfortable experience for patients, interventions that improve this process are critical for enhancing compliance. Linaclotide combined with PEG may offer a promising option for patients who are otherwise unlikely to adhere to traditional preparation regimens, as the addition of linaclotide appears to reduce the required volume of PEG. Moving forward, RCTs with larger sample sizes are needed to further evaluate this combination and to compare different dosage regimens in order to determine the optimal preparation strategy. Additionally, studies involving diverse populations are essential to ensure the generalizability of the findings.
In conclusion, linaclotide in combination with PEG significantly improves BBPS scores and increases willingness to repeat colonoscopy. It also reduces the incidence of vomiting, and the resulting better patient experience is likely to enhance compliance. Future studies should include diverse populations and explore the effects of different dosage regimens to optimize bowel preparation strategies.
Supplementary Table 1. Detailed search strategy of each database.
ce-2025-073-Supplementary-Table-1.pdf
Supplementary Table 2. Definitions of clinical outcomes provided by the included studies.
ce-2025-073-Supplementary-Table-2.pdf
Supplementary Table 3. Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence assessment.
ce-2025-073-Supplementary-Table-3.pdf
Supplementary Table 4. Full-text screening results with reasons of exclusion.
ce-2025-073-Supplementary-Table-4.pdf
Supplementary Fig. 1. Traffic light plot showing risk of bias assessment.
ce-2025-073-Supplementary-Fig-1.pdf
Supplementary Fig. 2. Summary plot showing risk of bias assessment.
ce-2025-073-Supplementary-Fig-2.pdf
Supplementary Fig. 3. Pooled adenoma detection rate from studies consuming low volume bowel preparation.
ce-2025-073-Supplementary-Fig-3.pdf
Supplementary Fig. 4. Leave-one-analysis for polyp detection rate.
ce-2025-073-Supplementary-Fig-4.pdf
Supplementary Fig. 5. Pooled polyp detection rate from studies consuming low volume bowel preparation.
ce-2025-073-Supplementary-Fig-5.pdf
Supplementary Fig. 6. Leave-one-analysis for Boston bowel preparation scale.
ce-2025-073-Supplementary-Fig-6.pdf
Supplementary Fig. 7. Pooled Boston bowel preparation scale from studies consuming low volume bowel preparation.
ce-2025-073-Supplementary-Fig-7.pdf
Supplementary Fig. 8. Forest plot of pooled adequate bowel preparation.
ce-2025-073-Supplementary-Fig-8.pdf
Supplementary Fig. 9. Forest plot of pooled cecal insertion time.
ce-2025-073-Supplementary-Fig-9.pdf
Supplementary Fig. 10. Forest plot of pooled cecal intubation rate.
ce-2025-073-Supplementary-Fig-10.pdf
Supplementary Fig. 11. Leave-one-analysis for cecal insertion time.
ce-2025-073-Supplementary-Fig-11.pdf
Supplementary Fig. 12. Leave-one-analysis for willingness to repeat colonoscopy.
ce-2025-073-Supplementary-Fig-12.pdf
Supplementary Fig. 13. Leave-one-analysis for vomiting.
ce-2025-073-Supplementary-Fig-13.pdf
Supplementary Fig. 14. Leave-one-analysis for nausea.
ce-2025-073-Supplementary-Fig-14.pdf
Supplementary Fig. 15. Leave-one-analysis for abdominal pain.
ce-2025-073-Supplementary-Fig-15.pdf
Supplementary materials related to this article can be found online at https://doi.org/10.5946/ce.2025.073.
Fig. 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram representing the study selection process.
ce-2025-073f1.jpg
Fig. 2.
Forest plot of pooled adenoma detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
ce-2025-073f2.jpg
Fig. 3.
Subgroup analysis (constipated vs non-constipated patients) of pooled adenoma detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
ce-2025-073f3.jpg
Fig. 4.
Forest plot of pooled polyp detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
ce-2025-073f4.jpg
Fig. 5.
Subgroup analysis (constipated vs non-constipated patients) of pooled polyp detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
ce-2025-073f5.jpg
Fig. 6.
Forest plot of pooled Boston bowel preparation scale (BBPS) score. PEG, polyethylene glycol; SD, standard deviation; IV, intravenous; CI, confidence interval.
ce-2025-073f6.jpg
Fig. 7.
Subgroup analysis (constipated vs non-constipated patients) of Boston bowel preparation scale scores. PEG, polyethylene glycol; SD, standard deviation; IV, intravenous; CI, confidence interval.
ce-2025-073f7.jpg
Fig. 8.
Forest plot of pooled willingness to repeat colonoscopy. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
ce-2025-073f8.jpg
ce-2025-073f9.jpg
Table 1.
Baseline characteristics of the individual studies included in the systematic review and meta-analysis
Baseline characteristic Song et al.36 Wang et al.35 Yang et al.33 Zhang et al.31 Zhang et al.32 Liu et al.37 Xu et al.34 Wu et al.30
Study location China China China China China China China China
Study design RCT RCT RCT RCT RCT RCT RCT RCT
Colonoscopy time Afternoon Afternoon N/R Afternoon Morning and afternoon N/R N/R N/R
Colonoscopy setting N/R N/R Outpatient Outpatient and inpatient Outpatient N/R Outpatient N/R
Regimen Split dose Split dose Split dose Split dose and same day dose Split dose Split dose Split dose Split dose
Intervention PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide
Control PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone
Sample size (n)
 Intervention 128 376 142 273 144 498 160 231
 Control 127 126 124 275 288 251 159 227
Age (yr, mean±SD)
 Intervention 50.4±12.4 49.6±9.6 48.6±13.3 45.1±11.8 50.7±10.9 50.8±10.8 53.7±11.9 42.0±12.5
 Control 49.8±11.0 50.0±10.4 49.8±12.4 46.4±11.5 51.2±10.7 50.7±12.0 53.2±11.5 42.0±12.2
Sex (M/F)
 Intervention 45/83 76/300 67/75 140/133 74/70 241/257 82/78 170/61
 Control 52/75 22/104 54/70 156/119 155/133 127/124 85/74 146/81
BMI (kg/m2, mean±SD)
 Intervention 22.9±3.1 22.8±3.1 N/R 22.4±2.1 24.3±3.9 23.2±3.2 22.9±2.1 23.0±3.3
 Control 23.1±2.9 23.5±3.5 N/R 22.5±2.1 24.5±3.5 23.7±3.5 23.1±2.0 23.5±3.2

RCT, randomized controlled trial; N/R, not reported; PEG, polyethylene glycol; SD, standard deviation; M, male; F, female; BMI, body mass index.

Table 2.
Pooled adverse events included in the meta-analysis
Adverse event No. of studies Events/total
 RR CI (p) I2(%) L1O analysis
PEG+linaclotide PEG alone
Bloating 7 647/2,007 515/1,193 0.76 0.67–0.85 (<0.01) 9 Wu et al.30 (RR, 0.72; 95% CI, 0.65–0.81; p<0.01; I2=0%)
Nausea 6 357/1,576 381/1,217 0.61 0.46–0.81 (<0.01) 50 Wang et al.35 (RR, 0.57; 95% CI, 0.48–0.68; p<0.01; I2=0%)
Vomiting 6 68/1,576 144/1,217 0.48 0.32–0.74 (<0.01) 20 Zhang et al.32 (RR, 0.42; 95% CI, 0.27–0.67; p<0.01; I²=0%)
Xu et al.34 (RR, 0.54; 95% CI, 0.37–0.79; p=0.01; I²= 0%)
Abdominal pain 6 199/1,509 227/1,148 0.61 0.41–0.89 (<0.01) 50 Wu et al.30 (RR, 0.55; 95% CI, 0.41–0.75; p<0.01; I2=0%)
Headache 2 5/288 6/286 0.83 0.06–10.62 (0.52) 0 -
Dizziness 2 8/288 11/286 0.73 0.11–5.0 (0.28) 0 -

PEG, polyethylene glycol; RR, risk ratio; CI, confidence interval; I2, heterogeneity; L1O, leave-one-out; -, not possible.

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    • Linaclotide combined with polyethylene glycol for bowel preparation in colonoscopy: a systematic review and meta-analysis of randomized controlled trials
      Gilmara Coelho Meine, Gregory Thomas Brennan, Lucas Monteiro Delgado, Paula Santo, Olufemi Osikoya
      Surgical Endoscopy.2025;[Epub]     CrossRef

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      Efficacy and safety of polyethylene glycol in combination with linaclotide versus polyethylene glycol alone for colonoscopy: a grade-assessed systematic review and meta-analysis
      Clin Endosc. 2025;58(5):670-683.   Published online September 1, 2025
      DOI: https://doi.org/10.5946/ce.2025.073
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    Efficacy and safety of polyethylene glycol in combination with linaclotide versus polyethylene glycol alone for colonoscopy: a grade-assessed systematic review and meta-analysis
    Image Image Image Image Image Image Image Image Image
    Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram representing the study selection process.
    Fig. 2. Forest plot of pooled adenoma detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
    Fig. 3. Subgroup analysis (constipated vs non-constipated patients) of pooled adenoma detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
    Fig. 4. Forest plot of pooled polyp detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
    Fig. 5. Subgroup analysis (constipated vs non-constipated patients) of pooled polyp detection rates. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
    Fig. 6. Forest plot of pooled Boston bowel preparation scale (BBPS) score. PEG, polyethylene glycol; SD, standard deviation; IV, intravenous; CI, confidence interval.
    Fig. 7. Subgroup analysis (constipated vs non-constipated patients) of Boston bowel preparation scale scores. PEG, polyethylene glycol; SD, standard deviation; IV, intravenous; CI, confidence interval.
    Fig. 8. Forest plot of pooled willingness to repeat colonoscopy. PEG, polyethylene glycol; MH, Mantel-Haenszel; CI, confidence interval.
    Graphical abstract

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    Graphical abstract

    Efficacy and safety of polyethylene glycol in combination with linaclotide versus polyethylene glycol alone for colonoscopy: a grade-assessed systematic review and meta-analysis
    Baseline characteristic Song et al.36 Wang et al.35 Yang et al.33 Zhang et al.31 Zhang et al.32 Liu et al.37 Xu et al.34 Wu et al.30
    Study location China China China China China China China China
    Study design RCT RCT RCT RCT RCT RCT RCT RCT
    Colonoscopy time Afternoon Afternoon N/R Afternoon Morning and afternoon N/R N/R N/R
    Colonoscopy setting N/R N/R Outpatient Outpatient and inpatient Outpatient N/R Outpatient N/R
    Regimen Split dose Split dose Split dose Split dose and same day dose Split dose Split dose Split dose Split dose
    Intervention PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide PEG+linaclotide
    Control PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone PEG alone
    Sample size (n)
     Intervention 128 376 142 273 144 498 160 231
     Control 127 126 124 275 288 251 159 227
    Age (yr, mean±SD)
     Intervention 50.4±12.4 49.6±9.6 48.6±13.3 45.1±11.8 50.7±10.9 50.8±10.8 53.7±11.9 42.0±12.5
     Control 49.8±11.0 50.0±10.4 49.8±12.4 46.4±11.5 51.2±10.7 50.7±12.0 53.2±11.5 42.0±12.2
    Sex (M/F)
     Intervention 45/83 76/300 67/75 140/133 74/70 241/257 82/78 170/61
     Control 52/75 22/104 54/70 156/119 155/133 127/124 85/74 146/81
    BMI (kg/m2, mean±SD)
     Intervention 22.9±3.1 22.8±3.1 N/R 22.4±2.1 24.3±3.9 23.2±3.2 22.9±2.1 23.0±3.3
     Control 23.1±2.9 23.5±3.5 N/R 22.5±2.1 24.5±3.5 23.7±3.5 23.1±2.0 23.5±3.2
    Adverse event No. of studies Events/total
    		 RR CI (p) I2(%) L1O analysis
    PEG+linaclotide PEG alone
    Bloating 7 647/2,007 515/1,193 0.76 0.67–0.85 (<0.01) 9 Wu et al.30 (RR, 0.72; 95% CI, 0.65–0.81; p<0.01; I2=0%)
    Nausea 6 357/1,576 381/1,217 0.61 0.46–0.81 (<0.01) 50 Wang et al.35 (RR, 0.57; 95% CI, 0.48–0.68; p<0.01; I2=0%)
    Vomiting 6 68/1,576 144/1,217 0.48 0.32–0.74 (<0.01) 20 Zhang et al.32 (RR, 0.42; 95% CI, 0.27–0.67; p<0.01; I²=0%)
    Xu et al.34 (RR, 0.54; 95% CI, 0.37–0.79; p=0.01; I²= 0%)
    Abdominal pain 6 199/1,509 227/1,148 0.61 0.41–0.89 (<0.01) 50 Wu et al.30 (RR, 0.55; 95% CI, 0.41–0.75; p<0.01; I2=0%)
    Headache 2 5/288 6/286 0.83 0.06–10.62 (0.52) 0 -
    Dizziness 2 8/288 11/286 0.73 0.11–5.0 (0.28) 0 -
    Table 1. Baseline characteristics of the individual studies included in the systematic review and meta-analysis

    RCT, randomized controlled trial; N/R, not reported; PEG, polyethylene glycol; SD, standard deviation; M, male; F, female; BMI, body mass index.

    Table 2. Pooled adverse events included in the meta-analysis

    PEG, polyethylene glycol; RR, risk ratio; CI, confidence interval; I2, heterogeneity; L1O, leave-one-out; -, not possible.

    Table 1.

    Table 2.

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