Li WM, Wang XP, Li YX, Wang YD, Sun YJ, Li GD, Wu JQ. Efficacy of linaclotide with polyethylene glycol at high risk of inadequate bowel preparation: A randomized controlled trial. World J Gastrointest Surg 2026; 18(6): 119538 [DOI: 10.4240/wjgs.119538]
Corresponding Author of This Article
Jia-Qi Wu, MD, Doctor, Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Hangzhou 310000, Zhejiang Province, China. wujiaqi_12@126.com
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Li WM, Wang XP, Li YX, Wang YD, Sun YJ, Li GD, Wu JQ. Efficacy of linaclotide with polyethylene glycol at high risk of inadequate bowel preparation: A randomized controlled trial. World J Gastrointest Surg 2026; 18(6): 119538 [DOI: 10.4240/wjgs.119538]
Wei-Min Li, Xiao-Peng Wang, Yi-Jie Sun, Guo-Dong Li, Jia-Qi Wu, Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310000, Zhejiang Province, China
Yu-Xuan Li, School of Clinical Medicine, Hangzhou Normal University, Hangzhou 310000, Zhejiang Province, China
Yi-Dong Wang, Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Author contributions: Li WM and Wang XP contributed equally to this work as co-first authors, and were primarily responsible for conceptualization, design, data collection, formal analysis and writing-original draft; Wu JQ contributed to conceptualization, design, data collection, formal analysis and writing-original draft; Li YX and Sun YJ contributed to data collection, formal analysis; Wang YD and Li GD contributed to design, formal analysis, writing-review and editing, supervision; and all authors read and approved the final manuscript.
Supported by the Hangzhou Biomedical and Health Industry Development Support Technology Special Project, No. 2023WJC080; and the Hangzhou Medical and Health Science and Technology Project, No. A20251519.
Institutional review board statement: The study was approved by the Institutional Review Board of the Affiliated Hospital of Hangzhou Normal University, No. 2023(E2)-HS-033.
Clinical trial registration statement: This trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2500111663).
Informed consent statement: All study participants were fully informed. Written informed consents were obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets used in this study are available from the corresponding author on reasonable request.
Corresponding author: Jia-Qi Wu, MD, Doctor, Department of Gastroenterology, The Affiliated Hospital of Hangzhou Normal University, No. 126 Wenzhou Road, Hangzhou 310000, Zhejiang Province, China. wujiaqi_12@126.com
Received: February 2, 2026 Revised: March 11, 2026 Accepted: April 1, 2026 Published online: June 27, 2026 Processing time: 144 Days and 22.5 Hours
Abstract
BACKGROUND
Adequate bowel preparation is fundamental for colonoscopy. The traditional strategy of 3 L polyethylene glycol (PEG) is often unsatisfactory for people at high risk of inadequate bowel preparation (HR-IBP).
AIM
To evaluate bowel preparation quality and adverse events associated with 3 L PEG combined with linaclotide in the HR-IBP population.
METHODS
This single-center, endoscopist-blinded, randomized controlled trial enrolled patients scheduled for colonoscopy. A total of 167 patients were randomly allocated to either the 3 L PEG group or the 3 L PEG plus linaclotide group. The quality of bowel preparation was assessed using the Boston bowel preparation scale (BBPS). The adenoma detection rate (ADR), polyp detection rate (PDR), polyp characteristics, and adverse events were also analyzed.
RESULTS
BBPS scores were significantly higher in the 3 L PEG plus linaclotide group than in the 3 L PEG alone group (6.800 ± 1.444 vs 5.593 ± 1.579, P < 0.001). The adequate bowel preparation rate was also markedly higher in the 3 L PEG plus linaclotide group (86.250% vs 58.025%, P < 0.001). ADR, PDR, polyp characteristics, and adverse events were comparable between the groups.
CONCLUSION
The combination of 3 L PEG and linaclotide is optimal for bowel cleansing in high-risk cohorts.
Core Tip: This randomized controlled trial evaluated the efficacy of 3 L polyethylene glycol combined with linaclotide in patients at high risk of inadequate bowel preparation. Linaclotide significantly improved bowel cleansing and the adequacy of bowel preparation. No differences were observed between the groups in adenoma detection rate, polyp detection rate, polyp characteristics, or adverse events. This novel evidence supports the use of 3 L polyethylene glycol with linaclotide for bowel cleansing in high-risk populations.
Citation: Li WM, Wang XP, Li YX, Wang YD, Sun YJ, Li GD, Wu JQ. Efficacy of linaclotide with polyethylene glycol at high risk of inadequate bowel preparation: A randomized controlled trial. World J Gastrointest Surg 2026; 18(6): 119538
Colonoscopy is the most effective strategy for detecting and diagnosing colorectal lesions and is especially valuable for early screening of colorectal cancer. Prompt diagnosis and treatment of precancerous lesions can significantly reduce colorectal cancer mortality[1]. The quality of bowel preparation directly determines the effectiveness of colonoscopy. Adequate bowel preparation not only improves lesion detection rates but also facilitates smoother endoscopic procedures by reducing patient discomfort and the risk of potential complications[2]. Currently, a split-dose regimen of 3 L polyethylene glycol (PEG) is recommended for bowel preparation[3]. However, in patients at high risk of inadequate bowel preparation (HR-IBP), such as older adults, or patients with constipation and diabetes, the recommended regimen often fails to achieve optimal bowel cleanliness, thereby compromising the diagnostic accuracy of colonoscopy[4-6]. To date, no official protocol for bowel preparation is available for these populations, and more clinical evidence is needed to guide future practice.
Given that increasing PEG volume inevitably reduces patient tolerability, researchers have focused on combining PEG with prokinetic agents for bowel preparation. Linaclotide, a guanylate cyclase-C agonist, is widely administrated to alleviate chronic constipation and constipation-predominant irritable bowel syndrome by enhancing intestinal secretion and providing visceral analgesia[7,8]. These pharmacological effects align well with the requirements for bowel preparation for colonoscopy. Recently, emerging studies have revealed that the combination of linaclotide and PEG is an effective and well-tolerated regimen for bowel preparation[9-11]. However, this combined regimen has not been sufficiently investigated in high risk populations. Our study evaluated the efficacy of linaclotide plus 3 L PEG vs 3 L PEG alone in HR-IBP populations, as a more personalized and effective bowel preparation regimen would be valuable in clinical practice.
MATERIALS AND METHODS
Study design
This prospective, single-blind, randomized controlled trial was conducted at the Endoscopy Center of the Affiliated Hospital of Hangzhou Normal University (Hangzhou, Zhejiang Province, China). The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Hangzhou Normal University, No. 2023(E2)-HS-033 and registered in the Chinese Clinical Trial Registry (No. ChiCTR2500111663).
Participants recruitment
Participant recruitment occurred between August 1, 2023, and December 31, 2024. The inclusion criteria were: (1) Patients with HR-IBP and at least one of the following: Chronic constipation, age ≥ 70 years, body mass index > 25 kg/m2, diabetes mellitus, a history of abdominopelvic surgery, or chronic use of high-risk medications (tricyclic antidepressants, opioids, or antidepressants)[4-6]; (2) Age ≥ 19 years, regardless of sex; (3) Ability to understand the study procedures and methods; (4) Willingness to provide written informed consent; and (5) Ability to adhere strictly to the clinical trial protocol. The exclusion criteria were as follows: (1) A history of acute cardiovascular or cerebrovascular accident within previous 6 months; (2) Severe underlying conditions such as cardiac, pulmonary, hepatic, or renal dysfunction; (3) Known coagulation disorders; (4) A history of severe gastroparesis or bowel obstruction; (5) Known or suspected gastrointestinal perforation or obstruction; (6) Severe psychiatric disorders that would impair the ability to comply with the study protocol; (7) Known hypersensitivity to bowel preparation agents; and (8) Any other condition deemed by the investigator to make the patient unsuitable for participation in the trial.
Sample size
The sample size was calculated dependent on our center’s prior experience and prior studies of linaclotide in chronic constipation patients[12,13]. To achieve 90% power at a significance level of 0.05, the sample size was calculated using power analysis and sample size 11, yielding an estimated sample size of approximately 67 participants per group. Considering potential dropout and noncompliance, we increased the sample size by 20%, resulting in a target enrollment of approximately 80 participants for the study.
Randomization and blinding
Each eligible patient was randomly assigned in a 1:1 ratio to either the 3 L PEG alone group or the 3 L PEG plus linaclotide group using computer-generated random numbers. The randomization codes were sealed in opaque envelopes and kept by an independent nurse who was not involved in data collection or outcome analysis. All experienced endoscopists and investigators involved in data collection were blinded to group assignment, the randomization process, and subsequent procedures.
Bowel preparation protocol and colonoscopy
Patients were informed about the procedure. A low-residue diet was recommended for 2 days before colonoscopy. In the 3 L PEG alone group, patients received a bowel preparation regimen consisting of 1 L of compounded PEG electrolyte solution (Hengkangzhengqing, Jiangxi Hengkang Pharmaceutical Co., Ltd., China) taken orally at 18:00 on the evening before colonoscopy. In addition, 2 L of compounded PEG electrolyte solution with 20 mL of dimethyl silicone oil (Sichuan Jianeng Pharmaceutical Co., Ltd., Leshan, Sichuan Province, China) was taken orally 6 hours before colonoscopy. In the 3 L PEG plus linaclotide group, patients took one tablet (290 μg) of linaclotide (Linzess, AstraZeneca, Cambridge, United Kingdom) on the morning before the procedure. Similarly, 1 L of the PEG solution was administered orally at 18:00 on the evening before colonoscopy. Six hours before the examination on the day of colonoscopy, each patient took another linaclotide tablet (290 μg) orally, together with 2 L of PEG electrolyte solution. Colonoscopy was performed by experienced endoscopists (more than 5 years of endoscopic experience) using an Olympus CF-290 L colonoscope (Olympus, Tokyo, Japan).
Outcome evaluation
The Boston bowel preparation scale (BBPS), a well-recognized instrument, was used to measure bowel preparation quality[14]. Briefly, the colon consisted of three segments: The right colon (cecum and ascending colon), transverse colon (including the hepatic and splenic flexures), and left colon (descending colon, sigmoid colon, and rectum). The preparation quality of each segment was scored from 0 to 3.
A total BBPS score of ≥ 6, with ≥ 2 for each segment, was defined as adequate bowel preparation. All participating endoscopists received thorough training in the appropriate application of the BBPS. BBPS scores were assessed independently by two endoscopists. In addition, the polyp detection rate (PDR), adenoma detection rate (ADR), and incidence of adverse events were collected and analyzed. PDR was the percentage of colonoscopies in which at least one polyp was identified among the total number of colonoscopies performed. ADR was the percentage of colonoscopies in which at least one adenoma was identified among the total number of colonoscopies performed. The number and size of colorectal polyps, as well as the number of adenomas, were recorded during colonoscopy. After colonoscopy, adverse events, including nausea, bloating, vomiting, and abdominal pain, were evaluated in patients administrated with PEG plus linaclotide or PEG alone.
Statistical analysis
Statistical analyses were conducted using SPSS version 25.0 (IBM, Armonk, NY, United States). Continuous variables were presented as mean ± SD and were analyzed using the Mann-Whitney U test. Categorical variables were analyzed using Pearson’s χ2 test or Pearson’s χ2 test with Yates’ continuity correction. A P value < 0.05 was considered statistically significant.
RESULTS
Participants characteristics
The study’s flowchart is shown in Figure 1. A total of 179 participants with HR-IBP were screened for enrollment. After excluding three who were involved in exclusion criteria and nine who refused to participate, 167 patients were eligible for the study. After randomization, 81 patients were assigned to the 3 L PEG group, and 80 to the 3 L PEG plus linaclotide group. Baseline patient characteristics showed no difference between the groups (Table 1).
Outcomes of bowel preparation and colonoscopy results
Bowel cleansing quality was evaluated using the BBPS. Our study showed that the overall BBPS score was 5.593 ± 1.579 in the 3 L PEG group and 6.800 ± 1.444 in the 3 L PEG plus linaclotide group (P < 0.001, Table 2). In each bowel segment, the BBPS score was also significantly higher in the 3 L PEG plus linaclotide group than in the 3 L PEG group (Table 2). The rate of adequate bowel preparation was 58.025% in the 3 L PEG group and 86.250% in the 3 L PEG plus linaclotide group (P < 0.001, Table 2). PDR and ADR are two quality indicators for colonoscopy. Our findings showed that ADR and PDR were comparable between the groups (Table 3). We also analyzed polyp characteristics in patients with detected polyps. The results showed that the number and size of polyps, as well as the number of adenomas, did not differ between two groups (Table 4).
Table 2 Comparison of the Boston score between the two groups, mean ± SD.
In our study, patients reported mild discomfort during procedure, including nausea, vomiting, abdominal pain, abdominal bloating, dizziness, and headache (Table 5). All adverse events resolved without treatment, highlighting the tolerability of this strategy. No severe adverse events occurred in the study population. Furthermore, no significant difference was observed in these adverse events between two groups (Table 5).
Table 5 Comparison of adverse events between the two groups.
To date, colonoscopy has been regarded as the gold standard for screening colorectal lesions, particularly colorectal cancer. Adequate bowel preparation is indispensable for ensuring a high-quality colonoscopy, whereas inadequate bowel preparation undermines its effectiveness. Our study indicated that split-dose 3 L PEG plus linaclotide markedly improved bowel preparation quality in the HR-IBP population, as reflected in the BBPS score and rate of adequate preparation. Thus, this study provides clinical evidence supporting the use of modified regimens to improve colonoscopy in HR-IBP populations.
PEG is the most widely used intestinal preparation agent because of its strong cleansing efficacy and favorable safety profile[15]. In China, a split-dose regimen of 3 L PEG is the preferred bowel preparation regimen for colonoscopy[3]. With population aging, the number of individuals with HR-IBP is increasing, and conventional bowel preparation regimens often result in suboptimal cleansing[4-6]. These issues are closely associated with factors such as bowel motility disorders, drug-related adverse effects, disease-induced pathophysiological changes, and anatomical alterations resulting from previous surgeries[4,16-18]. To date, no standard strategy has been recommended for HR-IBP populations, partly because of the lack of clinical evidence. Recently, Song et al[19] investigated the PEG plus linaclotide in patients with chronic constipation, an independent risk factor for inadequate bowel preparation. Among the different strategies evaluated, namely, 4 L PEG, 3 L PEG, 3 L PEG + linaclotide, and 2 L PEG + linaclotide, 3 L PEG + linaclotide was found to be the most effective, consistent with our results[19,20]. Similarly, another study by Wang et al[13] found that addition of linaclotide in 3 L or 4 L PEG regimens significantly improved bowel preparation quality in constipation patients. Interestingly, the researchers found that administering linaclotide twice, on day of colonoscopy and 2 days before colonoscopy, resulted in a higher BBPS score than administering it only on the day of colonoscopy. This finding may be related to the therapeutic effects of linaclotide on constipation. Our study further extends the use of the 3 L PEG plus linaclotide regimen to all HR-IBP patients, and the findings support its suitability for this population.
Early detection of adenomas and polyps is crucial for reducing colorectal cancer mortality, and studies have confirmed that ADR and PDR are two important symbols of bowel preparation quality[21,22]. Accumulating evidence suggests that regimens with the same volume, such as 1 L, 2 L, and 3 L PEG with or without linaclotide, do not affect ADR or PDR[9,13,23]. Consistent with these findings, our study showed no significant differences between the groups in ADR, PDR, or polyp characteristics. The overall PDR and ADR in both groups appeared to be higher than those reported in previous studies[9,13,23]. This discrepancy may be resulted from the inclusion of a population at relatively high risk for adenomas and polyps, because factors such as age, obesity, and diabetes mellitus are closely associated with both inadequate bowel preparation and the development of adenomas and polyps[24,25]. Therefore, these data suggest that high-quality bowel preparation provides a clearer view for endoscopists, but does not necessarily result in a higher detection rate of different types of polyps[26].
Ingesting a large volume of liquid over a short period can cause adverse events such as nausea and vomiting during bowel preparation. Therefore, low-volume, well-tolerated regimens are desirable. According to recent studies, the combination of 1 L or 2 L PEG plus linaclotide may represent a promising future strategy. Two studies reported that the addition of linaclotide to 2 L PEG significantly improved the quality of bowel preparation compared with 3 L or 4 L PEG alone[11,19]. Two other studies suggested that bowel cleanliness was similar between 2 L PEG with linaclotide and 4 L PEG alone[9,27]. These findings indicate that the addition of linaclotide to 2 L PEG provides bowel preparation that is similar or superior to that achieved with the standard regimen. Promisingly, these findings suggest that reduced-volume regimens are associated with fewer adverse reactions[9,11,19,27]. Furthermore, Zhang et al[10] explored the use of 1 L PEG with linaclotide in low-risk patients and found that 1 L PEG with linaclotide was noninferior to 2 L PEG and was associated with fewer adverse events. In HR-IBP populations, we currently use 3 L PEG for bowel preparation, and our results showed that adverse effects were comparable between the groups. To date, it remains unclear whether low-volume regimens can be applied in HR-IBP populations. Although Maeda et al[23] reported that the addition of linaclotide to 1 L PEG plus ascorbic acid resulted in a high rate of adequate bowel preparation (94%), more clinical evidence is needed in HR-IBP populations.
This study had some limitations. First, this was a single-center study, which limits the generalizability of our findings. In addition, the sample size was relatively small, and a larger sample could be included in future studies. Second, there is no gold standard for defining HR-IBP populations. In this study, predictive factors for inadequate bowel preparation were used to define the HR-IBP population, as per previous studies. Third, low-volume regimens for high-risk patients, such as 1 L or 2 L PEG plus linaclotide, were not included in the study design. Finally, data such as adverse events largely depend on participants’ subjective reporting, making some degree of bias inevitable.
CONCLUSION
Our study demonstrated that the addition of linaclotide to 3 L PEG markedly improved bowel cleanliness in the HR-IBP population, highlighting its potential for future clinical practice. Further studies are required to evaluate the effects of increasing the linaclotide dose or reducing the PEG dose on bowel cleanliness in HR-IBP populations.
ACKNOWLEDGEMENTS
We sincerely thank all the participants who enrolled in this study. Specially, we thank Shen N, from Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, for her assistance in biostatistics.
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