Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy

Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy Haifeng Lan, Qiuyan Yang, Changqing Sun, Mei Shao, Qing Gao, Juan Wei, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7391900/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Aim This study aims to evaluate the efficacy and safety of low-dose 2L lactulose combined with linaclotide for bowel preparation prior to colonoscopy. Methods This was a single-blind, randomized controlled clinical study enrolling patients undergoing colonoscopy. All participants were randomly assigned in a 1:1:1 ratio to three groups: the 2L lactulose + linaclotide (L) group, the 2L lactulose group, and the 3L polyethylene glycol (PEG) group. The primary outcome was bowel cleansing quality evaluated using the Boston Bowel Preparation Scale (BBPS). Secondary outcomes included colonoscopy findings, palatability, tolerability, and acceptability, assessed via the Visual Analog Scale (VAS), sleep quality, and willingness to repeat the preparation. Safety was evaluated based on adverse events. Additionally, a subgroup analysis was conducted for patients with constipation. Results A total of 366 patients were included in the intention-to-treat (ITT) analysis. The adequate bowel preparation rates were significantly higher in the 2L lactulose + L group (90.1%; 95% confidence interval [CI], 83.5%-94.2%) and the 2L lactulose group (83.5%; 95% CI, 75.8%-89.0%) compared to the 3L PEG group (74.2%; 95% CI, 65.8%-81.1%; p = 0.004). The 2L lactulose + L group had significantly lower incidence of nausea (19.0% vs 32.3%, p = 0.018), vomiting (9.1% vs 18.5%, p = 0.032), and bloating (15.7% vs 35.5%, p < 0.001) compared to the 3L PEG group. There were no significant differences between the combined 2L lactulose + L group and the 2L lactulose group in terms of bowel preparation efficacy, palatability, tolerability, or willingness to repeat the regimen; however, both groups were superior to the 3L PEG group in these aspects. The 3L PEG group was more likely to cause sleep disturbances compared to the 2L lactulose group (p = 0.016). No significant differences were observed among the three groups in Boston Bowel Preparation Scale (BBPS) scores, polyp detection rate, adenoma detection rate, or cancer detection rate. In the subgroup analysis of patients with constipation, the three groups showed comparable efficacy; however, the 2L lactulose + L group had a higher BBPS score in the right colon compared to the 2L lactulose group (p = 0.014). Conclusion Low-dose 2L Lactulose combined with linaclotide regimen demonstrates superior potential than 3L PEG in terms of efficacy, safety, and patient experience, offering a more optimal alternative for bowel preparation. lactulose linaclotide bowel preparation colonoscopy Figures Figure 1 Figure 2 Background Colorectal cancer (CRC) has emerged as a major global public health issue, with rising mortality and prevalence rates and an increasingly younger age of onset, imposing a significant economic burden worldwide [ 1 ] .According to an analysis of 2022 global cancer statistics, approximately 1,925,828 individuals were diagnosed with CRC and 903,643 died from the disease in 2022. Nearly 30% of global new CRC cases and deaths annually occur in China [ 2 ] .Consequently, population-based, organized CRC screening programs have been implemented in China and European countries [ 3 , 4 ] .Early detection and resection of colorectal adenomas can effectively block their progression to cancer, thereby preventing the occurrence and development of CRC [ 5 , 6 ] .Colonoscopy is the gold standard for evaluating colonic lesions, and the adequacy of bowel preparation is crucial for optimal colonoscopy performance [ 7 ] .Although various clinical bowel preparation regimens are available, 18%-35% of patients still have suboptimal bowel preparation [ 6 ] ,highlighting the necessity for further optimization of bowel preparation protocols. Polyethylene glycol (PEG), an inert polymer of ethylene oxide, is a non-absorbable isotonic solution and one of the most common methods for colon cleansing [ 8 ] . In European and American countries, high-dose 4L PEG is predominantly used as the conventional bowel preparation regimen for colonoscopy [ 9 ] . However, the large volume of fluid intake required for 4L PEG increases the incidence of adverse events such as nausea, vomiting, and bloating. Currently, a modified split-dose 3L PEG regimen is widely recommended for bowel preparation before colonoscopy in the Chinese population [ 10 , 11 ] . Nevertheless, due to the poor palatability of PEG, which leads to an unpleasant experience for patients, compliance and tolerance are reduced, thereby affecting the quality of bowel preparation [ 12 ] . Lactulose, a non-absorbable disaccharide, has demonstrated favorable application effects in bowel preparation for adult colonoscopy in clinical practice. It features a better taste profile, less intestinal irritation, good patient compliance, and broad applicability, particularly suitable for children and sensitive populations [ 11 , 13 ] .It has emerged as a novel alternative for bowel preparation prior to colonoscopy, with multiple studies showing that lactulose outperforms PEG in terms of colon cleansing efficacy, patient tolerance, and palatability [ 13 – 15 ] .Although occasional mild discomfort may occur [ 15 ] , its effectiveness and safety as a bowel preparation agent for colonoscopy have been well-established [ 16 ] . Linaclotide stimulates intestinal motility and fluid secretion by activating guanylate cyclase-C, thereby alleviating symptoms such as bloating, abdominal pain, and discomfort to some extent [ 17 ] .Current studies have shown that linaclotide can serve as an effective adjuvant for bowel preparation when combined with polyethylene glycol (PEG) of varying volumes (1L/2L/3L), enhancing colon cleansing efficacy while reducing fluid intake and the incidence of adverse events [ 18 – 20 ] .However, the optimal combination regimen, dosing, and treatment duration for linaclotide remain under exploration [ 21 ] . To our knowledge, no prior studies have investigated the combination of linaclotide and lactulose as an alternative bowel preparation regimen. According to the consensus recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer, low-volume regimens are advised for patients at low risk of inadequate bowel preparation [ 7 ] .Therefore, this study conducted a single-center, single-blind, randomized controlled trial to evaluate the efficacy and safety of a novel low-volume (2L) lactulose regimen combined with 290 µg linaclotide for bowel preparation. Materials and Methods Study Design and Patients This study was a single-center, observer-blind, randomized controlled clinical trial conducted in the Department of Gastroenterology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. Outpatients undergoing colonoscopy between December 2024 and April 2025 were enrolled. All participants were assigned to groups in the outpatient clinic, followed by scheduling of colonoscopy appointments. Inclusion Criteria: (1) Signed a written informed consent form; (2) Aged ≥ 18 years, regardless of gender; (3) Able to comply with the follow-up plan, objectively describe symptoms, and cooperate in completing questionnaires; (4) Not participating in any other clinical trials within 3 months prior to the trial or during the trial period. Exclusion Criteria: (1) Any contraindications for colonoscopy (e.g., gastrointestinal obstruction or perforation, severe acute inflammatory bowel disease, toxic megacolon, severe heart failure, renal failure, or hepatic failure); (2) Patients with galactosemia; (3) Lactating or pregnant women, or those planning to become pregnant during the trial; (4) Patients with allergies to bowel preparation medications; (5) Patients who withdraw from the trial for any other reason. This study strictly adhered to the principles of the Declaration of Helsinki and was approved by the hospital’s Medical Ethics Committee (approval number: DZQH-KYLL-24-35). It was also registered on ClinicalTrials.gov (registration number: NCT06748638). All participants signed an informed consent form after being fully informed. Detailed information on the study drugs and procedures were provided in Supplement 1 and 2. Intervention All participants were instructed to follow a low-fiber, easily digestible, and colorless diet 1–3 days prior to the examination [ 22 ] .Dinner was concluded at 6:00 PM the day before the procedure, followed by fasting for 6 hours and water restriction for 4 hours prior to the examination. 2L Lactulose Group: At 8:00 PM the day before the examination, participants dissolved two boxes of lactulose in 1000 mL of water and slowly consumed the solution within 2 hours. An additional third box of lactulose was dissolved in 1000 mL of water and slowly ingested 4–6 hours prior to the examination. 2L Lactulose + Linaclotide (2L Lactulose + L) Group: Participants received a single 290 µg dose of linaclotide at 12:00 PM (noon) the day before the examination. Subsequently, lactulose was administered following the same protocol as the 2L Lactulose Group: two boxes dissolved in 1000 mL of water at 8:00 PM the day before, and a third box dissolved in 1000 mL of water 4–6 hours prior to the examination. 3L PEG Group: Polyethylene glycol (PEG) at 8:00 PM the day before the examination, followed by 2L of PEG 4–6 hours prior to the procedure. All participants in this group added one bottle of simethicone emulsion (20 mL/bottle) to the final 2L PEG dose, which was then consumed. Participants were advised to engage in moderate physical activity after each dose until clear or pale yellow liquid stool was achieved. To enhance adherence, trained physicians provided face-to-face explanations to participants, along with printed instructions and educational videos. These materials covered detailed steps of bowel preparation, precautions, management of adverse events, and the consequences of inadequate bowel preparation. Primary Outcome The primary outcome was the adequacy rate of bowel preparation, which was evaluated using the Boston Bowel Preparation Scale (BBPS) to assess bowel cleansing quality. An adequate bowel preparation was defined as a BBPS score of ≥ 6, with each colonic segment (left colon, transverse colon, right colon) scoring > 2 points. The adequacy rate was calculated as (number of successful cases / total number of cases) × 100%. Each colonic segment was scored on a scale of 0–3 points, with a total score ranging from 0–9 points. Higher scores indicated better bowel preparation quality. Secondary Outcomes The secondary outcomes included the Bowel Bubble Score (BBS), colonoscopy findings, including polyp detection rate (proportion of patients with at least one detected polyp), adenoma detection rate, and cancer detection rate (proportion of patients with at least one pathologically confirmed adenoma or cancer), cecal intubation rate (proportion of patients with successful cecal intubation), palatability (taste satisfaction, rated as good/fair/poor), tolerability (via the Visual Analog Scale, VAS), acceptability, including sleep quality (rated as good/same as before/poor), willingness to repeat the procedure (yes/no), and compliance, safety assessed by adverse events (AEs). Additionally, a subgroup analysis was conducted for patients with constipation. BBPS, VAS and BBS scoring criteria see Supplement 1 for details. Sample Size Estimation and Statistical Analysis Sample size calculation was performed using PASS 15 software. Based on prior studies [ 7 , 16 , 23 , 24 ] ,the assumed adequacy rates of bowel preparation were 90% for the 2L Lactulose + L Group, 86% for the 2L Lactulose Group, and 69% for the 3L PEG Group. A two-sided significance level of α = 0.05 was set for both pairwise comparisons, with 80% power. Participants were allocated in a 1:1:1 ratio. Considering a potential 20% dropout rate, approximately 138 patients were planned for each group, resulting in a minimum total enrollment of approximately 414 patients. Efficacy endpoints were assessed in the intention-to-treat (ITT) population (all randomized patients), while safety was evaluated in the treated population. The 95% confidence intervals (CIs) for the bowel preparation adequacy rate were summarized using the Wilson method. All p-values were not adjusted using the Bonferroni correction. All data analyses were conducted with R version 4.5.0. Data analysis included both the ITT and per-protocol (PP) analysis sets. The ITT analysis set comprised all patients who were randomized and received treatment, excluding those who met inclusion criteria but did not take any study medication or undergo colonoscopy. The PP analysis set included patients who completed all study procedures, excluding those with inadequate bowel preparation, incomplete colonoscopy, or non-compliance with the study drug regimen. Randomization and Masking Participants were allocated in a 1:1:1 ratio using randomization software, with a mixed block design and fixed enrollment method, the width of the interval is 6. Endoscopists were blinded to the participants' group allocation, and participants were explicitly instructed not to disclose their study allocation to either the endoscopists or the investigators. Results Baseline Characteristics A total of 444 participants were randomized, with 148 participants in each group. Among them, 366 participants (121 in the 2L Lactulose + L Group, 121 in the 2L Lactulose Group, and 124 in the 3L PEG Group) were included in the ITT analysis. Additionally, 337 participants (113 in the 2L Lactulose + L Group, 110 in the 2L Lactulose Group, and 114 in the 3L PEG Group) were included in the per-protocol (PP) analysis (Supplement 1). In the ITT population, the median age was 36 years (interquartile range: 28 to 54 years), with 263 participants (71.8%) being male. The mean Body Mass Index (BMI) was 23.6 kg/m², and 37 participants (10.1%) had a history of constipation. A total of 266 participants (72.7%) underwent colonoscopy for the first time. Colonoscopy procedures were performed by 8 endoscopists. The baseline characteristics, including age, gender, BMI, constipation history, and prior colonoscopy experience, were evenly distributed across the three groups (Table 1 ). Table 1 Baseline characteristics (intention-to-treat population) 2L Lactulose + L (n = 121) 2L Lactulose (n = 121) 3L PEG (n = 124) Age (yr), median (IQR) 37.0 (29.5,54.0) 36.0 (27.0,50.5) 34.0 (28.0,58.8) Sex, n(%) Male 87 (71.9) 83 (68.6) 93 (75.0) Female 34 (28.1) 38 (31.4) 31 (25.0) BMI (kg/m 2 ), mean ± SD 23.6 ± 2.54 23.5 ± 2.65 23.85 ± 2.71 Medical history, n(%) Drinking 25 (20.7) 19 (15.7) 24 (19.4) Smoking 37 (30.6) 29 (24.0) 44 (35.5) Hypertension 14 (11.6) 15 (12.4) 14 (11.3) Diabetes 2 (1.7) 4 (3.3) 5 (4.0) Coronary heart disease 1 (0.8) 5 (4.1) 3 (2.4) Abdominal pelvic surgery 8 (6.6) 7 (5.8) 2 (1.6) Previous colectomy 3 (2.5) 2 (1.7) 2 (1.6) Constipation 14 (11.6) 10 (8.3) 13 (10.5) Others 21 (17.4) 24 (19.8) 24 (19.4 First colonoscopy, n (%) 86 (71.1) 95 (78.5) 85 (68.5) Indication, n (%) Screening 26 (21.5) 28 (23.1) 20 (16.1) Diagnosis 71 (58.7) 79 (65.3) 84 (67.7) Surveillance 24 (19.8) 14 (11.6) 20 (16.1) General anesthesia, n (%) 114 (94.2) 117 (96.7) 116 (93.5) Endoscopist, n (%) Ⅰ 36 (29.8) 29 (24.0) 43 (34.7) Ⅱ 27 (22.3) 30 (24.8) 26 (21.0) Ⅲ 14 (11.6) 23 (19.0) 11 (8.9) Ⅳ 14 (11.6) 12 (9.9) 13 (10.5) Ⅴ 11 (9.1) 16 (13.2) 12 (9.7) Ⅵ 12 (9.9) 5 (4.1) 13 (10.5) Ⅶ 5 (4.1) 5 (4.1) 5 (4.0) Ⅷ 2 (1.7) 1 (0.8) 1 (0.8) 2L Lactulose + L = 2L Lactulose + 290ug Linaclotide. 3L PEG = 3L Polyethylene glycol. BMI, Body Mass Index. *Screening: Screening or Physical Examination. This mainly includes individuals requesting colonoscopy due to reasons such as elevated tumor markers, esophagitis, gastritis, gastric ulcer, and other gastric symptoms. Diagnosis: Diagnosis with Definite Symptoms. This includes abdominal symptoms such as diarrhea, abdominal pain, occult blood or blood in stool, weight loss, etc. Surveillance: Follow-up or Re-examination. This applies to individuals with a history of enteritis, intestinal polyps, tumors, surgery, or hemorrhoids. Data are presented as [Median (IQR)], mean ± standard deviation (SD) or n (%). Primary Outcome The adequacy rate of bowel preparation in the 2L Lactulose + L group (90.1% [95% CI: 83.5 to 94.2]) was significantly higher than that in the 3L PEG group (74.2% [95% CI: 65.8 to 81.1]) and similar to that in the 2L Lactulose group (83.5% [95% CI: 75.8 to 89.0]). The adequacy rate of bowel preparation in the 2L Lactulose group was comparable to that in the 3L PEG group(Fig. 1 ). However, a significant difference was observed between the two groups in the PP analysis. In both ITT and PP analyses, the 2L Lactulose + L group outperformed the 3L PEG group in terms of total BBPS scores and segmental scores (right colon, transverse colon, and left colon), with no statistically significant differences compared to the 2L Lactulose group. The 2L Lactulose group showed superior total BBPS scores and right/left colon segmental scores compared to the 3L PEG group, but no significant difference was found in the transverse colon segmental score (Supplement 1: Table S1 ). No significant differences in bowel bubble scores were observed among the three groups ( Supplement 1: Table S2 ). Secondary Outcomes Colonoscopy Finds Colonoscopy finds, including the detection rates of polyps, adenomas, and cancers, as well as the cecal intubation rate. In the PP population, there were no significant differences among the three groups in terms of polyp detection rate (46.0% vs 40.0% vs 46.5%, p = 0.554), adenoma detection rate (13.3% vs 17.3% vs 16.7%, p = 0.675), or cancer detection rate. Cecal intubation was successfully completed in all patients (Table S3 ). Palatability, Tolerability, and Acceptability There were no significant differences between the 2L Lactulose + L group and the 2L Lactulose group in terms of palatability proportion (p = 0.180), tolerability VAS scores (p = 0.620, Fig. 2 ), and willingness to repeat the regimen (p = 1.000). However, both the 2L Lactulose + L and 2L Lactulose groups scored significantly higher than the 3L PEG group in these aspects (p < 0.05). The 3L PEG group had a higher incidence of sleep disturbances compared to the 2L Lactulose group (p = 0.016). No significant differences in compliance were observed among the three groups (p = 0.895)(Table 2 ). Table 2 Palatability and acceptability (intention-to-treat population). 2L Lactulose + L (n = 121) 2L Lactulose (n = 121) 3L PEG (n = 124) p-value p-value * p-value & p-value # Palatability, n(%) <0.001 <0.001 0.180 <0.001 Best 98(81.0) 108(89.3) 54(43.5) Moderate 22(18.2) 12(9.9) 50(40.3) Worse 1(0.8) 1(0.8) 20(16.1) Sleep quality, n (%) 0.068 0.402 0.179 0.016 Best 81(66.9) 91(75.2) 73(58.9) Same as before 34(28.1) 22(18.2) 42(33.9) Worse 6(5.0) 8(6.6) 9(7.3) Willing to repeat,n(%) 108(89.3) 108(89.3) 73(58.9) <0.001 <0.001 1.000 <0.001 Compliance, n (%) 117(96.7) 117(96.7) 121(97.6) 0.895 0.974 1.000 0.974 2L Lactulose + L = 2L Lactulose + 290ug Linaclotide. 3L PEG = 3L Polyethylene glycol . p-value * , 2L Lactulose + L vs 3L PEG; p -value & , 2L Lactulose + L vs 2L Lactulose; p -value # , 2L Lactulose vs 3L PEG. Data are presented as n (%). Adverse Events Table 3 presents the incidence of adverse events (including nausea, vomiting, bloating, and abdominal pain) in the ITT population. The 2L Lactulose + L group had a significantly lower incidence of overall adverse events (28.9% vs 47.6%, p = 0.003), nausea (19.0% vs 32.3%, p = 0.018), vomiting (9.1% vs 18.5%, p = 0.032), and bloating (15.7% vs 35.5%, p < 0.001) compared to the 3L PEG group. No significant differences were observed between the 2L Lactulose + L group and the 2L Lactulose group in these adverse events. The 2L Lactulose group also showed a lower incidence of vomiting (9.1% vs 18.5%, p = 0.032) and bloating (21.5% vs 35.5%, p = 0.015) compared to the 3L PEG group, but no significant differences were found in overall adverse events or nausea incidence (p > 0.05). The three groups had similar incidences of abdominal pain. Table 3 Adverse events (intention-to-treat population). 2L Lactulose + L (n = 121) 2L Lactulose (n = 121) 3L PEG (n = 124) p-value p-value * p-value & p-value # Adverse events, n (%) Total 35(28.9) 46(38.0) 59(47.6) 0.011 0.003 0.134 0.130 Nausea 23(19.0) 27(22.3) 40(32.3) 0.043 0.018 0.525 0.081 Vomiting 11(9.1) 11(9.1) 23(18.5) 0.033 0.032 1.000 0.032 Bloating 19(15.7) 26(21.5) 44(35.5) 0.001 <0.001 0.247 0.015 Abdominal pain 14(11.6) 18(14.9) 15(12.1) 0.710 0.899 0.448 0.524 2L Lactulose + L = 2L Lactulose + 290ug Linaclotide. 3L PEG = 3L Polyethylene glycol . p-value * , 2L Lactulose + L vs 3L PEG; p -value & , 2L Lactulose + L vs 2L Lactulose; p -value # , 2L Lactulose vs 3L PEG. Data are presented as n (%). Analysis of Constipation Subgroups In the PP population, a subgroup of 35 patients with constipation (14 cases in the 2L Lactulose + L group, 10 cases in the 2L Lactulose group, and 11 cases in the 3L PEG group) was analyzed for bowel preparation quality. The results showed that the 2L Lactulose + L group had higher values than the 2L Lactulose and 3L PEG groups in terms of bowel preparation adequacy rate (85.7% vs 70.0% vs 72.7%, p = 0.608), total BBPS scores [7 (6,8) vs 7 (4,8) vs 6 (5,8), p = 0.699], right colon segmental score [2 (2,3) vs 2 (1,2) vs 2 (1,2), p = 0.043], transverse colon segmental score [2 (2,3) vs 2 (1,3) vs 2 (2,3), p = 0.673], and left colon segmental score [3 (2,3) vs 3 (2,3) vs 2 (2,3), p = 0.813], with no statistically significant differences observed. Notably, the 2L Lactulose + L group had a higher right colon segmental score compared to the 2L Lactulose group [2 (2,3) vs 2 (1,2), p = 0.014], while the 2L Lactulose group and the 3L PEG group showed comparable bowel cleansing efficacy (Table S5). Discussion Early colonoscopy is the most intuitive method for colorectal cancer (CRC) screening. Inadequate bowel preparation can lead to reduced detection rates of polyps and adenomas, unsuccessful screening, and an increased likelihood of repeated procedures [ 21 , 25 ] . Therefore, providing patients with regimens that offer good palatability, high comfort, and require a low volume of fluid intake is crucial. A study investigating the efficacy of lactulose versus PEG based on body mass index (BMI) showed that lactulose oral solution outperformed PEG in terms of bowel preparation quality and palatability, particularly in the normal BMI group and the higher BMI group. It can be considered a potential and promising bowel preparation agent for clinical use [ 13 ] . Linaclotide, as a novel adjuvant medication for bowel preparation, has only been preliminarily explored in randomized controlled trials in combination with PEG or magnesium sulfate [ 5 , 6 ] . Due to the small sample sizes and limited data, larger-scale studies are needed to evaluate the efficacy of linaclotide. Therefore, this study adopted a low dose of 2L lactulose and investigated whether combining it with linaclotide could improve the adequacy rate of bowel cleansing [ 26 ] , aiming to further explore the efficacy of linaclotide in various bowel preparation regimens. The results of this study demonstrated that the 2L Lactulose + Linaclotide group achieved an adequate bowel preparation rate of 90.1%, meeting the minimum threshold of > 90% recommended by the US Multi-Society Task Force on Colorectal Cancer [ 7 ] . In terms of efficacy and BBPS scores, this group outperformed the 3L PEG group and showed comparable performance to the 2L Lactulose group. The 2L Lactulose group exhibited superior cleansing efficacy in the entire colon, right colon, and left colon compared to the 3L PEG group. Notably, while previous bowel preparation regimens often showed suboptimal cleansing in the right colon, both the 2L Lactulose + L and 2L Lactulose groups in this study demonstrated better right colon cleansing than the 3L PEG group. However, the underlying reason for this observation remains unclear, as the addition of linaclotide did not further enhance efficacy compared to lactulose alone. Consequently, it was not possible to determine whether linaclotide enhanced or diminished its role in bowel preparation. Linaclotide is known to increase intestinal fluid secretion and accelerate intestinal motility [ 26 , 27 ] . We hypothesize that the similar efficacy between the 2L Lactulose + L and 2L Lactulose groups may be due to a greater volume of residual fluid in the colon, which could lower BBPS scores, or potentially related to the relatively low dose of linaclotide used or its early administration time. No significant differences in intestinal bubble scores were observed among the three groups, likely attributable to the administration of simethicone defoaming agent 4–6 hours prior to colonoscopy. No serious adverse events other than common gastrointestinal symptoms were reported in any participants before or after colonoscopy. The incidence of adverse events (nausea, vomiting, bloating) in the 2L Lactulose + L group was significantly lower than that in the 3L PEG group. Compared with the 2L Lactulose group, the 2L Lactulose + L group did not show a reduced incidence of adverse events. The 2L Lactulose group demonstrated a lower incidence of vomiting and abdominal distension compared to the 3L PEG group, while the incidence of abdominal pain was comparable across all three groups. Overall, both the 2L Lactulose + L and 2L Lactulose regimens effectively reduced the occurrence of adverse events, indicating reliable safety profiles. Regarding palatability, tolerance (VAS scores), and willingness to repeat the regimen, there were no significant differences between the 2L Lactulose + L and 2L Lactulose groups, but both groups outperformed the 3L PEG group. The 3L PEG group had a statistically significantly higher incidence of sleep disturbances compared to the 2L Lactulose group. Compliance did not differ significantly among the three groups, ruling out its impact on bowel preparation quality. These findings suggest that the 2L Lactulose + L regimen enhanced patient experience to some extent.。 A single-center randomized controlled trial (RCT) using 870 µg linaclotide combined with 3L polyethylene glycol (PEG) for bowel preparation in patients with constipation demonstrated superior efficacy compared to 4L PEG, particularly in elderly patients [ 28 ] . Additionally, a 1L PEG with ascorbic acid (PEG-Asc) plus 500 mg linaclotide regimen significantly improved efficacy and adenoma detection rate compared to a senna-based regimen, without compromising tolerability [ 29 ] . Therefore, a subgroup analysis was conducted in the per-protocol (PP) population of patients with constipation in this study. The 2L Lactulose + Linaclotide group showed higher bowel preparation success rates (85.7% vs. 70.0% vs. 72.7%, p = 0.608) and segmental BBPS scores compared to the 2L Lactulose and 3L PEG groups, though the differences were not statistically significant. Notably, the 2L Lactulose + Linaclotide group had statistically significantly higher right colon scores than the 2L Lactulose group. This suggests that linaclotide use may enhance right colon cleanliness in patients with constipation, but given the small sample size in the subgroup analysis, further confirmation is warranted. This study has several limitations. First, a significant number of patients did not undergo colonoscopy, resulting in a small sample size for analysis. Second, the subgroup analysis focused only on patients with constipation; the quality of bowel preparation in patients with irritable bowel syndrome (IBS) or other diseases (particularly inflammatory bowel disease, IBD) was not assessed. Future studies are needed to analyze bowel preparation efficacy based on specific diseases. Third, data on adverse events, patient satisfaction, and sleep quality were collected using unvalidated questionnaires, introducing potential subjectivity. Finally, certain metrics—such as adverse reactions specifically related to linaclotide, time to first bowel movement, and bowel movement frequency—were not recorded separately. Additionally, objective indicators including waiting time, colonoscopy duration, and electrolyte levels were not measured. In conclusion, the 2L Lactulose + Linaclotide regimen demonstrated superior performance compared to the 3L PEG group in terms of efficacy, safety, tolerability, and acceptability, while requiring less fluid intake, making it an effective alternative for bowel preparation. However, future studies should aim to expand the sample size and conduct multicenter clinical trials. Additionally, further research is needed to determine the optimal dosage and administration method of linaclotide as an adjunctive medication for bowel preparation. Conclusions The 2L Lactulose + L regimen is an effective and safe bowel preparation protocol. The 2L Lactulose + L regimen outperforms the 3L PEG regimen in terms of bowel cleansing efficacy, palatability, and incidence of adverse events (nausea, vomiting, abdominal distension). The addition of linaclotide reduces fluid intake volume and enhances patient satisfaction. Abbreviations Abbreviations /acronyms Definitions ADR Adenoma Detection Rate AEs Adverse Events BBPS Boston Bowel Preparation Scale BBS Bowel Bubble Score BMI Body Mass Index CI Confidence Interval ESGE European Society of Gastrointestinal Endoscopy GC-C Guanylate Cyclase-C IBS Irritable Bowel Syndrome ITT Intention-to-Treat PP Per-Protocol PDR Polyp Detection Rate PEG Polyethylene Glycol RCT Randomized Controlled Trial VAS Visual Analogue Scale Declarations Ethics approval and consent to participate This study strictly followed the principles of the Declaration of Helsinki. It has been approved by the Medical Ethics Committee of Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University (approval number: DZQH-KYLL-24-35) and registered on ClinicalTrials.gov (registration number: NCT06748638). All participants signed the informed consent form with full knowledge. Consent for publication Not applicable. Availability of data and materials The data underlying this article will be shared on reasonable request to the corresponding author. Conflict of Interest There are no conflicts of interest to declare by the authors. Funding This study received financial support from the Clinical Special Project of Nanjing General Hospital of Nanjing Military Command (2023LCYYQH024) and the Jiangsu Province Elderly Health Research Project (LKM2022030). All authors are very appreciative of the financial support. Author Contributions The project and experimental designs were formulated by JX, JW and QY. HL and QY conducted experiments and analyzed the resulting data. QY, MS, CS and QG assisted in certain experiments and data analyses. HL wrote this manuscript. The manuscript was revised by JX. All authors have read and approved the final version of the manuscript. Acknowledgements Not applicable. References Li J, Kuang X. 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Theunissen F, Lantinga MA, Ter Borg PCJ, et al. Efficacy of different bowel preparation regimen volumes for colorectal cancer screening and compliance with European Society of Gastrointestinal Endoscopy performance measures [J]. United European Gastroenterol J, 2023,11(5): 448–457. Pan P, Zhao S, Wang S, et al. Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial [J]. Gastrointest Endosc, 2023,98(6): 977–986 e914. Huang C, Liu H, Luo J, et al. A prospective, single-blinded, non-inferiority, randomized controlled study comparing the effectiveness and safety of oral lactulose combined with carbohydrate-containing clear liquids versus 3-L polyethylene glycol electrolyte for colonoscopy bowel preparation [J]. Eur J Med Res, 2025,30(1): 105. Dai C, Tian W, Huang YH, et al. Effectiveness of 4 L, 2 L, and 1 L PEG bowel preparation for colonoscopy in patients with ulcerative colitis: a retrospective study [J]. Rev Esp Enferm Dig, 2023. Wenqi S, Bei Z, Yunrong W, et al. Lactulose vs Polyethylene Glycol for Bowel Preparation: A Single-Center, Prospective, Randomized Controlled Study Based on BMI [J]. Clin Transl Gastroenterol, 2024,15(1): e00652. Li CX, Guo Y, Zhu YJ, et al. Comparison of Polyethylene Glycol versus Lactulose Oral Solution for Bowel Preparation prior to Colonoscopy [J]. Gastroenterol Res Pract, 2019,2019: 2651450. Jagdeep J, Sawant G, Lal P, et al. Oral Lactulose vs. Polyethylene Glycol for Bowel Preparation in Colonoscopy: A Randomized Controlled Study [J]. Cureus, 2021,13(4): e14363. Ramos JA, Carvalho D, Arantes VN. Novel regimen for colonoscopy bowel preparation with oral lactulose: a prospective comparative study [J]. Clin Endosc, 2024,57(6): 775–782. Maeda N, Higashimori A, Kabata D, et al. Efficacy of 1 L Polyethylene Glycol Plus Ascorbic Acid With Linaclotide Versus Senna for Bowel Preparation: A Multicenter, Endoscopist-Blinded, Randomized Controlled Trial (Apple Trial) [J]. Am J Gastroenterol, 2025. Yang J, Wei Q, Xiang Z, et al. Bowel preparation efficacy and safety of compound polyethylene glycol electrolyte powder combined with linaclotide for colonoscopy: A randomized controlled trial [J]. JGH Open, 2023,7(9): 636–639. Zhang M, Zou W, Xu C, et al. Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial [J]. Eur J Gastroenterol Hepatol, 2021,33(1S Suppl 1): e625-e633. Elgendy MS, Rajab I, Najah Q, et al. Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials [J]. Int J Colorectal Dis, 2025,40(1): 143. Pan P, Chen H, Wang T, et al. Effect of 3-day linaclotide administration to reduce the PEG volume for colonoscopy bowel preparation: A multicenter, noninferiority, randomized controlled trial [J]. Am J Gastroenterol, 2025. Wang F, Huang X, Wang Z, et al. One-day versus three-day low-residue diet bowel preparation regimens before colonoscopy: a meta-analysis of randomized controlled trials [J]. J Gastroenterol Hepatol, 2024. Cheng P, Chen Q, Li J, et al. 3 liters of polyethylene glycol vs. standard bowel preparation have equal efficacy in a Chinese population: a randomized, controlled trial [J]. Am J Transl Res, 2022,14(8): 5641–5650. Hassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019 [J]. Endoscopy, 2019,51(8): 775–794. Zhang C, Chen X, Tang B, et al. A novel ultra-low-volume regimen combining 1 L polyethylene glycol and linaclotide versus 2 L polyethylene glycol for colonoscopy cleansing in low-risk individuals: a randomized controlled trial [J]. Gastrointest Endosc, 2023,97(5): 952–961 e951. Liu WQ, Shu L, Zhou X, et al. Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study [J]. Int J Colorectal Dis, 2024,39(1): 143. Rao SS, Manabe N, Karasawa Y, et al. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm [J]. BMC Gastroenterol, 2024,24(1): 12. Xu H, He Z, Liu Y, et al. Application of linaclotide in bowel preparation for colonoscopy in patients with constipation: A prospective randomized controlled study [J]. J Gastroenterol Hepatol, 2024,39(12): 2752–2759. Maeda N, Higashimori A, Yamamoto I, et al. Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients [J]. Scand J Gastroenterol, 2024,59(10): 1209–1215. Additional Declarations No competing interests reported. Supplementary Files Supplement1Supplementonlinecontent.docx Supplement2Protocol.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Nov, 2025 Reviews received at journal 15 Oct, 2025 Reviewers agreed at journal 15 Oct, 2025 Reviews received at journal 12 Oct, 2025 Reviewers agreed at journal 30 Sep, 2025 Reviewers invited by journal 22 Sep, 2025 Editor assigned by journal 22 Aug, 2025 Submission checks completed at journal 21 Aug, 2025 First submitted to journal 17 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":16353,"visible":true,"origin":"","legend":"\u003cp\u003eAdequate Bowel Preparation Rate in the Intent-to-Treat (ITT) Population.\u003c/p\u003e\n\u003cp\u003eThe figure illustrates the adequate bowel preparation rates with 95% confidence intervals (CIs) across three intervention groups, assessed using the Boston Bowel Preparation Scale (BBPS). Adequate bowel preparation was defined as a total BBPS score of ≥6, with each colonic segment (left, transverse, and right colon) scoring \u0026gt;2 points. The adequate rate was calculated as (number of successful cases / total cases) × 100%. The 95% CIs for the adequate bowel preparation rates were computed using the Wilson score method.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7391900/v1/590c439938a2a2b02bffa4c0.png"},{"id":92801153,"identity":"d247fadd-5013-42ed-b2f4-3e1aea7ae27e","added_by":"auto","created_at":"2025-10-05 11:38:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":23917,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of Visual Analog Scale Scores for Tolerability Assessment in the Intent-to-Treat (ITT) Population.\u003c/p\u003e\n\u003cp\u003eThe figure illustrates the distribution of Visual Analog Scale (VAS) scores for tolerability assessment in the Intent-to-Treat (ITT) Population. Scores range from 0 to 10, with higher values indicating worse patient-reported tolerability. The scoring categories are defined as follows: 0 = comfortable, 1-3 = mild discomfort, 4-6 = moderate discomfort, and 7-10 = severe discomfort.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7391900/v1/ce38b9f126805ff5468477ac.png"},{"id":92803440,"identity":"094c4aaf-dcef-4b84-87d8-a743ee926714","added_by":"auto","created_at":"2025-10-05 12:02:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":964358,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7391900/v1/075d3348-e4e6-4502-839c-f90ae85d0e1f.pdf"},{"id":92801154,"identity":"15294887-8285-44d2-9e95-4ad2c7af4268","added_by":"auto","created_at":"2025-10-05 11:38:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":60915,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement1Supplementonlinecontent.docx","url":"https://assets-eu.researchsquare.com/files/rs-7391900/v1/3f6e89263c68f06d0f8fe4ba.docx"},{"id":92801155,"identity":"bcf08489-fb1a-4577-9572-46d7f9e301aa","added_by":"auto","created_at":"2025-10-05 11:38:03","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":324692,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement2Protocol.docx","url":"https://assets-eu.researchsquare.com/files/rs-7391900/v1/c0dcdd67745f4dc59ef5043c.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy","fulltext":[{"header":"Background","content":"\u003cp\u003eColorectal cancer (CRC) has emerged as a major global public health issue, with rising mortality and prevalence rates and an increasingly younger age of onset, imposing a significant economic burden worldwide\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e.According to an analysis of 2022 global cancer statistics, approximately 1,925,828 individuals were diagnosed with CRC and 903,643 died from the disease in 2022. Nearly 30% of global new CRC cases and deaths annually occur in China\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.Consequently, population-based, organized CRC screening programs have been implemented in China and European countries\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.Early detection and resection of colorectal adenomas can effectively block their progression to cancer, thereby preventing the occurrence and development of CRC\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.Colonoscopy is the gold standard for evaluating colonic lesions, and the adequacy of bowel preparation is crucial for optimal colonoscopy performance\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.Although various clinical bowel preparation regimens are available, 18%-35% of patients still have suboptimal bowel preparation\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e,highlighting the necessity for further optimization of bowel preparation protocols.\u003c/p\u003e\u003cp\u003ePolyethylene glycol (PEG), an inert polymer of ethylene oxide, is a non-absorbable isotonic solution and one of the most common methods for colon cleansing\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. In European and American countries, high-dose 4L PEG is predominantly used as the conventional bowel preparation regimen for colonoscopy\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. However, the large volume of fluid intake required for 4L PEG increases the incidence of adverse events such as nausea, vomiting, and bloating. Currently, a modified split-dose 3L PEG regimen is widely recommended for bowel preparation before colonoscopy in the Chinese population\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Nevertheless, due to the poor palatability of PEG, which leads to an unpleasant experience for patients, compliance and tolerance are reduced, thereby affecting the quality of bowel preparation\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eLactulose, a non-absorbable disaccharide, has demonstrated favorable application effects in bowel preparation for adult colonoscopy in clinical practice. It features a better taste profile, less intestinal irritation, good patient compliance, and broad applicability, particularly suitable for children and sensitive populations\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.It has emerged as a novel alternative for bowel preparation prior to colonoscopy, with multiple studies showing that lactulose outperforms PEG in terms of colon cleansing efficacy, patient tolerance, and palatability \u003csup\u003e[\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.Although occasional mild discomfort may occur\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, its effectiveness and safety as a bowel preparation agent for colonoscopy have been well-established\u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eLinaclotide stimulates intestinal motility and fluid secretion by activating guanylate cyclase-C, thereby alleviating symptoms such as bloating, abdominal pain, and discomfort to some extent\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.Current studies have shown that linaclotide can serve as an effective adjuvant for bowel preparation when combined with polyethylene glycol (PEG) of varying volumes (1L/2L/3L), enhancing colon cleansing efficacy while reducing fluid intake and the incidence of adverse events\u003csup\u003e[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e.However, the optimal combination regimen, dosing, and treatment duration for linaclotide remain under exploration\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eTo our knowledge, no prior studies have investigated the combination of linaclotide and lactulose as an alternative bowel preparation regimen. According to the consensus recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer, low-volume regimens are advised for patients at low risk of inadequate bowel preparation\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e.Therefore, this study conducted a single-center, single-blind, randomized controlled trial to evaluate the efficacy and safety of a novel low-volume (2L) lactulose regimen combined with 290 \u0026micro;g linaclotide for bowel preparation.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and Patients\u003c/h2\u003e\u003cp\u003eThis study was a single-center, observer-blind, randomized controlled clinical trial conducted in the Department of Gastroenterology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University. Outpatients undergoing colonoscopy between December 2024 and April 2025 were enrolled. All participants were assigned to groups in the outpatient clinic, followed by scheduling of colonoscopy appointments.\u003c/p\u003e\u003cp\u003e Inclusion Criteria: (1) Signed a written informed consent form; (2) Aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years, regardless of gender; (3) Able to comply with the follow-up plan, objectively describe symptoms, and cooperate in completing questionnaires; (4) Not participating in any other clinical trials within 3 months prior to the trial or during the trial period.\u003c/p\u003e\u003cp\u003eExclusion Criteria: (1) Any contraindications for colonoscopy (e.g., gastrointestinal obstruction or perforation, severe acute inflammatory bowel disease, toxic megacolon, severe heart failure, renal failure, or hepatic failure); (2) Patients with galactosemia; (3) Lactating or pregnant women, or those planning to become pregnant during the trial; (4) Patients with allergies to bowel preparation medications; (5) Patients who withdraw from the trial for any other reason.\u003c/p\u003e\u003cp\u003e This study strictly adhered to the principles of the Declaration of Helsinki and was approved by the hospital\u0026rsquo;s Medical Ethics Committee (approval number: DZQH-KYLL-24-35). It was also registered on ClinicalTrials.gov (registration number: NCT06748638). All participants signed an informed consent form after being fully informed. Detailed information on the study drugs and procedures were provided in Supplement 1 and 2.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003eAll participants were instructed to follow a low-fiber, easily digestible, and colorless diet 1\u0026ndash;3 days prior to the examination\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e.Dinner was concluded at 6:00 PM the day before the procedure, followed by fasting for 6 hours and water restriction for 4 hours prior to the examination.\u003c/p\u003e\u003cp\u003e 2L Lactulose Group: At 8:00 PM the day before the examination, participants dissolved two boxes of lactulose in 1000 mL of water and slowly consumed the solution within 2 hours. An additional third box of lactulose was dissolved in 1000 mL of water and slowly ingested 4\u0026ndash;6 hours prior to the examination.\u003c/p\u003e\u003cp\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;Linaclotide (2L Lactulose\u0026thinsp;+\u0026thinsp;L) Group: Participants received a single 290 \u0026micro;g dose of linaclotide at 12:00 PM (noon) the day before the examination. Subsequently, lactulose was administered following the same protocol as the 2L Lactulose Group: two boxes dissolved in 1000 mL of water at 8:00 PM the day before, and a third box dissolved in 1000 mL of water 4\u0026ndash;6 hours prior to the examination.\u003c/p\u003e\u003cp\u003e3L PEG Group: Polyethylene glycol (PEG) at 8:00 PM the day before the examination, followed by 2L of PEG 4\u0026ndash;6 hours prior to the procedure. All participants in this group added one bottle of simethicone emulsion (20 mL/bottle) to the final 2L PEG dose, which was then consumed. Participants were advised to engage in moderate physical activity after each dose until clear or pale yellow liquid stool was achieved.\u003c/p\u003e\u003cp\u003eTo enhance adherence, trained physicians provided face-to-face explanations to participants, along with printed instructions and educational videos. These materials covered detailed steps of bowel preparation, precautions, management of adverse events, and the consequences of inadequate bowel preparation.\u003c/p\u003e\n\u003ch3\u003ePrimary Outcome\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the adequacy rate of bowel preparation, which was evaluated using the Boston Bowel Preparation Scale (BBPS) to assess bowel cleansing quality. An adequate bowel preparation was defined as a BBPS score of \u0026ge;\u0026thinsp;6, with each colonic segment (left colon, transverse colon, right colon) scoring\u0026thinsp;\u0026gt;\u0026thinsp;2 points. The adequacy rate was calculated as (number of successful cases / total number of cases) \u0026times; 100%. Each colonic segment was scored on a scale of 0\u0026ndash;3 points, with a total score ranging from 0\u0026ndash;9 points. Higher scores indicated better bowel preparation quality.\u003c/p\u003e\n\u003ch3\u003eSecondary Outcomes\u003c/h3\u003e\n\u003cp\u003eThe secondary outcomes included the Bowel Bubble Score (BBS), colonoscopy findings, including polyp detection rate (proportion of patients with at least one detected polyp), adenoma detection rate, and cancer detection rate (proportion of patients with at least one pathologically confirmed adenoma or cancer), cecal intubation rate (proportion of patients with successful cecal intubation), palatability (taste satisfaction, rated as good/fair/poor), tolerability (via the Visual Analog Scale, VAS), acceptability, including sleep quality (rated as good/same as before/poor), willingness to repeat the procedure (yes/no), and compliance, safety assessed by adverse events (AEs). Additionally, a subgroup analysis was conducted for patients with constipation. BBPS, VAS and BBS scoring criteria see Supplement 1 for details.\u003c/p\u003e\n\u003ch3\u003eSample Size Estimation and Statistical Analysis\u003c/h3\u003e\n\u003cp\u003eSample size calculation was performed using PASS 15 software. Based on prior studies\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e,the assumed adequacy rates of bowel preparation were 90% for the 2L Lactulose\u0026thinsp;+\u0026thinsp;L Group, 86% for the 2L Lactulose Group, and 69% for the 3L PEG Group. A two-sided significance level of α\u0026thinsp;=\u0026thinsp;0.05 was set for both pairwise comparisons, with 80% power. Participants were allocated in a 1:1:1 ratio. Considering a potential 20% dropout rate, approximately 138 patients were planned for each group, resulting in a minimum total enrollment of approximately 414 patients.\u003c/p\u003e\u003cp\u003eEfficacy endpoints were assessed in the intention-to-treat (ITT) population (all randomized patients), while safety was evaluated in the treated population. The 95% confidence intervals (CIs) for the bowel preparation adequacy rate were summarized using the Wilson method. All p-values were not adjusted using the Bonferroni correction. All data analyses were conducted with R version 4.5.0.\u003c/p\u003e\u003cp\u003eData analysis included both the ITT and per-protocol (PP) analysis sets. The ITT analysis set comprised all patients who were randomized and received treatment, excluding those who met inclusion criteria but did not take any study medication or undergo colonoscopy. The PP analysis set included patients who completed all study procedures, excluding those with inadequate bowel preparation, incomplete colonoscopy, or non-compliance with the study drug regimen.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eRandomization and Masking\u003c/h2\u003e\u003cp\u003e Participants were allocated in a 1:1:1 ratio using randomization software, with a mixed block design and fixed enrollment method, the width of the interval is 6. Endoscopists were blinded to the participants' group allocation, and participants were explicitly instructed not to disclose their study allocation to either the endoscopists or the investigators.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eBaseline Characteristics\u003c/h2\u003e\u003cp\u003eA total of 444 participants were randomized, with 148 participants in each group. Among them, 366 participants (121 in the 2L Lactulose\u0026thinsp;+\u0026thinsp;L Group, 121 in the 2L Lactulose Group, and 124 in the 3L PEG Group) were included in the ITT analysis. Additionally, 337 participants (113 in the 2L Lactulose\u0026thinsp;+\u0026thinsp;L Group, 110 in the 2L Lactulose Group, and 114 in the 3L PEG Group) were included in the per-protocol (PP) analysis (Supplement 1). In the ITT population, the median age was 36 years (interquartile range: 28 to 54 years), with 263 participants (71.8%) being male. The mean Body Mass Index (BMI) was 23.6 kg/m\u0026sup2;, and 37 participants (10.1%) had a history of constipation. A total of 266 participants (72.7%) underwent colonoscopy for the first time. Colonoscopy procedures were performed by 8 endoscopists. The baseline characteristics, including age, gender, BMI, constipation history, and prior colonoscopy experience, were evenly distributed across the three groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics (intention-to-treat population)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2L Lactulose\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3L PEG\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (yr), median (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.0 (29.5,54.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e36.0 (27.0,50.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e34.0 (28.0,58.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e87 (71.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83 (68.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e93 (75.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34 (28.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38 (31.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e31 (25.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23.85\u0026thinsp;\u0026plusmn;\u0026thinsp;2.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedical history, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrinking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e25 (20.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (15.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24 (19.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37 (30.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29 (24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e44 (35.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e15 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14 (11.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (4.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3 (2.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pelvic surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8 (6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e7 (5.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (1.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious colectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (2.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2 (1.6)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConstipation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e10 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13 (10.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e24 (19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24 (19.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst colonoscopy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e86 (71.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e95 (78.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e85 (68.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndication, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScreening\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e26 (21.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28 (23.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20 (16.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiagnosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e71 (58.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e79 (65.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e84 (67.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurveillance\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24 (19.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e14 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20 (16.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGeneral anesthesia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e114 (94.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e117 (96.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e116 (93.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndoscopist, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅠ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e36 (29.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29 (24.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e43 (34.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅡ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27 (22.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e30 (24.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e26 (21.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e23 (19.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11 (8.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅣ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13 (10.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅤ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16 (13.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12 (9.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅥ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12 (9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13 (10.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅦ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5 (4.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5 (4.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅧ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1 (0.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u0026thinsp;=\u0026thinsp;2L Lactulose\u0026thinsp;+\u0026thinsp;290ug Linaclotide.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e3L PEG\u0026thinsp;=\u0026thinsp;3L Polyethylene glycol.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI, Body Mass Index.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Screening: Screening or Physical Examination. This mainly includes individuals requesting colonoscopy due to reasons such as elevated tumor markers, esophagitis, gastritis, gastric ulcer, and other gastric symptoms. Diagnosis: Diagnosis with Definite Symptoms. This includes abdominal symptoms such as diarrhea, abdominal pain, occult blood or blood in stool, weight loss, etc. Surveillance: Follow-up or Re-examination. This applies to individuals with a history of enteritis, intestinal polyps, tumors, surgery, or hemorrhoids.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as [Median (IQR)], mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or n (%).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePrimary Outcome\u003c/h2\u003e\u003cp\u003eThe adequacy rate of bowel preparation in the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group (90.1% [95% CI: 83.5 to 94.2]) was significantly higher than that in the 3L PEG group (74.2% [95% CI: 65.8 to 81.1]) and similar to that in the 2L Lactulose group (83.5% [95% CI: 75.8 to 89.0]). The adequacy rate of bowel preparation in the 2L Lactulose group was comparable to that in the 3L PEG group(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). However, a significant difference was observed between the two groups in the PP analysis. In both ITT and PP analyses, the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group outperformed the 3L PEG group in terms of total BBPS scores and segmental scores (right colon, transverse colon, and left colon), with no statistically significant differences compared to the 2L Lactulose group. The 2L Lactulose group showed superior total BBPS scores and right/left colon segmental scores compared to the 3L PEG group, but no significant difference was found in the transverse colon segmental score (Supplement 1: Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). No significant differences in bowel bubble scores were observed among the three groups ( Supplement 1: Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eSecondary Outcomes\u003c/h2\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003eColonoscopy Finds\u003c/h2\u003e\u003cp\u003eColonoscopy finds, including the detection rates of polyps, adenomas, and cancers, as well as the cecal intubation rate. In the PP population, there were no significant differences among the three groups in terms of polyp detection rate (46.0% vs 40.0% vs 46.5%, p\u0026thinsp;=\u0026thinsp;0.554), adenoma detection rate (13.3% vs 17.3% vs 16.7%, p\u0026thinsp;=\u0026thinsp;0.675), or cancer detection rate. Cecal intubation was successfully completed in all patients (Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePalatability, Tolerability, and Acceptability\u003c/h2\u003e\u003cp\u003eThere were no significant differences between the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group and the 2L Lactulose group in terms of palatability proportion (p\u0026thinsp;=\u0026thinsp;0.180), tolerability VAS scores (p\u0026thinsp;=\u0026thinsp;0.620, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and willingness to repeat the regimen (p\u0026thinsp;=\u0026thinsp;1.000). However, both the 2L Lactulose\u0026thinsp;+\u0026thinsp;L and 2L Lactulose groups scored significantly higher than the 3L PEG group in these aspects (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The 3L PEG group had a higher incidence of sleep disturbances compared to the 2L Lactulose group (p\u0026thinsp;=\u0026thinsp;0.016). No significant differences in compliance were observed among the three groups (p\u0026thinsp;=\u0026thinsp;0.895)(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePalatability and acceptability (intention-to-treat population).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2L Lactulose\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3L PEG\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-value\u003csup\u003e\u0026amp;\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep-value\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalatability, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBest\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e98(81.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e108(89.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e54(43.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22(18.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12(9.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e50(40.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWorse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1(0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20(16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep quality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.068\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.402\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.179\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBest\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e81(66.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e91(75.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e73(58.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSame as before\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34(28.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22(18.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e42(33.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWorse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6(5.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8(6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9(7.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWilling to repeat,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e108(89.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e108(89.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e73(58.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCompliance, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e117(96.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e117(96.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e121(97.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.895\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.974\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.974\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u0026thinsp;=\u0026thinsp;2L Lactulose\u0026thinsp;+\u0026thinsp;290ug Linaclotide.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e3L PEG\u0026thinsp;=\u0026thinsp;3L Polyethylene glycol .\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003ep-value\u003csup\u003e*\u003c/sup\u003e, 2L Lactulose\u0026thinsp;+\u0026thinsp;L vs 3L PEG;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e\u0026amp;\u003c/sup\u003e, 2L Lactulose\u0026thinsp;+\u0026thinsp;L vs 2L Lactulose;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e#\u003c/sup\u003e, 2L Lactulose vs 3L PEG.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eData are presented as n (%).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eAdverse Events\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the incidence of adverse events (including nausea, vomiting, bloating, and abdominal pain) in the ITT population. The 2L Lactulose\u0026thinsp;+\u0026thinsp;L group had a significantly lower incidence of overall adverse events (28.9% vs 47.6%, p\u0026thinsp;=\u0026thinsp;0.003), nausea (19.0% vs 32.3%, p\u0026thinsp;=\u0026thinsp;0.018), vomiting (9.1% vs 18.5%, p\u0026thinsp;=\u0026thinsp;0.032), and bloating (15.7% vs 35.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to the 3L PEG group. No significant differences were observed between the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group and the 2L Lactulose group in these adverse events. The 2L Lactulose group also showed a lower incidence of vomiting (9.1% vs 18.5%, p\u0026thinsp;=\u0026thinsp;0.032) and bloating (21.5% vs 35.5%, p\u0026thinsp;=\u0026thinsp;0.015) compared to the 3L PEG group, but no significant differences were found in overall adverse events or nausea incidence (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The three groups had similar incidences of abdominal pain.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAdverse events (intention-to-treat population).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2L Lactulose\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;121)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3L PEG\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;124)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep-value\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-value\u003csup\u003e\u0026amp;\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ep-value\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse events, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35(28.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46(38.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e59(47.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23(19.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27(22.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40(32.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.043\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11(9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11(9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e23(18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBloating\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19(15.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26(21.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e44(35.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.247\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAbdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14(11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18(14.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e15(12.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.710\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.899\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.448\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.524\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e2L Lactulose\u0026thinsp;+\u0026thinsp;L\u0026thinsp;=\u0026thinsp;2L Lactulose\u0026thinsp;+\u0026thinsp;290ug Linaclotide.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e3L PEG\u0026thinsp;=\u0026thinsp;3L Polyethylene glycol .\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003ep-value\u003csup\u003e*\u003c/sup\u003e, 2L Lactulose\u0026thinsp;+\u0026thinsp;L vs 3L PEG;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e\u0026amp;\u003c/sup\u003e, 2L Lactulose\u0026thinsp;+\u0026thinsp;L vs 2L Lactulose;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003ep\u003c/em\u003e-value\u003csup\u003e#\u003c/sup\u003e, 2L Lactulose vs 3L PEG.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"8\"\u003eData are presented as n (%).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eAnalysis of Constipation Subgroups\u003c/h2\u003e\u003cp\u003eIn the PP population, a subgroup of 35 patients with constipation (14 cases in the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group, 10 cases in the 2L Lactulose group, and 11 cases in the 3L PEG group) was analyzed for bowel preparation quality. The results showed that the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group had higher values than the 2L Lactulose and 3L PEG groups in terms of bowel preparation adequacy rate (85.7% vs 70.0% vs 72.7%, p\u0026thinsp;=\u0026thinsp;0.608), total BBPS scores [7 (6,8) vs 7 (4,8) vs 6 (5,8), p\u0026thinsp;=\u0026thinsp;0.699], right colon segmental score [2 (2,3) vs 2 (1,2) vs 2 (1,2), p\u0026thinsp;=\u0026thinsp;0.043], transverse colon segmental score [2 (2,3) vs 2 (1,3) vs 2 (2,3), p\u0026thinsp;=\u0026thinsp;0.673], and left colon segmental score [3 (2,3) vs 3 (2,3) vs 2 (2,3), p\u0026thinsp;=\u0026thinsp;0.813], with no statistically significant differences observed. Notably, the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group had a higher right colon segmental score compared to the 2L Lactulose group [2 (2,3) vs 2 (1,2), p\u0026thinsp;=\u0026thinsp;0.014], while the 2L Lactulose group and the 3L PEG group showed comparable bowel cleansing efficacy (Table S5).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eEarly colonoscopy is the most intuitive method for colorectal cancer (CRC) screening. Inadequate bowel preparation can lead to reduced detection rates of polyps and adenomas, unsuccessful screening, and an increased likelihood of repeated procedures\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Therefore, providing patients with regimens that offer good palatability, high comfort, and require a low volume of fluid intake is crucial. A study investigating the efficacy of lactulose versus PEG based on body mass index (BMI) showed that lactulose oral solution outperformed PEG in terms of bowel preparation quality and palatability, particularly in the normal BMI group and the higher BMI group. It can be considered a potential and promising bowel preparation agent for clinical use\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e. Linaclotide, as a novel adjuvant medication for bowel preparation, has only been preliminarily explored in randomized controlled trials in combination with PEG or magnesium sulfate\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e. Due to the small sample sizes and limited data, larger-scale studies are needed to evaluate the efficacy of linaclotide. Therefore, this study adopted a low dose of 2L lactulose and investigated whether combining it with linaclotide could improve the adequacy rate of bowel cleansing\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e, aiming to further explore the efficacy of linaclotide in various bowel preparation regimens.\u003c/p\u003e\u003cp\u003eThe results of this study demonstrated that the 2L Lactulose\u0026thinsp;+\u0026thinsp;Linaclotide group achieved an adequate bowel preparation rate of 90.1%, meeting the minimum threshold of \u0026gt;\u0026thinsp;90% recommended by the US Multi-Society Task Force on Colorectal Cancer \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. In terms of efficacy and BBPS scores, this group outperformed the 3L PEG group and showed comparable performance to the 2L Lactulose group. The 2L Lactulose group exhibited superior cleansing efficacy in the entire colon, right colon, and left colon compared to the 3L PEG group. Notably, while previous bowel preparation regimens often showed suboptimal cleansing in the right colon, both the 2L Lactulose\u0026thinsp;+\u0026thinsp;L and 2L Lactulose groups in this study demonstrated better right colon cleansing than the 3L PEG group. However, the underlying reason for this observation remains unclear, as the addition of linaclotide did not further enhance efficacy compared to lactulose alone. Consequently, it was not possible to determine whether linaclotide enhanced or diminished its role in bowel preparation. Linaclotide is known to increase intestinal fluid secretion and accelerate intestinal motility\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. We hypothesize that the similar efficacy between the 2L Lactulose\u0026thinsp;+\u0026thinsp;L and 2L Lactulose groups may be due to a greater volume of residual fluid in the colon, which could lower BBPS scores, or potentially related to the relatively low dose of linaclotide used or its early administration time. No significant differences in intestinal bubble scores were observed among the three groups, likely attributable to the administration of simethicone defoaming agent 4\u0026ndash;6 hours prior to colonoscopy.\u003c/p\u003e\u003cp\u003eNo serious adverse events other than common gastrointestinal symptoms were reported in any participants before or after colonoscopy. The incidence of adverse events (nausea, vomiting, bloating) in the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group was significantly lower than that in the 3L PEG group. Compared with the 2L Lactulose group, the 2L Lactulose\u0026thinsp;+\u0026thinsp;L group did not show a reduced incidence of adverse events. The 2L Lactulose group demonstrated a lower incidence of vomiting and abdominal distension compared to the 3L PEG group, while the incidence of abdominal pain was comparable across all three groups. Overall, both the 2L Lactulose\u0026thinsp;+\u0026thinsp;L and 2L Lactulose regimens effectively reduced the occurrence of adverse events, indicating reliable safety profiles.\u003c/p\u003e\u003cp\u003eRegarding palatability, tolerance (VAS scores), and willingness to repeat the regimen, there were no significant differences between the 2L Lactulose\u0026thinsp;+\u0026thinsp;L and 2L Lactulose groups, but both groups outperformed the 3L PEG group. The 3L PEG group had a statistically significantly higher incidence of sleep disturbances compared to the 2L Lactulose group. Compliance did not differ significantly among the three groups, ruling out its impact on bowel preparation quality. These findings suggest that the 2L Lactulose\u0026thinsp;+\u0026thinsp;L regimen enhanced patient experience to some extent.。\u003c/p\u003e\u003cp\u003eA single-center randomized controlled trial (RCT) using 870 \u0026micro;g linaclotide combined with 3L polyethylene glycol (PEG) for bowel preparation in patients with constipation demonstrated superior efficacy compared to 4L PEG, particularly in elderly patients\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. Additionally, a 1L PEG with ascorbic acid (PEG-Asc) plus 500 mg linaclotide regimen significantly improved efficacy and adenoma detection rate compared to a senna-based regimen, without compromising tolerability\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Therefore, a subgroup analysis was conducted in the per-protocol (PP) population of patients with constipation in this study. The 2L Lactulose\u0026thinsp;+\u0026thinsp;Linaclotide group showed higher bowel preparation success rates (85.7% vs. 70.0% vs. 72.7%, p\u0026thinsp;=\u0026thinsp;0.608) and segmental BBPS scores compared to the 2L Lactulose and 3L PEG groups, though the differences were not statistically significant. Notably, the 2L Lactulose\u0026thinsp;+\u0026thinsp;Linaclotide group had statistically significantly higher right colon scores than the 2L Lactulose group. This suggests that linaclotide use may enhance right colon cleanliness in patients with constipation, but given the small sample size in the subgroup analysis, further confirmation is warranted.\u003c/p\u003e\u003cp\u003eThis study has several limitations. First, a significant number of patients did not undergo colonoscopy, resulting in a small sample size for analysis. Second, the subgroup analysis focused only on patients with constipation; the quality of bowel preparation in patients with irritable bowel syndrome (IBS) or other diseases (particularly inflammatory bowel disease, IBD) was not assessed. Future studies are needed to analyze bowel preparation efficacy based on specific diseases. Third, data on adverse events, patient satisfaction, and sleep quality were collected using unvalidated questionnaires, introducing potential subjectivity. Finally, certain metrics\u0026mdash;such as adverse reactions specifically related to linaclotide, time to first bowel movement, and bowel movement frequency\u0026mdash;were not recorded separately. Additionally, objective indicators including waiting time, colonoscopy duration, and electrolyte levels were not measured.\u003c/p\u003e\u003cp\u003eIn conclusion, the 2L Lactulose\u0026thinsp;+\u0026thinsp;Linaclotide regimen demonstrated superior performance compared to the 3L PEG group in terms of efficacy, safety, tolerability, and acceptability, while requiring less fluid intake, making it an effective alternative for bowel preparation. However, future studies should aim to expand the sample size and conduct multicenter clinical trials. Additionally, further research is needed to determine the optimal dosage and administration method of linaclotide as an adjunctive medication for bowel preparation.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe 2L Lactulose\u0026thinsp;+\u0026thinsp;L regimen is an effective and safe bowel preparation protocol.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe 2L Lactulose\u0026thinsp;+\u0026thinsp;L regimen outperforms the 3L PEG regimen in terms of bowel cleansing efficacy, palatability, and incidence of adverse events (nausea, vomiting, abdominal distension).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe addition of linaclotide reduces fluid intake volume and enhances patient satisfaction.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"641\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations /acronyms\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDefinitions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eADR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAdenoma Detection Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eAdverse Events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBBPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBoston Bowel Preparation Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBowel Bubble Score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eESGE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eEuropean Society of Gastrointestinal Endoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eGC-C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eGuanylate Cyclase-C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eIBS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eIrritable Bowel Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eITT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eIntention-to-Treat\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePer-Protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePDR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePolyp Detection Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePEG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003ePolyethylene Glycol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eRandomized Controlled Trial\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eVAS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 321px;\"\u003e\n \u003cp\u003eVisual Analogue Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study strictly followed the principles of the Declaration of Helsinki. It has been approved by the Medical Ethics Committee of Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University (approval number: DZQH-KYLL-24-35) and registered on ClinicalTrials.gov (registration number: NCT06748638). All participants signed the informed consent form with full knowledge.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere are no conflicts of interest to declare by the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received financial support from the Clinical Special Project of Nanjing General Hospital of Nanjing Military Command (2023LCYYQH024) and the Jiangsu Province Elderly Health Research Project (LKM2022030). All authors are very appreciative of the financial support.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe project and experimental designs were formulated by JX, JW and QY. HL and QY conducted experiments and analyzed the resulting data. QY, MS, CS and QG assisted in certain experiments and data analyses. HL wrote this manuscript. The manuscript was revised by JX. All authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLi J, Kuang X. Global cancer statistics of young adults and its changes in the past decade: Incidence and mortality from GLOBOCAN 2022 [J]. Public Health, 2024,237: 336\u0026ndash;343.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi Q, Xia C, Li H, et al. Disparities in 36 cancers across 185 countries: secondary analysis of global cancer statistics [J]. Front Med, 2024,18(5): 911\u0026ndash;920.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu B, Luo J, Yan Y, et al. Evaluation of long-term benefits and cost-effectiveness of nation-wide colorectal cancer screening strategies in China in 2020\u0026ndash;2060: a modelling analysis [J]. Lancet Reg Health West Pac, 2024,51: 101172.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOla I, Cardoso R, Hoffmeister M, et al. Recent trends in self-reported utilization of colonoscopy and fecal occult blood test in Europe: analysis of the European Health Interview Surveys 2013\u0026ndash;2015 and 2018\u0026ndash;2020 [J]. Eur J Epidemiol, 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo C, Wang J, Li L, et al. Effects of the combined use of linaclotide and oral sulfate solution in bowel preparation for patients with chronic constipation undergoing colonoscopy: protocol of a prospective, randomised, controlled, single-blind clinical trial from a single centre in China [J]. BMJ Open, 2025,15(5): e099687.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao HY, Cai XF, Chen PP, et al. Efficacy of linaclotide in combination with polyethylene glycol for bowel preparation in Chinese patients undergoing colonoscopy polypectomy: protocol for a randomised controlled trial [J]. BMJ Open, 2024,14(7): e080723.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJacobson BC, Anderson JC, Burke CA, et al. Optimizing bowel preparation quality for colonoscopy: consensus recommendations by the US Multi-Society Task Force on Colorectal Cancer [J]. Gastrointest Endosc, 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDehghani SM, Javaherizadeh H, Haghighat M, et al. BOWEL PREPARATION BEFORE COLONOSCOPY FOR CHILDREN: comparison of efficacy of three different methods [J]. Arq Gastroenterol, 2015,52(4): 311\u0026ndash;314.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTheunissen F, Lantinga MA, Ter Borg PCJ, et al. Efficacy of different bowel preparation regimen volumes for colorectal cancer screening and compliance with European Society of Gastrointestinal Endoscopy performance measures [J]. United European Gastroenterol J, 2023,11(5): 448\u0026ndash;457.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePan P, Zhao S, Wang S, et al. Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial [J]. Gastrointest Endosc, 2023,98(6): 977\u0026ndash;986 e914.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang C, Liu H, Luo J, et al. A prospective, single-blinded, non-inferiority, randomized controlled study comparing the effectiveness and safety of oral lactulose combined with carbohydrate-containing clear liquids versus 3-L polyethylene glycol electrolyte for colonoscopy bowel preparation [J]. Eur J Med Res, 2025,30(1): 105.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDai C, Tian W, Huang YH, et al. Effectiveness of 4 L, 2 L, and 1 L PEG bowel preparation for colonoscopy in patients with ulcerative colitis: a retrospective study [J]. Rev Esp Enferm Dig, 2023.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWenqi S, Bei Z, Yunrong W, et al. Lactulose vs Polyethylene Glycol for Bowel Preparation: A Single-Center, Prospective, Randomized Controlled Study Based on BMI [J]. Clin Transl Gastroenterol, 2024,15(1): e00652.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLi CX, Guo Y, Zhu YJ, et al. Comparison of Polyethylene Glycol versus Lactulose Oral Solution for Bowel Preparation prior to Colonoscopy [J]. Gastroenterol Res Pract, 2019,2019: 2651450.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJagdeep J, Sawant G, Lal P, et al. Oral Lactulose vs. Polyethylene Glycol for Bowel Preparation in Colonoscopy: A Randomized Controlled Study [J]. Cureus, 2021,13(4): e14363.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRamos JA, Carvalho D, Arantes VN. Novel regimen for colonoscopy bowel preparation with oral lactulose: a prospective comparative study [J]. Clin Endosc, 2024,57(6): 775\u0026ndash;782.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaeda N, Higashimori A, Kabata D, et al. Efficacy of 1 L Polyethylene Glycol Plus Ascorbic Acid With Linaclotide Versus Senna for Bowel Preparation: A Multicenter, Endoscopist-Blinded, Randomized Controlled Trial (Apple Trial) [J]. Am J Gastroenterol, 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang J, Wei Q, Xiang Z, et al. Bowel preparation efficacy and safety of compound polyethylene glycol electrolyte powder combined with linaclotide for colonoscopy: A randomized controlled trial [J]. JGH Open, 2023,7(9): 636\u0026ndash;639.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang M, Zou W, Xu C, et al. Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial [J]. Eur J Gastroenterol Hepatol, 2021,33(1S Suppl 1): e625-e633.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eElgendy MS, Rajab I, Najah Q, et al. Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials [J]. Int J Colorectal Dis, 2025,40(1): 143.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePan P, Chen H, Wang T, et al. Effect of 3-day linaclotide administration to reduce the PEG volume for colonoscopy bowel preparation: A multicenter, noninferiority, randomized controlled trial [J]. Am J Gastroenterol, 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang F, Huang X, Wang Z, et al. One-day versus three-day low-residue diet bowel preparation regimens before colonoscopy: a meta-analysis of randomized controlled trials [J]. J Gastroenterol Hepatol, 2024.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCheng P, Chen Q, Li J, et al. 3 liters of polyethylene glycol vs. standard bowel preparation have equal efficacy in a Chinese population: a randomized, controlled trial [J]. Am J Transl Res, 2022,14(8): 5641\u0026ndash;5650.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019 [J]. Endoscopy, 2019,51(8): 775\u0026ndash;794.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang C, Chen X, Tang B, et al. A novel ultra-low-volume regimen combining 1 L polyethylene glycol and linaclotide versus 2 L polyethylene glycol for colonoscopy cleansing in low-risk individuals: a randomized controlled trial [J]. Gastrointest Endosc, 2023,97(5): 952\u0026ndash;961 e951.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu WQ, Shu L, Zhou X, et al. Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study [J]. Int J Colorectal Dis, 2024,39(1): 143.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRao SS, Manabe N, Karasawa Y, et al. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm [J]. BMC Gastroenterol, 2024,24(1): 12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu H, He Z, Liu Y, et al. Application of linaclotide in bowel preparation for colonoscopy in patients with constipation: A prospective randomized controlled study [J]. J Gastroenterol Hepatol, 2024,39(12): 2752\u0026ndash;2759.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaeda N, Higashimori A, Yamamoto I, et al. Bowel preparation with linaclotide and 1 L polyethylene glycol plus ascorbic acid prior to colonoscopy in chronic constipated patients [J]. Scand J Gastroenterol, 2024,59(10): 1209\u0026ndash;1215.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"lactulose, linaclotide, bowel preparation, colonoscopy","lastPublishedDoi":"10.21203/rs.3.rs-7391900/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7391900/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eAim\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study aims to evaluate the efficacy and safety of low-dose 2L lactulose combined with linaclotide for bowel preparation prior to colonoscopy.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis was a single-blind, randomized controlled clinical study enrolling patients undergoing colonoscopy. All participants were randomly assigned in a 1:1:1 ratio to three groups: the 2L lactulose\u0026thinsp;+\u0026thinsp;linaclotide (L) group, the 2L lactulose group, and the 3L polyethylene glycol (PEG) group. The primary outcome was bowel cleansing quality evaluated using the Boston Bowel Preparation Scale (BBPS). Secondary outcomes included colonoscopy findings, palatability, tolerability, and acceptability, assessed via the Visual Analog Scale (VAS), sleep quality, and willingness to repeat the preparation. Safety was evaluated based on adverse events. Additionally, a subgroup analysis was conducted for patients with constipation.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 366 patients were included in the intention-to-treat (ITT) analysis. The adequate bowel preparation rates were significantly higher in the 2L lactulose\u0026thinsp;+\u0026thinsp;L group (90.1%; 95% confidence interval [CI], 83.5%-94.2%) and the 2L lactulose group (83.5%; 95% CI, 75.8%-89.0%) compared to the 3L PEG group (74.2%; 95% CI, 65.8%-81.1%; p\u0026thinsp;=\u0026thinsp;0.004). The 2L lactulose\u0026thinsp;+\u0026thinsp;L group had significantly lower incidence of nausea (19.0% vs 32.3%, p\u0026thinsp;=\u0026thinsp;0.018), vomiting (9.1% vs 18.5%, p\u0026thinsp;=\u0026thinsp;0.032), and bloating (15.7% vs 35.5%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to the 3L PEG group. There were no significant differences between the combined 2L lactulose\u0026thinsp;+\u0026thinsp;L group and the 2L lactulose group in terms of bowel preparation efficacy, palatability, tolerability, or willingness to repeat the regimen; however, both groups were superior to the 3L PEG group in these aspects. The 3L PEG group was more likely to cause sleep disturbances compared to the 2L lactulose group (p\u0026thinsp;=\u0026thinsp;0.016). No significant differences were observed among the three groups in Boston Bowel Preparation Scale (BBPS) scores, polyp detection rate, adenoma detection rate, or cancer detection rate. In the subgroup analysis of patients with constipation, the three groups showed comparable efficacy; however, the 2L lactulose\u0026thinsp;+\u0026thinsp;L group had a higher BBPS score in the right colon compared to the 2L lactulose group (p\u0026thinsp;=\u0026thinsp;0.014).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eLow-dose 2L Lactulose combined with linaclotide regimen demonstrates superior potential than 3L PEG in terms of efficacy, safety, and patient experience, offering a more optimal alternative for bowel preparation.\u003c/p\u003e","manuscriptTitle":"Clinical Study on the Application of Low-Dose 2L Lactulose Combined with Linaclotide in Bowel Preparation Before Colonoscopy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-05 11:37:59","doi":"10.21203/rs.3.rs-7391900/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-11-09T13:12:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T20:42:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"228795226882908945068046709009216364438","date":"2025-10-15T19:23:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-12T08:14:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"279374749437171339447367387220989127630","date":"2025-09-30T19:42:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-22T17:37:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-22T07:06:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-21T15:09:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Medical Research","date":"2025-08-17T10:43:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-medical-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejmr","sideBox":"Learn more about [European Journal of Medical Research](http://eurjmedres.biomedcentral.com)","snPcode":"40001","submissionUrl":"https://submission.nature.com/new-submission/40001/3","title":"European Journal of Medical Research","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5a933d54-1644-403d-b2e8-24c4dbceb064","owner":[],"postedDate":"October 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-03T11:56:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-05 11:37:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7391900","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7391900","identity":"rs-7391900","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}