Efficacy and Safety of Linaclotide as an Adjunct to Polyethylene Glycol in Bowel Preparation: A Meta-Analysis

Abstract

Objectives

Linaclotide, a guanylyl cyclase-C agonist, may enhance efficacy and tolerability when combined with polyethylene glycol (PEG) for bowel preparation. This meta-analysis evaluated linaclotide plus PEG versus PEG alone for bowel preparation prior to colonoscopy.

Methods

Randomized controlled trials (RCTs) including adults undergoing colonoscopy that compared linaclotide plus PEG with PEG alone for bowel preparation were identified via database search up to March 2024. Statistical analysis was performed in RevMan Web using random-effects models.

Results

Eleven RCTs were analyzed. Adequate bowel preparation rate was comparable (risk ratio [RR] 1.01, 95% confidence interval [CI] 0.98–1.04; I² = 23%), as was cecal intubation rate (RR 1.01, 95% CI 1.00–1.01). Subgroup analyses showed that compared with 3-L PEG alone, 2-L PEG plus linaclotide was non-inferior, while 3-L PEG plus linaclotide was superior regarding bowel preparation adequacy (RR 1.11, 95% CI 1.01–1.23) and total Boston Bowel Preparation Scale (BBPS) score (mean difference 0.44, 95% CI 0.04–0.85). Right and left colon BBPS scores were also higher with linaclotide. Polyp detection rate improved significantly in the 3-L PEG plus linaclotide subgroup (RR 1.78, 95% CI 1.32–2.40), whereas adenoma detection rate and withdrawal time were comparable. Linaclotide reduced abdominal pain, bloating, nausea, and sleep disturbance, and increased willingness to repeat colonoscopy.

Conclusions

Linaclotide with PEG provides comparable overall bowel cleansing to PEG alone while reducing adverse events and improving patient acceptance. Importantly, 2-L PEG plus linaclotide was non-inferior compared with 3-L PEG, whereas 3-L PEG plus linaclotide showed superiority over 3-L PEG alone, supporting its use in low-volume bowel preparation strategies.