Combined linaclotide and polyethylene glycol electrolyte for colonoscopy preparation: a network meta-analysis of 14 randomized controlled trials

Abstract

Purpose: Recent evidence supports linaclotide (Lin) for colonoscopy preparation. This network meta-analysis evaluates the combination of different pill numbers of Lin with polyethylene glycol (PEG) (high and low volumes in liters (L)) for bowel cleansing. Methods: This systematic review and frequentist network meta-analysis, conducted in October 2024, assessed randomized controlled trials (RCTs) from Scopus, PubMed, Cochrane, WOS, and Embase. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were calculated for categorical and continuous outcomes. PROSPERO ID: CRD42024618272. Results: Fourteen RCTs with 4,764 participants showed that total Boston Bowel Preparation Scale improved significantly with 2L PEG + 2Lin (MD = 2.03, 95%CI: [0.30:3.76], P = 0.0217), 3L-PEG + 3Lin (MD = 1.30, 95%CI: [0.42:2.18], P = 0.0038), and 4L-PEG (MD = 1.11, 95%CI: 0.23–1.98, P = 0.0129). Adenoma detection was highest with 3L-PEG + 3Lin (RR = 1.60, 95%CI: [1.05:2.43], P = 0.0280), while polyp detection improved with 2L PEG + 3Lin (RR = 1.72, 95%CI: [1.13:2.62], P = 0.0114) and 3L-PEG + 3Lin (RR = 1.33, 95%CI: [1.00:1.77], P = 0.0505). Procedure times were significantly reduced with 3L-PEG + 3Lin (MD = -4.6, 95%CI: [-6.24:-3.24], P < 0.0001), 3L-PEG + 1Lin (P = 0.035), and 4L-PEG (P < 0.01). Abdominal pain and abdominal bloating decreased with 2L PEG + 1Lin (P < 0.01) and 2L PEG + 2Lin (P = 0.021) but increased with 4L-PEG (P = 0.0178). Conclusions: Combining PEG with Lin improves bowel cleanliness compared to 3L-PEG, with 2L PEG + 2Lin being the most effective and well-tolerated. Despite some heterogeneity, the findings suggest that adding Lin may enhance bowel preparation with comparable safety, warranting consideration of individual patient factors.