Efficacy and tolerability of plecanatide for irritable bowel syndrome with constipation and chronic idiopathic constipation: a systematic review and meta-analysis

Constipation is a common gastrointestinal disorder with limited effective treatments and a significant impact on quality of life. Plecanatide, a guanylate cyclase-C agonist, has shown promise in improving symptoms with a favorable safety profile. This meta-analysis aimed to evaluate the effectiveness and tolerability of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC). A comprehensive search was performed across Medline, Embase, Cochrane CENTRAL, and ClinicalTrials.gov up till March 2025. Only randomized controlled trials (RCTs) comparing plecanatide with placebo in IBS-C and CIC were included. A random-effects model was used to calculate risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals. Study quality was assessed using the Cochrane risk of bias tool (RoB 2.0) and evidence certainty with the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data from seven RCTs involving 6319 patients (CIC: 3707 and IBS-C: 2612) were pooled. Among these, 4350 patients received plecanatide and 1969 received a placebo. In patients with CIC, plecanatide significantly improved spontaneous bowel movements (SBMs) per week (MD = 1.39), stool consistency (MD = 0.70), SBMs within 24 h (RR = 1.35), complete SBMs within 24 h (RR = 1.88), and overall responders (RR = 1.73). In patients with IBSC, it improved stool consistency (MD = 0.79), SBMs within 24 h (RR = 1.42), and overall responders (RR = 1.64). Diarrhea risk was higher with plecanatide (RR = 4.11), while other adverse events were comparable to placebo. In conclusion, plecanatide significantly improves bowel symptoms in CIC and IBS-C patients. None of the adverse events showed significant treatment differences except diarrhea, which showed a fourfold higher risk in the plecanatide group.