This network meta-analysis evaluated the comparative efficacy and safety of secretagogues (linaclotide, lubiprostone, plecanatide, tenapanor) for treating IBS-C, analyzing data from 15 randomized controlled trials involving 8,462 patients. All secretagogues demonstrated superiority over placebo, with linaclotide 290 µg once daily consistently ranked highest for overall efficacy, particularly for improving abdominal pain and stool frequency. Tenapanor ranked highest for bloating improvement, though differences among drugs were generally minimal.

In terms of safety, plecanatide 6 mg once daily had the most favorable overall adverse event profile, while lubiprostone had the lowest diarrhea rates but was associated with higher rates of nausea. Given the absence of direct head-to-head trials and the limitation of available data beyond 12 weeks, these results provide valuable indirect comparisons to guide clinicians in selecting the most appropriate IBS-C treatment, balancing efficacy, safety, and patient-specific symptom priorities.

Reference: Black CJ, Burr NE, Quigley EMM, et al. Efficacy of Secretagogues in Patients With Irritable Bowel Syndrome With Constipation: Systematic Review and Network Meta-analysis. Gastroenterology. 2018 Dec;155(6):1753-1763. doi: 10.1053/j.gastro.2018.08.021. Epub 2018 Aug 23. Erratum in: Gastroenterology. 2021 May;160(6):2227-2228. doi: 10.1053/j.gastro.2021.04.017. PMID: 30144426.