This network meta-analysis aimed to compare the efficacy of secretagogues for treating irritable bowel syndrome with constipation (IBS-C) by evaluating randomized controlled trials (RCTs) published until June 2018. The study included 15 eligible trials with 8,462 patients and analyzed the effects of linaclotide, lubiprostone, plecanatide, and tenapanor, all of which were superior to placebo. Linaclotide (290 μg once daily) ranked first in terms of efficacy, including outcomes like abdominal pain and complete spontaneous bowel movements, while tenapanor (50 mg twice daily) ranked first for decreasing bloating. The analysis also revealed that diarrhea was more common with all drugs except lubiprostone, and nausea was more frequent with lubiprostone.

Despite finding that all secretagogues outperformed placebo, the study highlighted that the long-term efficacy of these treatments remains unclear, as the data were assessed at the 12-week time point. While the efficacy across most endpoints was similar among the drugs, safety profiles varied. Plecanatide (6 mg once daily) was ranked first for safety, although linaclotide and plecanatide at higher doses had significantly more adverse events compared to placebo. The findings suggest that all four secretagogues are effective for IBS-C, but further research is needed to determine their long-term efficacy and safety profiles.

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.