Assessing the Efficacy and Safety of Multiple Drugs for IBS-C: A Systematic Review and Network Meta-Analysis

Background and Aims: Intestinal secretagogues and prokinetic agents are commonly used for managing irritable bowel syndrome with constipation (IBS-C). However, no studies have provided direct head-to-head comparisons of these medications. This study aimed to evaluate the dose-stratified relationships and safety profiles of multiple agents to treat IBS-C.Methods: We searched PubMed, Embase, Cochran Library, and Web of Science for randomized controlled trials (RCTs) from their inception until 21 November 2024. Eligible trials assessed the efficacy and safety of intestinal secretagogues or prokinetic agents in patients with IBS-C. The outcomes were abdominal symptoms, stool characteristics, and the incidence of adverse events.Results: A total of 1,152 articles were identified, and 16 trials involving five drugs with various dosing regimens were included. Our results suggest that linaclotide (62.5 μg qd, 290 μg qd, 500 μg qd and tenapanor 50mg bid) may be superior to placebo and tenapanor (5 mg bid) in improving abdominal pain. Linaclotide (290 μg qd) was significantly more effective than placebo in alleviating abdominal cramping and increasing bowel movement frequency. Regarding safety, linaclotide (125 μg qd) was associated with a higher incidence of adverse events than both linaclotide (62.5 μg qd) and placebo. Tenapanor (50 mg bid) and linaclotide (125 μg qd) were linked to more adverse events than tenapanor (20 mg bid). Linaclotide (290 μg qd) also had a higher incidence of adverse reactions than placebo.Conclusions: For patients with IBS-C, higher doses of linaclotide and tenapanor may provide enhanced symptom relief, but caution is warranted regarding their safety profiles.