Systematic review and network meta-analysis: efficacy of licensed drugs for abdominal bloating in irritable bowel syndrome with constipation

Aliment Pharmacol Ther. 2021 Jul;54(2):98-108. doi: 10.1111/apt.16437.Epub 2021 Jun 11.

Alfred D Nelson 1, Christopher J Black 2 3, Lesley A Houghton 3, Nahyr Sofía Lugo-Fagundo 4, Brian E Lacy 1, Alexander C Ford 2 3


Author information

  • 1Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA.
  • 2Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.
  • 3Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
  • 4Internal Medicine, Mayo Clinic, Jacksonville, FL, USA.


Background: Although bloating is a highly prevalent and troublesome symptom in irritable bowel syndrome with constipation (IBS-C), treatment is empirical with no specific guidelines for its management.

Aim: To conduct a pairwise and network meta-analysis, using a frequentist approach, of Food and Drug Administration-licensed drugs for IBS-C comparing their efficacy for abdominal bloating as a specific endpoint.

Methods: We searched the medical literature through December 2020 to identify randomised controlled trials (RCTs) in IBS-C, with abdominal bloating reported as a dichotomous assessment. Efficacy of each drug was reported as a pooled relative risk (RR) with 95% confidence intervals (CIs) to summarise effect of each comparison tested. Treatments were ranked according to their P-score.

Results: We identified 13 eligible RCTs, containing 10 091 patients. Linaclotide 290 µg o.d., lubiprostone 8 µg b.d., tenapanor 50 mg b.d. and tegaserod 6 mg b.d. were all superior to placebo for abdominal bloating in patients with IBS-C, in both pairwise and the network meta-analyses. Linaclotide demonstrated the greatest improvement in abdominal bloating in both pairwise and network meta-analysis (RR of failure to achieve an improvement in abdominal bloating = 0.78; 95% CI 0.74-0.83, number needed to treat = 7, P-score 0.97). Indirect comparison revealed no significant differences between individual drugs.

Conclusions: We found all licensed drugs for IBS-C to be superior to placebo for abdominal bloating. Linaclotide appeared to be the most efficacious at relieving abdominal bloating. Further research is needed to assess long-term efficacy of these agents and to better understand the precise mechanism of improving bloating.



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