Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta-analysis

Clin Gastroenterol Hepatol. 2013 Sep;11(9):1084-1092.e3; quiz e68. doi: 10.1016/j.cgh.2013.04.032. Epub 2013 May 2.


Background & aims: Linaclotide is a minimally absorbed, 14-amino acid peptide used to treat patients with irritable bowel syndrome with constipation (IBS-C) or chronic constipation (CC). We performed a meta-analysis to determine the efficacy of linaclotide, compared with placebo, for patients with IBS-C or CC.

Methods: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched for randomized, placebo-controlled trials examining the effect of linaclotide in adults with IBS-C or CC. Dichotomous results were pooled to yield a relative risk (RR), 95% confidence intervals (CIs), and number needed to treat (NNT).

Results: The search identified 7 trials of linaclotide in patients with IBS-C or CC; 6 were included in the analysis. Two of 3 trials of IBS-C used the end point recommended by the U.S. Food and Drug Administration: an increase from baseline of 1 or more complete spontaneous bowel movement (CSBM)/week and a 30% or more reduction from baseline in the weekly average of daily worst abdominal pain scores for 50% of the treatment weeks. On the basis of this end point, the RR for response to treatment with 290 μg linaclotide, compared with placebo, was 1.95 (95% CI, 1.3-2.9), and the NNT was 7 (95% CI, 5-11). For CC, on the basis of data from 3 trials of patients with CC, the RR for the primary end point (more than 3 CSBMs/week and an increase in 1 or more CSBM/week, for 75% of weeks) was 4.26 for 290 μg linaclotide vs placebo (95% CI, 2.80-6.47), and the NNT was 7 (95% CI, 5-8). Linaclotide also improved stool form and reduced abdominal pain, bloating, and overall symptom severity in patients with IBS-C or CC.

Conclusions: On the basis of a meta-analysis, linaclotide improves bowel function and reduces abdominal pain and overall severity of IBS-C or CC, compared with placebo.

Keywords: BSFS; Bristol Stool Form Scale; CC; CI; CSBM; Clinical Trials; Colon; FDA; Food and Drug Administration; Functional Bowel; IBS-C; ITT; NNT; RCT; RR; Systematic Review; TEAE; chronic constipation; complete spontaneous bowel movement; confidence interval; intention to treat; irritable bowel syndrome with constipation; number needed to treat; randomized controlled trial; relative risk; treatment emergent adverse event.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abdominal Pain / prevention & control
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Constipation / drug therapy*
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Irritable Bowel Syndrome / complications*
  • Male
  • Middle Aged
  • Peptides / therapeutic use*
  • Placebos / administration & dosage
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • United States
  • Young Adult


  • Gastrointestinal Agents
  • Peptides
  • Placebos
  • linaclotide