PMID-29380823 – GC-C Agonists IBS-C CIC Systematic Review Meta-Analysis
Shah ED, Kim HM, Schoenfeld P. "Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic Review and Meta-Analysis," Am J Gastroenterol, 2018;113(3):329-338.
Quick Reference
| Property | Value |
|---|---|
| PMID | 29380823 |
| DOI | 10.1038/ajg.2017.495 |
| Year | 2018 |
| Journal | American Journal of Gastroenterology |
| Study Type | Systematic Review / Meta-Analysis |
| Evidence Level | I |
| Sample | 10 RCTs pooled (linaclotide and plecanatide) |
| Peptide(s) Studied | Linaclotide, Plecanatide |
Key Findings
- Both linaclotide and plecanatide (GC-C agonists) demonstrated significantly greater efficacy than placebo in IBS-C and CIC
- Linaclotide 290 mcg was superior to placebo for FDA composite endpoint in IBS-C (RR 1.95, 95% CI 1.3-2.9)
- Plecanatide showed comparable efficacy to linaclotide for CIC endpoints
- Diarrhea was the most common adverse event across all GC-C agonist trials, generally mild-to-moderate
- NNT (number needed to treat) for GC-C agonists was approximately 6-8 for IBS-C
- Both agents demonstrate low systemic absorption, acting locally in the GI lumen
Study Design
Systematic review and meta-analysis of all published RCTs evaluating GC-C agonists (linaclotide and plecanatide) in IBS-C and CIC. Searched PubMed, EMBASE, Cochrane databases, ClinicalTrials.gov, FDA websites. Outcomes assessed using FDA composite endpoints and individual symptom measures. Random-effects model used for pooled analyses.
Limitations
- Heterogeneity in endpoint definitions across trials limits direct comparison
- Indirect comparison of linaclotide vs plecanatide (no head-to-head trials)
- Short trial durations (12 weeks) may not capture long-term efficacy
- Industry-sponsored trials for both agents
Clinical Relevance
This meta-analysis establishes the GC-C agonist class as effective therapy for IBS-C and CIC with consistent results across multiple trials. The local GI mechanism and minimal systemic absorption make these peptides attractive for chronic use. The data support guideline recommendations for GC-C agonists as first-line pharmacotherapy for IBS-C. For the vault, this study links the mechanistic science of guanylate cyclase-C signaling to clinical efficacy outcomes.
Related
#research #systematic-review #meta-analysis #evidence-level-I #gastrointestinal #linaclotide #plecanatide