The guanylate cyclase-C (GCC) agonists linaclotide and plecanatide are similarly effective in treating both chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C), according to new research published in The American Journal of Gastroenterology.

Researchers aimed to evaluate the safety and efficacy of GCC treatment as no prior meta-analysis has collected randomized controlled trial (RCT) data for this drug class. Data from PubMED, EMABSE, Cochrane,, the FDA and U.S. Securities and Exchange Commission filings were used to identify RCT of CIC or IBS-C patients.

A total of 15 trials involving over 10,000 patients were used for the final analysis; 8 assessed linaclotide (5 CIC; 3 IBS-C) and 7 assessed plecanatide (4 CIC; 3 IBS-C). In the CIC trials, linaclotide at 72μg and 145μg doses demonstrated greater likelihood than placebo for meeting the FDA’s responder endpoint (Odds ratio [OR] 3.11, 95% 1.81-5.34; and OR 3.25, 95% CI: 2.15-4.91, respectively). Results were similar for plecanatide 3mg (OR 1.99, 95% CI: 1.57-2.51).

Efficacy was also seen for both linaclotide and plecanatide when treating IBS-C (linaclotide 290μg [OR 2.43, 95% CI:1.48–3.98]; plecanatide 3mg [OR 1.87, 95% CI: 1.47–2.38]; plecanatide 6mg [OR 1.92, 95% CI: 1.48–2.48]). 

No significant differences were seen between the two therapies in ORs for efficacy, diarrhea, or diarrhea-related study withdrawals. Diarrhea did occur more often in the treatment groups compared to placebo (CIC: linaclotide 72μg [OR: 3.07], linaclotide 145μg [OR: 3.70], plecanatide 3mg [OR 3.86]; IBS-C: linaclotide 290μg [OR: 8.02], plecanatide 3mg [OR: 5.55], and plecanatide 6mg [OR: 4.13]. 

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The authors concluded that linaclotide and plecanatide showed comparable efficacy and tolerability in the treatment of IBS-C and CIC with no significant differences in the likelihood of diarrhea.

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