Trulance
Evidence Grade A — Regulatory approved. 120 published studies. 14 registered clinical trials.
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Plecanatide (sold as Trulance) is a daily tablet for irritable bowel syndrome with constipation (IBS-C) and chronic constipation. It targets the same gut pathway as linaclotide (Linzess) but was designed to more closely resemble the body's own natural gut hormone, potentially offering better tolerability. Notably, it can be taken with or without food — unlike linaclotide which requires an empty stomach.
120 published studies: 79 human, 0 animal, 0 in-vitro, 56 reviews
Plecanatide is marketed as Trulance (approved January 2017 for chronic constipation; January 2018 for IBS-C). It is taken as a 3 mg tablet once daily, and unlike linaclotide, it can be taken with or without food.
The main clinical differentiator from linaclotide is tolerability: the diarrhoea rate in IBS-C trials was 4.3% for plecanatide compared to approximately 20% for linaclotide. Post-marketing diarrhoea rates have been even lower. Efficacy on constipation symptoms is broadly comparable between the two agents. Plecanatide carries the same boxed warning against use in children under 6 years. The choice between linaclotide and plecanatide often comes down to tolerability profile and individual response.
Plecanatide activates the same GC-C receptors in the intestinal lining as linaclotide, stimulating fluid secretion and reducing visceral pain sensitivity. The key design difference is that plecanatide has pH-dependent binding — it works most strongly in the slightly acidic environment of the upper small intestine (where GC-C receptors are most concentrated), rather than throughout the entire gut. This more targeted action may explain its lower rate of diarrhoea compared to linaclotide.
The key differentiator from linaclotide is the diarrhoea rate — 4.3% for plecanatide versus approximately 20% for linaclotide in IBS-C trials. Since diarrhoea is the main reason patients stop taking these medications, this lower rate may translate to better long-term adherence. Effectiveness for constipation symptoms appears broadly comparable between the two drugs. No head-to-head efficacy trials exist, so definitive superiority claims cannot be made. With linaclotide now available as a generic, plecanatide faces significant pricing pressure. It carries the same boxed warning against use in children under 6 years. Market uptake has been modest, and no major ongoing research programmes are expanding its indications.
GCC Agonist Signal in the Small Intestine
Efficacy and Safety of Plecanatide Comparing With Placebo in the Treatment of Functional Constipation
Efficacy and Safety of Plecanatide in Children 6 to <18 Years With Irritable Bowel Syndrome With Constipation (IBS-C)
A Postmarketing Study of Plecanatide in Breast Milk of Lactating Women Treated With TRULANCE®
An Efficacy and Safety Study of Plecanatide in Adolescents 12 to <18 Years of Age With Chronic Idiopathic Constipation
FDA ORIG 1
FDA SUPPL 1
FDA SUPPL 2
FDA SUPPL 10
FDA SUPPL 7
FDA SUPPL 11
Health Canada Market Authorisation
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