Linaclotide
An approved oral peptide for IBS with constipation and chronic idiopathic constipation. It acts entirely inside the gut and is essentially not absorbed.
Gut & Digestive
Plecanatide
An approved oral peptide for chronic constipation and IBS-C, designed to mimic uroguanylin and act preferentially in the acidic upper intestine.
Overview
Plecanatide is built to resemble uroguanylin, one of the body's own gut peptides, rather than the bacterial toxin that linaclotide is modelled on. The practical difference is pH sensitivity: uroguanylin is most active in the slightly acidic environment of the upper small intestine and less so further down. The intent is fluid secretion where it is useful without overshooting into the colon, which in principle should mean less diarrhoea.
A 16-amino-acid analogue of human uroguanylin, differing by a single Asp3Glu substitution that improves stability. Agonises guanylate cyclase-C with pH-dependent binding affinity that peaks in the acidic proximal duodenum, in contrast to the pH-independent binding of the heat-stable-enterotoxin-derived linaclotide. cGMP elevation activates CFTR-mediated chloride and bicarbonate secretion. Minimal systemic absorption. Phase 3 trials demonstrated efficacy on complete spontaneous bowel movement endpoints in chronic idiopathic constipation and on abdominal pain plus stool frequency in IBS-C.
Research areas
Chronic constipationIBS with constipationIntestinal secretion
Dosing reported in the literature
Every protocol below is reproduced from a published study or approved labelling, with its source named. These are records of what was studied — not recommendations, and not a suggestion that any of them is appropriate for any person.
| Protocol as reported | Source |
|---|---|
| 3 mg orally once daily for chronic idiopathic constipation | Approved product labelling |
| 3 mg or 6 mg once daily over 12 weeks in IBS with constipationThe 6 mg dose gave no additional benefit, so 3 mg is the approved dose. | Brenner et al., American Journal of Gastroenterology 2018 |
Trial status
Multiple completed phase 3 trials in both indications.
Reported safety signals
- Diarrhoea is the most common adverse effect, though reported rates are lower than with linaclotide in their respective trials.
- Contraindicated in patients under 6 years old, with a boxed warning based on juvenile animal mortality.
- Contraindicated with known or suspected mechanical gastrointestinal obstruction.
- No head-to-head trial against linaclotide has been published, so tolerability comparisons across separate trials should be read cautiously.
Common questions
Is plecanatide gentler than linaclotide?
Its pH-dependent design is intended to achieve that, and reported diarrhoea rates in its own trials were lower. But there has been no head-to-head trial, and comparing adverse event rates across separately designed studies is not reliable evidence of a real difference.
Primary sources
- 01
Efficacy and safety of plecanatide in patients with chronic idiopathic constipation: results of two phase 3 randomized clinical trials
- 02
Efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials
- 03
Trulance (plecanatide) prescribing information
Medical disclaimer
This page is for informational and research purposes only. Nothing here constitutes medical advice. The compounds discussed are research chemicals. Consult a qualified clinician before starting any protocol.
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