Plecanatide
Guanylate cyclase-C agonist
Also Trulance, SP-304, SP304, Plecanatide tablets
- Evidence
- AStrong human evidence
- FDA status
- FDA approvedas of 2026-10-26
- Route
- Oral
- Studies cited
- 2 human0 animal or cell
It is a daily pill for long-lasting constipation and for irritable bowel syndrome with constipation. In a trial of 1,394 adults, about 20% improved, versus 10% on placebo.
Sold for
Plecanatide is prescribed as a once-daily pill for chronic constipation and constipation-type IBS that is meant to work like the gut's own fluid-regulating peptide.
Studies say
Large randomized trials show plecanatide roughly doubles the chance of a durable improvement in bowel movements compared with placebo, with diarrhea as the main side effect, which earns an A for its approved use.
Why grade A. Approval rested on randomized, placebo-controlled phase 3 trials; the published chronic constipation trial randomized 1,394 adults over 12 weeks, and companion trials covered IBS with constipation. The effect size is modest (roughly one in five responders versus one in ten on placebo), but the trial evidence for the approved use is as good as it gets. 12
FDA. Plecanatide is FDA-approved as Trulance for adults with chronic idiopathic constipation (January 2017) and irritable bowel syndrome with constipation (2018). The label carries a boxed warning about serious dehydration in children; it is contraindicated under age 6 and not recommended under 18. 2
Written from 2 cited sources. Fact-checked 2026-10-27: 15 claims checked, 4 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Long-lasting constipation, constipation-type IBS
- Can a US doctor prescribe it?
- Yes, FDA approved for long-lasting constipation and IBS with constipation in adults.
- Properly tested in people?
- Yes, in large controlled trials, including one of 1,394 adults.
Evidence checklist
- Randomised controlled trial Placebo-controlled phase 3 trialsyes
- Human study over 100 people 1,346 adults in constipation trialyes
- More than one research group Sponsor-run trialsno
- Clinical outcomes, not surrogate markers Bowel movement and symptom scoresno
- Human safety data beyond case reports Diarrhea rates; pediatric dehydration warningyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Plecanatide is a 16-amino-acid peptide that is a near copy of uroguanylin, a hormone the small intestine releases after a meal to regulate fluid in the gut. It differs from uroguanylin by a single amino acid, a change that makes it more stable. It was developed by Synergy Pharmaceuticals and is now sold by Salix as Trulance, a tablet taken once a day. 12
It belongs to the same class as linaclotide (Linzess): both are guanylate cyclase-C agonists. Plecanatide's developers argued that, because it mimics uroguanylin and uroguanylin's activity depends on acidity, it would act mainly in the upper small intestine and cause less diarrhea than linaclotide. That claim has never been tested in a head-to-head trial. 1
How it works
Plecanatide binds guanylate cyclase-C, a receptor on the inner surface of the intestinal lining. Activation raises levels of cyclic GMP inside those cells, which opens a chloride channel (CFTR) and pushes chloride and bicarbonate, followed by water, into the gut. More fluid in the intestine softens stool and speeds its passage. The drug stays almost entirely in the gut; very little is absorbed into the blood. 12
What human research shows
In the phase 3 chronic idiopathic constipation trial, 1,394 adults were randomized to one of two plecanatide doses or placebo for 12 weeks. The primary endpoint, a durable overall responder, required at least three complete spontaneous bowel movements a week plus an increase of at least one from baseline in most of the 12 weeks. About 20 percent of plecanatide patients met it (21.0 and 19.5 percent at the two trial doses) versus 10.2 percent on placebo. Stool consistency, straining and quality-of-life scores also improved. 1
The IBS with constipation approval drew on two further 12-week phase 3 trials in which plecanatide improved the combined endpoint of abdominal pain and bowel movements more often than placebo. Those trials are summarized in the prescribing information. 2
| Study | Model | Finding |
|---|---|---|
| Phase 3 chronic constipation trial | Humans, n=1,394, randomized, double-blind, placebo-controlled, 12 weeks | Durable overall responder rate roughly doubled versus placebo, with diarrhea the main side effect. 1 |
| IBS-C phase 3 trials (label summary) | Humans, two randomized placebo-controlled trials, 12 weeks | More patients had combined improvement in abdominal pain and bowel movements than on placebo. 2 |
Safety
Diarrhea is the main adverse effect, reported by about 6 percent of patients in the constipation trial against 1.3 percent on placebo, and it led a small number to stop treatment. Serious dehydration from severe diarrhea is the reason for the boxed warning in children: in young juvenile mice the drug caused deaths from dehydration, so the label forbids use under age 6 and advises against it under 18. Because so little reaches the bloodstream, drug interactions are not expected. Long-term safety data beyond the trial extensions are limited. 12
Questions for your clinician
- How large is the benefit over placebo, and is it worth trying for me?
- What should I do if diarrhea becomes severe?
- Could the constipation have another cause I should have checked?
Questions people ask
How does plecanatide differ from linaclotide?
Both activate the same gut receptor and both are approved for chronic constipation and IBS with constipation. Plecanatide mimics uroguanylin and its activity is sensitive to acidity, which its developers say concentrates its action in the upper small intestine. No trial has compared the two directly, so claims that one causes less diarrhea rest on separate trials with different designs. 12
Is plecanatide a laxative?
Not in the usual sense. Stimulant and osmotic laxatives work by irritating the bowel or drawing water in through osmosis. Plecanatide signals the intestinal lining to secrete fluid the way the body's own uroguanylin does, and it also appears to reduce pain signaling from the gut in animal models. 1
Why is there a boxed warning about children?
In animal studies, very young mice given the drug died from dehydration caused by severe diarrhea. The FDA requires the label to state that plecanatide is contraindicated under age 6 and should be avoided under 18 until pediatric safety is established. 2