Plecanatide
A once-daily tablet modelled on uroguanylin that draws water into the gut, approved for chronic constipation and IBS-C
Plecanatide copies uroguanylin, a gut hormone that tells the intestinal lining to release fluid. It acts in the gut and is barely absorbed. Approved as Trulance for adults with chronic idiopathic constipation and IBS with constipation, it carries a boxed warning because it killed young juvenile mice through dehydration.
What is it?
Uroguanylin is a hormone made by the gut lining. It binds guanylate cyclase-C on intestinal cells, which pumps chloride and bicarbonate into the gut, water follows, and stool softens and moves. Plecanatide is a copy of it that acts on the same receptor, from inside the gut, and barely reaches the blood: in a 2025 trial its levels stayed below the limit of measurement at every time point.
It is the second drug of its kind after linaclotide, and the two work the same way. The label sets one dose, 3 mg once daily, for both approved conditions, and allows the tablet to be crushed for people who cannot swallow it. It can be taken with or without food.
A phase 2 dose-ranging trial of 951 adults with chronic idiopathic constipation found 0.3 mg and 3.0 mg both increased complete spontaneous bowel movement responder rates against placebo, shortened the time to the first such movement and reduced constipation severity, with diarrhoea the most frequent adverse event.
In the phase 3 constipation trial, about one in five responded durably on 3 or 6 mg against one in ten on placebo, and complete spontaneous bowel movements rose by 2.5 a week against 1.2. Two IBS-C trials found overall responders at 21.5% to 30.2% against 14.2% to 17.8% on placebo. Diarrhoea was the commonest side effect, in about 4% to 6%.
Bloating, the symptom many people with IBS-C mention first, was analysed across the two phase 3 IBS-C trials. Of 1,436 patients, 76.9% reported moderate to severe bloating at the start; in that group plecanatide reduced bloating severity (−1.7 against −1.3), abdominal pain (−1.7 against −1.3) and increased complete bowel movements more than placebo, and more were combined pain-and-bloating responders (33.6% against 26.8%).
Pooled analyses of the phase 3 trials looked at harder cases and at other medicines. About a quarter of patients had severe constipation at the start, and their response rates were similar to the overall results: 20.9% durable responders on 3 mg against 11.3% on placebo in chronic constipation, and 33.0% against 19.0% overall responders in IBS-C. In the 12.8% of patients also taking acid-suppressing drugs, response was 23.6% on 3 mg against 7.6% on placebo, similar to those not taking them, although serious adverse events were more frequent in that group (3.3% against 1.0%). In a 2025 analysis of 605 adults aged 18 to 40 with IBS-C, more improved on a combined pain, bloating and bowel-movement endpoint with plecanatide (23.3% against 13.4%).
Long-term and international data were consistent. In an open-label study of 2,370 patient exposures, mostly at 6 mg, diarrhoea affected 7.1% and urinary tract infection 2.2%. A 2025 phase 3 trial in Chinese patients with functional constipation found 3 mg effective, with diarrhoea in 4.3% against 0.6% on placebo.
The boxed warning is about age, not interactions: a single dose killed young juvenile mice through dehydration, so the label contraindicates it under 6 years old. The label also advises avoiding it between ages 6 and 18, where safety and effectiveness are not established, and says to stop dosing and rehydrate if severe diarrhoea occurs. Plasma levels after 3 mg were below the limit of quantitation in most samples, so no half-life could be calculated, and the label has no drug interactions section.
Mechanism of Action
Plecanatide copies uroguanylin, activating guanylate cyclase-C on the gut lining so chloride, bicarbonate and water move into the bowel; it is barely absorbed.
Fluid into the gut
Guanylate cyclase-C activation drives chloride and bicarbonate into the gut, water follows and stool softens.
Acts locally
Plasma levels were below the limit of quantitation in most samples after 3 mg (label).
Age-dependent risk
Deaths from dehydration in young juvenile mice are the basis of the boxed warning (label).
Published Research
The studies behind plecanatide, read from their PubMed abstracts: phase 2 and 3 trials in chronic constipation and IBS-C, bloating, long-term safety and a trial in China.
Phase 3 in chronic constipation
Durable responders were 21.0% on 3 mg and 19.5% on 6 mg against 10.2% on placebo over 12 weeks, and weekly complete spontaneous bowel movements rose by 2.5 and 2.2 against 1.2. Diarrhoea affected 5.9% and 5.7% against 1.3%.
Phase 2 dose-ranging, 951 adults
Plecanatide 0.3 and 3.0 mg increased overall complete spontaneous bowel movement responder rates against placebo (P = 0.016 and 0.009), with diarrhoea the most frequent adverse event.
Two trials in IBS-C
Overall responders were 30.2% and 29.5% on 3 and 6 mg against 17.8% on placebo in one trial, and 21.5% and 24.0% against 14.2% in the other. Diarrhoea occurred in 4.3% and 4.0% against 1.0%, rarely leading to stopping.
Bloating in IBS-C
Among 1,104 patients with moderate to severe bloating, plecanatide reduced bloating (−1.7 against −1.3) and abdominal pain and raised bowel movements; composite responders were 33.6% against 26.8%.
Long-term safety
In an open-label study of 2,370 patient exposures, mostly on 6 mg, the commonest side effects were diarrhoea (7.1%) and urinary tract infection (2.2%); 5.3% stopped because of side effects, 3.1% because of diarrhoea.
Phase 3 in China
In Chinese patients with functional constipation, 3 mg was effective and well tolerated; diarrhoea affected 4.3% against 0.6% on placebo, and blood levels of the drug and its metabolite stayed below the limit of measurement.
Severe constipation: post hoc analysis
In the roughly quarter of patients with severe constipation, durable responders were 20.9% on 3 mg against 11.3% (CIC) and overall responders 33.0% against 19.0% (IBS-C).
With acid-suppressing drugs
In the 12.8% taking acid suppressants, response was 23.6% on 3 mg against 7.6% on placebo, similar to non-users; serious adverse events were 3.3% against 1.0% in users and non-users.
Adults 18 to 40 with IBS-C: a three-symptom endpoint
23.3% on plecanatide against 13.4% on placebo improved pain and bloating by at least 30% and gained at least one complete bowel movement a week.
Dosing Data
Trulance is one 3 mg tablet a day for either indication.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above and the Trulance prescribing information (DailyMed set fe2895bf, version 15, effective April 4, 2024).
Contraindications & Cautions
From the label, which carries a boxed warning.
Legal Status
Plecanatide is approved in the US as Trulance.
Frequently Asked Questions
?What is plecanatide?
A copy of uroguanylin, a gut hormone that makes the intestine release fluid, sold as Trulance for constipation.
?What is the dose?
The label sets 3 mg by mouth once daily for both chronic idiopathic constipation and IBS-C.
?How is it different from linaclotide?
Both activate guanylate cyclase-C in the gut. Plecanatide is modelled on uroguanylin; linaclotide on a bacterial toxin.
?Why the boxed warning?
A single dose killed young juvenile mice through dehydration, so it is contraindicated under 6 years old.
?Does it help bloating?
In IBS-C patients with moderate to severe bloating, it reduced bloating and pain more than placebo, though the differences were modest (−1.7 against −1.3 on a symptom scale).
?Can it be crushed or taken with food?
Yes. It can be taken with or without food, and the label gives instructions for crushing it into applesauce or water or giving it by feeding tube.
?Is it absorbed?
Barely; plasma levels were below the limit of quantitation in most samples, so the label gives no half-life.
References
- [fda-pi] Trulance (plecanatide) tablets Prescribing Information, sections 1, 2 and boxed warning (DailyMed version 15, effective April 4, 2024; read September 30, 2026).
- [pubmed] Miner PB Jr, et al. "A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation." Am J Gastroenterol, 2017;112(4):613-621. PMID: 28169285.
- [pubmed] Barish C, et al. "Plecanatide Is Effective and Safe in the Treatment for Chronic Idiopathic Constipation: Results of a Phase II Trial." Dig Dis Sci, 2021;66(2):537-540. PMID: 32185662.
- [pubmed] Brenner DM, et al. "Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials." Am J Gastroenterol, 2018;113(5):735-745. PMID: 29545635.
- [pubmed] Brenner DM, et al. "Plecanatide Improves Abdominal Bloating and Bowel Symptoms of Irritable Bowel Syndrome with Constipation." Dig Dis Sci, 2024;69(5):1731-1738. PMID: 38594429.
- [pubmed] Barish CF, et al. "Safety and tolerability of plecanatide in patients with chronic idiopathic constipation: long-term evidence from an open-label study." Curr Med Res Opin, 2018;34(4):751-755. PMID: 29343131.
- [pubmed] Bai T, et al. "Efficacy and Safety of Plecanatide in Chinese Patients with Functional Constipation: A Phase III Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial." Drugs, 2025;85(8):1033-1048. PMID: 40571893.
- [pubmed] Cash BD, et al. "Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation." Neurogastroenterol Motil, 2023;35(9):e14632. PMID: 37332239.
- [pubmed] Moshiree B, et al. "The Effect of Acid Suppression Therapy on the Safety and Efficacy of Plecanatide: Analysis of Randomized Phase III Trials." Clin Ther, 2022;44(1):98-110.e1. PMID: 35086735.
- [pubmed] Brenner DM, et al. "The Effectiveness of Plecanatide for Treating Constipation and Bloating in Patients Aged 18 to 40 Years With Irritable Bowel Syndrome: Utilization of a New Composite Trisymptom Endpoint." J Gastroenterol Hepatol, 2025;40(12):2890-2897. PMID: 41214272.
Sources & Citations
Studies were read from their PubMed records (October 6, 2026); the label and Drugs@FDA are listed below with their read dates.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.