# Plecanatide

Approved uroguanylin-like GC-C agonist tablet for constipation and IBS-C; linaclotide's sibling.

- Page: https://peprank.xyz/peptides/plecanatide
- Category: Gut (Research peptide)
- Also known as: Trulance; uroguanylin analogue; GC-C agonist
- Routes: Oral
- Safety tier: Strict: Avoid · Balanced: Caution · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 2, Mechanism 2, Data gap 0, Silent harm 0, Product 0
- Positive: 45% of 25 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #45 of 61 research peptides
- Graded reports: 25 (Glowing 4, Positive 7, Mixed 3, Nothing 4, Negative 5, Bad reaction 2)
- Evidence: Approved drug — FDA-approved 2017 for chronic idiopathic constipation, later extended to IBS-C, adults only; four phase 3 RCTs with over 3,000 adults on drug or placebo
- Access: Approved drug
- Onset: Usually within 1-4 hours of a dose; bloating and pain improve over the first weeks
- Lasts: About a day per dose; taken once daily
- Cost per month: ≈ €540–650 (researchers' estimate)
- Updated: 2026-10-30

**Why Avoid under the strict bar:** The label warns of severe diarrhoea (0.6-1% in trials, most within the first days) with instructions to stop and rehydrate, and Reddit users describe days of watery diarrhoea leaving them badly dehydrated. Its sibling linaclotide has post-marketing hospitalisations for the same harm. It is obvious and stops when the drug does, so under a doctor it is a reasonable constipation treatment, but it is a real route to serious harm and does not belong on a clean wellness list.

## What users report

Much like Linzess, and the two are often tried in turn because insurers require it. 11 of 25 reports are favourable: some who got nowhere on Linzess call Trulance a godsend or 'more predictable', and a few long-term users with almost no colon motility say they cannot go without it. The rest describe the same class problems: a first dose that empties the bowel for hours, days of liquid stools, accidents at work, insane bloating, or cramps with no result. Two describe dehydration bad enough to feel faint or set off a rheumatoid flare. For several, the effect faded after a few weeks. Felt nothing: 4 of 25 reports (16%) felt nothing; a few more found it stopped working after weeks.

**Effects:** more frequent, softer bowel movements, usually within hours; less bloating and IBS-C abdominal pain; a second chance for people Linzess failed or overwhelmed

**Downsides:** diarrhoea (5% vs 1% placebo on the label's stricter definition), often explosive in the first days; bloating or cramping without a bowel movement in some; effect can fade after weeks; insurers usually require a Linzess trial first; costly uninsured

**Risks:** Severe diarrhoea and dehydration (0.6-1% severe in trials, mostly within the first 1-3 days); Boxed warning: contraindicated under 6 years and to be avoided under 18 (juvenile mice died of dehydration); Contraindicated with known or suspected mechanical bowel obstruction; Rare hypersensitivity (itching, hives, rash) and isolated liver-enzyme rises in trials

**Caveat:** Plecanatide's label shows less diarrhoea than linaclotide's, but its trials used a stricter definition, and a meta-regression found no real difference; whether it is gentler for a given person is trial and error, and people switch between the two (never combine them) when one fades or is too harsh. Gains over placebo are modest (about 1 in 10 extra responders). It stays in the gut and has no known slow or hidden harm.

**Typical use:** 3 mg once daily, with or without food (both CIC and IBS-C). Users sometimes halve the tablet or take it every other day to tame diarrhoea.

**Getting it:** Prescription drug in the US (Trulance, Salix/Bausch). Pharmacy-dispensed and minimally absorbed, so product quality is not an issue; US insurers often cover it only after Linzess (or Amitiza) has failed.

**Stacked with:** Prucalopride (Motegrity) (Added for slow transit by users for whom Trulance alone is not enough.); Magnesium oxide or Miralax (Osmotic laxatives on top, or on off days by those who take Trulance every other day to avoid liquid stools.)

## Risk profile

- **Seen harm 2/3:** The label has an adult warning and precaution for severe diarrhoea (0.6% in the CIC trials and 1% vs 0.1% placebo in IBS-C, starting within the first 1-3 days), with instructions to stop and rehydrate. Post-marketing adds hives and rash, and two trial patients had ALT 5-15 times normal. Unlike linaclotide's label, it lists no post-marketing hospitalisations; the score rests on the label warning plus two of 25 Reddit reports of dehydration (near-fainting, a rheumatoid flare). This is the weaker end of a 2.
- **Mechanism 2/3:** Same GC-C pathway as linaclotide: intestinal chloride and water secretion that can tip into dehydration and electrolyte loss. In young juvenile mice a single dose killed by dehydration, hence the paediatric boxed warning. It acts only in the gut, with no systemic hormone, growth or immune pathway.
- **Data gap 0/3:** FDA-approved since 2017, with four phase 3 RCTs (over 3,000 adults randomised to drug or placebo) and years of post-marketing use. Not approved outside the US, and no paediatric data.
- **Silent harm 0/3:** Diarrhoea and dehydration start within hours to days of a dose (severe cases within the first 3 days in trials), are obvious, and resolve on stopping. It is minimally absorbed with no known delayed harm; the rare liver-enzyme rises in trials were found on routine labs.
- **Product 0/3:** A regulated oral prescription tablet dispensed by pharmacies; there is no grey-market channel.
- **Never if:** Children under 6 years (boxed warning); avoid under 18; Known or suspected mechanical bowel obstruction

## Top reports

- Glowing, gut: “I take trulance myself and guys I gotta tell you it changed my life. I was so constipated I was going ten days without a single bowel movement.” — [r/ibs](https://www.reddit.com/r/ibs/comments/8jc4vt/trulance_is_a_very_powerful_drug_ibsc/dyzz9f0/)
- Glowing, gut: “Glad I ignored people saying that Trulance was going to give the same effect as Linzess.” — [r/ibs](https://www.reddit.com/r/ibs/comments/1hle1ge/success_with_trulance/)
- Glowing, gut: “I can’t imagine living without Trulance. It’s been a lifesaver for me.” — [r/Constipation](https://www.reddit.com/r/Constipation/comments/1nt6pu4/trulance_nightmare/ngs6tb8/)
- Glowing, gut: “Trulance is A GODSEND.” — [r/ibs](https://www.reddit.com/r/ibs/comments/8jc4vt/trulance_is_a_very_powerful_drug_ibsc/mpakirl/)
- Positive, gut, 3 mg: “Only Trulance seems to help me deal with CIC/STC (informally diagnosed by my GE, with no testing to rule out other possible issues).” — [r/Constipation](https://www.reddit.com/r/Constipation/comments/195u4lv/trulance_experience/)

## Studies

- [Miner et al., A randomized phase III clinical trial of plecanatide in chronic idiopathic constipation (Am J Gastroenterol 2017)](https://pubmed.ncbi.nlm.nih.gov/28169285/) (rct, n=1394, 2017): Over 12 weeks, 21.0% (3 mg) and 19.5% (6 mg) were durable responders on complete spontaneous bowel movements vs 10.2% on placebo; diarrhoea in 5.9% vs 1.3%.
- [Brenner et al., Efficacy, safety, and tolerability of plecanatide in IBS-C: two phase 3 randomized trials (Am J Gastroenterol 2018)](https://pubmed.ncbi.nlm.nih.gov/29545635/) (rct, n=2189, 2018): Overall responders (pain plus bowel movements) were 21.5-30.2% on 3 mg vs 14.2-17.8% on placebo; diarrhoea in 4.3% vs 1.0%, and only 1.2% stopped for it.
- [Shah et al., Efficacy and tolerability of guanylate cyclase-C agonists for IBS-C and CIC: systematic review and meta-analysis (Am J Gastroenterol 2018)](https://doi.org/10.1038/ajg.2017.495) (meta-analysis, n=10369, 2018): Across 15 trials, plecanatide and linaclotide had no significant differences in efficacy, diarrhoea or diarrhoea dropouts once the trials' different diarrhoea definitions were accounted for, so plecanatide's 'gentler' label rate is not evidence that it is gentler.
- [Black et al., Efficacy of secretagogues in IBS-C: systematic review and network meta-analysis (Gastroenterology 2018)](https://pubmed.ncbi.nlm.nih.gov/30144426/) (meta-analysis, n=8462, 2018): All secretagogues beat placebo with broadly similar efficacy; plecanatide 6 mg ranked first for safety, linaclotide 290 mcg first for efficacy.

## Sources

- [TRULANCE (plecanatide) full prescribing information (revised 03/2024)](https://www.trulance.com/globalassets/bhc/pi/trulance-pi.pdf)
- [DailyMed: Trulance](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fe2895bf-71a6-493a-b0ca-e06b2dfefc82)
- [Superpower peptide guide: Plecanatide](https://superpower.com/guides/peptides/plecanatide)