PepRank

Plecanatide

45%positive25 reports

Also: Trulance · uroguanylin analogue · GC-C agonist

ExcludedOral

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

#45 of 61 research peptides · updated
Access
Approved drug
Cost / month
≈ €540–650
researchers' estimate; no listing to price
OralFelt in 1–4 h, lasts 24 h
25 user reports
Glowing 4Positive 7Mixed 3Nothing 4Negative 5Bad reaction 2

  • r/ibs· · 23 upvotesOriginal ↗

    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.

    GlowingOral

    severe constipation where diet, supplements and laxatives failed

  • r/ibs· · 8 upvotesOriginal ↗

    Glad I ignored people saying that Trulance was going to give the same effect as Linzess.

    GlowingOral · about 3 weeks

    switched after Linzess had little effect

  • r/ConstipationAdvice· · 8 upvotesOriginal ↗

    It is now 3am and I’m still running to the toilet at least once every 30 minutes. This can’t be healthy I was literally just in the hospital

    NegativeOral · first dose

    taken two days after a hospital stay for gastroenteritis

Strict case
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.
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.
Best 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
Watch
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
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
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.

User reports 25

  • r/ibs· · 23 upvotesOriginal ↗

    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.

    GlowingOral

    severe constipation where diet, supplements and laxatives failed

  • r/ibs· · 8 upvotesOriginal ↗

    Glad I ignored people saying that Trulance was going to give the same effect as Linzess.

    GlowingOral · about 3 weeks

    switched after Linzess had little effect

  • r/Constipation· · 4 upvotesOriginal ↗

    I can’t imagine living without Trulance. It’s been a lifesaver for me.

    GlowingOral

  • r/ibs· · 2 upvotesOriginal ↗

    Trulance is A GODSEND.

    GlowingOral

    chronic constipation since years of fentanyl/morphine for back surgery; 3.5 years of painful, failed Linzess first

  • r/Constipation· · 9 upvotesOriginal ↗

    Only Trulance seems to help me deal with CIC/STC (informally diagnosed by my GE, with no testing to rule out other possible issues).

    Positive3 mg · Oral · 3 weeks

    CIC/slow transit after sigmoid resection; Linzess caused hives, Amitiza and Ibsrela were hit and miss

  • r/ibs· · 4 upvotesOriginal ↗

    Trulance is helping me but it is best to stay home so.you will be near a toilet or wear adult diapers.

    PositiveOral

    Linzess failed and insurance stopped paying for it

  • r/Constipation· · 2 upvotesOriginal ↗

    I am more regular now by taking Trulance every day. My body adjusted after a week.

    PositiveOral

    gastroparesis, methane and hydrogen SIBO, colon resection and adhesions

  • r/ibs· · 2 upvotesOriginal ↗

    After being on Trulance for over a year, I have cut down to every other day and have not experienced that liquid diarrhea.

    Positive3 mg every other day · Oral · over a year

  • r/ibs· · 2 upvotesOriginal ↗

    Started trulance like two weeks ago and it truly helped my bloating SO much! It was basically gone and I was so thrilled.

    PositiveOral · about two weeks

  • r/SIBO· · 2 upvotesOriginal ↗

    Hi, Dr gave me a sample. I like it better. It’s more predictable.

    PositiveOral · a sample pack

  • r/Constipation· · 2 upvotesOriginal ↗

    I have zero colon motility. Without trulance I don't go

    PositiveOral

    no colonic motility

  • r/Constipation· · 16 upvotesOriginal ↗

    It works amazingly well for my constipation, gas and bloating. I truly thought it was a miracle drug when I first started taking it. Unfortunately, my chronic headaches have gotten much worse as well as my fatigue.

    MixedOral · about a month

    IBS-C with an autoimmune disorder

  • r/Constipation· · 3 upvotesOriginal ↗

    After a few weeks, it started taking longer to work and became less predictable. The results started being less dramatic. Then some days there were no results at all.

    MixedOral

    long-standing CIC after Linzess failed

  • r/ibs· · 1 upvotesOriginal ↗

    The prescription causes me to go back and forth into the bathroom for a few hours, and it takes like an hour for it to kick in, not to mention you have to drink a lot of water with it.

    MixedOral · about a month of daily use

  • r/Constipation· · 3 upvotesOriginal ↗

    It just caused cramps for me with no bowel movement at all

    NothingOral

  • r/ibs· · 2 upvotesOriginal ↗

    It actually stopped doing anything for me after a couple of days. Just feels like it makes the cramping a bit stronger..

    NothingOral · about a month

  • r/ibs· · 2 upvotesOriginal ↗

    From all the things I heard, I thought I’d be running to the washroom every other second, or have some or other crazy GI side effect. But no, absolutely nothing has changed.

    NothingOral · a couple of days

    17-year-old (the label says to avoid under 18)

  • r/Constipation· · 2 upvotesOriginal ↗

    Trulance did absolutely nothing for me.

    NothingOral

    IBS-C; Amitiza at maximum dose works instead

  • r/ConstipationAdvice· · 8 upvotesOriginal ↗

    It is now 3am and I’m still running to the toilet at least once every 30 minutes. This can’t be healthy I was literally just in the hospital

    NegativeOral · first dose

    taken two days after a hospital stay for gastroenteritis

  • r/ibs· · 3 upvotesOriginal ↗

    I've been on trulance for 6 months and at first it worked great. The past few months I think it's making my constipation worse.

    NegativeOral · 6 months

  • r/ibs· · 3 upvotesOriginal ↗

    I've been taking Trulance for over a month now, and still feel like I've done a colonoscopy prep every time.

    NegativeOral · over a month

  • r/Constipation· · 2 upvotesOriginal ↗

    It was hell for me and I was not even on that high of a dose. Once it kicked in Ria for hours , barely anytime to get to a shitter. Cannot live life that way.

    NegativeOral

  • r/Constipation· · 2 upvotesOriginal ↗

    Linzess and Trulance didn’t work for me. Trulance just caused insane bloating.

    NegativeOral

    now on Ibsrela, Motegrity, Metamucil and Miralax

  • r/ibs· · 6 upvotesOriginal ↗

    I was shitting liquid for three days straight no joke. Did not know the human body could hold that much waste. 😭 Thought I was gonna pass out by day two. I was extremely dehydrated so make sure you drink PLENTY of water.

    Bad reactionOral · a few days

  • r/ibs· · 1 upvotesOriginal ↗

    Only took it once and it did help with instigating bowel movement. But, the dehydration caused my RA to flare up real bad.

    Bad reactionOral · one dose

    rheumatoid arthritis

Safety

Tier by safety barStrict ExcludedBalanced CautionEvidence only Caution

Seen harmMechanismData gapSilent harmProduct

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. TRULANCE prescribing information, 5.2 Diarrhea, 6.1 and 6.2 ↗r/ibs: 'Need some input on Trulance. Ended up with dehydration' ↗
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. TRULANCE prescribing information, 5.1 Risk of serious dehydration in pediatric patients ↗
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. Miner et al. 2017, phase 3 CIC trial (n=1,394) ↗Brenner et al. 2018, two phase 3 IBS-C trials (n=2,189) ↗
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. TRULANCE prescribing information, 6.1 ↗
Product 0/3
A regulated oral prescription tablet dispensed by pharmacies; there is no grey-market channel. DailyMed: Trulance ↗
Never if
Children under 6 years (boxed warning); avoid under 18 · Known or suspected mechanical bowel obstruction

Studies 4

Sources 3

More in Gut all 6 →

  1. 1KPV KPV (3 residues) Caution Oral / Topical / Injection≈ €31–61 / month58%positive47 reportsAnti-inflammatory alpha-MSH fragment for gut, skin and allergy inflammation; animal data only.
  2. 2Larazotide GGVLVQPG (8 residues) Clean Oral≈ €54–140 / month56%positive6 reportsTight-junction (zonulin) blocker trialled for celiac; very safe, but efficacy failed phase 3.
  3. 3Bovine colostrum CautionSupplement Oral≈ €28–56 / month47%positive24 reportsCow's first milk: immunoglobulins, lactoferrin and growth-factor peptides for gut lining and fewer colds.
  4. 4Polaprezinc (zinc L-carnosine) AH (2 residues) ExcludedSupplement Oral≈ €32 / month54%positive25 reportsJapanese ulcer drug sold as a supplement; the go-to oral 'stomach lining' option for gastritis.
  5. 5Linaclotide Excluded Oral≈ €450 / month45%positive25 reportsApproved gut-only GC-C agonist pill for IBS-C and constipation; works for many, often too well.The label warns of severe diarrhoea (2% in trials), and post-marketing reports describe dehydration with fainting, low blood pressure and low potassium or sodium that needed IV fluids or hospital, plus rare anaphylaxis and angioedema. The harm is obvious at once and stops when the drug does, so under a doctor it is a reasonable IBS-C treatment, but it is a real route to serious harm and does not belong on a clean wellness list.

Sequence beads

Each bead is one amino acid in the peptide's chain, coloured by its side chain: grey for non-polar, cyan for polar, blue for positively charged and fuchsia for negatively charged. Length and mix tell related peptides apart at a glance, from a two-residue dipeptide like carnosine to a 43-residue protein like thymosin beta-4. The colours describe chemistry only and predict neither effect nor safety.

non-polarpolarpositivenegative

Report grades

Every first-hand Reddit or X report is graded on its own, from glowing through positive, mixed, nothing and negative to bad reaction, and the bar shows how those grades split. Posts that look vendor-adjacent stay on the peptide's page but are left out of the counts.

GlowingPositiveMixedNothingNegativeBad reaction

% positive

The share of a peptide's graded Reddit and X reports that are glowing or positive, vendor-adjacent posts left out. A peptide with few reports is pulled toward the average of all reports, as if it had eight average ones besides its own, so two glowing posts cannot top the list. Kept peptides rank by the same reports' mean grade, shrunk the same way, and excluded ones follow in that order.

Researcher estimate

No first-hand report of this peptide has been graded yet, so the figure is the researchers' own rating out of 10 from what they read about it. It ranks alongside the computed scores until reports arrive.

Safety tier

Each peptide is tiered clean, caution or excluded from its five risk axes under the chosen safety bar. An excluded peptide has a plausible route to serious harm, so it stays listed with the reason but ranks behind every other entry, however good its reviews.

Safety bar

The safety bar sets how much risk it takes to exclude a peptide. Strict: out on any serious mechanism with little human data, or any documented serious harm. Balanced: out on documented serious harm (unless it is obvious, reversible and from a regulated product), or a serious mechanism whose harm would be silent with no human data at all. Evidence only: out only on documented serious harm in humans that is lasting, delayed or from grey-market product.

Seen harm

Documented serious adverse events in humans, from 0 for none despite real exposure to 3 for deaths or several well-documented serious harms. Serious means a hospital or emergency visit or harm lasting weeks, so a headache or a bad night does not count.

Mechanism

A plausible biological route to serious harm at the doses people use, such as growth-factor signalling, hormone-axis suppression, heart or blood-pressure effects or immune activation. It runs from 0 when none is known to 3 when a dangerous pathway has been shown in living animals.

Data gap

How little human safety data exists for the molecule actually sold, from 0 for an approved drug with large trials and years of use to 3 for no human safety data at all. A modified analogue does not inherit its parent's trials.

Silent harm

Whether the feared harm would show quickly or stay hidden, from 0 when it is obvious and goes on stopping to 3 when it is silent and delayed, like tumour promotion or slow organ damage. User reports cannot reveal a harm that takes years to appear, so a high score here limits what good reviews can tell you.

Product

The risk of what people actually buy, from 0 for a regulated pharmacy or supplement product taken by mouth or on the skin to 3 for a grey-market injectable. In one dataset of 6,441 grey-market samples, 42–71% failed basic quality criteria and 15% carried endotoxin.

Evidence

The strongest kind of study behind the peptide's effects, from an approved drug through human controlled trials and small human studies to animal work or nothing of its own. Animal results often fail to carry over to people.

Access

How people get it: as an approved drug, a compounded prescription, an over-the-counter supplement or from the grey market, where nobody checks the vial. The channel decides both the legal position and the risk of a bad batch.

Price per month

Thirty days of the typical dose, from its low end to its high end, priced at the listing a careful buyer would choose: in stock, from a shop scoring 4 of 5 on trust (third-party tested where no score is set), failing that 3, a pure pack before a blend, a European shop first, then the cheapest per mg. The range is the dose's, not the shops'. A per-dose amount counts once a day unless the dose says otherwise. Prices are in euros at ECB rates of 2026-10-29, before shipping; the shop table keeps each listing's price per mg, per gram for bulk supplements. Where no listing can be priced the researchers' own estimate stands in, and says so.

Dose users report

The middle half of the daily doses stated in at least five first-hand reports, vendor posts left out. Where its middle sits more than twice above or below the declared dose, the month is priced at it as well, since what people take is what they pay for.

Testing

Whether the shop publishes lab results: third-party tested means an independent lab checks each batch, own COA means the shop's own certificate of analysis, and no public tests means neither. A certificate shows purity, not safety.

Added peptide

Some packs sold under one peptide's name hold a second one, such as 5 mg GHK-Cu in a nasal kit, stated only in the description. Sprayed in the nose or injected it reaches the blood like an injection, so it carries the risk of that route and is tiered as the injectable form, whatever its tier on the skin. A pack whose page gives no contents list may hold more than its name.