Approved uroguanylin-like GC-C agonist tablet for constipation and IBS-C; linaclotide's sibling.
Safety tier
Avoid
strict bar
Positive
45%
of 25 reports
Per month
≈ €540–650
estimate
Rank
#45
of 61 research peptides
At a glance
Access
Approved drug
OralFelt in 1–4 h, lasts 24 h
15 min1 h6 h1 day1 week
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.
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
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.
Stacked with
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.
Safety
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
Tier by safety barStrict AvoidBalanced CautionEvidence only Caution
Seen harm2 of 3
Mechanism2 of 3
Data gap0 of 3
Silent harm0 of 3
Product0 of 3
Never if
Children under 6 years (boxed warning); avoid under 18 · Known or suspected mechanical bowel obstruction
Why each score
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 ↗
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 ↗
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.
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
Studies
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.
The peptide's chain of amino acids from its start (the N-terminus) to its end, one bead and one letter for each: A alanine, C cysteine, D aspartic acid, E glutamic acid, F phenylalanine, G glycine, H histidine, I isoleucine, K lysine, L leucine, M methionine, N asparagine, P proline, Q glutamine, R arginine, S serine, T threonine, V valine, W tryptophan, Y tyrosine. A modification such as an N-acetyl cap or a C-terminal amide changes how long it lasts in the body. Length tells related peptides apart, from a two-residue dipeptide like carnosine to a 43-residue protein like thymosin beta-4, and predicts neither effect nor safety.
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. Peptides rank by this figure, those with no graded report yet after those with one, and Avoid ones after every other entry.
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 after every peptide with graded reports until its own arrive.
Safety tier
Each peptide is tiered Clean, Caution or Avoid from its five risk axes under the chosen safety bar. An Avoid peptide carries a real risk of harm, a plausible route to serious harm rather than mere unpleasantness, 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 rate a peptide Avoid. 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; taken by mouth or in the nose, a pack avoids the injection risks.
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.
Shop trust
Each shop's trust on a 1–5 scale, read from its testing and its reputation: 1 for serious red flags (fabricated COAs, scam reports, impersonation, a closed shop), 2 for no public testing, a new shop or active complaints such as seized parcels, 3 for its own COAs or a short track record, 4 for verified third-party testing or a strong reputation, and 5 for third-party batch reports that name the shop, with years of good independent reputation. A shop without a score counts third-party batch testing as 4, its own COAs as 3 and no public tests as 2.
Best value
Within a category or a goal, a peptide that no other beats on both counts: none is rated more positively for the same or a lower monthly price, and none costs less for the same or a higher rating. The chart joins these into the best-value line; the cheapest of them and the best-rated of them both make it, so the line spans the trade-off from cheap to best. Avoid entries never count, and a peptide needs both a % positive and a price to be compared.
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.