Approved gut-only GC-C agonist pill for IBS-C and constipation; works for many, often too well.
Safety tier
Avoid
strict bar
Positive
45%
of 25 reports
Per month
≈ €450
estimate
Rank
#44
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 (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.
Best effects
More frequent, softer bowel movements, often within hours · less IBS-C abdominal pain and bloating over weeks · relief where fibre and laxatives failed
Downsides
Diarrhoea (20% at 290 mcg vs 3% placebo), often urgent, mostly in the first 2 weeks · morning tied to the toilet; must dose 30+ min before the first meal · abdominal pain, gas and bloating in some · effect can fade over months or be erratic day to day · cost without insurance
Typical use
IBS-C 290 mcg once daily; chronic constipation 145 mcg (or 72 mcg); children 72-145 mcg. Take on an empty stomach at least 30 minutes before the first meal; users split capsules or dose every other day to tame diarrhoea.
Stacked with
Stacked with
Polyethylene glycol (Miralax): Taken alongside by many long-term users for whom linaclotide alone is not enough, even at 290 mcg. · Prucalopride (Motegrity): The usual add-on or next step for slow transit when linaclotide fails or fades. · Senna or bisacodyl: A stimulant laxative alongside, for example one ten-year user on 290 mcg plus five senna tablets each evening. Plecanatide (Trulance) is the same-class alternative people switch to, not something to combine.
Safety
Watch
Severe diarrhoea and dehydration (2% severe in trials); post-marketing reports of fainting, low blood pressure and low potassium or sodium needing IV fluids or hospital · Boxed warning: contraindicated under 2 years of age (neonatal mice died of dehydration) · Contraindicated with known or suspected mechanical bowel obstruction · Rare hypersensitivity: anaphylaxis, angioedema, hives (post-marketing)
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 2 years (boxed warning, risk of fatal dehydration) · Known or suspected mechanical bowel obstruction · Previous anaphylaxis or angioedema on linaclotide
GC-C activation pumps chloride, bicarbonate and water into the gut. At use doses this is the intended effect, but it can tip into volume and electrolyte loss with low blood pressure, as seen post-marketing; in neonatal mice one adult-equivalent dose killed by dehydration. It acts only in the gut, so there is no systemic hormone, growth or immune pathway. LINZESS prescribing information, 5.1 Risk of serious dehydration in pediatric patients ↗
Sharply split, and Reddit skews towards problems. 11 of 25 reports are favourable, several from people on it for 8-10+ years who call it the only thing that ever worked, despite daily morning diarrhoea. The commonest complaint is that it works too well: hours of urgent watery stools, accidents at work or in sleep, a whole morning planned around the toilet, worst in the first weeks and at a 290 mcg starting dose. Two describe dehydration or hives. A fair number find it stops working after weeks to months, or never works in severe slow-transit, endometriosis or EDS bowels. Felt nothing: 3 of 25 reports (12%) felt nothing even at 290 mcg; more found it faded after weeks or months.
So I took a colonoscopy prep drink, waited a few days to start Linzess consistently since I've only used it as needed in the past, and guys, I feel AMAZING 😭🙏🏼
GlowingOral · days to weeks of daily use
IBS-C and slow-transit constipation; cleared out with a colonoscopy prep first
So I take the pill and I go to work, I feel the urge to use the restroom before my shift starts but nothing happens. Typical IBS-C problems. I leave and throughout the next hour my stomach pain goes from slight pressure to absolutely debilitating
Negative290 mcg (as a starting dose) · Oral · first dose
IBS; started on the highest dose with no warning that it acts like a strong laxative
Studies
Evidence
Approved drug — FDA-approved 2012 (IBS-C, chronic idiopathic constipation; later paediatric functional constipation and IBS-C), EU-approved as Constella for IBS-C; phase 3 RCTs in over 4,000 adults
Caveat
The trial gains over placebo are modest (about 1 in 5 extra responders), and a sizeable minority stop for diarrhoea or find the effect fades. Linaclotide stays in the gut and has no known slow or hidden harm; it does not work on mechanical blockage or most severe slow-transit colons.
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.