PepRank

Linaclotide

45%positive25 reports

Also: Linzess · Constella · GC-C agonist

ExcludedOral

Approved gut-only GC-C agonist pill for IBS-C and constipation; works for many, often too well.

#49 of 61 research peptides · updated
Access
Approved drug
Cost / month
≈ €450
researchers' estimate; no listing to price
OralFelt in 1–4 h, lasts 24 h
25 user reports
Glowing 3Positive 8Mixed 3Nothing 3Negative 6Bad reaction 2

  • r/ibs· · 18 upvotesOriginal ↗

    Linzess is the only thing that keeps me going everyday. 145mcg

    Glowing145 mcg · Oral

    IBS

  • r/ibs· · 4 upvotesOriginal ↗

    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

  • r/ibs· · 315 upvotesOriginal ↗

    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

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.
Users report
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.
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
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)
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.
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.
Getting it
Prescription drug: Linzess in the US (AbbVie/Ironwood), Constella in the EU and Canada. Bought from a pharmacy and minimally absorbed, so product quality is not the issue; insurers often make patients try it before Trulance or Ibsrela.
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.

User reports 25

  • r/ibs· · 18 upvotesOriginal ↗

    Linzess is the only thing that keeps me going everyday. 145mcg

    Glowing145 mcg · Oral

    IBS

  • r/ibs· · 4 upvotesOriginal ↗

    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

  • r/ibs· · 3 upvotesOriginal ↗

    Yes! I don’t have crazy abdominal pain like I use to. If I feel cramping, I know it’s temporary.

    Glowinglowest dose (72 mcg) · Oral

    IBS-M after years of failed laxatives, diets and probiotics; posted 'Linzess has changed my life'

  • r/ibs· · 21 upvotesOriginal ↗

    Constipation- basically gone, BM every day or close to

    PositiveOral · about a week

    IBS-C for a year

  • r/ibs· · 10 upvotesOriginal ↗

    I agree, it’s not my favorite med but there’s a reason I take it. Any time I’ve stopped, I’ve regretted it greatly!

    PositiveOral

  • r/Constipation· · 9 upvotesOriginal ↗

    I have to be contrarian and note that I have had positive experiences with Linzess. I have been taking the high dose for about two years.

    Positive290 mcg · Oral · about two years

  • r/ibs· · 8 upvotesOriginal ↗

    For me, Linzess is a life saver! I do get diarrhea every morning, but that’s it.

    Positive145 mcg · Oral · 8+ years

  • r/Constipation· · 7 upvotesOriginal ↗

    It's been more than 10 years with this routine. It's the only thing that worked.

    Positive290 mcg plus 5 sennosides, evenings · Oral · 10+ years

    15 years of failed treatments before it

  • r/Constipation· · 6 upvotesOriginal ↗

    When I first started taking it (at lowest dose) I had diarrhea two or three times in the morning. But after a couple weeks, it went away. I think it’s working pretty decently.

    Positive145 mcg (started at 72 mcg) · Oral · 2-3 months

    slow motility and incomplete emptying after Motegrity; also pelvic-floor therapy

  • r/ibs· · 5 upvotesOriginal ↗

    Some days I have solid stool, most days it’s liquid and urgent. But i will take it any day over the constipation.

    Positive72 mcg · Oral · about 3 years

  • r/Gastroparesis· · 3 upvotesOriginal ↗

    I...liked it because it worked but it worked too well sometimes? It wasn’t awful it was just...when your guts were ready to go you had to be prepared. I only ever had diarrhea once.

    PositiveOral

    took part in a pre-approval clinical trial, before a gastroparesis diagnosis

  • r/Constipation· · 5 upvotesOriginal ↗

    It worked for me for a few weeks, and then it failed.

    MixedOral

  • r/ibs· · 3 upvotesOriginal ↗

    I had diarrhea a lot when I first started it. Now it ebbs and flows on whether it works for me at all.

    MixedOral

  • r/ibs· · 1 upvotesOriginal ↗

    I’ve been on Linzess for about two weeks now and I’ve only had one bad flare up(my fault) which is great news in my opinion!! However, this medicine, is dehydrating.

    MixedOral · about two weeks

  • r/Constipation· · 6 upvotesOriginal ↗

    I’m a little over a week of taking it and there has been no movement at all. I’m now a week and two days without using the bathroom. Not even an enema worked for me, and I am in PAIN.

    Nothinglowest dose (72 mcg) · Oral · just over a week

    bowel endometriosis

  • r/Constipation· · 3 upvotesOriginal ↗

    So what does it mean if you're on the highest dose of Linzess 290 mcg and you're lucky it produces anything, except some morning gas?

    Nothing290 mcg · Oral

  • r/Constipation· · 3 upvotesOriginal ↗

    I was on it for about a decade and it never worked. After I had everything removed, it works a teeeeeny bit in the small intestine.

    NothingOral · about a decade

    severe motility disorder, later had the colon removed

  • r/ibs· · 315 upvotesOriginal ↗

    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

  • r/ibs· · 39 upvotesOriginal ↗

    You go from being debilitated due to bloating from constipation to debilitation because you can’t leave the house from this medication.

    NegativeOral

  • r/ibs· · 8 upvotesOriginal ↗

    Late to the party, but I've been on 145mg for the last month and have pooped myself TWICE during two different naps.

    Negative145 mcg · Oral · about a month

  • r/Constipation· · 8 upvotesOriginal ↗

    Eventually I was unable to go on my “off days” and I’d be left feeling bloated and full, even worse than before.

    Negativemedium dose (145 mcg) every other day · Oral

  • r/ibs· · 5 upvotesOriginal ↗

    Linzess was also my hell I had 10 days oh essentially shitting myself until my doctor told me 25% of patients get the opposite affect and it gives you chronic diarrhea.

    NegativeOral · about 10 days

  • r/Constipation· · 3 upvotesOriginal ↗

    I tried Linzess and it mainly just gave me balloon belly.

    NegativeOral

    moved to Trulance plus magnesium oxide

  • r/Constipation· · 9 upvotesOriginal ↗

    I’ve been taking Trulance 3-mg for the past 3-weeks after trying Linzess, Amitiza and Ibsrela with either no success (Linzess, due to a hives reaction) or hit & miss success.

    Bad reactionOral

    CIC/slow transit after sigmoid resection; stopped Linzess over hives and later did well on Trulance

  • r/ibs· · 2 upvotesOriginal ↗

    The short answer is yes. I was taking the strongest dose, for a little bit and was a mess. As others have said, make sure to get electrolytes with your hydration, otherwise you'll be making another trip into the emergency for fluids.

    Bad reaction290 mcg · Oral

Safety

Tier by safety barStrict ExcludedBalanced CautionEvidence only Caution

Seen harmMechanismData gapSilent harmProduct

Seen harm 2/3
The label carries an adult warning for severe diarrhoea (2% at 145-290 mcg in trials vs under 1% on placebo). Post-marketing reports describe severe diarrhoea with dizziness, fainting, low blood pressure and low potassium or sodium that needed hospital or IV fluids, plus anaphylaxis and angioedema. Two of 25 Reddit reports describe dehydration or hives. The harm depends on dose and is avoided by stopping and rehydrating; the scale gives no discount for that. LINZESS prescribing information, 5.2 Diarrhea and 6.2 Postmarketing Experience ↗Chey et al. 2012, 26-week IBS-C trial (diarrhoea discontinuation 4.5% vs 0.2%) ↗
Mechanism 2/3
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 ↗
Data gap 0/3
FDA-approved since 2012 and EU-approved as Constella, with phase 3 RCTs in over 4,000 adults, open-label safety studies of up to 18 months in more than 3,000, paediatric trials, and over a decade of post-marketing use. Lembo et al. 2011, two RCTs of linaclotide in chronic constipation (NEJM) ↗EMA EPAR: Constella ↗
Silent harm 0/3
The harm is diarrhoea and dehydration, mostly in the first two weeks and within hours of a dose; it is obvious at once and resolves on stopping. The drug is minimally absorbed and has no known delayed or silent harm. LINZESS prescribing information, 6.1 (most diarrhoea starts within the first 2 weeks) ↗
Product 0/3
A regulated oral prescription capsule from a pharmacy (Linzess, Constella); there is no grey-market channel. LINZESS prescribing information ↗
Never if
Children under 2 years (boxed warning, risk of fatal dehydration) · Known or suspected mechanical bowel obstruction · Previous anaphylaxis or angioedema on linaclotide

Studies 5

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. 5Plecanatide Excluded Oral≈ €540–650 / month45%positive25 reportsApproved uroguanylin-like GC-C agonist tablet for constipation and IBS-C; linaclotide's sibling.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.

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.