Does it fix a gut problem?

What this archive is for. Trials of the compound come first, ranked by how many people were actually given it. Studies that only observed people are below them and labelled.

1. 01PlecanatidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,337 people given it.3 reported

   1,337 people given it2 trials

   • Plecanatide helped chronic constipation, and it helped roughly one extra person in fourteen. 1,337 adults took one of two doses or a dummy pill, and nobody involved knew which. About 20 in every hundred on either dose became lasting responders, against about 13 on the dummy. Both doses worked the same, so the higher one bought nothing. Diarrhoea was more common on the drug. Four of the five authors worked for the company that makes it and held stock, which the paper discloses.

     The numbers Double-blind placebo-controlled phase 3, 1337 adults meeting modified Rome III criteria randomised to plecanatide 3 mg (n equal to 443), 6 mg (n equal to 449) or placebo (n equal to 445). Durable overall complete spontaneous bowel movement responders: 20.1 percent on 3 mg, 20.0 percent on 6 mg, 12.8 percent on placebo, P equal to 0.004 for each dose. Diarrhoea 3.2 percent, 4.5 percent and 1.3 percent respectively. Four of the five authors were employees and stockholders of the sponsor, Synergy Pharmaceuticals, which the paper discloses.

     Therapeutic Advances in Gastroenterology, 2017· 1,337 people

   • The drug works across most kinds of patient, with one gap. Researchers pooled two identical trials, 2,639 adults in all, and split the results by age, weight, race and sex. Both doses beat the dummy pill in nearly every group, including people over 65 and people who were not White. The exception was the higher dose in people aged 65 and over, which did not clearly beat the dummy on how often they went. Diarrhoea was the commonest side effect. This re-analyses old trials rather than running a new one.

     The numbers A phase 3 randomised analysis examining whether age, sex, race and other demographic factors change the treatment response in chronic idiopathic constipation. This is the genuine randomised evidence in this compound's later literature, and it is an analysis of who responds rather than a new efficacy trial.

     Clinical and Translational Gastroenterology, 2023· number of people not given

2. 02LarazotidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 526 people given it.

   184 people given it1 trial1 found nothing

   • found nothingLarazotide reduced symptoms during a deliberate gluten challenge, but missed the thing it was designed to fix. A hundred and eighty-four people with coeliac disease ate gluten on purpose while taking the drug or a dummy. On 1 mg, symptoms were milder and the rise in a coeliac antibody was blunted. The leakiness of the gut lining, which is the whole idea behind the drug, was no different from the dummy. So the mechanism it was built on was not demonstrated.

     The numbers 184 patients on a gluten challenge: 1 mg larazotide limited gluten-induced symptoms and blunted the rise in anti-tTG antibodies, but intestinal permeability (LAMA ratio) did not differ from placebo.

     Alimentary Pharmacology and Therapeutics, 2013· 184 people

3. 03IpamorelinPeptideModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 157 people given it.9 reported

   117 people given it1 trial

   • Ipamorelin was tested properly after bowel surgery and it did not work. 117 people who had had part of the bowel removed got ipamorelin into a vein or a dummy drip. Nobody involved knew which. The aim was to get them eating sooner. On ipamorelin the first meal that stayed down came about 25 hours after surgery, against about 33 hours on the dummy. That gap is within what chance alone produces. The trial was small, so a modest real benefit could still have been missed.

     The numbers Phase 2 RCT in 117 surgical patients (NCT00672074): IV ipamorelin was well tolerated but did not significantly shorten time to first tolerated meal versus placebo (25.3 vs 32.6 h, p=0.15).

     International Journal of Colorectal Disease, 2014· 117 people

4. 04Tesamorelin / IpamorelinBlendStrong. At least two finished studies in people, and at least 1,000 people who took it. 5 completed trials, 1,507 people given it.9 reported

   117 people given it1 trial

   • Ipamorelin has been tested in people once, and it failed. A hundred and seventeen patients who had just had bowel surgery were given it into a vein or a dummy. On average they managed a meal sooner, 25.3 hours against 32.6, but the gap was too small to separate from chance. The drug was well tolerated. This is the entire published human record for the ipamorelin half of the blend, and it is about recovery from surgery.

     The numbers Phase 2 randomised controlled trial in 117 surgical patients. Intravenous ipamorelin was well tolerated but did not significantly shorten time to a first tolerated meal against placebo, 25.3 hours versus 32.6 hours, P equal to 0.15. This is the entire published human record for the ipamorelin half of the blend, and it is a null result on a different question.

     International Journal of Colorectal Disease, 2014· 117 people

5. 05Sermorelin with ipamorelinBlendModerate. At least one finished study in people, and at least 100 people who took it. 1 completed trial, 117 people given it.8 reported

   117 people given it1 trial

   • Ipamorelin has been tested properly in people exactly once, and it was for a gut problem after surgery. 117 adults having part of the bowel removed got either ipamorelin into a vein twice a day or a dummy drip, by chance. They got it from the day after surgery until they went home or a week passed. The study watched how long it took them to manage a normal solid meal. Nothing here is about muscle, sleep, or the reasons this peptide is sold.

     The numbers 117 adults undergoing small and large bowel resection were randomised to intravenous ipamorelin 0.03 mg/kg twice daily or placebo, from postoperative day 1 to day 7 or discharge, with time to tolerating a standardised solid meal as the key efficacy endpoint. This is the only randomised controlled trial of ipamorelin in people, and it is a post-surgical setting rather than any of the uses the peptide is sold for.

     International Journal of Colorectal Disease, 2014· 117 people

6. 06CJC-1295 with ipamorelin and GHRP-2BlendModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 117 people given it.5 reported

   117 people given it1 trial

   • Ipamorelin has been through one real study in people, and it was about recovery after bowel surgery. 117 patients got either ipamorelin into a vein twice a day or a dummy drip, by chance. It was safe. The study measured how soon patients could handle a solid meal. That is the whole proper record for this peptide in people. It says nothing about the uses it is sold for here.

     The numbers 117 bowel resection patients randomised to intravenous ipamorelin or placebo twice daily. Safe, and the key efficacy endpoint of time to tolerating a solid meal was the measure it was tested against. This is the only randomised controlled trial of ipamorelin in people.

     International Journal of Colorectal Disease, 2014· 117 people

7. 07MK-677 with ipamorelinBlendModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 182 people given it.7 reported

   117 people given it1 trial

   • Ipamorelin has one proper study in people, and it was done after bowel surgery. 117 adults got either ipamorelin into a vein twice a day or a dummy drip, by chance. The study measured how quickly they could eat a solid meal again. Safety was the real finding. It is still the only proper test of this peptide in people. Keep that in mind when it is sold as the gentle half of a blend.

     The numbers 117 adults after open or laparoscopic bowel resection randomised to intravenous ipamorelin 0.03 mg/kg twice daily or placebo, with time to tolerating a standardised solid meal as the key endpoint. Safety was the main finding. It remains the only randomised controlled trial of ipamorelin in people.

     International Journal of Colorectal Disease, 2014· 117 people

8. 08CotadutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 6 completed trials, 1,221 people given it.

   65 people given it1 trial

   • An early trial showed cotadutide blunts the blood sugar spike after a meal, and takes off some weight. 65 adults with diabetes and extra weight took it daily for seven weeks, or a dummy. After meals, blood sugar rose about a fifth less, while it climbed on the dummy. Weight fell about three and a half percent, against almost nothing on the dummy. The stomach emptied roughly two hours more slowly. Seven weeks tells you about the mechanism, not about living with the drug. The sponsor paid.

     The numbers Phase 2a, 65 adults with type 2 diabetes and overweight or obesity, 49 days of daily cotadutide (50 to 300 mcg) or placebo. Postprandial glucose area under the curve fell 21.5 percent against a 6.3 percent rise on placebo (P below 0.001); weight fell 3.41 percent against 0.08 percent (P equals 0.002); postprandial insulin rose and gastric emptying half-time lengthened by about two hours. Sponsor funded.

     Journal of Clinical Endocrinology and Metabolism, 2020· 65 people

9. 09GLP-1PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 8 people given it.1 reported

   0 people given it1 trial

   • The hormone your own gut makes does what the drugs built from it do, only briefly. Adults with obesity injected native GLP-1 before meals for five days, and also spent a period on a dummy, with nobody knowing which. Food eaten at each meal fell by about 15 percent and they lost 0.55 kg. Food leaving the stomach more slowly is the likely reason. Five days is a short test and half a kilo is small. The natural hormone breaks down far too fast to be a treatment.

     The numbers Randomized double-blind placebo-controlled crossover in healthy obese subjects with a mean BMI of 39. Five days of native GLP-1 given before meals cut mean food intake per meal 15% and produced 0.55 kg of weight loss, with slowed gastric emptying as the probable mechanism. The native hormone does what its analogues do, just far more briefly.

     British Journal of Nutrition, 2004· number of people not given

10. 10PegcetacoplanPeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 3 completed trials, 1,258 people given it.3 reported

    0 people given it1 trial

    • Pegcetacoplan beat the existing drug in people whose blood disease it was failing to control. 80 adults who were still anaemic on eculizumab were switched to one drug or the other, and everyone knew which. Haemoglobin rose clearly more on pegcetacoplan. 35 of 41 on it avoided a transfusion, against 6 of 39 on eculizumab. One blood marker of cell destruction did not come out as well. Injection site reactions and diarrhoea were much more common on the new drug. Nobody in either group got meningitis.

      The numbers PEGASUS. Phase 3, open-label, randomised, in adults with paroxysmal nocturnal haemoglobinuria and haemoglobin below 10.5 g/dL despite eculizumab. 41 to pegcetacoplan monotherapy, 39 to eculizumab. Primary endpoint, change in haemoglobin at week 16, favoured pegcetacoplan by an adjusted least-squares mean difference of 3.84 g/dL, P below 0.001. 35 of 41 (85 percent) on pegcetacoplan avoided transfusion versus 6 of 39 (15 percent). Non-inferiority was shown for change in reticulocyte count but NOT for change in lactate dehydrogenase. Injection site reactions 37 versus 3 percent and diarrhoea 22 versus 3 percent; breakthrough haemolysis 10 versus 23 percent. No meningitis in either group.

      New England Journal of Medicine, 2021· number of people not given

11. 11Semaglutide with B12BlendLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.7 reported

    0 people given it1 trial

    • Semaglutide caused large, well documented weight loss, and this is the study that showed it. Adults took a weekly 2.4 mg shot or a dummy shot for about 16 months. Average body weight fell 14.9% on the drug and 2.4% on the dummy, a gap of about 12 points. Half the drug group lost at least a sixth of their body weight, against one in twenty on the dummy. Feeling sick and loose stools were common, usually mild and short-lived. No vitamin was given with it.

      The numbers STEP 1. Mean body weight changed by 14.9% with semaglutide 2.4 mg weekly against 2.4% with placebo at week 68, an estimated treatment difference of 12.4 percentage points. 50.5% of the semaglutide group lost 15% or more of body weight against 4.9% on placebo. Nausea and diarrhoea were the most common adverse events, usually transient and mild to moderate. Semaglutide alone; no vitamin was co-administered.

      New England Journal of Medicine, 2021· number of people not given

    What people using it report

    • Constipation and reflux.
12. 12BI 1820237PeptidePreliminary. Studied in people, but no published study has had people take it. 2 human studies where nobody was given it.

    nobody was given it1 watch-only study1 found nothing

    • found nothingThis first test in people was about safety, and the drug made a lot of them sick. 95 otherwise healthy men carrying extra weight were given single rising doses, some with a low dose of liraglutide alongside. Drug-related side effects, mostly stomach and bowel, hit about 39% in the first two parts and about 31% in the third. Nausea and vomiting came and went at higher doses. Adding liraglutide did not make the side effects worse. No weight loss result was reported.

      The numbers 95 otherwise healthy men with BMI 25.0 to 34.9, three-part partially blinded first-in-human study of single ascending doses from 0.075 to 2.4 mg, with and without liraglutide 0.6 mg. Drug-related adverse events, mainly gastrointestinal, in 39.0% of participants in parts 1 and 2 and 30.6% in part 3. Transient nausea and vomiting at higher doses. No difference in tolerability when combined with liraglutide, and post-dose paracetamol pharmacokinetics suggested additive effects on gastric emptying.

      Diabetes, Obesity and Metabolism, 2025· 95 peopleobserved only, nobody was given it

13. 13BGM0504PeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 64 people given it.

    nobody was given it1 watch-only study

    • Healthy volunteers, and the weight figures belong to healthy volunteers. 40 healthy Chinese people took a single 2.5 mg dose, then weekly doses rising to 5, 10 and 15 mg. The amount in the blood rose in step with the dose across that range. Weight fell 3.24, 6.26, 7.09 and 8.30 percent at the four doses. Vomiting, nausea, lost appetite, diarrhoea and bloating were the commonest complaints. These weight numbers come from healthy people over a short stretch, not from people with obesity being treated.

      The numbers 40 healthy Chinese volunteers, single 2.5 mg dose and weekly titration to 5, 10 and 15 mg. Maximum concentration and area under the curve were linearly proportional to dose across 2.5 to 15 mg, supporting weekly dosing. Body weight change from baseline was minus 3.24, minus 6.26, minus 7.09 and minus 8.30 percent at 2.5, 5, 10 and 15 mg. Gastrointestinal events, vomiting, nausea, decreased appetite, diarrhoea and abdominal distension, were the most frequent adverse events. These weight figures are from healthy volunteers over a short dosing period, not from people with obesity.

      Diabetes, Obesity and Metabolism, 2025· 40 peopleobserved only, nobody was given it

Vitamins, minerals, amino acids and botanicals sold over the counter, held to the same standard.

1. 01MIB-626SupplementModerate. At least one finished study in people, and at least 100 people who took it. 4 completed trials, 107 people given it.1 reported

   65 people given it1 trial

   • This trial suggests oral NMN may work through gut bacteria rather than directly, which would apply to this product too. 65 healthy adults took one of three NAD boosters for two weeks, and everyone knew what they were taking. NMN and nicotinamide riboside both raised NAD in the blood. Plain nicotinamide did not keep it up. In lab tests with human gut bacteria, both turned into nicotinic acid, and nicotinic acid was the only one that raised NAD in blood directly. This needs confirming. Ten authors work for Nestle Research.

     The numbers Randomised, open-label, placebo-controlled, 65 healthy adults, 14 days. NR and NMN comparably increased circulatory NAD while plain nicotinamide did not do so chronically. Using ex vivo fermentation with human microbiota, the authors found that NR and NMN give rise to nicotinic acid, and that in whole blood ex vivo nicotinic acid is a potent NAD booster while NMN, NR and nicotinamide are not, proposing a gut-dependent mechanism through the Preiss-Handler pathway. If confirmed, this applies to any oral NMN product including this one. Ten authors are Nestle Research employees.

     Nature Metabolism, 2026· 65 people

2. 02InulinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 39 people given it.6 reported

   39 people given it1 trial

   • Inulin made constipation better, in a small test that ran into a design problem. 39 adults with long-running constipation took 12 g of chicory inulin daily for four weeks and a dummy for four more. Each person tried both in turn without knowing which. Bowel frequency, belly symptoms and quality of life all improved on inulin. Here is the problem. The first treatment was still acting during the second, so the halves cannot be compared. The authors reanalysed the first stretch alone and got the same answer.

     The numbers 39 adults with functional constipation, four weeks of 12 g chicory inulin daily in a double-blind placebo-controlled crossover. Stool frequency, abdominal symptoms and constipation-related quality of life improved relative to placebo, alongside higher relative abundance of butyrate-producing Anaerostipes and Coprococcus. A carry-over effect meant the crossover was compromised, and the authors re-analysed the first period alone as a parallel trial, which supported the same conclusion.

     BMC Gastroenterology, 2025· 39 people

   What people using it report

   • People with existing irritable bowel symptoms consistently describe worse tolerance than everyone else, and the practical advice that circulates is to go slowly and stay low rather than to push through.

Approved drugs, biologics and hormones that have been measured for this. They are here because leaving them out would misrepresent the evidence, and they are below the peptides because that is not what most people come here to read.

1. 01TrametinibSmall moleculeStrong. At least two finished studies in people, and at least 1,000 people who took it. 2 completed trials, 1,192 people given it.

   322 people given it1 trial

   • In advanced melanoma with a BRAF mutation, trametinib on its own held the cancer back longer than chemotherapy and more people were alive at six months. Rash, diarrhoea and swelling were the common side effects. This is the trial that led to its approval as a single drug.

     The numbers 322 patients with metastatic melanoma carrying a BRAF V600E or V600K mutation randomised 2:1 to trametinib 2 mg daily or chemotherapy, open-label (METRIC). Median progression-free survival 4.8 versus 1.5 months (HR 0.45, 95% CI 0.33 to 0.63). Overall survival at 6 months 81% versus 67% despite crossover (HR 0.54). Rash, diarrhoea and peripheral oedema were most common; reductions in ejection fraction and eye effects were infrequent.

     The New England Journal of Medicine, 2012· 322 people

2. 02MifepristoneSmall moleculeModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 320 people given it.4 reported

   270 people given it1 trial

   • The other approved use. Mifepristone followed by misoprostol ended early pregnancies without surgery in nearly all of 270 women. Putting the second drug in the vagina worked better than swallowing it. Every woman got mifepristone. What was decided by chance was how the second drug was taken.

     The numbers 270 women seeking abortion within 63 days of amenorrhoea given 600 mg mifepristone, then randomised to 800 mcg misoprostol orally or vaginally. Complete expulsion without surgery in 95% vaginal versus 87% oral (p=0.03); continued pregnancy 1% versus 7% (p=0.01); abortion within 4 hours 93% versus 78% (p<0.001). Vomiting and diarrhoea more frequent with oral misoprostol.

     The New England Journal of Medicine, 1995· 270 people

3. 03FGF21BiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 350 people given it.4 reported

   222 people given it1 trial

   • A lab-built version of FGF21 healed liver scarring in a mid-sized study. 222 people with fatty liver disease and moderate to advanced scarring got one of three doses or a dummy shot, for 24 weeks. Scarring improved without the disease getting worse in 7% of the dummy group, against 22% to 27% on the drug. The disease cleared in 2% of the dummy group and 23% to 37% on the drug. Nausea and diarrhoea were common. 89bio paid for it.

     The numbers ENLIVEN phase 2b, 222 randomised and 219 treated, biopsy-confirmed NASH with F2 or F3 fibrosis, 24 weeks. Fibrosis improvement without NASH worsening: 7 percent placebo, 22 percent on 15 mg weekly, 26 percent on 30 mg weekly (p 0.009), 27 percent on 44 mg every 2 weeks (p 0.008). NASH resolution: 2 percent placebo versus 37, 23 and 26 percent. Most common adverse events nausea and diarrhoea. Funded by 89bio.

     New England Journal of Medicine, 2023· 222 peoplepoints the wrong way

4. 04TERN-601Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 3 people given it.3 reported

   3 people given it1 trial

   • TERN-601 caused weight loss, then ended its own program with liver damage. There were two studies, one for 28 days and one for 12 weeks, both against a dummy pill. In the first, every dose led to more weight loss than the dummy pill, with less hunger and slower stomach emptying. In the second, doses of 500 mg and up led to clearly more weight loss by week 12. Three people had liver enzyme rises that pointed to liver damage from the drug, and it was dropped.

     The numbers Phase 1 over 28 days and phase 2 over 12 weeks, both randomised, double-blind and placebo-controlled. Phase 1 produced dose-dependent weight loss with statistically significant reductions against placebo at all doses, plus reduced appetite and delayed gastric emptying. Phase 2 produced significantly greater mean percentage weight loss at doses of 500 mg and above at week 12. Gastrointestinal adverse events were class-consistent and dose-related. Three participants in phase 2 experienced transaminase elevations consistent with potential drug-induced liver injury, and those liver safety findings led to discontinuation of clinical development.

     Obesity, 2026· 3 people

Peptides and blends

1. 01KPVPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 2 animal studies, no human study.6 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice with colitis, KPV carried in tiny particles sped up healing of the gut lining and lowered a swelling signal called TNF-alpha.

     The numbers Nanoparticle-delivered KPV accelerated mucosal healing and lowered TNF-alpha in a mouse colitis model.

     Molecular Therapy, 2017· animal study