Does it actually make you less hungry?

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. 01PramlintidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 684 people given it.

   204 people given it1 trial

   • In people with obesity but no diabetes, pramlintide produced a small amount of weight loss. Two hundred and four of them took it or a dummy injection for four months, with the dose built up slowly. The drug group ended 3.6 kg lighter than the dummy group, about 3.7% of body weight. That is far less than newer weight drugs deliver. Its value is that it showed the amylin pathway affects appetite at all, which is the idea later drugs were built on.

     The numbers 16 weeks in 204 obese subjects without insulin: placebo-corrected weight loss of 3.7% (3.6 kg), showing the amylin pathway's appetite effect that later informed cagrilintide.

     Journal of Clinical Endocrinology and Metabolism, 2007· 204 people

2. 02DapiglutidePeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 54 people given it.

   54 people given it1 trial1 found nothing

   • found nothingThis early weight loss trial missed its target. 54 adults with obesity in Denmark were split by chance between two doses of dapiglutide and a dummy injection, weekly for three months. Nobody was asked to change their diet or exercise. The higher dose took off about two percent more body weight than the dummy, which is too small to separate from chance. The drug was tolerated well, with reduced appetite and nausea the usual complaints. Zealand Pharma funded it.

     The numbers 54 adults with obesity in Denmark, 63 percent women, mean bodyweight 101.3 kg and BMI 35.2, randomised 1:1:1 to dapiglutide 4 mg, 6 mg or placebo weekly for 12 weeks with no concurrent lifestyle intervention. Primary endpoint percentage bodyweight change. The 6 mg dose produced a mean change of minus 2.1 percent against placebo (95% CI minus 4.3 to 0.2, p = 0.076), not statistically significant. Safe and well tolerated, with reduced appetite and nausea the common adverse events and no discontinuations for drug-induced adverse events. Dropout 0 percent on placebo, 11 percent on 4 mg and 6 percent on 6 mg. Funded by an unrestricted grant from Zealand Pharma.

     EClinicalMedicine, 2026· 54 people

3. 03GhrelinPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 27 people given it.1 reported

   27 people given it2 trials

   • Put straight into the blood, the hormone set off a big release of growth hormone and people coped with it. 18 men got one of two doses or a dummy, and nobody involved knew which. Both doses drove growth hormone up strongly. The body cleared half of the active hormone in about 9 to 13 minutes, which is very fast. Hunger tended to rise as the dose rose, but not by enough to be sure of. 18 healthy young men and a single exposure is a small test.

     The numbers Double-blind randomized placebo-controlled trial in 18 male volunteers given 1 or 5 micrograms per kilogram intravenously. Both doses strongly stimulated GH release and were well tolerated, with an elimination half-life of 9 to 13 minutes for acylated ghrelin; hunger tended to rise dose-dependently but not significantly.

     European Journal of Endocrinology, 2004· 18 people

   • Giving people ghrelin made them hungry, and they ate more. Nine healthy volunteers got the hormone through a drip, then sat down to a buffet. They ate roughly a quarter more food than they otherwise would. This was the first time a hormone circulating in the blood had been shown to drive eating in people. Nine is a very small group, and this was one meal in a laboratory, not a test of weight over time.

     The numbers Intravenous ghrelin raised buffet energy intake by about 28% in nine healthy volunteers; first circulating hormone shown to stimulate food intake in man.

     Journal of Clinical Endocrinology and Metabolism, 2001· 9 people

   Also measured in animals or in the lab

   • In rats and mice. Ghrelin given into the body made them eat more and put on body fat.

     The numbers Peripheral ghrelin increased food intake and body fat in rodents, establishing its role in energy balance.

     Nature, 2000· animal study

4. 04OxyntomodulinPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 13 people given it.

   13 people given it1 trial, 2 watch-only1 found nothing

   • found nothingGiven the hormone, people ate less at the next meal. 13 healthy volunteers had sessions on oxyntomodulin and on a dummy drip, and nobody knew which was which. Food eaten at a buffet fell by about a fifth, and food over the next 12 hours fell by about a tenth. Their hunger hormone went down. Nobody felt sick and food did not taste different, which sets it apart from some later drugs. 13 healthy people and one buffet is a very small test.

     The numbers 13 healthy volunteers, randomised double-blind placebo-controlled crossover. Buffet energy intake fell 19.3% and 12-hour intake 11.3%, with ghrelin suppressed. Notably it caused no nausea and did not change how food tasted, which separates it from some later drugs in the class.

     Journal of Clinical Endocrinology and Metabolism, 2003· 13 people

   • Four weeks of shots before meals took weight off. People with extra weight gave themselves oxyntomodulin three times a day before eating, or a dummy shot. They lost 2.3 kg, against 0.5 kg on the dummy, roughly 0.45 kg a week. How much they ate at a test meal fell by a quarter at the start and by a third by the end. Four weeks is short. Nothing here says whether the loss would last or come straight back.

     The numbers Self-administered three times daily before meals for four weeks. Bodyweight fell 2.3 kg against 0.5 kg on control (p = 0.0106), roughly 0.45 kg a week, with energy intake at the study meal down 25% at the start and 35% by the end.

     Diabetes, 2005· number of people not givenobserved only, nobody was given it

   • People ate less, and they did not burn more. 15 healthy young men got oxyntomodulin, GLP-1, glucagon, the last two together, or salt water before a meal, on separate days. Every hormone cut how much they ate, by about the same amount. Giving GLP-1 and glucagon together added nothing. Oxygen use, which is how energy burn is measured, did not shift on any of them. The weight effect comes from eating less, not from burning more.

     The numbers The trial that separates the appetite claim from the energy expenditure claim by running oxyntomodulin against its two component signals and against the combination. Read this before believing the raises-your-metabolism half of the story.

     Journal of Clinical Endocrinology and Metabolism, 2015· number of people not givenobserved only, nobody was given it

5. 05GHRP-2PeptideModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 102 people given it.7 reported

   10 people given it1 trial, 1 watch-only1 found nothing

   • found nothingOral GHRP-2 made children hungrier and did not change their build. Ten children with a growth hormone deficiency swallowed it twice a day for a year. Seven of the ten reported a clear rise in appetite in the first six months. Their weight for height barely moved across the year, and the authors report that change as too small to mean anything. There was no comparison group. Appetite is the ghrelin system working as designed, and it is the opposite of what most buyers want.

     The numbers 10 prepubertal children given 900 micrograms/kg orally twice daily for 12 months: 7 of 10 reported increased appetite in the first 6 months, while body mass index standard deviation score moved from 0.21 to 0.25, which was not significant.

     Journal of Pediatric Endocrinology and Metabolism, 2003· 10 people

   • GHRP-2 makes people eat more. Seven lean men were given it as a drip and then offered food freely. They ate about a third more than they otherwise would, and growth hormone rose sharply at the same time. That appetite push is a real effect of the drug, not a side note. Seven men is a very small group, and they were all lean and healthy. Nobody has tested what repeated dosing does to weight over weeks or months.

     The numbers A GHRP-2 infusion increased ad libitum intake by about 36% in seven lean men alongside a strong GH rise, so its appetite effect is reduced rather than absent.

     Journal of Clinical Endocrinology and Metabolism, 2005· 7 peopleobserved only, nobody was given it

   What people using it report

   • The clearest negative is carpal tunnel type symptoms, night cramping, arm pain and numbness from the elbow down, described as dose related and as resolving on stopping. Lightheadedness and a low blood sugar feeling that does not match measured glucose also recur, along with swelling and water retention. Compared with GHRP-6 it is described as raising hunger less, and compared with ipamorelin as raising cortisol and prolactin more.
6. 06Melanotan II with PT-141BlendLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 10 people given it.7 reported

   10 people given it1 trial

   • Melanotan II caused erections in most of a very small group of men. Ten men whose erection trouble had no physical cause each took the peptide and a dummy shot on separate days. Nobody knew which was which on the day. Eight of the ten got a clear erection on the drug. A monitor recorded firmness above four fifths of full for 38 minutes on average, against 3 minutes on the dummy. Nausea, stretching, yawning and loss of appetite were all more common on the drug.

     The numbers Ten men with erectile dysfunction of no known organic cause, double-blind placebo-controlled crossover with real-time RigiScan monitoring over six hours. Clinically apparent erections developed in 8 of 10 men on melanotan II. Mean duration of tip rigidity above 80% was 38.0 minutes on melanotan II against 3.0 minutes on placebo, p = 0.0045. Transient nausea, stretching and yawning, and decreased appetite were more frequent on melanotan II.

     Journal of Urology, 1998· 10 people

   What people using it report

   • Less appetite.
7. 07Peptide YYPeptideLimited. People have taken it in a published study, but fewer than 100 of them. 3 completed trials, 12 people given it.3 reported

   0 people given it2 trials1 found nothing

   • Two gut hormones together cut eating more than either one alone. Twelve overweight or obese volunteers each tried the combination, the single hormones and a dummy infusion, in turn, without knowing which. At a test meal during the combined infusion they ate about 43% less than on salt water, and less than on either hormone by itself. This was one meal in a laboratory, not weeks of living with it. Public money paid for the work.

     The numbers 12 overweight or obese volunteers, randomised double-blind placebo-controlled crossover. Energy intake at a test meal during combined PYY3-36 and oxyntomodulin infusion was 42.7 percent below saline and significantly below either hormone alone. Non-US government funded.

     Diabetes, 2010· number of people not given

   • found nothingCopying the hormone mix that follows stomach bypass surgery cut food intake by about a third. Obese volunteers wore a pump under the skin for about ten and a half hours, delivering three gut hormones at post-surgery levels, or a dummy infusion. Each person tried both, in turn, and did not know which was running. They ate roughly 32% less on the hormones. Resting energy burn did not change, so the whole effect was on appetite. Public money paid for the work.

     The numbers Single-blind randomised placebo-controlled crossover in obese volunteers: a 10.5-hour ambulatory subcutaneous infusion of GLP-1, oxyntomodulin and PYY at doses matching post-gastric-bypass levels (PYY 0.4 pmol/kg/min) cut food intake by a mean 32 percent with no change in resting energy expenditure. Non-US government funded.

     Journal of Clinical Endocrinology and Metabolism, 2017· number of people not given

   Also measured in animals or in the lab

   • Mostly in rats and mice. PYY3-36 cut eating and weight gain in rats. It cut eating in normal mice but not in mice missing the Y2 receptor. A small human part found that a drip cut eating by 33 percent over a day. The rodent part is the one other labs could not repeat.

     The numbers Peripheral PYY3-36 inhibited food intake and reduced weight gain in rats, and inhibited intake in wild-type but not Y2 receptor knockout mice, with arcuate c-Fos induction and reduced hypothalamic NPY mRNA. A human arm reported that infusion at postprandial concentrations cut intake by 33 percent over 24 hours. The rodent arm is the one that failed replication.

     Nature, 2002· animal study

8. 08GLP-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

9. 09BofanglutidePeptideModerate. At least one finished study in people, and at least 100 people who took it. 5 completed trials, 750 people given it.4 reported

   0 people given it1 trial

   • This study measured how the drug behaves in blood, not whether it helps anyone. Healthy American and Chinese adults took steadily rising doses. The body took about seven days to clear half of it in both groups, and the amount reaching the blood was near identical, so no difference between the two populations showed up. Losing appetite and feeling sick were the commonest complaints. This is the only study in the whole programme that included any American participants at all.

     The numbers Phase 1 dose-escalation studies in healthy American and Chinese adults. Half-life was approximately seven days in both populations and exposure was comparable between them, with geometric mean ratios for area under the curve and maximum concentration close to 1, so no ethnic pharmacokinetic difference was detected. Decreased appetite and nausea were the most frequent treatment-emergent events. This is the only study in the programme that included American participants at all.

     Diabetes, Obesity and Metabolism, 2025· number of people not given

10. 10CotadutidePeptideStrong. At least two finished studies in people, and at least 1,000 people who took it. 6 completed trials, 1,221 people given it.

    0 people given it1 trial1 found nothing

    • found nothingPeople lost weight on cotadutide because they ate less, not because they burned more. This small study followed 12 people on the drug and 7 on a dummy for six weeks. The drug group lost four percent of their body weight against one and a half percent on the dummy. They ate far less food. Energy burned, measured properly, did not change at all. Nineteen people is a very small number for a question this specific. AstraZeneca funded it.

      The numbers Phase 2a energy balance study; 12 cotadutide and 7 placebo completers over 42 days. Weight change minus 4.0 percent against minus 1.4 percent (P equals 0.011); energy intake fell 41.3 percent against placebo; energy expenditure by doubly labelled water did not differ (1.0 percent, P equals 0.784). Weight loss was driven by eating less, not by burning more. Funded by AstraZeneca.

      Diabetes, Obesity and Metabolism, 2024· number of people not given

    Also measured in animals or in the lab

    • In mice. In mice with fatty liver inflammation, cotadutide's weight and blood sugar effects came mainly through GLP-1. Its effects on liver fat, stored sugar and the cell's energy factories came through glucagon. At the same weight loss, it cut liver scarring more than liraglutide or obeticholic acid. AstraZeneca staff wrote it. It has been wrongly cited as a human study, and it is not one.

      The numbers Mouse models of steatohepatitis. Weight, food intake and glucose effects ran mainly through GLP-1 signalling; liver lipid, glycogen flux and mitochondrial effects through the glucagon receptor. Cotadutide reduced fibrosis more than liraglutide or obeticholic acid at matched weight loss. This is animal and mechanistic work with AstraZeneca employee authors; it has been miscited elsewhere as a human randomised trial and is not one.

      Nature Metabolism, 2020· animal study

11. 11BGM0504PeptideLimited. 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

12. 12Sermorelin / GHRPBlendLimited. People have taken it in a published study, but fewer than 100 of them. 4 completed trials, 56 people given it.9 reported

    nobody was given it1 watch-only study

    • The hunger is not a rumour, it was measured. Seven lean men given this peptide ate about a third more when left to help themselves, alongside a large rise in growth hormone. Seven men is a very small study and one free meal is easy to sway. Even so, appetite is the effect people report most and the one that most often ends a course. In a blend you cannot dial it down without dialling down the sermorelin at the same time.

      The numbers A GHRP-2 infusion increased ad libitum food intake by about 36 percent in seven lean men alongside a strong growth hormone rise. This is the side effect that most often ends a blend course, and the one you cannot remove without also removing the sermorelin.

      Journal of Clinical Endocrinology and Metabolism, 2005· 7 peopleobserved only, nobody was given it

    What people using it report

    • A strong wave of hunger 20 to 30 minutes after the shot. It is much stronger on GHRP-6 blends than GHRP-2 blends, which fits how the ghrelin switch works.
13. 13SetmelanotidePeptideLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 38 people given it.4 reported

    nobody was given it1 watch-only study

    • In rare genetic forms of obesity most patients lost serious weight, and there was nobody to compare them against. After about a year, 8 of 10 people with one gene fault and 5 of 11 with the other had lost at least a tenth of their body weight. Reported hunger fell by roughly a third in one group and nearly half in the other. Nearly everyone got darker skin and reactions where they injected. These gene faults are very rare, and this says nothing about ordinary obesity.

      The numbers At about one year, 8 of 10 (80%) POMC-deficiency and 5 of 11 (45%) LEPR-deficiency participants lost at least 10% of body weight, with hunger scores down 27% and 44%; hyperpigmentation and injection-site reactions were near-universal.

      The Lancet Diabetes & Endocrinology, 2020· number of people not givenobserved only, nobody was given it

14. 14CJC-1295 with GHRP-2BlendLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, none stating how many people.8 reported

    nobody was given it1 watch-only study

    • GHRP-2 makes healthy men hungrier. That is the drug itself at work, not a side story. It works on the same switch as the hunger hormone, and does the same job. That matters because the hunger comes with the product. Which GHRP a seller puts in the vial decides whether you spend the cycle fighting hunger. This was tested in healthy men, not in anyone trying to lose weight.

      The numbers GHRP-2 increased food intake in healthy men in the way ghrelin does. The appetite effect is a direct pharmacological property of this half of the blend, and it is the reason the choice of GHRP changes the experience of the product.

      Journal of Clinical Endocrinology and Metabolism, 2005· number of people not givenobserved only, nobody was given it

    What people using it report

    • Strong hunger. This comes from GHRP-2 and is the usual reason people switch to ipamorelin.
15. 15CJC-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

    nobody was given it1 watch-only study

    • GHRP-2 makes healthy men eat more, and that matters here more than anywhere. Ipamorelin was picked from this drug family because it lifts growth hormone without dragging hunger along. Put GHRP-2 in the same vial and the hunger comes right back. The one thing the ipamorelin in this blend was chosen for is cancelled by the peptide next to it.

      The numbers GHRP-2 increased food intake in healthy men. This is the profile ipamorelin was selected to avoid, and it returns to the vial the moment GHRP-2 is added alongside it.

      Journal of Clinical Endocrinology and Metabolism, 2005· number of people not givenobserved only, nobody was given it

    What people using it report

    • Strong hunger. People put this down to the GHRP-2, and it often surprises those who chose ipamorelin to avoid it.
16. 16Sermorelin with GHRP-2 and GHRP-6BlendLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 9 people given it.6 reported

    nobody was given it1 watch-only study

    • GHRP-2 makes healthy men eat more, the same way the hunger hormone ghrelin does. This vial holds two peptides that press that same hunger switch. Their effects there add up. They do not cancel out. So the hunger is not a quirk of one ingredient that the other might balance. It is the expected result of stacking two drugs that do the same thing.

      The numbers GHRP-2 increased food intake in healthy men in the way ghrelin does. Both ghrelin-receptor components of this blend drive appetite, and their effects at that receptor add.

      Journal of Clinical Endocrinology and Metabolism, 2005· number of people not givenobserved only, nobody was given it

    What people using it report

    • Strong hunger soon after the shot. This is the main report.

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

1. 01ForskolinSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 53 people given it.5 reported

   23 people given it1 trial1 found nothing

   • found nothingThe same supplement was tested in women and it did not work. 23 mildly overweight women took a 10 percent Coleus forskohlii extract twice a day or a dummy for 12 weeks, seven on the extract. Fat mass, lean mass and body fat percentage came out the same in both groups. Slight leanings toward less weight gain were too weak to call. Blood fats, liver enzymes, thyroid, insulin, heart rate and blood pressure were unchanged. Seven people is too few to spot anything but a huge effect.

     The numbers 23 women randomised double-blind to 250 mg of a 10 percent Coleus forskohlii extract twice daily (n equals 7) or placebo (n equals 12) for 12 weeks. No significant differences in fat mass, fat-free mass or body fat percentage. Non-significant trends toward mitigating gains in body mass (p equals 0.10) and scanned mass (p equals 0.08). Treated participants reported less hunger and fullness. No clinically significant changes in blood lipids, liver or muscle enzymes, thyroid hormones, insulin, heart rate or blood pressure. The authors concluded it does not appear to promote weight loss but may help mitigate weight gain.

     Journal of the International Society of Sports Nutrition, 2005· 23 people

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. 01GDF15BiologicModerate. At least one finished study in people, and at least 100 people who took it. 2 completed trials, 313 people given it.3 reported

   187 people given it1 trial, 1 watch-only

   • Blocking GDF15 put weight back on people with cancer who were wasting away. 187 patients with cancer wasting and high GDF15 were put into four groups. Three got the antibody at rising doses. One got a dummy shot. Shots came every four weeks, three times. By twelve weeks the drug groups had gained about 1.2 to 2.8 kilograms more than the dummy group. Appetite and daily activity got better at the top dose. Pfizer paid for the study.

     The numbers 187 patients with cancer cachexia and GDF15 of at least 1,500 pg/mL (40 percent non-small-cell lung, 32 percent pancreatic, 29 percent colorectal) randomised 1:1:1:1 to ponsegromab 100, 200 or 400 mg or placebo every 4 weeks for three doses. Median weight gain versus placebo at 12 weeks: 1.22 kg (95 percent credible interval 0.37 to 2.25), 1.92 kg (0.92 to 2.97) and 2.81 kg (1.55 to 4.08). Appetite, cachexia symptoms and physical activity improved at 400 mg. Adverse events in 70 percent on ponsegromab and 80 percent on placebo. Funded by Pfizer.

     New England Journal of Medicine, 2024· 187 people

   • The clearest picture of what GDF15 does in people comes from pregnancy. Most of the hormone in a pregnant woman's blood comes from the baby and the placenta, traced using a naturally tagged version of it. Women whose genes gave them low GDF15 before pregnancy were more likely to suffer severe pregnancy sickness. Women with beta-thalassaemia, who run high GDF15 for life, reported almost no nausea. Getting used to the hormone seems to protect against it. Public money paid for the work.

     The numbers Most GDF15 in maternal plasma is fetal or placental in origin, shown by mass spectrometry of a naturally labelled variant. Carriers of variants giving low pre-pregnancy GDF15 had higher risk of hyperemesis gravidarum; women with beta-thalassaemia, who have chronically high GDF15, reported very little nausea. In mice, prior GDF15 exposure blunted the food intake response, consistent with desensitisation. NIH and non-US government funded.

     Nature, 2024· number of people not givenobserved only, nobody was given itpoints the wrong way

   Also measured in animals or in the lab

   • In mice and monkeys. GDF15 made obese mice and monkeys lose weight. It works by docking on GFRAL in the brainstem, which needs a partner called RET. Mice without GFRAL did not eat less or lose weight on it. The same docking spot shows up in the human brainstem.

     The numbers Recombinant GDF15 induced weight loss in mice on a high-fat diet and in non-human primates with spontaneous obesity. GDF15 binds GFRAL, expressed in area postrema and nucleus of the solitary tract neurons in mice and humans; deleting GFRAL abolished the food intake and weight effects in mice. Signalling requires the co-receptor RET.

     Nature Medicine, 2017· animal study

   • In mice. Metformin raised GDF15, and its effects on appetite and weight depended on it. This is where the claim that metformin works through GDF15 comes from. It is mouse work.

     The numbers In mice, metformin raised GDF15 and the appetite and weight effects of metformin depended on it. This is the source of the claim that metformin works through GDF15; it is mouse work.

     Nature Metabolism, 2019· animal study

2. 02TERN-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

3. 03LeptinBiologicModerate. At least one finished study in people, and at least 100 people who took it. 6 completed trials, 844 people given it.5 reported

   3 people given it1 trial

   • Give leptin to the rare children who have none and it transforms them. Three children born unable to make leptin were injected daily for up to four years. Appetite fell, fat mass fell, insulin and blood fats came back towards normal, and puberty arrived at the right age. Immune cells that had been depleted recovered too. This is replacing a missing hormone in people who lack it. It says nothing about giving leptin to people who have plenty. Public money paid for the work.

     The numbers Three children with congenital leptin deficiency treated with daily subcutaneous recombinant human leptin for up to 4 years: sustained reductions in appetite, fat mass, hyperinsulinaemia and hyperlipidaemia, rapid rise in thyroid hormones, appropriately timed puberty, and reversal of reduced CD4 T cell numbers and impaired T cell function. Non-US government funded.

     Journal of Clinical Investigation, 2002· 3 people

4. 04MibavademabBiologicLimited. People have taken it in a published study, but fewer than 100 of them. 2 completed trials, 1 person given it.

   1 people given it1 trial1 found nothing

   • found nothingThe antibody only worked in people who were already short of leptin. In an early study in people, compared with a dummy shot, it was well tolerated. In the authors' words, it reduced body weight over twelve weeks in people with low leptin in the blood, and had no effect on weight in people whose leptin was higher. One patient given it outside a trial had better triglycerides and less liver fat. In mice bred without leptin, it brought weight, eating and blood sugar back to normal.

     The numbers A fully human antibody activating the leptin receptor with or without leptin. In obese leptin knockout mice it normalised body weight, food intake, blood glucose and insulin sensitivity. In a randomised double-blind placebo-controlled two-part phase 1 it was well tolerated. Verbatim: treatment of individuals with overweight or obesity decreased body weight over 12 weeks in those with low circulating leptin concentrations, under 8 ng/mL, but had no effect on body weight in individuals with higher baseline leptin. Compassionate use in one patient with atypical partial lipodystrophy and neutralising antibodies to metreleptin was associated with improvements in triglycerides and hepatic steatosis.

     Science Translational Medicine, 2023· 1 people

5. 05TesofensineSmall moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.8 reported

   0 people given it1 trial

   • The weight came off because people ate less, not because the drug burned anything. This was a smaller study run inside the main trial, looking at hunger. People taking tesofensine reported weaker appetite and took in less food. That is the mechanism behind the weight loss reported in the main result. Appetite was measured by asking people how they felt, which is the only way to measure it and also the softest kind of measure.

     The numbers Phase 2 sub-study: weight loss was driven mainly by reduced appetite and energy intake.

     Obesity, 2012· number of people not given

   What people using it report

   • The live disagreement is not about this compound at all but about whether cutting appetite with a stimulant is ever a long term answer, which several posters argue it is not.
6. 06ARD-101Small moleculeLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, 20 people given it.3 reported

   nobody was given it1 watch-only study

   • ARD-101 made people less hungry. The headline weight loss belongs to mice. Adults with obesity took 200 mg twice a day for 28 days, or a dummy pill. They lost 0.8 kg more than the dummy group by day 28, and 1.3 kg by the end. They also reported less hunger and fewer food cravings. The bigger weight loss in the paper came from obese mice, and only when a second drug was added. The drug's maker employs most of the authors.

     The numbers Reports reduced hunger in adults from a gut-restricted bitter taste receptor agonist, alongside weight loss in diet-induced obese mice when combined with a DPP-4 inhibitor. Note the split: the human result is on hunger, and the weight loss result is in mice and required a second drug.

     Molecular Metabolism, 2026· number of people not givenobserved only, nobody was given it

Peptides and blends

1. 01IGF-1 LR3PeptidePreliminary. Studied in people, but no published study has had people take it. 1 human study where nobody was given it.8 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In pigs. It went the wrong way. Four days of IGF-1 LR3 lowered the pigs' weight gain, how much they ate, their growth hormone and their own IGF-1.

     The numbers A cautionary species difference: four days of LR3 IGF-I infusion in pigs decreased daily gain, food intake, plasma GH, IGFBP-3 and endogenous IGF-I.

     Journal of Endocrinology, 1997· animal study

2. 02HGH Fragment 176-191PeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 4 animal studies, no human study.5 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In obese mice, 30 days of the growth hormone fragment by mouth slowed weight gain without changing how much they ate. In a dish, it also sped up fat breakdown in fat tissue taken from obese rodents and from people.

     The numbers 30 days of oral hGH fragment (AOD-9401) lowered weight gain in ob/ob mice without changing food intake and increased lipolysis in obese rodent and human adipose tissue ex vivo.

     American Journal of Physiology: Endocrinology and Metabolism, 2000· animal study

3. 03BRPPeptideAnimal or lab only. Only animal or lab studies on this page. No study in people yet. 1 animal study, no human study.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice and minipigs. One dose cut how much they ate by up to half.

     The numbers Up to 50% reduction in food intake in mice and minipigs after a single dose.

     Nature, 2025· animal study

Supplements

1. 01(R/S)-1,3-ButanediolSupplementLimited. People have taken it in a published study, but fewer than 100 of them. 1 completed trial, none stating how many people.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In mice. Mice missing a key ketone-making enzyme (HMGCS2) died early, and a 1,3-butanediol diet prevented that. In normal mice, the same diet started early in life raised midlife deaths. Started in old mice, it extended lifespan. It also prevented deaths from clogged arteries in mice bred to get them (ApoE-deficient). A keto diet with no limit on food sharply raised deaths. An independent Japanese group did the work.

     The numbers Mice lacking the ketogenesis enzyme HMGCS2 died early, which a 1,3-butanediol diet prevented. In normal mice the same diet started early in life increased midlife mortality, while started in aged mice it extended lifespan and prevented atherosclerosis deaths in ApoE-deficient mice. An ad libitum ketogenic diet markedly increased mortality. Independent Japanese group.

     Aging Cell, 2023· animal study

Other compounds

1. 01HalofuginoneSmall moleculePreliminary. Studied in people, but no published study has had people take it. 3 human studies where nobody was given it, 1 registered with no result.2 reported

   1 animal or lab study

   Measured in animals or in the lab

   • In obese mice and in pigs. Halofuginone cut how much the animals ate, raised the energy they burned, and caused weight loss. It worked by raising two hormones, FGF21 and GDF15. Mice bred without those hormones did not respond. Note that the paper calls halofuginone FDA-approved for scleroderma. The FDA's approved drug list does not back that up.

     The numbers In diet-induced obese mice and in pigs, halofuginone suppressed food intake, raised energy expenditure and produced weight loss via integrated stress response induction of FGF21 and GDF15; both hormones were required in knockout mice. Animal only. Note that the abstract describes halofuginone as FDA-approved for scleroderma, which the FDA approved drugs database does not support.

     Science Advances, 2025· animal study

2. 02SupaglutideBiologicModerate. At least one finished study in people, and at least 100 people who took it. 3 completed trials, 190 people given it.

   1 animal or lab study

   Measured in animals or in the lab

   • In diabetic monkeys. One shot lowered blood sugar for a while, more at higher doses. Four weeks of weekly shots lowered fasting blood sugar. The monkeys ate less and lost weight, and they handled sugar better. This study is filed under the old name. It is one reason a search for supaglutide makes an approved drug look untested.

     The numbers Diabetic rhesus monkeys. A single subcutaneous injection transiently reduced blood glucose dose-dependently; over four weeks of weekly dosing fasting and random glucose fell dose-dependently with declining plasma fructosamine, body weight decreased alongside reduced food intake, glucose tolerance improved and glucose-stimulated insulin secretion increased. A monkey study, indexed under the development name, and one of the reasons a search on supaglutide makes an approved medicine look preclinical.

     Journal of Endocrinology, 2021· animal study

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

   1 animal or lab study

   Measured in animals or in the lab

   • In mice bred to make extra FGF21. They lived much longer without eating less. It seems to work by turning down growth hormone signals in the liver. The same mice had stunted growth and bone loss. There is no human lifespan data.

     The numbers Transgenic overexpression of FGF21 markedly extended lifespan in mice without reducing food intake, apparently by blunting hepatic growth hormone and IGF-1 signalling. The same paper records that FGF21 blocks somatic growth and causes bone loss in mice. There is no human lifespan data.

     eLife, 2012· animal study