Body composition
Does it actually make you less hungry?
Separate from weight loss on purpose. Appetite is what people feel and report; weight is what the scale shows. A trial can move one without the other.
579
people in trials
28
human studies
7
compounds, animal or cell only
6
trials found nothing
Measured in people
Ranked by how many people, which is a fact about the evidence and not a judgement about the compound. The one at the top is the most studied, which is not the same as the best. Counts are never added across compounds, because the same person can appear in more than one trial.
- 204 people1 human study
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
- 187 people2 human studies
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
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 · no headcount in the line
Also measured, in animals or cells
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
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
- 54 people1 human study1 found nothing
found nothing54 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
- 40 people1 human study
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 people
- 27 people2 human studies
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
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 cells
Peripheral ghrelin increased food intake and body fat in rodents, establishing its role in energy balance.
Nature, 2000 · animal
- 23 people1 human study1 found nothing
found nothing23 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
- 13 people3 human studies1 found nothing
found nothing13 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
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 · no headcount in the line
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 · no headcount in the line
- 10 people1 human study
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
- Appetite suppression.
- 7 people1 human study
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 people
- 7 people1 human study
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 people
What people using it report
- A strong hunger surge starting 20 to 30 minutes after the injection, which is much more pronounced on GHRP-6 blends than GHRP-2 blends and matches the ghrelin receptor pharmacology.
- 3 people1 human study
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 people1 human study
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
- 1 people1 human study1 found nothing
found nothingA 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
- no headcount stated2 human studies1 found nothing
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 · no headcount in the line
found nothingSingle-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 · no headcount in the line
Also measured, in animals or cells
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
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
Phase 2 sub-study: weight loss was driven mainly by reduced appetite and energy intake.
Obesity, 2012 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
- no headcount stated1 human study
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 · no headcount in the line
What people using it report
- Marked hunger, which is specific to GHRP-2 and is the usual reason people switch to ipamorelin.
- no headcount stated1 human study
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 · no headcount in the line
What people using it report
- Strong hunger, which people attribute to the GHRP-2 and which often surprises those who chose ipamorelin to avoid it.
- no headcount stated1 human study
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 · no headcount in the line
What people using it report
- Intense hunger shortly after injecting, the dominant report.
- Weight gain that people find hard to separate from the appetite effect.
- no headcount stated1 human study1 found nothing
found nothingPhase 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 · no headcount in the line
Also measured, in animals or cells
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
Measured in animals or cells, not yet in people
These are separated from the trials above rather than ranked against them, because they answer a different question. A result in a rat is a real result and a reason somebody ran the study; it is not a measurement of what happens in you. Where the human work is missing, the reason is usually money rather than failure, and that is set out at the bottom of this page.
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
Up to 50% reduction in food intake in mice and minipigs after a single dose.
Nature, 2025 · animal
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
- 1 preclinical study
Measured in animals or cells
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
What people using these actually report
Uncontrolled self-reports, gathered from clinic write-ups, regulatory complaint records and public forums, and reproduced here as written. They are the best guide on this page to what people actually do, what they expect, and what goes wrong, and they cannot show that anything works, because nobody was measured against a placebo and the people who saw no effect mostly stopped posting. Both halves of that are true at once. The negative reports are kept in for the same reason.
- Appetite suppression.
Sources: The nausea, yawning and stretching appear in the melanotan II controlled trial. The pigment changes and the rest come from forums including r/peptides and from the dermatological review of unregulated alpha-MSH analogue use.
- A strong hunger surge starting 20 to 30 minutes after the injection, which is much more pronounced on GHRP-6 blends than GHRP-2 blends and matches the ghrelin receptor pharmacology.
Sources: Flushing is documented in the controlled GHRP-6 plus GHRH diagnostic study, and the appetite effect is documented in the GHRP-2 food intake trial, so those two are trial-derived. The sleep, recovery, water retention and fade-over-time reports come from peptide user forums and from clinic write-ups and are not from any trial of a compounded blend. The 2026 Frontiers in Endocrinology review of self-administered growth hormone axis peptides lists the same adverse effect domains, including prolactin and cortisol elevations, fluid retention, myalgia and arthralgia and dysglycaemia.
- Marked hunger, which is specific to GHRP-2 and is the usual reason people switch to ipamorelin.
Sources: Peptide and bodybuilding forums including r/peptides, clinic write-ups and vendor pages. The appetite effect is also documented in the controlled study cited above, which is the rare case where a forum report and a trial finding agree.
- Strong hunger, which people attribute to the GHRP-2 and which often surprises those who chose ipamorelin to avoid it.
Sources: Peptide and bodybuilding forums, vendor listings and clinic write-ups. Uncontrolled self-reports. The appetite effect has controlled human support for GHRP-2 specifically.
- Intense hunger shortly after injecting, the dominant report.
- Weight gain that people find hard to separate from the appetite effect.
Sources: Clinic write-ups, men's health forums and peptide forums. Uncontrolled self-reports, except the appetite effect, which is supported by controlled human work on GHRP-2.
- Hunger that arrives within minutes of injecting and is described as difficult to ignore.
- People abandoning it for ipamorelin specifically because of the appetite.
Sources: Peptide and bodybuilding forums, clinic write-ups and vendor pages. Uncontrolled reports. The appetite effect is the one item here that is also supported by controlled human work on this drug class.
- The effect people describe valuing most is appetite and food preoccupation falling away rather than the number on the scale, and it is frequently described in terms of no longer having to spend attention on food.
Sources: Public discussion in r/Semaglutide, r/Zepbound, r/glp1 and general subreddits where GLP-1 drugs come up, read through the PullPush Reddit archive on 2026-09-13 because Reddit's own endpoints are unreachable from this environment. 62 comments reviewed. Nothing above is attributed to any specific post and no comment is reproduced.
- Reduced appetite is usually described not as hunger going away but as the constant mental chatter about food going quiet, which is the single most consistent positive report in the whole sample and is frequently described as the thing that made the difference rather than the weight itself.
Sources: Public discussion in r/Zepbound, r/tirzepatidecompound, r/TirzepatideRX, r/glp1, r/Semaglutide, r/PCOS and general subreddits where these drugs come up, read through the PullPush Reddit archive on 2026-09-13 because Reddit's own endpoints are unreachable from this environment. 84 comments reviewed. Nothing above is attributed to any specific post and no comment is reproduced.
- Pairing with cagrilintide is commonly described by people who want stronger appetite suppression than retatrutide alone gives them, and pairing with growth hormone secretagogues appears in body composition stacks.
Sources: Public discussion in r/Retatrutide, r/PEDs, r/zepbound_support and adjacent weight loss subreddits, read through the PullPush Reddit archive on 2026-09-13 because Reddit's own endpoints are unreachable from this environment. 86 comments reviewed. Nothing above is attributed to any specific post and no comment is reproduced.
- Hunger, which is inconsistent and is one of the ways users guess whether their vial actually contains what the label says.
Sources: Peptide user forums including r/Peptides, clinic and vendor write-ups, and the adverse-effect domains listed in the 2026 Frontiers in Endocrinology review of self-administered growth hormone axis peptides, which names fluid retention, myalgia and arthralgia, dysglycaemia, prolactin and cortisol elevations and injection site reactions. None of this comes from a trial of the blend, because no trial of the blend exists.
- Little or no appetite change, which is why prescribers pick ipamorelin over the older GHRPs.
Sources: Clinic write-ups, prescriber patient materials and peptide forums. Uncontrolled self-reports. The absence of appetite change is consistent with ipamorelin's receptor selectivity but has not been measured in a trial of this blend.
- Very large appetite increase on the oral component, often the dominant effect people describe.
Sources: Peptide and bodybuilding forums including r/peptides, plus clinic write-ups. Uncontrolled self-reports. The appetite and fluid retention effects also appear in the controlled literature on sustained ghrelin-receptor agonism.
- Sulphur burps and early fullness.
Sources: Trial adverse event tables for the gastrointestinal pattern. The rest from forums including r/tirzepatidecompound and telehealth patient communities, uncontrolled and self-reported.
- Very strong appetite suppression, described as stronger than either component alone.
Sources: Forums including r/Retatrutide and r/peptides, plus vendor listings. The heart rate observation also appears in the retatrutide phase 2 trial; everything else here is uncontrolled self-report from people using unverified material.
- Appetite suppression described as stronger and steadier than semaglutide alone.
Sources: The gastrointestinal figures come from the REDEFINE 1 adverse event table. The rest comes from forums including r/Semaglutide and r/peptides, and is uncontrolled self-report from people using unverified material.
- Reduced appetite and slow fat loss, credited to the NNMT inhibitor.
Sources: Forums including r/peptides and r/nootropics, and vendor product pages. Entirely uncontrolled self-report from people taking unverified material, usually while also training.
Why the trial record looks like this
A missing trial is usually a missing sponsor. Nobody runs a nine-figure programme on a molecule they cannot own, so the compounds with the thinnest human records are often the oldest and most freely available ones rather than the weakest. Taking Halofuginone as the example, because it states the problem most clearly:
The NIA Interventions Testing Program runs each compound in parallel at three sites (The Jackson Laboratory, the University of Michigan and UT Health San Antonio) in genetically heterogeneous UM-HET3 mice, tests both sexes, analyses them separately, pools the sites in a site-stratified log-rank test, and publishes every result whether or not the compound worked. It is publicly funded by the National Institute on Aging with no pharmaceutical sponsorship. In the 2021 cohort halofuginone produced an 8.8 percent increase in male median lifespan (p = 0.002) and a 6.9 percent increase in 90th percentile survival, and nothing in females. In the same cohort the male result was the strongest of the three positives by p value, and the effect on late survival is the part that distinguishes a candidate geroprotector from a compound that only prevents early deaths. It has been tested once, at one dose and start age.
The reason nobody knows what it does in people is that both human programmes stopped. Tempostatin's oral development did not proceed past the phase 1 that found the chronic dose limited to 0.5 mg a day by nausea. The Duchenne programme changed hands between three small companies and ended with all three registry records terminated and unreported; the public record gives "dosing stopped" and nothing more, so the reason cannot be stated here. Halofuginone is an old molecule with veterinary generics, so there is no exclusivity to pay for a new human programme, and without one the mouse result will stay a mouse result. That cuts both ways: the absence of trials is not evidence it fails in people, and it equally leaves any harm unmeasured.
A compound appears here only when a citation on its own page states this outcome and reports a result for it; naming it is not enough. Human, animal and cell work are counted separately and never merged. Participant counts are read from the study lines and deliberately undercount. Nothing here is advice, and nothing here is a recommendation to take or to avoid anything.