GDF15 dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
GDF15 is a stress signal your body makes when cells are in trouble.
Evidence grade for GDF15: Moderate. The rule: at least one finished study in people, and at least 100 people who took it. The sum on this page: 2 completed trials, 313 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 313
- Human studies
- 2
- Found nothing
- 0
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
2 completed trials, 313 people given it
3 effects reported, 2 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Fat loss and metabolism, Ageing and longevity, Injury, healing and recovery, Heart and circulation, Immune system and inflammation, Gut health
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
GDF15 is a stress signal. Your body makes more of it when cells are in trouble. It acts on the part of the brain that makes you feel sick and stop eating. It is not a fat burning hormone. It is also not the same thing as GDF11.
What people take it for
- Weight loss, because it makes mice eat less.
- A blood test for how fast you are ageing.
- Stopping weight and muscle loss in people with cancer.
What studies in people showed
The drug that worked in people blocks GDF15. In 187 people with cancer who were wasting away, the blocker added 1.2 to 2.8 kg more than a dummy shot over 12 weeks. At the top dose, appetite and activity got better too. Pfizer paid, and a study of 982 people is now running. Going the other way failed. A long lasting form of GDF15 was given to 126 adults with obesity for 14 weeks. They lost very little weight and had stomach problems. In 53,026 UK adults, high GDF15 went with more long-term illness. In 876 men, it went with dying sooner. That makes it a warning light, not a cause.
What people report
Reports, not study results
The good
- In the cancer study, people on the blocker ate more, moved more and gained back some weight.
The bad
- In the obesity study, stomach and gut problems were the most common side effect.
- In the cancer study, 70 percent on the blocker had some side effect, against 80 percent on the dummy shot.
Where these come from: No user reports. These come from the ponsegromab study in 187 people and the MBL949 study in 126 people on this page.
My bottom line
GDF15 is the body's stop eating alarm. For weight loss it flopped in people. A high blood level tells you something is under stress, so go find out what. Start with your kidney and liver numbers.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals GDF15 has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Feeling less hungry187 people · 2 studies
- Cancer and tumours187 people · 1 study
- Losing weight126 people · 1 study
- Inflammation53,902 people · 2 studies
- Kidney function53,026 people · 1 study
- Living longer876 people · 1 study
- Biological age markers876 people · 1 study
29 of the 36 indexed goals have no study of any kind behind GDF15
No study in people, animals or cells on this page reports a result for these. That does not prove GDF15 does nothing for them. It does mean anything you have heard about GDF15 and one of these did not come from a study cited here.
Show full evidence
What is GDF15?
GDF15 is a stress signal your body makes when cells are in trouble. It acts on the part of the brain that makes you feel sick and turn away from food. In 187 people with cancer who were wasting away, a drug that blocks it helped them gain 1.2 to 2.8 kg more than a dummy shot. A drug that boosts it, given to 126 adults with obesity, caused very little weight loss.
GDF15 is a stress signal. Your body makes more of it when cells are under strain. That includes damaged tissue, swelling, cancer drugs, pregnancy and the diabetes drug metformin. It docks on a spot called GFRAL, found almost only in the brainstem. That part of the brain makes you feel sick and turn away from food. So GDF15 is best thought of as a "stop eating, something is wrong" signal. It is not really a fat hormone. That one idea explains everything the studies found.
GDF15 is not GDF11. The names are close, but the proteins are not. GDF11 is the one in the disputed young blood research. Nothing on the GDF11 page applies here.
The largest human studies only watched people over time. In 53,026 UK adults, higher GDF15 went with 20 to 24 different long-term illnesses later on. In 876 Swedish men, those with high GDF15 had 3.38 times the odds of dying during the study. These are warning signs, not proof. They do not show that changing GDF15 in a healthy person changes anything.
The best treatment result goes the opposite way from a weight loss drug. Pfizer paid for a study in 187 people with cancer who were wasting away and had GDF15 of at least 1,500 pg/mL. They got a drug that blocks GDF15, called ponsegromab, at 100, 200 or 400 mg, or a dummy shot. Shots came every 4 weeks, three times. At 12 weeks, the drug groups had gained more weight than the dummy group: 1.22 kg, 1.92 kg and 2.81 kg more. At 400 mg, appetite, wasting symptoms and daily activity also got better. Side effects showed up in 70 percent on the drug and 80 percent on the dummy shot. A bigger study planned for 982 people with pancreatic cancer is now signing people up.
The other way has been tried too. A long lasting form of GDF15, called MBL949, was first given as single doses to 65 people. Then 126 adults with obesity got it every other week for 14 weeks. They lost very little weight. Stomach and gut problems were the most common side effects. The authors say the big weight loss seen in mice, rats, dogs and monkeys did not happen in people.
Pregnancy tells us the most about what GDF15 does. A 2024 study found most of the GDF15 in a pregnant woman's blood comes from the baby and the placenta. Women whose genes gave them low GDF15 before pregnancy were more likely to get severe pregnancy sickness. Women with beta-thalassaemia, a blood disorder that keeps GDF15 high for life, reported very little nausea. No drug that boosts or blocks GDF15 is approved.
How does GDF15 work?
In people, GDF15 goes up when cells are under almost any kind of stress. It runs high in people with cancer who are wasting away. Blocking it with an antibody helped those people gain weight, eat more and move more. In pregnancy, GDF15 from the baby reaching the mother's brainstem is the leading explanation for morning sickness. Earlier exposure seems to make the brain less sensitive to it. Giving a long lasting form to people with obesity caused very little weight loss. Stomach problems were the most common side effect. Human brainstem tissue carries the same GFRAL docking spot. In mice, GDF15 docks on GFRAL, which needs a partner called RET to work. These sit on nerve cells in the brainstem. Switching them on cuts food intake and teaches the animal to avoid a taste. Mice without GFRAL do not lose weight on GDF15. In mice, GDF15 also makes fat break down through the nervous system. A 2023 mouse paper found it raises energy use in muscle. The common claim that metformin works partly through GDF15 comes from a 2019 mouse study.
What have studies in people found about GDF15?
Both directions have been tested in people. Blocking GDF15 with ponsegromab helped 187 people with cancer who were wasting away gain weight, eat more and move more. Boosting it with a long lasting form called MBL949 caused very little weight loss in 126 adults with obesity. Genes tie GDF15 to pregnancy sickness. In very large groups watched over time, high GDF15 goes with more illness and earlier death.
- Long-term illness (Metabolism 2025): 53,026 UK Biobank adults. Higher GDF15 went with 20 to 24 different long-term illnesses later on.
- Death risk (Aging Cell 2010): 876 men watched for up to 14 years. High GDF15 meant 3.38 times the odds of dying. The same pattern held in 324 twins.
- Ponsegromab (NEJM 2024, NCT05546476): 187 people with cancer who were wasting away and had GDF15 of at least 1,500 pg/mL, for 12 weeks. They gained 1.22, 1.92 and 2.81 kg more than the dummy group at 100, 200 and 400 mg. Side effects in 70 percent on the drug and 80 percent on the dummy shot. Pfizer paid.
- MBL949, a drug that boosts GDF15 (JCEM 2025): 126 adults with obesity got 8 doses, one every two weeks, over 14 weeks. Weight loss was very small. Stomach and gut problems were most common. An earlier study gave single doses up to 20 mg to 65 people who were overweight or obese. The drug lasted 18 to 22 days in the body, and higher doses showed some weight loss.
- Pregnancy sickness (Nature 2024): most of the mother's GDF15 comes from the baby, shown by weighing it directly. Genes that meant low GDF15 before pregnancy raised the risk of severe pregnancy sickness. Women with beta-thalassaemia, who have high GDF15 for life, had very little nausea.
- Still running: a ponsegromab study (NCT06989437) plans 982 people with pancreatic cancer that has spread. It is signing people up, with main results expected January 2028. A small early lung cancer study (NCT07663630, 80 planned) has not started signing people up.
- A second blocking antibody, visugromab, is being tested in 131 people with lung cancer that has spread (NCT07246863, signing up). They also get the cancer drug nivolumab. The aim is to help fight the cancer, not to stop wasting.
What this does not tell you: The ponsegromab result covers 12 weeks in people with cancer who were wasting away and had high GDF15. It says nothing about people without cancer. It says nothing about living longer. It says nothing about blocking GDF15 in someone whose level is normal. The MBL949 result is one drug at one set of doses for 14 weeks. One failed drug does not rule out every drug that boosts GDF15, but it is the only human test of that idea published so far. The links to death and illness are warning signs of an illness underneath. They cannot show that GDF15 causes death, or that lowering it would help. GDF15 goes up because cells are stressed, and the stress is the problem. The metformin link has not been shown in people.
The state of the research
GDF15 is a rare case. Drug makers pushed the same molecule both ways, and the human results point one way.
Boosting it was the obvious idea after the 2017 papers. GDF15 makes mice and monkeys eat less and lose weight. So a long lasting GDF15 should work as an obesity drug. The MBL949 program tested that in 191 people across two studies. The drug lasted about three weeks in the body and was reasonably safe. It caused stomach problems and very little weight loss. The 2024 pregnancy research helps explain why. GDF15 works through a brainstem circuit that makes you avoid food, and that circuit seems to get used to it. Its natural job is to make you stop eating when something is wrong. It is not there to manage body fat.
Blocking it was the less obvious idea, and it is the one with a good mid-sized study. Pfizer paid for the ponsegromab study and is paying for the 982 person follow-up. No independent study of blocking GDF15 has reported.
The blood test research is easy to misread. In group after group, GDF15 is one of the best single blood proteins for predicting death and a pile-up of long-term illness. That has led some people to call it an ageing hormone. But the same papers say most of the level comes down to kidney function, liver function, inflammation and body fat. A warning light that comes on when cells are damaged will predict death without causing it. There is no human evidence that lowering GDF15 in a healthy person helps. The only people in whom lowering it has been tested had cancer and were losing weight. Finally, because people mix them up, GDF15 is not GDF11. They share none of the same biology or arguments.
The evidence, in charts
Fig. 1a · how many people
54,215people, across 4 studies in people cited here
| Study | People | Share |
|---|---|---|
| Metabolism 2025 | 53,026 | 98% |
| Aging Cell 2010 | 876 | 2% |
| New England Journal of Medicine 2024 | 187 | 0% |
| Journal of Clinical Endocrinology and Metabolism 2025 | 126 | 0% |
One study holds 98% of these people, so the total rests more on one study than its size suggests. Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 2 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
6 of 10 sources here are studies in people. The rest are not.
- Study in people · done in people660%
- Animal study · done in animals330%
- Review of studies · sums up other studies110%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
The studies cover 7 different years, 2010 to 2025, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 4 · how much does what
Nobody has tested different amounts in people
This chart would show how the effect changes as the amount goes up. For this compound, nobody has measured that in people. So we leave it empty. We will not borrow an animal chart and pretend it works the same in people.
Fig. 5 · what the molecule is
- Kind of compound
- Biologic
- Molecule weight
- 34,140 Da precursor (308 residues, UniProt Q99988); mature domain residues 195 to 308, 114 amino acids, circulating as a disulfide-linked dimer of about 25 kDa
- Half-life
- None on file
- Chain length
- None on file
No amino acid sequence is on file for GDF15, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2024Ponsegromab for the Treatment of Cancer Cachexia
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.
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.
- Study in people2025Ponsegromab in adults with metastatic pancreatic cancer, weight loss and fatigue (phase 2/3)
The big test of this drug is running now and has reported nothing. Pfizer is enrolling an estimated 982 people with advanced pancreatic cancer who are losing weight and feeling exhausted. It started in October 2025 and is not expected to finish its main measurements until January 2028. Until then the only human result for ponsegromab is the mid-sized trial above. Status checked in September 2026.
Pfizer, phase 2/3, estimated enrolment 982, recruiting, started October 2025, primary completion estimated January 2028. Status checked 11 September 2026.
- Study in people2025A Growth Differentiation Factor 15 Receptor Agonist in Randomized Placebo-Controlled Trials in Healthy or Obese Persons
Pushing GDF15 up, rather than blocking it, barely worked in people. A first study gave single doses to 65 overweight or obese volunteers, and the drug hung around for about three weeks. A second gave 126 people with obesity repeated doses over fourteen weeks. Weight loss was minimal. Stomach and bowel side effects were the most common problem. The authors say the strong weight loss seen in animals did not carry over to humans. A company developed the drug.
MBL949, a half-life extended recombinant GDF15 dimer. Phase 1: 65 overweight or obese healthy volunteers, single doses 0.03 to 20 mg, terminal half-life 18 to 22 days, evidence of weight loss at higher doses. Phase 2: 126 participants with obesity, five dose regimens every other week for 8 doses over 14 weeks; weight loss was minimal. Gastrointestinal adverse events were most frequent. The authors conclude that the robust weight loss in mice, rats, dogs and monkeys did not translate to humans. Company-developed compound.
- Study in people2024GDF15 linked to maternal risk of nausea and vomiting during pregnancy
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.
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.
- Study in people2010Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality
Higher GDF15 marked out men who died sooner, but nobody was given anything. 876 Swedish men aged 35 to 80 gave a blood sample and were then followed for up to 14 years. Those with more GDF15 at the start were roughly three times as likely to die of any cause. The pattern held in a separate set of 324 twins. This is a group watched over time, not a trial. It cannot tell you whether lowering GDF15 would help anyone.
876 Swedish men aged 35 to 80 followed up to 14 years: serum GDF15 at entry predicted all-cause mortality with an adjusted odds ratio of 3.38 (95 percent CI 1.38 to 8.26), validated in 324 same-sex twins and independent of telomere length, IL-6 and CRP. An association in a cohort, not an intervention.
- Study in people2025Identifying proteins and pathways associated with multimorbidity in 53,026 adults
GDF15 tracks with getting sick in general, not with any one disease. Researchers measured thousands of blood proteins in 53,026 UK adults and followed them for over 13 years. Higher GDF15 went with later diagnosis of more than twenty different long-term illnesses, and with having several at once. Much of the level was explained by kidney function, liver function, inflammation and body fat. Nobody was given anything here. This is a marker of trouble, not a proven cause of it.
UK Biobank proteomics, 53,026 participants, 13.3 years of follow-up: GDF15 was positively associated with 20 to 24 incident chronic diseases (hazard ratios 1.21 to 3.77) and with multimorbidity, with levels largely explained by renal function, liver function, inflammation and obesity.
- Review of studies2021The GDF15-GFRAL Pathway in Health and Metabolic Disease: Friend or Foe?
A review of the field. It calls GDF15 a stress signal that makes you avoid food. It explains why drug makers tried boosting it for obesity and blocking it for wasting.
Field review that frames GDF15 as a stress-induced aversion signal and lays out why agonism for obesity and antagonism for cachexia were both being pursued.
- Animal study2017GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates
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.
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.
- Animal study2019Metformin-induced increases in GDF15 are important for suppressing appetite and promoting weight loss
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.
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.
- Animal study2020Antibody-mediated inhibition of GDF15-GFRAL activity reverses cancer cachexia in mice
In mice with tumours. An antibody that blocks GDF15's docking spot stopped the wasting. It showed GDF15 burns off fat and muscle through the nervous system, not only by killing appetite. This is the animal work behind blocking GDF15 in people.
An antibody against GFRAL prevented cachexia in tumour-bearing mice, reversing excess lipid oxidation, and identified a sympathetic lipolytic axis by which GDF15 wastes fat and muscle independently of anorexia. The preclinical basis for blocking the pathway in people.
Common questions
Has GDF15 been tested in people?
Yes. 313 people given it across 2 completed trials cited here, 0 of which found nothing. GDF15 is a stress signal your body makes when cells are in trouble.
What is the GDF15 dosage?
No human dose established. Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose. 2 completed trials, 313 people given it
Is GDF15 FDA-approved?
Not FDA-approved. No drug that mimics or blocks GDF15 is listed in the FDA drug database (Drugs@FDA) as of 11 September 2026. Ponsegromab, an antibody that blocks GDF15, is in combined mid-stage and final-stage studies for cancer cachexia, the weight and muscle loss that comes with cancer. MBL949, a drug that mimics GDF15, caused very little weight loss in a 2025 mid-stage study.
Is GDF15 a weight-loss hormone?
Not in people. In mice and monkeys, giving GDF15 causes weight loss by making the brain avoid food. In people, the only published test gave a long lasting form called MBL949 to 126 adults with obesity for 14 weeks. They lost very little weight and had stomach side effects. The GDF15 drug that worked in people does the opposite. Ponsegromab blocks GDF15. In 187 people with cancer who were wasting away, it added 1.2 to 2.8 kg more than a dummy shot.
Is GDF15 the same as GDF11?
No. They come from different genes and are different proteins. GDF11 is the one in the disputed young blood research. GDF15 works in the brainstem and is tied to nausea and wasting. What is true of one does not apply to the other.
Does metformin work through GDF15?
In mice, a 2019 study found metformin raises GDF15, and its effects on appetite and weight depended on it. Metformin does raise GDF15 in people too. Nobody has shown that this explains any of what metformin does in people.
My GDF15 is high. Does that mean I am ageing faster?
Not necessarily. High GDF15 predicts death and long-term illness in large groups of people. In one study of 876 men, high GDF15 meant 3.38 times the odds of dying. But GDF15 goes up with kidney and liver problems, inflammation, obesity, cancer and problems in the cell's power plants. So it is a warning light for stressed cells, not a cause of ageing. There is no evidence that lowering it in a healthy person changes anything.
Does GDF15 cause morning sickness?
A 2024 genetics study is the strongest evidence that it does. Most of a pregnant woman's GDF15 comes from the baby and the placenta. Women whose genes gave them low GDF15 before pregnancy were more likely to get severe pregnancy sickness. Women with beta-thalassaemia, who have high GDF15 for life, had very little nausea. That makes GDF15 a sensible target for severe pregnancy sickness. No such treatment has been tested.