FGF21 dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
FGF21 is a hormone your liver makes when you fast, eat sugar or eat less protein. Lab-built versions healed liver scarring in two mid-sized studies of 222 and 128 people with fatty liver disease. Longer life has only been seen in mice bred to make extra FGF21.
Evidence grade for FGF21: 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, 350 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 350
- 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, 350 people given it
4 effects reported, 3 unwanted, 1 wanted, by people using it, not a trial
Goal pages: Fat loss and metabolism, Ageing and longevity, Hormones and growth hormone, 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.
FGF21 is a hormone your liver makes when you fast, eat sugar or eat less protein. It seems to turn down the taste for sweets. Lab-built versions are being tested for fatty liver disease. None is approved.
What people take it for
- Living longer, because mice bred to make extra lived longer.
- Healing a fatty liver.
- Cutting sugar cravings.
What studies in people showed
The human studies used lab-built versions, not the hormone itself. In 222 people with fatty liver disease and scarring, scarring got better in 22 to 27 percent on pegozafermin. It got better in 7 percent on a dummy shot, after 24 weeks. In 128 people, scarring got better in 49 percent on the higher dose of efruxifermin, against 19 percent on a dummy shot, after 96 weeks. The lower dose did not clearly help. Nausea and diarrhoea were common. Three big studies are running now. In 6,514 Danes, one gene version went with eating more sweets. Longer life is only in mice, and those mice also lost bone.
What people report
Reports, not study results
The good
- In the liver studies, more people saw their liver scarring get better than on a dummy shot.
The bad
- Nausea and diarrhoea were the most common side effects of pegozafermin.
- Nearly everyone reported some side effect in the efruxifermin study, dummy group included.
- Bone loss is a known worry for drugs in this family.
Where these come from: No user reports. These come from the pegozafermin and efruxifermin studies on this page.
My bottom line
If you have a fatty liver, the drugs in these studies may matter to you one day. For a longer life, all you have is mice with weaker bones. Get your liver numbers checked and fix the diet first.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals FGF21 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.
- Liver fat and liver health350 people · 2 studies
- Gut and digestion222 people · 1 study
Animal and lab work, not yet tested in people
Real results, but from animals or cells, not people. What works in a mouse often does not work the same way in a person. Nobody can patent this, so nobody would ever earn back the cost of a study in people. That is usually why there is none. The record on this one is set out below.
- Living longer2 animal or lab studies
- Feeling less hungry1 animal or lab study
- Growth hormone and IGF-11 animal or lab study
31 of the 36 indexed goals have no study of any kind behind FGF21
No study in people, animals or cells on this page reports a result for these. That does not prove FGF21 does nothing for them. It does mean anything you have heard about FGF21 and one of these did not come from a study cited here.
Show full evidence
What is FGF21?
FGF21 is a hormone your liver makes when you fast, eat sugar or eat less protein. Lab-built versions healed liver scarring in two mid-sized studies of 222 and 128 people with fatty liver disease. Longer life has only been seen in mice bred to make extra FGF21.
FGF21 is a hormone made mostly by the liver. It goes up when you fast, eat very low carb, eat less protein or eat sugar. Unlike its close cousins, it travels around the body in the blood. It can only act on cells that carry a partner protein called beta-klotho. Those are mainly fat, liver and parts of the brain. Beta-klotho is not the same as alpha-klotho, which has its own page on this site. People mix the two up all the time.
The natural hormone has never been made into a drug, but lab-built versions have. This page is the hub for three of them on this site: efruxifermin, pegozafermin and efimosfermin. The human evidence is in fatty liver disease with scarring, called MASH. Doctors checked the liver with a needle sample.
The biggest result so far is the ENLIVEN study, paid for by 89bio. It enrolled 222 people with fatty liver disease and moderate to advanced scarring. They got pegozafermin at 15 mg or 30 mg weekly, 44 mg every two weeks, or a dummy shot, for 24 weeks. Scarring got better by at least one stage, without the disease getting worse, in 7 percent on the dummy shot. It got better in 22 percent on 15 mg, 26 percent on 30 mg and 27 percent on 44 mg. The liver disease cleared in 2 percent on the dummy shot and in 23 to 37 percent on the drug. Nausea and diarrhoea were the most common side effects.
In the HARMONY study, Akero paid to test efruxifermin in 128 people over 96 weeks. Scarring got better in 19 percent on the dummy shot, 30 percent on 28 mg and 49 percent on 50 mg. Only the 50 mg dose clearly beat the dummy shot. Efruxifermin now has three large final-stage studies signing up 1,650, 2,150 and 700 people. No FGF21 drug had FDA approval on 11 September 2026.
The natural hormone has one solid human finding. In 6,514 Danish people, one version of the FGF21 gene went with eating more sweets. FGF21 in the blood also rose soon after people drank sugar. So FGF21 looks like a sugar-triggered hormone that turns down the taste for sweets and alcohol. Exercise training also raises FGF21 in the blood. That comes from 13 study groups with 280 adults who were overweight or obese.
The longer life claim is mice only. Mice bred to make extra FGF21 lived much longer. It seems to work by turning down growth hormone signals in the liver. The same paper says FGF21 stunts growth and causes bone loss in mice. There is no human data on lifespan of any kind. Bone loss is a known worry for drugs in this family. We did not check how big that effect is in people from the study reports.
How does FGF21 work?
In people, FGF21 rises soon after eating sugar. A common version of the FGF21 gene goes with eating more sweets and drinking more alcohol. Exercise training raises FGF21 in the blood. Lab-built versions, given as a weekly shot, cut liver fat, heal scarring in liver samples and lower blood fats in people with fatty liver disease. Nausea and diarrhoea are the main side effects. A 2026 review asks whether those effects come from the whole body or just the liver. In mice, fasting makes the liver release FGF21. FGF21 then drives fat burning and the making of ketones. It makes the body respond better to insulin. It turns down growth hormone and causes bone loss. It works through a receptor called FGFR1c, but only where beta-klotho is present. That limits it to fat, liver and certain brain areas. 2025 mouse work found FGF21 reverses fatty liver disease through both the brain and the liver. It also made obese mice live longer, without slowing their growth.
What have studies in people found about FGF21?
The human studies tested lab-built versions, not the natural hormone. They were in people with fatty liver disease and scarring, checked by liver samples. Pegozafermin (222 people, 24 weeks) and efruxifermin (128 people, 96 weeks) both healed scarring better than a dummy shot. For the natural hormone, the human data come from genes and body chemistry. A gene version goes with eating sweets, sugar raises the hormone, and exercise raises it too.
- Inter99 (Cell Metab 2017): 6,514 Danes. One version of the FGF21 gene went with eating more sweets. FGF21 in the blood rose after drinking sugar.
- Exercise (Sports Med 2026 review): 13 study groups, 280 adults who were overweight or obese. Training raised FGF21 in the blood.
- ENLIVEN (NEJM 2023): 222 people, pegozafermin. Scarring improved in 22 to 27 percent against 7 percent on the dummy shot at 24 weeks. The disease cleared in 23 to 37 percent against 2 percent. 89bio paid.
- HARMONY (Lancet 2025): 128 people, efruxifermin. Scarring improved in 49 percent on 50 mg against 19 percent on the dummy shot at 96 weeks. The 28 mg dose did not clearly beat the dummy shot. Akero paid.
- Efruxifermin large final-stage studies: 1,650 people (signing up), 2,150 people (signing up) and 700 people (under way, no longer signing up). None has reported.
- No human study has given the natural hormone. No human study has tested any FGF21 drug mainly for weight loss, for ageing or for lifespan.
What this does not tell you: These studies were in people with fatty liver disease proven by a liver sample. They say nothing about FGF21 in people without liver disease. A better-looking liver sample at 24 to 96 weeks is not the same as fewer people getting sick or dying. The large studies that could show that are years from finishing. The lab-built versions last much longer in the body and act differently from the natural hormone. So their results are not results for the hormone itself. The longer life in mice has no human match of any kind. Bone loss is a known worry for drugs in this family. We did not pull human bone density numbers from the study reports, and we do not claim one. Both main studies were paid for by the drug makers.
The state of the research
FGF21 is the clearest case on this site of a natural hormone whose evidence belongs almost entirely to its lab-built copies. The natural hormone wears off too fast to be a drug, and nobody can patent it. So nobody has given it to people. The lab-built versions are each owned by a company. Each company has paid for studies that measure what a liver drug needs to measure. That is why the human record is deep on liver samples in fatty liver disease and empty everywhere else. Efruxifermin has already had a setback, reported on its own page. Its SYMMETRY study in people with early liver cirrhosis missed its main goal at 36 weeks. The pegozafermin program moved to Roche in 2025. Efimosfermin, a once a month version, has its own page.
The longer life story comes from one line of mouse work. Mice bred to make extra FGF21 lived longer in 2012. A 2025 follow-up found the same in obese mice. The proposed reason is that FGF21 turns down growth hormone signals. That same effect links FGF21 to stunted growth and bone loss in those mice. Nothing in people speaks to this either way. Any product sold as FGF21 for a longer life is stretching from specially bred mice across a gap the liver studies were never built to close.
The evidence, in charts
Fig. 1a · how many people
6,864people, across 3 studies in people cited here
| Study | People | Share |
|---|---|---|
| Cell Metabolism 2017 | 6,514 | 95% |
| New England Journal of Medicine 2023 | 222 | 3% |
| HARMONY, Lancet 2025 | 128 | 2% |
One study holds 95% 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. 1 more study in people gives no headcount and is not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
4 of 10 sources here are studies in people. The rest are not.
- Study in people · done in people440%
- Animal study · done in animals440%
- Review of studies · sums up other studies220%
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, 2009 to 2026, 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
- 22,300 Da precursor (209 residues, UniProt Q9NSA1); mature secreted chain residues 29 to 209, 181 amino acids
- Half-life
- None on file
- Chain length
- None on file
No amino acid sequence is on file for FGF21, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2017FGF21 Is a Sugar-Induced Hormone Associated with Sweet Intake and Preference in Humans
A common gene variant near FGF21 goes with a sweeter tooth, and sugar itself raises the hormone. Among 6,514 Danes, people carrying one version reported eating more sweets, with weaker hints towards more alcohol and smoking. In a separate clinical study, FGF21 rose in the blood shortly after people drank sucrose, and fasting levels were higher in people who disliked sweet things. Nobody was given FGF21 here. This is how the hormone behaves, not what taking it would do.
In 6,514 participants of the Danish Inter99 cohort, FGF21 variant rs838133 was associated with higher candy consumption, with nominal associations to alcohol intake and smoking. In a separate clinical study plasma FGF21 rose acutely after oral sucrose and was higher in fasted sweet-disliking people.
- Study in people2023Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH
A lab-built version of FGF21 healed liver scarring in a mid-sized study. 222 people with fatty liver disease and moderate to advanced scarring got one of three doses or a dummy shot, for 24 weeks. Scarring improved without the disease getting worse in 7% of the dummy group, against 22% to 27% on the drug. The disease cleared in 2% of the dummy group and 23% to 37% on the drug. Nausea and diarrhoea were common. 89bio paid for it.
ENLIVEN phase 2b, 222 randomised and 219 treated, biopsy-confirmed NASH with F2 or F3 fibrosis, 24 weeks. Fibrosis improvement without NASH worsening: 7 percent placebo, 22 percent on 15 mg weekly, 26 percent on 30 mg weekly (p 0.009), 27 percent on 44 mg every 2 weeks (p 0.008). NASH resolution: 2 percent placebo versus 37, 23 and 26 percent. Most common adverse events nausea and diarrhoea. Funded by 89bio.
- Study in people2025Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results from a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial
The higher dose worked at two years and the lower dose did not. 128 people with fatty liver disease and moderate to advanced scarring got one of two doses or a dummy shot. After 96 weeks, scarring improved by at least one stage in 19% of the dummy group, 30% on the lower dose and 49% on the higher. Only the higher dose clearly beat the dummy. Almost everyone in every group reported side effects, dummy group included. Akero Therapeutics paid for it.
128 randomised at 41 US centres, MASH with F2 or F3 fibrosis, efruxifermin 28 mg or 50 mg weekly or placebo. At 96 weeks, fibrosis improvement of at least one stage without MASH worsening: 19 percent placebo, 30 percent on 28 mg (difference 12 points, p 0.19), 49 percent on 50 mg (difference 31 points, 95 percent CI 12 to 49, p 0.003). Adverse events in 95 to 100 percent of every group including placebo. Sponsor Akero Therapeutics.
- Study in people2023Efruxifermin phase 3 in non-cirrhotic MASH with fibrosis
The trials that will settle this are running and have published nothing. Akero Therapeutics is enrolling an estimated 1,650 people in a late-stage trial in fatty liver disease with scarring, and its main results are not expected until February 2033. Two more late-stage trials are registered, one in 2,150 people with liver cirrhosis and one in 700 people diagnosed without a biopsy. None has reported. Statuses checked in September 2026.
Akero Therapeutics, phase 3, estimated enrolment 1,650, recruiting, primary completion estimated February 2033. Two further phase 3 trials: NCT06528314 in compensated MASH cirrhosis (2,150, recruiting) and NCT06161571 in non-invasively diagnosed MASH (700, active, not recruiting). Statuses checked 11 September 2026.
- Review of studies2026The Use of FGF21 Analogues in MASH and MASH Cirrhosis: Metabolic Master Regulators or Liver-Specific Mechanisms?
A review asking whether the liver healing from FGF21 drugs comes from effects on the whole body or on the liver alone. That decides whether anything on this page applies beyond the liver.
Review asking whether the histological benefit of FGF21 analogues reflects systemic metabolic action or liver-specific mechanisms, a question that bears directly on whether anything on this page generalises beyond the liver.
- Review of studies2019Fibroblast growth factor 21: an endocrine inhibitor of sugar and alcohol appetite
A review of how FGF21 may carry a signal from the liver to the brain to turn down the taste for sweets and alcohol. It covers work in mice and monkeys. It also covers the human data.
Review of the mouse, primate and human evidence that FGF21 signals from liver to brain to reduce sweet and alcohol preference.
- Animal study2012The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
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.
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.
- Animal study2025FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression
In obese mice. FGF21 made them live longer, and it did not need to slow growth to do it. Mice only.
In mice with diet-induced obesity, FGF21 extended lifespan through metabolic effects that did not depend on suppressing growth. Mouse only.
- Animal study2009FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response
In mice. FGF21 ran the liver's fasting response: burning fat, making ketones and making new sugar. This is the basic mouse science.
In mice, FGF21 induced hepatic PGC-1alpha and coordinated the fasting response, including fatty acid oxidation, ketogenesis and gluconeogenesis. Foundational mouse mechanism.
- Animal study2025FGF21 reverses MASH through coordinated actions on the CNS and liver
In mice. Reversing fatty liver disease with FGF21 needed signals in both the brain and the liver. This is the mouse science behind the human liver results.
In mice, FGF21's reversal of MASH required signalling in both the brain and the liver. Mouse mechanism for the human liver histology findings.
Common questions
Has FGF21 been tested in people?
Yes. 350 people given it across 2 completed trials cited here, 0 of which found nothing. FGF21 is a hormone your liver makes when you fast, eat sugar or eat less protein. Lab-built versions healed liver scarring in two mid-sized studies of 222 and 128 people with fatty liver disease. Longer life has only been seen in mice bred to make extra FGF21.
What is the FGF21 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, 350 people given it
Is FGF21 FDA-approved?
Not FDA-approved. Natural FGF21 is not a drug. No lab-made version of FGF21 (efruxifermin, pegozafermin, efimosfermin) was listed in the FDA drug database (Drugs@FDA) on 11 September 2026. Efruxifermin and pegozafermin are in final-stage studies.
Does FGF21 extend lifespan?
In mice bred to make extra FGF21, yes. That was in a 2012 paper and a 2025 follow-up in obese mice. There is no data on lifespan, longer life or ageing for FGF21 or any of its drug versions in people. The same mouse work found stunted growth and bone loss.
What has FGF21 done in human trials?
The studies tested lab-built versions, not the hormone itself. Pegozafermin healed liver scarring in 22 to 27 percent of 222 people with fatty liver disease, against 7 percent on a dummy shot, at 24 weeks. Efruxifermin 50 mg healed scarring in 49 percent against 19 percent on a dummy shot at 96 weeks, in 128 people. Neither is approved. Efruxifermin is in three large final-stage studies.
Is FGF21 the same thing as klotho?
No, but they are linked. FGF21 can only act on cells that carry beta-klotho, its partner protein. Beta-klotho is a different gene and protein from alpha-klotho, the kidney and brain protein on the klotho page. Alpha-klotho is the partner for a different hormone, FGF23.
Does FGF21 reduce sugar cravings?
In 6,514 Danes, one version of the FGF21 gene went with eating more sweets. FGF21 in the blood also rises after a dose of sugar. That suggests FGF21 responds to sugar and may shape how much you want it. No study has given FGF21 or a drug version to people to test appetite. In mice and monkeys, it cuts how much sweet food they take.