Efruxifermin
A once-weekly, long-acting form of the hormone FGF21, in phase 3 trials for fatty-liver hepatitis with scarring
Efruxifermin is the liver and metabolism hormone fibroblast growth factor 21 (FGF21), engineered and fused to the Fc tail of a human antibody so that two FGF21 units travel together and last for days. Injected once a week, it cut liver fat sharply in phase 2a, and in the phase 2b HARMONY trial roughly twice as many people with MASH and moderate or severe scarring improved by a fibrosis stage as on placebo. In compensated cirrhosis it missed its 36-week goal. Three phase 3 trials are running, now under Novo Nordisk, which acquired its developer, Akero Therapeutics, in December 2025. It is not approved anywhere.
Used in human trials: 28 mg or 50 mg, Once weekly, Subcutaneous (Study: MASH with stage 2-3 fibrosis (HARMONY)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Fibroblast growth factor 21 (FGF21) is a hormone that regulates metabolism and protects cells under stress. It signals through FGF receptors 1c, 2c and 3c, but only with the help of a partner receptor, β-Klotho, which it grips with the far (C-terminal) end of the protein. Efruxifermin is an engineered FGF21 fused to the Fc portion of a human IgG1 antibody. The fusion pairs two FGF21 units on one molecule and stretches the half-life to three to three and a half days, long enough for weekly injections. Because a version clipped at that far end would no longer act, the developers built a blood test that measures only the intact, active form.
Its first human study, run under the code AKR-001 in people with type 2 diabetes, found effects on markers of insulin sensitivity and favourable shifts in triglycerides and cholesterol at doses up to 70 mg weekly. The BALANCED phase 2a trial then gave 28, 50 or 70 mg weekly for 16 weeks to 80 people with MASH (then called NASH). Liver fat fell by 12 to 14 percentage points against no change on placebo. A cohort with compensated cirrhosis showed better markers of liver injury and scarring, and a small biopsy subset showed fibrosis improvement.
HARMONY, the phase 2b trial, enrolled 128 people with biopsy-proven MASH and stage 2 or 3 fibrosis. After 24 weeks, 39% on 28 mg and 41% on 50 mg improved by at least one fibrosis stage without worsening MASH, against 20% on placebo. Treatment continued to 96 weeks: in the full analysis the 50 mg group reached 49% against 19%, and among those with a final biopsy, 75% against 24%. Another cohort added efruxifermin to existing GLP-1 drugs in people with type 2 diabetes and cut liver fat by about 65% more over 12 weeks.
Cirrhosis is harder. In SYMMETRY, 181 people with compensated MASH cirrhosis received 28 mg, 50 mg or placebo. At 36 weeks the share whose fibrosis improved without worsening MASH (18% and 19% against 13%) did not differ significantly from placebo. By 96 weeks it was 29% on 50 mg against 11%, a difference whose confidence interval excluded zero, though this was a secondary outcome. Meta-analyses of the four phase 2 trials agree on fewer and less-scarred livers and lower liver fat, and on more nausea, diarrhoea and stopping for side effects.
Three phase 3 trials, the SYNCHRONY programme, are under way: one in stage 2 to 3 MASH with biopsy end points and long-term outcomes, one safety study in people diagnosed without a biopsy, and one in compensated cirrhosis measuring clinical events. They test 28 mg and 50 mg weekly. Until they report and a regulator approves it, efruxifermin is an investigational drug available only in trials. The doses below are trial doses.
Mechanism of Action
Efruxifermin is a long-acting copy of the hormone FGF21, made to signal through the same receptors for a week at a time.
FGF receptor agonism
Activates FGF receptors 1c, 2c and 3c with the partner receptor β-Klotho, reproducing FGF21's action (PMID 37802088).
Bivalent Fc fusion
Two FGF21 units on a human IgG1 Fc give a half-life of 3 to 3.5 days (PMIDs 37141854, 33205064).
Liver fat and scarring
Cut liver fat by 12 to 14 points in 12 weeks and improved fibrosis stage in biopsies (PMIDs 34239138, 37802088).
Metabolic markers
Improved insulin-sensitivity markers, triglycerides and HbA1c (PMIDs 33205064, 40937291).
Published Research
Studies of efruxifermin (also called AKR-001) read from their PubMed abstracts: its first study in type 2 diabetes, the BALANCED, HARMONY and SYMMETRY trials and the GLP-1 combination cohort, three meta-analyses and a network meta-analysis, a review, a laboratory method paper and a rat toxicology study.
AKR-001 in type 2 diabetes
In a phase 1 multiple-ascending-dose study in type 2 diabetes, the Fc-FGF21 fusion had a half-life of 3 to 3.5 days and a peak-to-trough ratio near 2 with weekly dosing. It improved serum markers of insulin sensitivity and moved triglycerides, non-HDL and HDL cholesterol in a favourable direction, and was acceptably tolerated up to 70 mg weekly.
BALANCED: liver fat in MASH
80 people with MASH and stage 1 to 3 fibrosis received 28, 50 or 70 mg or placebo weekly for 16 weeks. At week 12, liver fat on MRI fell by 12.3, 13.4 and 14.1 percentage points against a 0.3-point rise on placebo. Most side effects were mild, mainly gastrointestinal (46% drug-related).
BALANCED cohort C: cirrhosis
30 people with compensated MASH cirrhosis received 50 mg or placebo weekly for 16 weeks. Treatment was tolerated, with mostly mild diarrhoea and nausea, and lowered markers of liver injury and fibrosis (Pro-C3, ELF score). Of 12 treated patients with a repeat biopsy, 4 improved by a fibrosis stage, against none of 5 on placebo.
HARMONY: fibrosis at 24 weeks
128 adults with biopsy-confirmed MASH and stage 2 or 3 fibrosis were randomised to 28 mg, 50 mg or placebo weekly. At 24 weeks, fibrosis improved by at least one stage without worse MASH in 39% and 41% against 20% among those biopsied. Diarrhoea and nausea were the most common related events, and five patients stopped for side effects.
HARMONY: 96 weeks
After 96 weeks of treatment, fibrosis improved without worsening MASH in 49% on 50 mg and 30% on 28 mg against 19% on placebo; among the 88 with a week-96 biopsy the figures were 75%, 46% and 24%. Gastrointestinal events were more common on efruxifermin; there was no drug-induced liver injury and no death.
SYMMETRY: compensated cirrhosis
181 people with compensated MASH cirrhosis received 28 mg, 50 mg or placebo weekly. At 36 weeks fibrosis improved without worse MASH in 18% and 19% against 13%, not significant. At 96 weeks, a secondary outcome, it was 21% and 29% against 11%. Gastrointestinal side effects were more frequent and mostly mild or moderate.
Added to a GLP-1 drug
31 adults with type 2 diabetes and MASH already on semaglutide, dulaglutide or liraglutide added 50 mg efruxifermin or placebo weekly for 12 weeks. Liver fat fell 65% against 10%, markers of liver injury, fibrosis, glucose and lipids improved, and the GLP-1 weight loss was preserved; one patient stopped for nausea.
Systematic review of safety
Pooling four phase 2 trials (450 people), 50 mg raised the risk of stopping for side effects about threefold, with more nausea and diarrhoea, and both doses raised appetite. Severe and serious adverse events matched placebo, and efruxifermin improved liver fat, fibrosis markers and histology, HbA1c and lipids.
Updated meta-analysis
Four randomised trials with 419 participants showed efruxifermin roughly doubled the chance of at least one stage of fibrosis improvement (relative risk 2.18) and made MASH resolution with fibrosis improvement about five times as likely, with large gains in liver fat reduction, but more gastrointestinal events and stopping for side effects.
Meta-analysis of fibrosis
In four trials with 325 biopsy-proven patients across fibrosis stages 1 to 4, efruxifermin gave a relative risk of 1.97 for fibrosis improvement without worsening MASH and improved ELF score, Pro-C3 and liver stiffness; the excess of adverse events was not robust in sensitivity analysis.
Against resmetirom, indirectly
A network meta-analysis of eight randomised trials found efruxifermin reduced MRI liver fat (mean difference about -63%) and AST more than resmetirom, the first approved MASH drug, and lowered triglycerides more; the comparison is indirect, not head to head.
Investigational drug review
This review describes efruxifermin (also AKR-001 or AMG876) as an engineered Fc-FGF21 fusion with an improved pharmacokinetic profile, summarises phase 2 data on glycaemic control, safety and effect on scarring, and notes that some other FGF21 agonists, such as pegbelfermin, had been dropped.
Measuring the active drug
Because FGF21 needs an intact far (C-terminal) end to bind β-Klotho, the authors validated an immunoassay that captures only intact efruxifermin in serum. Used in BALANCED, it showed dose-proportional exposure that did not differ between fibrosis and cirrhosis.
Rats on high doses for 26 weeks
Weekly high doses in rats for 4 or 26 weeks reduced weight gain despite more eating. Unlike at least one other FGF21 analogue, it lowered rather than raised urine volume, and markers of sympathetic activation did not change.
Dosing Data
Efruxifermin is not approved, so there is no label. These are the weekly doses given in the trials carded above; the phase 3 SYNCHRONY trials test 28 mg and 50 mg.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Efruxifermin is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 10 mg vial mixed with 3 mL of bacteriostatic water holds 3,333.3 mcg per mL, so 28 mg, the first amount in the “Study: MASH with stage 2-3 fibrosis (HARMONY)” row (28 mg or 50 mg) would be 840.0 units, more than a 1 mL U-100 syringe holds. Put your own vial's numbers into the reconstitution calculator.
Source: dose: Used in human trials, PMID 37802088 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Efruxifermin, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Efruxifermin stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Once weekly; Study: MASH with stage 2-3 fibrosis (HARMONY)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of 3 to 3.5 days (PMID 33205064). After about five half-lives almost none is left.
How long the doses were given: Study: MASH with stage 2-3 fibrosis (HARMONY): 96 weeks; Study: compensated MASH cirrhosis (SYMMETRY): 96 weeks; Study: MASH, stage 1-3 fibrosis (BALANCED): 16 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Efruxifermin. Results reported in the studies are under Published Research.
Source: half-life: PMID 33205064; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Diarrhoea and nausea, mostly mild to moderate, in up to about 40% (PMID 37802088); Increased appetite (PMID 40937291); More stopping for side effects at 50 mg than on placebo (PMIDs 40937291, 42007332); No drug-induced liver injury reported over 96 weeks in HARMONY (PMID 40818852). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Efruxifermin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials and meta-analyses above”).
Interactions
Unknown: a PubMed search for human interaction studies of Efruxifermin (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Efruxifermin products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: In Clinical Trials (Not approved anywhere). Sport: Unsettled (S2.3 may apply).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the trials and meta-analyses above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Efruxifermin is an investigational drug in phase 3; it has not been approved anywhere in the sources read.
Frequently Asked Questions
?What is efruxifermin?
A man-made, long-lasting version of the hormone FGF21, fused to part of a human antibody so it can be injected once a week. It is being developed for MASH, the inflammatory form of fatty liver disease.
?Does it reverse liver scarring?
In people with stage 2 or 3 fibrosis, about 40% improved by one fibrosis stage in 24 weeks against 20% on placebo, and the gap grew by 96 weeks. In cirrhosis, the 36-week result was not significant; a later 96-week figure favoured it.
?Is it approved?
No. Three phase 3 trials are running. Until they report and a regulator approves it, it is available only in trials.
?What are the side effects?
Mostly nausea and diarrhoea, usually mild, and increased appetite. More people stop treatment on 50 mg than on placebo.
?Can it be combined with semaglutide?
One 12-week cohort of 31 people already on GLP-1 drugs found it added a large further drop in liver fat without undoing weight loss. That is a small, short study.
?Who makes it?
Akero Therapeutics developed it; Novo Nordisk completed its purchase of Akero in December 2025.
References
- [other] Novo Nordisk A/S. Company announcement: Novo Nordisk completes acquisition of Akero Therapeutics, December 9, 2025. Read October 29, 2026. https://akerotx.com/wp-content/uploads/2025/12/pr251209-akero-closing.pdf
- [registry] ClinicalTrials.gov API v2, read October 29, 2026: NCT06215716 (phase 3, stage 2-3 MASH, recruiting), NCT06161571 (phase 3, non-invasively diagnosed MASH, active not recruiting), NCT06528314 (phase 3, compensated cirrhosis, recruiting), NCT04767529 (HARMONY, completed), NCT05039450 (SYMMETRY, completed), NCT03976401 (BALANCED, completed).
- [clinical-trial] Kaufman A, et al. "AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients." Cell Rep Med, 2020;1(4):100057. PMID: 33205064.
- [clinical-trial] Harrison SA, et al. "Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial." Nat Med, 2021;27(7):1262-1271. PMID: 34239138.
- [clinical-trial] Harrison SA, et al. "A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis." JHEP Rep, 2023;5(1):100563. PMID: 36644237.
- [clinical-trial] Harrison SA, et al. "Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial." Lancet Gastroenterol Hepatol, 2023;8(12):1080-1093. PMID: 37802088.
- [clinical-trial] Noureddin M, et al. "Safety 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." Lancet, 2025;406(10504):719-730. PMID: 40818852.
- [clinical-trial] Noureddin M, et al. "Efruxifermin in Compensated Liver Cirrhosis Caused by MASH." N Engl J Med, 2025;392(24):2413-2424. PMID: 40341827.
- [clinical-trial] Harrison SA, et al. "Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study." Clin Gastroenterol Hepatol, 2025;23(1):103-113. PMID: 38447814.
- [review] Kamrul-Hasan ABM, et al. "Safety and efficacy of efruxifermin in metabolic dysfunction-associated steatohepatitis: A systematic review." World J Gastrointest Pharmacol Ther, 2025;16(3):110709. PMID: 40937291.
- [review] Xiao YJ, et al. "Efficacy and safety of efruxifermin for patients with NASH/MASH: an updated systematic review and meta-analysis." Front Pharmacol, 2025;16:1731065. PMID: 42007332.
- [review] Li S, et al. "A systematic review and meta-analysis of efruxifermin's efficacy in improving liver fibrosis in patients with NASH/MASH." Front Pharmacol, 2025;16:1594091. PMID: 40520164.
- [review] Jaber D, et al. "Comparative Efficacy and Safety of Resmetirom and Efruxifermin for Metabolic Dysfunction-Associated Steatohepatitis: A Network Meta-Analysis of Randomized Controlled Trials." Endocrinol Diabetes Metab, 2026;9(3):e70218. PMID: 41947319.
- [review] Puengel T, et al. "Efruxifermin, an investigational treatment for fibrotic or cirrhotic nonalcoholic steatohepatitis (NASH)." Expert Opin Investig Drugs, 2023;32(6):451-461. PMID: 37376813.
- [pubmed] Kinne AS, et al. "Noncompetitive immunoassay optimized for pharmacokinetic assessments of biologically active efruxifermin." J Pharm Biomed Anal, 2023;232:115402. PMID: 37141854.
- [pubmed] Tillman EJ, et al. "Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats." Br J Pharmacol, 2022;179(7):1384-1394. PMID: 34773249.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Trial status comes from ClinicalTrials.gov and approval status from Drugs@FDA (openFDA) and the EMA medicines list, read the same day; the acquisition date from Novo Nordisk's closing announcement of December 9, 2025. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.