Pegbelfermin
The weekly FGF21 drug that lowered liver fat in NASH but missed its biopsy end points in the FALCON trials
Pegbelfermin is a lab-made version of FGF21, a hormone that tells the liver and fat tissue how to handle sugar and fat, with a polyethylene glycol chain attached so a weekly injection is enough. Bristol-Myers Squibb tested it in fatty liver disease (NASH, now called MASH). It cut liver fat in a short trial, then missed the main biopsy goal of both larger FALCON trials. It was never approved, and no trial has been registered since.
Used in human trials: 10, 20 or 40 mg, Once weekly, Subcutaneous (Study: FALCON 1 and 2 (NASH with stage 3 fibrosis or cirrhosis)) 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 helps regulate energy metabolism, including how the body handles fat and sugar, and unlike many growth factors it does not drive cell division. Drug makers have built several longer-lasting versions of it. Pegbelfermin is Bristol-Myers Squibb's: FGF21 with a polyethylene glycol (PEG) chain attached, which keeps the protein in circulation long enough for a once-weekly injection.
The first big target was obesity with type 2 diabetes. In a 12-week phase 2 trial of 120 people, pegbelfermin did not lower HbA1c, the usual blood-sugar measure, but it raised adiponectin (a fat-tissue hormone linked to better insulin sensitivity), improved HDL cholesterol and triglycerides at the top daily dose, and lowered PRO-C3, a blood marker of scar-tissue formation in the liver. That pattern, little effect on glucose but clear effects on fat metabolism and liver markers, pointed the programme at fatty liver disease.
NASH (now usually called MASH, metabolic dysfunction-associated steatohepatitis) is fatty liver with inflammation and cell injury, and it can scar the liver until it becomes cirrhosis. In a 16-week phase 2a trial of 75 patients, pegbelfermin cut the fraction of liver made up of fat by about 5 to 7 percentage points on MRI, against about 1 point on placebo. Side effects were mostly mild diarrhoea and nausea.
The FALCON trials were the real test, because they were judged on liver biopsies: does scarring (fibrosis) improve, or does the inflammation resolve, without the other getting worse? FALCON 1 enrolled 197 people with stage 3 (bridging) fibrosis. At week 24, 24% to 31% of the pegbelfermin groups met the biopsy goal against 14% on placebo, but the three doses did not do better in step with dose, which the pre-set statistical test required, so the result was not significant. FALCON 2, in 154 people with compensated cirrhosis, was plainly negative: 24% to 28% improved on the drug against 31% on placebo.
Other measures moved in pegbelfermin's favour in FALCON 1: liver fat, liver stiffness on MR elastography, PRO-C3 and liver enzymes. A post hoc analysis argued that non-invasive tests picked up more benefit than the biopsies did. Later meta-analyses are mixed: one pooling three trials found improvements in NASH at 10 mg but none in stiffness or fibrosis scores, and a 2026 network meta-analysis of the FGF21 class found that pegozafermin and efruxifermin improved fibrosis significantly while pegbelfermin did not.
No trial has followed FALCON: every pegbelfermin study registered on ClinicalTrials.gov is completed or withdrawn. Other FGF21 drugs built differently, notably efruxifermin and pegozafermin, did better on fibrosis in the comparison above and went on to larger trials; they have their own entries. Pegbelfermin is not sold as a medicine anywhere, and anything offered under its name outside a trial would be an unknown product.
Mechanism of Action
Pegbelfermin copies the hormone FGF21, which regulates energy metabolism; the PEG chain keeps it in the blood long enough for weekly dosing. Its measurable effects in people are on liver fat, adiponectin, blood fats and fibrosis markers.
An FGF21 mimic
Pegbelfermin is human FGF21 with a polyethylene glycol chain attached; the trials describe FGF21 as a hormone that regulates energy metabolism without driving cell growth.
Liver fat
In the phase 2a NASH trial liver fat fell by several percentage points in 16 weeks; liver fat was also the most consistent improvement in FALCON 1.
Adiponectin and lipids
Every regimen raised adiponectin in the diabetes trial, and the top daily dose improved HDL cholesterol and triglycerides; HbA1c did not change.
Fibrosis markers
PRO-C3, a blood marker of new collagen, fell in several trials, but fibrosis on biopsy did not improve significantly in either FALCON trial.
Bile acids and gut bacteria
Pegbelfermin lowered deoxycholic acid, a bile acid made by gut bacteria, and the bacterial gene that makes it; whether that matters clinically is unknown.
Published Research
Studies whose titles or abstracts name pegbelfermin, read from their PubMed abstracts on October 29, 2026: the four randomised trials and the FALCON design paper first, then their secondary analyses, three meta-analyses, a review and the year-long monkey study. Class reviews that mention it only in passing are left out.
Phase 2: obesity with type 2 diabetes
In 120 adults with type 2 diabetes and a BMI of 30 to 50, twelve weeks of pegbelfermin (1, 5 or 20 mg a day, or 20 mg a week) did not lower HbA1c compared with placebo. The 20 mg daily arm improved HDL cholesterol and triglycerides, every regimen raised adiponectin, and the 20 mg arms lowered PRO-C3, a blood marker of fibrosis. Most side effects were mild, chiefly bruising at the injection site and diarrhoea.
Phase 2a: liver fat in NASH
In 75 overweight or obese adults with biopsy-proven NASH (fibrosis stage 1 to 3) at 17 US centres, sixteen weeks of 10 mg daily or 20 mg weekly cut absolute liver fat on MRI by 6.8 and 5.2 percentage points, against 1.3 on placebo. Diarrhoea and nausea were the commonest events; nobody stopped because of a side effect and there were no treatment-related serious events. Bristol-Myers Squibb funded the trial.
The FALCON programme design
Describes the two placebo-controlled phase 2b trials: FALCON 1 in NASH with stage 3 (bridging) fibrosis and FALCON 2 in compensated cirrhosis, each giving weekly pegbelfermin 10, 20 or 40 mg or placebo for 48 weeks. FALCON 1's primary end point was read at week 24 and FALCON 2's at week 48, with bone density and antibodies to the drug among the safety measures.
FALCON 1: stage 3 fibrosis
In 197 patients with NASH and bridging fibrosis, the week-24 biopsy end point was met by 24% to 31% of the pegbelfermin arms and 14% on placebo, but the result was not statistically significant because the arms showed no dose response (P = .134). Liver fat, liver stiffness, PRO-C3 and liver enzymes moved in pegbelfermin's favour, adverse events were similar across arms, and the trial is reported as having missed its primary end point.
FALCON 2: compensated cirrhosis
In 154 treated patients with NASH cirrhosis, a one-stage fibrosis improvement without NASH worsening at week 48 occurred in 24% to 28% on pegbelfermin and 31% on placebo (P = .361): the trial missed its primary end point. Inflammation scores improved more often on the drug; liver stiffness and fat changes were not significant. Serious adverse events were more frequent with pegbelfermin, none judged treatment related, and one patient stopped for worsening ascites.
FALCON 1 biomarkers, post hoc
A post hoc look at FALCON 1 found that by week 24 pegbelfermin improved blood fibrosis scores (ELF, FIB-4, APRI), PRO-C3, adiponectin, CK-18 and liver fat on MRI. The clearest, most consistent effects were on liver fat and metabolism; the authors argue that non-invasive tests detected more improvement than the biopsies did.
Lower secondary bile acids
Exploratory analysis of the phase 2a NASH trial and a study in overweight or obese adults: pegbelfermin, not placebo, lowered blood levels of deoxycholic acid and its conjugates, a secondary bile acid made by gut bacteria, while primary bile acids did not change. Stool analyses showed less of the bacterial gene for the enzyme that makes secondary bile acids. The clinical meaning is unknown.
Dose and liver enzymes, four trials
A dose-response meta-analysis of four randomised trials (546 participants) found higher doses lowered ALT and AST more than lower doses, with no further gain above about 30 mg a week, and enzymes drifting back up after about 28 weeks of treatment. No participant stopped because of an adverse event.
Meta-analysis of three trials
Pooling three randomised trials (452 participants), pegbelfermin raised adiponectin and lowered PRO-C3 at 10 and 20 mg, and the 10 mg arm improved NASH, but neither dose improved liver stiffness, fibrosis scores, collagen area or liver enzymes, and side effects did not differ from placebo.
Against the other FGF21 drugs
A network meta-analysis of nine trials (1,277 patients, 263 of them on pegbelfermin) found that pegozafermin and efruxifermin improved liver fibrosis significantly, while pegbelfermin and the other agents did not reach significance. Gastrointestinal side effects were more common with pegozafermin, efimosfermin and efruxifermin.
Review before the FALCON results
A 2020 review of pegbelfermin's preclinical and early clinical work: it acts on many tissues, short-term side effects were limited, and the phase 2a trial looked promising, but trials showing benefit on liver biopsy, cirrhosis or survival, and longer safety data, were still needed.
A year of dosing in monkeys
Adult male cynomolgus monkeys given weekly pegbelfermin for a year (exposures 0.7 to 2.2 times the human 20 mg weekly exposure) showed raised adiponectin and lower body weight, with lean-mass loss at the higher dose, but no effect on bone turnover markers, bone density or bone strength, a concern raised by FGF21 work in mice.
Dosing Data
Pegbelfermin was never approved, so there is no label. These are the amounts given in the trials carded above, by subcutaneous injection.
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 Pegbelfermin 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 10 mg, the first amount in the “Study: FALCON 1 and 2 (NASH with stage 3 fibrosis or cirrhosis)” row (10, 20 or 40 mg) would be 300.0 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 37088457 (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 Pegbelfermin, 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 Pegbelfermin stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Once weekly; Study: FALCON 1 and 2 (NASH with stage 3 fibrosis or cirrhosis)).
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: not established by a measurement cited on this entry.
How long the doses were given: Study: FALCON 1 and 2 (NASH with stage 3 fibrosis or cirrhosis): 48 weeks; Study: phase 2a NASH trial, 75 patients: 16 weeks; Study: obesity with type 2 diabetes, 120 patients: 12 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Pegbelfermin. Results reported in the studies are under Published Research.
Source: 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 were the commonest events in the phase 2a NASH trial, mostly mild (PMID 30554783); Bruising at the injection site and diarrhoea were the commonest events in the diabetes trial (PMID 30520566); In FALCON 1, adverse events occurred at similar rates on drug and placebo (PMID 37088457); In FALCON 2 (cirrhosis), serious adverse events were more frequent on pegbelfermin, none judged treatment related; one patient stopped for worsening ascites (PMID 37088458); Bone loss, a concern from FGF21 studies in mice, was not seen in monkeys dosed for a year (PMID 34364948). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Pegbelfermin. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials carded above”).
Interactions
Unknown: a PubMed search for human interaction studies of Pegbelfermin (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 Pegbelfermin 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: Discontinued (Never approved: Drugs@FDA (openFDA) and the EMA medicines list hold no record (read October 29, 2026)). 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 carded above.
Contraindications & Cautions
No approved label exists, so there are no official contraindications. Points from the studies:
Legal Status
Pegbelfermin was investigational, no trial is running, and it has not been approved anywhere checked.
Frequently Asked Questions
?What is pegbelfermin?
A lab-made version of the hormone FGF21 with a polyethylene glycol chain attached, so it lasts long enough for weekly injections. Bristol-Myers Squibb developed it as BMS-986036 for fatty liver disease.
?Did it work in NASH?
Partly. It cut liver fat in a 16-week trial, and several blood and imaging markers improved, but both FALCON phase 2b trials missed their liver-biopsy primary end points. In FALCON 2, in cirrhosis, placebo did as well as the drug.
?Is it approved or still being tested?
Neither. Drugs@FDA and the EMA have no record of it, and all of its registered trials are completed or withdrawn.
?How is it different from efruxifermin and pegozafermin?
All three are long-acting FGF21 drugs, built in different ways. A 2026 network meta-analysis found significant fibrosis improvement with those two and not with pegbelfermin.
?Did it help blood sugar?
No. In the 12-week trial in obesity with type 2 diabetes, HbA1c did not change, although adiponectin rose and some blood fats improved.
?What doses were tested?
Between 1 and 20 mg a day, and 20 mg a week, in the phase 2 trials, and 10, 20 or 40 mg a week for 48 weeks in FALCON 1 and 2. These are study amounts, not recommendations.
References
- [other] ClinicalTrials.gov, search 'pegbelfermin' (read October 29, 2026): twelve registrations under BMS-986036, all completed except one withdrawn phase 1 study; they include the phase 2 trials NCT02097277 (obesity and type 2 diabetes), NCT02413372 (NASH) and the FALCON 1 and 2 trials NCT03486899 and NCT03486912. https://clinicaltrials.gov/search?term=pegbelfermin
- [clinical-trial] Charles ED, et al. "Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study." Obesity (Silver Spring), 2019;27(1):41-49. PMID: 30520566.
- [clinical-trial] Sanyal A, et al. "Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial." Lancet, 2019;392(10165):2705-2717. PMID: 30554783.
- [clinical-trial] Abdelmalek MF, et al. "The FALCON program: Two phase 2b randomized, double-blind, placebo-controlled studies to assess the efficacy and safety of pegbelfermin in the treatment of patients with nonalcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis." Contemp Clin Trials, 2021;104:106335. PMID: 33657443.
- [clinical-trial] Loomba R, et al. "Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study." Clin Gastroenterol Hepatol, 2024;22(1):102-112.e9. PMID: 37088457.
- [clinical-trial] Abdelmalek MF, et al. "Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study." Clin Gastroenterol Hepatol, 2024;22(1):113-123.e9. PMID: 37088458.
- [pubmed] Brown EA, et al. "Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial." JHEP Rep, 2023;5(4):100661. PMID: 36866389.
- [pubmed] Luo Y, et al. "Pegbelfermin selectively reduces secondary bile acid concentrations in patients with non-alcoholic steatohepatitis." JHEP Rep, 2022;4(1):100392. PMID: 34977519.
- [review] Lu Y, et al. "Pegbelfermin for reducing transaminase levels in patients with non-alcoholic steatohepatitis: a dose-response meta-analysis of randomized controlled trials." Front Med (Lausanne), 2024;11:1293336. PMID: 38646552.
- [review] Shahzil M, et al. "Evaluating the Effectiveness of Pegbelfermin in MASH-Associated Hepatic Fibrosis A Meta-Analysis and Systematic Review of Randomized Controlled Trials." JGH Open, 2025;9(3):e70131. PMID: 40104016.
- [review] Abdeljawad MM, et al. "Efficacy and safety of fibroblast growth factor 21 analogs in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: A systematic review and network meta-analysis." J Pharmacol Exp Ther, 2026;393(1):103786. PMID: 41529428.
- [review] Verzijl CRC, et al. "Pegbelfermin (BMS-986036): an investigational PEGylated fibroblast growth factor 21 analogue for the treatment of nonalcoholic steatohepatitis." Expert Opin Investig Drugs, 2020;29(2):125-133. PMID: 31899984.
- [pubmed] Thompson KE, et al. "Pegbelfermin, a PEGylated FGF21 analogue, has pharmacology without bone toxicity after 1-year dosing in skeletally-mature monkeys." Toxicol Appl Pharmacol, 2021;428:115673. PMID: 34364948.
Sources & Citations
Studies were read from their PubMed abstracts on October 29, 2026; trial registrations from ClinicalTrials.gov and status from Drugs@FDA the same day, and the EMA medicines list on October 28, 2026. 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.