Pegbelfermin (BMS‐986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study
Open accessAbstract
Objective: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis. This study assessed pegbelfermin (BMS‐986036), recombinant PEGylated human fibroblast growth factor 21 (FGF21), in patients with obesity and T2DM predisposed to fatty liver. Methods: In this randomized, double‐blind, placebo‐controlled study, patients with T2DM and BMI of 30 to 50 kg/m 2 received subcutaneous pegbelfermin (1, 5, or 20 mg daily or 20 mg weekly; n = 96) or placebo ( n = 24) for 12 weeks. Primary end points were safety, tolerability, and change in HbA1c. Additional end points included insulin sensitivity, lipids, adiponectin, and disease progression biomarkers. Results: There were no significant effects of pegbelfermin versus placebo on HbA1c. Pegbelfermin 20 mg/d significantly improved high‐density lipoprotein cholesterol ( P = 0.015) and triglycerides ( P = 0.037). All pegbelfermin regimens significantly increased adiponectin levels; 20‐mg daily and weekly regimens decreased serum PRO‐C3. Most adverse events were mild; the most frequent adverse events were injection‐site bruising and diarrhea. Conclusions: Twelve‐week pegbelfermin treatment did not impact HbA1c concentrations, but QW and higher daily doses were associated with improved metabolic parameters and fibrosis biomarkers in patients with obesity and T2DM predisposed to fatty liver. These results support evaluation of pegbelfermin in patients with obesity‐related metabolic diseases (e.g., nonalcoholic steatohepatitis).
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The magnitude of glucose-lowering effects of FGF21 analogues is clearly lower in humans than rodents.
“the magnitude of the glucose-lowering effects of FGF21 analogues is clearly lower in humans than rodents81,87–91, perhaps because of differences in brown adipose tissue metabolism between species65.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [90]
All FGF21 analogues consistently have a pronounced ability to decrease plasma triglyceride levels, in many cases by as much as ~70%.
“all analogues consistently have a pronounced ability to decrease plasma triglyceride levels, in many cases by as much as ~70% (refs. 81,87–91).”
From Metabolic messengers: FGF21 (2021) · cites this paper as [90]
Two other FGF21 analogues AKR-001 and pegbelfermin have not been found to significantly decrease body weight in people with obesity or type 2 diabetes.
“two other FGF21 analogues, AKR-001 (also known as efruxifermin)88 and pegbelfermin89,90, have not been found to significantly decrease body weight in people with obesity or type 2 diabetes.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [90]
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“Another 12-week phase 2 study with the administration of Pegbelfermin in patients with obesity and T2DM demonstrated a remarkable increase in HDL and adiponectin levels but no statistically significant decrease in weight, fasting insulin and HbA1C levels were observed (103, 109).”
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BackgroundProbiotic culture supernatant improves metabolic function through FGF21-adiponectin pathway in mice
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“Unfortunately, 12-week pegbelfermin treatment has not been shown to impact HbA1c concentrations in another randomized phase 2 study [72].”
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“Pegbelfermin Long-acting FGF21 analogue SC Phase III Yes Yes Yes No No [88,89]”
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“Among them, BMS‐986036 (also known as pegbelfermin) is a PEGylated human FGF21 analogue.(40,41,43) LY2405319 is an engineered human FGF21 variant produced in the fungus Pichia pastoris with improved formulation stability and protein expression.”
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“Endogenous FGF-21 has short half-life, so the use of FGF-21 analogs seems to be a therapeutic alternative aiming at providing a more prolonged action.(82) In a phase 2 RCT, pegbelfermin subcutaneous injection (1 mg/d, 5 mg/d, 20mg/d or 20 mg/week) in patients with T2DM and obesity, of whom 97% with presumable NAFLD, s…”
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“Similarly, fibroblast growth factor 21 (FGF21) analogs, such as pegbelfermin, have progressed into clinical development, showing beneficial effects on lipid metabolism, insulin sensitivity, and hepatic steatosis in obese individuals with type 2 diabetes [98].”
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“Conversely, 12-week pegbelfermin treatment did not affect HbA1c concentrations in another randomized phase 2 study [50].”
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“type 2 diabetes, 12 weeks pegbelfermin treatment was associated with improved metabolic parameters and serum fibrosis markers [76].”
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“Pegbelfermin (PGBF), a recombinant, polyethylene glycol-conjugated analogue of human FGF21, has an extended half-life compared with endogenous FGF21 and supports up to weekly dosing in clinical trials.(25,26) In the phase IIb FALCON 1 study, 24-week PGBF treatment in patients with NASH and stage 3 fibrosis was associa…”
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“However, the clinicalimplementation of FGF21-based therapies for the treatment of obesity is restricted by the complexity of pathophysiology of FGF21, the potentialdevelopment of FGF21 resistancein obesity and the poor pharmacokinetic of native FGF21 20 – 24 .”
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“Phase 2a trial of pegbelfermin in patients with type 2 diabetes [38]”
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“Similar to the previous study, we found no clear exposure‐ dependent trends in fasting blood glucose with BFKB8488A administration; however, patients with the highest BFKB8488A exposure trended toward insulin decreases similar to the MAD study and glycemic results reported in the pegbelfermin study in obese patients w…”
ResultInfluentialBeige Fat, Adaptive Thermogenesis, and Its Regulation by Exercise and Thyroid Hormone
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- Authors
- Charles, E. D., Neuschwander‐Tetri, B. A., Pablo Frias, J., Kundu, S., Luo, Y., Tirucherai, G. S., & Christian, R.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Saint Louis University (US)
- National Research Institute Los Angeles California USA
- Corresponding author
- Charles, Edgar D.
- Venue
- Obesity
- Publisher
- Wiley
- Published
- 2018-12-06
- Volume
- 27
- Issue
- 1
- Pages
- 41-49
- ISSN
- 1930-7381 (ISSN-L)
- 1930-739X
- PMC
- PMC6587787
- OpenAlex
- W2903736473
- Cited by
- 257
- References
- 39
- Citations by year
- 2026: 15 · 2025: 29 · 2024: 40 · 2023: 33 · 2022: 40 · 2021: 41 · 2020: 42 · 2019: 16 · 2018: 1
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Obesity (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- FGF21, type 2 diabetes, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, HbA1c, insulin sensitivity, HDL cholesterol, triglycerides, adiponectin, PRO-C3, fibrosis biomarkers, drug safety and tolerability
- MeSH terms
- Adult, Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, Obesity, Polyethylene Glycols, Young Adult, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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