The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
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
Abstract
Background Pegbelfermin (BMS-986036), a PEGylated human fibroblast growth factor 21 (FGF21) analogue, has previously been shown to improve markers of metabolism and liver fibrosis in obese patients with type 2 diabetes. In this phase 2a study, we aimed to evaluate the safety and efficacy of pegbelfermin in patients with non-alcoholic steatohepatitis.Methods In this multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2a study, we recruited adults (aged 21-75 years) with a body-mass index of at least 25 kg/m 2, biopsy-confirmed non-alcoholic steatohepatitis (fibrosis stage 1-3), and a hepatic fat fraction of at least 10% when assessed by magnetic resonance imaging-proton density fat fraction. These patients were enrolled at 17 medical centres in the USA. Eligible patients were stratified by type 2 diabetes status and they were randomly assigned (1:1:1) by a computer-based system to receive subcutaneous injections of placebo once a day, 10 mg pegbelfermin once a day, or 20 mg pegbelfermin once a week, all for 16 weeks. Participants, the study team administering treatment, and investigators analysing outcomes (who were independent of the study team and had no further involvement) were masked to treatment groups. The primary outcomes were safety and the absolute change in hepatic fat fraction after 16 weeks of treatment. All patients who were randomly assigned to groups and received the study drug or placebo were included in the primary analyses. This trial was registered with ClinicalTrials.gov, number NCT02413372.Findings Between May 12, 2015, and Aug 4, 2016, 184 overweight or obese patients with non-alcoholic steatohepatitis were screened for study inclusion. Of these, 95 (52%) patients were excluded because they no longer met study criteria and 80 (43%) patients entered the placebo lead-in phase. After further exclusions, 75 (94%) patients were randomly assigned to groups, received at least one dose of treatment (25 patients to receive 10 mg pegbelfermin once a day; 24 patients to receive 20 mg pegbelfermin once a week, and 26 patients to receive placebo), and were included in the primary analysis. A prespecified interim analysis at week 8 showed a greater than expected change in the primary outcome and supported early closing of patient enrolment, since this analysis indicated that the full planned sample size was not needed. We observed a significant decrease in absolute hepatic fat fraction in the group receiving 10 mg pegbelfermin daily (-6·8% vs -1·3%; p=0·0004) and in the group receiving 20 mg pegbelfermin weekly (-5·2% vs -1·3%; p=0·008) compared with the placebo group. Most adverse events were mild; the most common events were diarrhoea in eight (16%) of 49 patients treated with pegbelfermin and two (8%) of 26 patients treated with placebo and nausea in seven (14%) patients treated with pegbelfermin and two (8%) patients treated with placebo. There were no deaths, discontinuations due to adverse events, or treatment-related serious adverse events.Interpretation Treatment with subcutaneously administered pegbelfermin for 16 weeks was generally well tolerated and significantly reduced hepatic fat fraction in patients with non-alcoholic steatohepatitis. Further study of pegbelfermin is warranted in patients with non-alcoholic steatohepatitis. Additional studies that use liver biopsies would allow for the assessment of pegbelfermin's effects on liver histology. Moreover, further studies should allow assessments of the safety and effectiveness of pegbelfermin in a larger number of patients.Funding Bristol-Myers Squibb.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Pegbelfermin showed a reduction in hepatic fat (measured via MRI‐PDFF) and liver transaminases over a 16‐week treatment period as well as an improved lipid profile; [53] however, no histological readouts were available which hampers applicability of the results and warrants further studies on this compound.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [53]
In the citing paper
“Pegbelfermin showed a reduction in hepatic fat (measured via MRI‐PDFF) and liver transaminases over a 16‐week treatment period as well as an improved lipid profile; [53] however, no histological readouts were available which hampers applicability of the results and warrants further studies on this compound.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [53]
In the citing paper
“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 [89]
In the citing paper
“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 [89]
In the citing paper
“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 [89]
In the citing paper
“Administration of the FGF21 analogues AKR-001 (ref. 88) and pegbelfermin89 in humans with NASH results in marked absolute decreases in liver fat (up to 70%) and significant amelioration of liver fibrosis88,89.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [89]
In the citing paper
“clinical studies in patients with obesity and type 2 diabetes have found that FGF21-analogue administration markedly induces plasma adiponectin levels81,87–89”
From Metabolic messengers: FGF21 (2021) · cites this paper as [89]
In the citing paper
“PF-05231023 has been found to increase markers of bone turnover in humans81, whereas AKR-001 (ref. 88) and pegbelfermin89 have not.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [89]
Citations
Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791
Self-citationYounossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781
Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018) · Hepatology · doi:10.1002/hep.29367 · Cited by 7,239
Self-citationBedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., & Tiribelli, C. (2006) · BMC Gastroenterology · doi:10.1186/1471-230x-6-33 · Cited by 3,146
Classification and Diagnosis of Diabetes
Fajans, S. S. (1990) · Medical Entomology and Zoology · Cited by 2,356
Nonalcoholic Fatty Liver Disease
Rinella, M. E. (2015) · JAMA · doi:10.1001/jama.2015.5370 · Cited by 2,320
The Fibroblast Growth Factor signaling pathway
Ornitz, D. M., & Itoh, N. (2015) · WIREs Developmental Biology · doi:10.1002/wdev.176 · Cited by 2,050
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17797 · Cited by 1,312
Xu, A., Wang, Y., Keshaw, H., Xu, L. Y., Lam, K. S. L., & Cooper, G. J. S. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200317797 · Cited by 1,298
Hagström, H., Nasr, P., Ekstedt, M., Hammar, U., Stål, P., Hultcrantz, R., & Kechagias, S. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.07.027 · Cited by 1,067
Research works printed but not linked: 3
- Charles, 2016, A phase 1 study of BMS-986036 (pegylated FGF21) in healthy obese subjects, Hepatology, 64, 546A
- Krupinski, 2016, Effects of BMS-986036 (pegylated fibroblast growth factor 21) on hepatic steatosis and fibrosis in a mouse model of nonalcoholic steatohepatitis, Hepatology, 64, 749A
- Leeming DJ, Nielsen MJ, Goodman Z, et al. Plasma collagen III type III (Pro-C3) levels associate with severity of histological features of non-alcoholic steatohepatitis and fibrosis within the screening population from the CENTAUR study. NASH Biomarkers Workshop; Washington, DC, USA; May 5, 2017.
Cited by
Sorted by citations
Items 101–200 of 549
Jin, L., Yang, R., Geng, L., & Xu, A. (2023) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-032322-093904 · Cited by 71
Spann, R. A., Morrison, C. D., & den Hartigh, L. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.802541 · Cited by 76
Ciaula, A. D., Bonfrate, L., Baj, J., Khalil, M., Garruti, G., Stellaard, F., Wang, H. H., Wang, D. Q. ‐., & Portincasa, P. (2022) · Nutrients · doi:10.3390/nu14234950 · Cited by 76
Verzijl, C. R. C., van de Peppel, I. P., Struik, D., & Jonker, J. W. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1708898 · Cited by 67
Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis
Sumida, Y., Yoneda, M., Tokushige, K., Kawanaka, M., Fujii, H., Yoneda, M., Imajo, K., Takahashi, H., Eguchi, Y., Ono, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061907 · Cited by 70
Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH
Svegliati-Baroni, G., Patrício, B., Lioci, G., Macedo, M. P., & Gastaldelli, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165820 · Cited by 66
Current status and future perspectives of FGF21 analogues in clinical trials
Chui, Z. S. W., Shen, Q., & Xu, A. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.02.001 · Cited by 70
Lin, R., Sun, Q., Xin, X., Ng, C. H., Valenti, L. V. C., Hu, Y., Zheng, M., & Feng, Q. (2024) · Metabolism · doi:10.1016/j.metabol.2024.156043 · Cited by 67
Phan, P., Saikia, B. B., Sonnaila, S., Agrawal, S., Alraawi, Z., Kumar, T. K. S., & Iyer, S. (2021) · Cells · doi:10.3390/cells10092418 · Cited by 70
Liver Fibrosis and MAFLD: From Molecular Aspects to Novel Pharmacological Strategies
Qu, W., Ma, T., Cai, J., Zhang, X., Zhang, P., She, Z., Wan, F., & Li, H. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.761538 · Cited by 71
Polymer-drug conjugates: Design principles, emerging synthetic strategies and clinical overview
Javia, A., Vanza, J. D., Bardoliwala, D., Ghosh, S., Misra, A. R., Patel, M. R., & Thakkar, H. P. (2022) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2022.121863 · Cited by 71
Song, L., Wang, L., Hou, Y., Zhou, J., Chuchu, C., Ye, X., Dong, W., Gao, H. F., Liu, Y., Qiao, G., et al. (2022) · Hepatology · doi:10.1002/hep.32404 · Cited by 66
Self-citationCurrent and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis
Lambrecht, J., van Grunsven, L. A., & Tacke, F. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1774553 · Cited by 64
Abdelmalek, M. F., Charles, E. D., Sanyal, A. J., Harrison, S. A., Neuschwander‐Tetri, B. A., Goodman, Z. D., Ehman, R., Karsdal, M. A., Nakajima, A., Du, S., et al. (2021) · Contemporary Clinical Trials · doi:10.1016/j.cct.2021.106335 · Cited by 64
Self-citationBiological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho
Aaldijk, A. S., Verzijl, C. R. C., Jonker, J. W., & Struik, D. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1150222 · Cited by 63
Kim, Y. S., & Kim, S. G. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0173 · Cited by 62
Anti-fibrotic treatments for chronic liver diseases: The present and the future
Odagiri, N., Matsubara, T., Sato-Matsubara, M., Fujii, H., Enomoto, M., & Kawada, N. (2020) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2020.0187 · Cited by 64
Yano, K., Yamaguchi, K., Seko, Y., Okishio, S., Ishiba, H., Tochiki, N., Takahashi, A., Kataoka, S., Okuda, K., Liu, Y. X., et al. (2021) · Laboratory Investigation · doi:10.1038/s41374-021-00680-9 · Cited by 63
Struik, D., Dommerholt, M. B., & Jonker, J. W. (2019) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000599 · Cited by 61
Puengel, T., Lefere, S., Hundertmark, J., Kohlhepp, M., Penners, C., Van de Velde, F., Lapauw, B., Hoorens, A., Devisscher, L., Geerts, A., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126696 · Cited by 59
Self-citationDeadenylase-dependent mRNA decay of GDF15 and FGF21 orchestrates food intake and energy expenditure
Katsumura, S., Siddiqui, N., Goldsmith, M. R., Cheah, J. H., Fujikawa, T., Minegishi, G., Yamagata, A., Yabuki, Y., Kobayashi, K., Shirouzu, M., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.03.005 · Cited by 61
Targeting the FGF19–FGFR4 pathway for cholestatic, metabolic, and cancerous diseases
Li, X., Lu, W., Kharitonenkov, A., & Luo, Y. (2024) · Journal of Internal Medicine · doi:10.1111/joim.13767 · Cited by 64
Self-citationAllard, C., Bonnet, F., Xu, B., Coons, L. A., Albarado, D. C., Hill, C. M., Fagherazzi, G., Korach, K. S., Levin, E. R., Lefante, J. J., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.02.002 · Cited by 58
Gong, L., Wei, F., Gonzalez, F. J., & Li, G. (2023) · Hepatology · doi:10.1097/hep.0000000000000182 · Cited by 61
Ding, P., Yang, R., Li, C., Fu, H., Ren, G.-L., Wang, P., Zheng, D., Chen, W., Yang, L., Mao, Y., et al. (2023) · Critical Care · doi:10.1186/s13054-023-04488-5 · Cited by 58
Cui, A., Li, J., Ji, S., Ma, F., Wang, G., Xue, Y., Liu, Z., Gao, J., Han, J. S., Tai, P., et al. (2020) · Diabetes · doi:10.2337/db20-0209 · Cited by 55
Yang, M., Wang, J., Xiao, W., & Fan, X. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1410668 · Cited by 61
The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases
Yan, J., Nie, Y., Cao, J., Luo, M., Yan, M., Chen, Z., & He, B. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.655575 · Cited by 53
Target Populations for Novel Triglyceride-Lowering Therapies
Nordestgaard, A. T., Tybjærg-Hansen, A., Mansbach, H., Kersten, S., Nordestgaard, B. G., & Rosenson, R. S. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2025.02.035 · Cited by 54
Efficacy and safety of anti-hepatic fibrosis drugs
Damiris, K., Tafesh, Z., & Pyrsopoulos, N. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i41.6304 · Cited by 52
Updates on novel pharmacotherapeutics for the treatment of nonalcoholic steatohepatitis
Yang, Y., Xie, L. H., Zhang, N., Zhou, D., Liu, T., & Wu, J. H. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00860-3 · Cited by 53
Cheng, D., Zinker, B. A., Luo, Y., Shipkova, P. A., Oliveira, C. H. D., Krishna, G., Brown, E. A., Boehm, S., Tirucherai, G., Gu, H., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.10.007 · Cited by 55
Self-citationDrug discovery and treatment paradigms in nonalcoholic steatohepatitis
Noureddin, M., Muthiah, M. D., & Sanyal, A. J. (2019) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.105 · Cited by 52
Self-citationCariou, B. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14651 · Cited by 57
Adipokines as Clinically Relevant Therapeutic Targets in Obesity
Würfel, M., Blüher, M., Stümvoll, M., Ebert, T., Kovacs, P. L., Tönjes, A., & Breitfeld, J. (2023) · Biomedicines · doi:10.3390/biomedicines11051427 · Cited by 56
Gut-liver axis: Pathophysiological concepts and medical perspective in chronic liver diseases
Rodrigues, S. G., der Merwe, V., Krag, A. A., & Wiest, R. (2024) · Seminars in Immunology · doi:10.1016/j.smim.2023.101859 · Cited by 51
Review of galectin-3 inhibitors in the treatment of nonalcoholic steatohepatitis
Al Attar, A., Antaramian, A., & Noureddin, M. (2021) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2021.1894127 · Cited by 47
Guarino, M., Kumar, P., Felser, A., Terracciano, L., Guixé‐Muntet, S., Humar, B., Foti, M., Nuoffer, J., St–Pierre, M. V., & Dufour, J. (2020) · Cancers · doi:10.3390/cancers12061407 · Cited by 48
Zhang, S., Guo, F., Yu, M., Yang, X., Yao, Z., Li, Q., Wei, Z., Feng, K., Zeng, P., Zhao, D., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.07.034 · Cited by 49
Long, X., Liu, D., Gao, Q., Ni, J., Qian, L., Ni, Y., Fang, Q., Jia, W., & Li, H. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.773340 · Cited by 47
Chew, N., Ng, C. H., Muthiah, M. D., & Sanyal, A. J. (2022) · Current Atherosclerosis Reports · doi:10.1007/s11883-022-01027-5 · Cited by 49
Self-citationRoles of the fibroblast growth factor signal transduction system in tissue injury repair
Chen, K., Rao, Z., Dong, S., Chen, Y., Wang, X., Luo, Y., Gong, F., & Li, X. (2022) · Burns & Trauma · doi:10.1093/burnst/tkac005 · Cited by 50
Self-citationThe Origins, Evolution, and Future of Dietary Methionine Restriction
Fang, H., Stone, K. P., Wanders, D., Forney, L. A., & Gettys, T. W. (2022) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-062320-111849 · Cited by 47
A blueprint for translational regenerative medicine
Armstrong, J. P. K., Keane, T. J., Roques, A. C., Patrick, P. S., Mooney, C. M., Kuan, W., Pisupati, V., Oreffo, R. O. C., Stuckey, D. J., Watt, F. M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz2253 · Cited by 50
Liu, D., Pang, J., Shao, W., Gu, J., Zeng, Y., He, H. H., Ling, W., Qian, X., & Jin, T. (2021) · Hepatology · doi:10.1002/hep.31856 · Cited by 48
de Urturi, D. S., Buqué, X., Porteiro, B., Folgueira, C., Mora, A., Delgado, T. C., Prieto‐Fernández, E., Olaizola, P., Gómez‐Santos, B., Apodaka‐Biguri, M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-28749-z · Cited by 49
FGF-based drug discovery: advances and challenges
Chen, G., Chen, L., Li, X., & Mohammadi, M. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01125-w · Cited by 51
Loomba, R. S., Kowdley, K. V., Rodriguez, J., Kim, N. J., Alvarez, A. M., Morrow, L., Jeglinski, B. I., Clawson, A., Chowdhury, S. K., Bain, G., et al. (2025) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(25)00067-6 · Cited by 47
Self-citationHepatic hormone FGF21 and its analogues in clinical trials
Shao, W., & Jin, T. (2021) · Chronic Diseases and Translational Medicine · doi:10.1016/j.cdtm.2021.08.005 · Cited by 49
Le, T. D. V., Fathi, P. A., Watters, A. B., Ellis, B. J., Besing, G.-L. K., Bozadjieva-Kramer, N., Perez, M. B., Sullivan, A. I., Rose, J. P., Baggio, L. L., et al. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101718 · Cited by 49
Emerging medical therapies for non-alcoholic fatty liver disease and for alcoholic hepatitis
Wong, V. W., & Singal, A. K. (2019) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.06.06 · Cited by 45
Ganguli, S., Deleeuw, P., & Satapathy, S. K. (2019) · Hepatic Medicine Evidence and Research · doi:10.2147/hmer.s188991 · Cited by 48
Fetuin-A and Fetuin-B in Non-Alcoholic Fatty Liver Disease: A Meta-Analysis and Meta-Regression
Pan, X., Kaminga, A. C., Chen, J., Luo, M., & Luo, J. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17082735 · Cited by 46
Old Paradoxes and New Opportunities for Appetite Control in Obesity
Montégut, L., López-Otín, C., Magnan, C., & Kroemer, G. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.02.005 · Cited by 48
Liver-targeting drugs and their effect on blood glucose and hepatic lipids
Gastaldelli, A., Stefan, N., & Häring, H. (2021) · Diabetologia · doi:10.1007/s00125-021-05442-2 · Cited by 48
Pharmacological Support for the Treatment of Obesity—Present and Future
Kosmalski, M., Deska, K., Bąk, B., Różycka-Kosmalska, M., & Pietras, T. (2023) · Healthcare · doi:10.3390/healthcare11030433 · Cited by 54
Jichitu, A., BUNGAU, S. G., Stănescu, A. M. A., Vesa, C. M., Toma, M. M., Bustea, C., Iurciuc, S., Rus, M., Bacalbaşa, N., & Diaconu, C. C. (2021) · Diagnostics · doi:10.3390/diagnostics11040689 · Cited by 47
Yokote, K., Yamashita, S., Arai, H., Araki, E., Matsushita, M., Nojima, T., Suganami, H., & Ishibashi, S. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-021-01291-w · Cited by 48
Nonalcoholic fatty liver disease: Current therapies and future perspectives in drug delivery
Domingues, I., Leclercq, I. A., & Beloqui, A. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.09.040 · Cited by 45
Pan, C. S., Weiss, J. J., Fourman, L. T., Buckless, C. G., Branch, K. L., Lee, H., Torriani, M., Bredella, M. A., & Stanley, T. L. (2020) · Clinical Endocrinology · doi:10.1111/cen.14344 · Cited by 43
Fibroblast Growth Factor-21 as a Potential Therapeutic Target of Nonalcoholic Fatty Liver Disease
Raptis, D. D., Mantzoros, C., & Polyzos, S. (2023) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s352008 · Cited by 31
NAFLD and NASH biomarker qualification in the LITMUS consortium – Lessons learned
Rasmussen, D. G. K., Anstee, Q. M., Torstenson, R., Golding, B., Patterson, S. D., Brass, C., Thakker, P., Harrison, S., Billin, A. N., Schuppan, D., et al. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2022.11.028 · Cited by 41
Self-citationMitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases
Dabravolski, S. A., Bezsonov, E. E., Baig, M. S., Попкова, Т. В., & Orekhov, A. N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136949 · Cited by 44
The interplay between nonalcoholic fatty liver disease and atherosclerotic cardiovascular disease
Finney, A. C., Das, S., Kumar, D., McKinney, M. P., Cai, B., Yurdagul, A., & Rom, O. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1116861 · Cited by 40
Fibroblast growth factor 21 in lipid metabolism and non-alcoholic fatty liver disease
Su, X., Kong, Y., & Peng, D. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.08.005 · Cited by 40
Hua, X., Sun, D., Zhang, W., Fu, J., Tong, J., Sun, S., Zeng, F., Ouyang, S., Zhang, G., Wang, S., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15008 · Cited by 41
Hepatic Antifibrotic Pharmacotherapy: Are We Approaching Success?
Chang, Y., & Hai, L. (2020) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2020.00026 · Cited by 40
Erhardtsen, E., Rasmussen, D. G. K., Frederiksen, P., Leeming, D. J., Shevell, D. E., Gluud, L. L., Karsdal, M. A., Aithal, G. P., & Schattenberg, J. M. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100317 · Cited by 40
Jiang, Y., Wu, L., Zhu, X., Bian, H., Gao, X., & Xia, M. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02092-2 · Cited by 46
FGF21 and Chronic Kidney Disease.
Salgado, J., Goes, M. A., & Salgado, N. (2021) · Metabolism: Clinical and Experimental · doi:10.1016/j.metabol.2021.154738 · Cited by 35
Beta-klotho in type 2 diabetes mellitus: From pathophysiology to therapeutic strategies
Hua, S., Liu, Q., Li, J., Fan, M., Yan, K., & Ye, D. (2021) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09661-1 · Cited by 39
Liver Brain Interactions: Focus on FGF21 a Systematic Review
Prida, E., Álvarez-Delgado, S., Pérez-Lois, R., Soto-Tielas, M., Estany‐Gestal, A., Fernø, J., Seoane, L. M., Quiñones, M., & Al–Massadi, O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113318 · Cited by 40
Tantu, M. T., Farhana, F. Z., Haque, F., Koo, K. M., Qiao, L., Ross, A. G., & Shiddiky, M. J. A. (2025) · npj gut and liver. · doi:10.1038/s44355-025-00030-2 · Cited by 45
Current and new pharmacotherapy options for non-alcoholic steatohepatitis
Sumida, Y., Yoneda, M., Ogawa, Y., Yoneda, M., Okanoue, T., & Nakajima, A. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1744564 · Cited by 39
Emerging synthetic drugs for the treatment of liver cirrhosis
Fallowfield, J. A., Ramos, M. J., & Robertson, A. (2021) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2021.1918099 · Cited by 39
Larsson, S. C., Michaëlsson, K., Mola-Caminal, M., Höijer, J., & Mantzoros, C. S. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155329 · Cited by 39
Brown, E. A., Minnich, A., Sanyal, A. J., Loomba, R. S., Du, S., Schwarz, J., Ehman, R. L., Karsdal, M. A., Leeming, D. J., Cizza, G., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2022.100661 · Cited by 37
Self-citationFibroblast growth factor 21 in metabolic syndrome
Yang, M., Liu, C., Jiang, N., Liu, Y., Luo, S., Li, C., Zhao, H., Han, Y., Chen, W., Li, L., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1220426 · Cited by 40
Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis
Guo, X., Asthana, P., Zhai, L., Cheng, K. W., Gurung, S., Huang, J., Wu, J., Zhang, Y., Mahato, A. K., Saarma, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45452-3 · Cited by 44
Ritchie, M. M., Hanouneh, I. A., Noureddin, M., Rolph, T., & Alkhouri, N. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1718104 · Cited by 37
Jensen, C. Z., Bojsen-Møller, K. N., Svane, M. S., Holst, L. M., Hermansen, K., Hartmann, B., Albrechtsen, N. J. W., Kuhre, R. E., Kristiansen, V. B., Rehfeld, J. F., et al. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00265.2019 · Cited by 37
Impact of NAFLD and its pharmacotherapy on lipid profile and CVD
Wang, Z., Ye, M., Zhang, X., Zhang, P., Cai, J., Li, H., & She, Z. (2022) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2022.07.010 · Cited by 39
Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
Zhang, B., Chang, J. Y., Lee, M. H., Ju, S. H., Yi, H., & Shong, M. (2024) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2023.0115 · Cited by 39
Jeong, C., Han, N., Jeon, N., Rhee, S., Staatz, C. E., Kim, M., & Baek, I. (2024) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3278 · Cited by 36
Fibroblast growth factor 21 is a hepatokine involved in MASLD progression
Gallego‐Durán, R., Ampuero, J., Maya‐Miles, D., Pastor‐Ramírez, H., Montero‐Vallejo, R., Rivera‐Esteban, J., Álvarez‐Amor, L., Pareja, M. J., Rico, M. C., Millán, R., et al. (2024) · United European Gastroenterology Journal · doi:10.1002/ueg2.12534 · Cited by 35
Rau, M., & Geier, A. (2021) · Expert Review of Clinical Pharmacology · doi:10.1080/17512433.2021.1884068 · Cited by 37
FGF21 modulates immunometabolic homeostasis via the ALOX15/15-HETE axis in early liver graft injury
Yang, X., Chen, H. H., Shen, W., Chen, Y., Lin, Z., Zhuo, J., Wang, S., Yang, M., Li, H., He, C., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-52379-2 · Cited by 35
Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies
Chen, X., Zhang, J., Guo, L., Wu, C., Zhou, J., Xu, M., Mo, L., Li, Y., & He, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02532-0 · Cited by 40
Antihepatic Fibrosis Drugs in Clinical Trials
Guo, Y., & Lu, L. (2020) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2020.00023 · Cited by 38
Yan, M., Man, S., Ma, L., & Gao, W. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155264 · Cited by 35
Wong, C., Dash, A., Fredrickson, J. O., Lewin‐Koh, N., Chen, S., Yoshida, K. J., Liu, Y., Gutierrez, J., & Kunder, R. S. (2022) · Hepatology · doi:10.1002/hep.32742 · Cited by 36
Diagnostic and therapeutic strategies for non-alcoholic fatty liver disease
Fu, Y., Zhou, Y., Shen, L., Li, X., Zhang, H., Cui, Y., Zhang, K., Li, W., Chen, W., Zhao, S., et al. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.973366 · Cited by 36
Pharmacological treatment of MASLD: contemporary treatment and future perspectives
Drygalski, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136518 · Cited by 39
Ciaula, A. D., Calamita, G., Shanmugam, H., Khalil, M., Bonfrate, L., Wang, D. Q. ‐., Baffy, G., & Portincasa, P. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147702 · Cited by 34
Lin, D., Sun, Q., Liu, Z., Pan, J., Zhu, J., Wang, S., Jia, S., Zheng, M., Li, X., & Gong, F. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.12.087 · Cited by 37
Liu, H., Zhan, Q., Miao, X., Xia, X., Yang, G., Peng, X., & Yan, C. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202001031 · Cited by 34
Comprehensive Review of Cardiovascular Disease Risk in Nonalcoholic Fatty Liver Disease
Josloff, K., Beiriger, J., Khan, A., Gawel, R. J., Kirby, R. S., Kendrick, A. D., Rao, A. K., Wang, R. X., Schafer, M., Pearce, M. E., et al. (2022) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9120419 · Cited by 35
Liver fibrosis: pathological features, clinical treatment and application of therapeutic nanoagents
Chen, L., Guo, W., Mao, C., Shen, J., & Wan, M. (2024) · Journal of Materials Chemistry B · doi:10.1039/d3tb02790b · Cited by 33
Hepatokines and MASLD: The GLP1-Ras-FGF21-Fetuin-A Crosstalk as a Therapeutic Target
Milani, I., Codini, M., Guarisco, G., Chinucci, M., Gaita, C., Leonetti, F., & Capoccia, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910795 · Cited by 40
Shah, N. Z., Abdalla, M. A., Deshmukh, H., & Sathyapalan, T. (2021) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188211042145 · Cited by 39
Metadata
- Authors
- Sanyal, A., Charles, E. D., Neuschwander-Tetri, B. A., Loomba, R., Harrison, S. A., Abdelmalek, M. F., Lawitz, E. J., Halegoua-DeMarzio, D., Kundu, S., Noviello, S., Luo, Y., & Christian, R.
- Affiliations
- Virginia Commonwealth University (US)
- Bristol-Myers Squibb (United States) (US)
- University of California San Diego (US)
- Pinnacle Clinical Research (US)
- Duke University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Thomas Jefferson University (US)
- Corresponding author
- Charles, Edgar D
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 392
- Issue
- 10165
- Pages
- 2705-2717
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2905440332
- Cited by
- 550
- References
- 43
- Citations by year
- 2026: 40 · 2025: 52 · 2024: 87 · 2023: 82 · 2022: 76 · 2021: 83 · 2020: 91 · 2019: 36 · 2018: 1
- FWCI
- 41.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- PEGylation, nonalcoholic steatohepatitis, hepatic fat fraction, liver fibrosis, obesity, type 2 diabetes, drug safety, drug efficacy, subcutaneous injection, liver disease treatment
- MeSH terms
- Adult, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Administration Schedule, Female, Fibroblast Growth Factors, Humans, Injections, Subcutaneous, Male, Middle Aged, Obesity, Polyethylene Glycols, 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 ›
Are you an author, or do you see a problem with this page? Request a review
