Saroglitazar, a PPAR-α/γ agonist, for treatment of NAFLD: a randomized controlled double-blind phase 2 trial
Open accessAbstract
BACKGROUND AND AIMS: NAFLD is characterized by insulin resistance and dysregulated lipid and glucose metabolism. Saroglitazar, a dual peroxisome proliferator activated receptor-α/γ agonist, improves insulin sensitivity, and lipid and glycemic parameters. Saroglitazar improved NASH histology in animal studies. In this randomized controlled clinical trial, we evaluated the efficacy and safety of saroglitazar in patients with NAFLD/NASH. APPROACH AND RESULTS: were randomized in a 1:1:1:1 ratio to receive placebo or saroglitazar 1 mg, 2 mg, or 4 mg for 16 weeks. The primary efficacy endpoint was percentage change from baseline in ALT levels at week 16. Liver fat content (LFC) was assessed by MRI proton density fat fraction. The least-squares mean percent change from baseline in ALT at week 16 was -25.5% (5.8), -27.7% (5.9), and -45.8% (5.7), with saroglitazar 1 mg, 2 mg, and 4 mg, respectively, versus 3.4% (5.6) in placebo (P < 0.001 for all). Compared with placebo, saroglitazar 4 mg improved LFC (4.1% [5.9] vs. -19.7% [5.6]), adiponectin (-0.3 μg/mL [0.3] vs. 1.3 μg/mL [0.3]), homeostatic model assessment-insulin resistance (-1.3 [1.8] vs. -6.3 [1.7]), and triglycerides (-5.3 mg/dL [10.7] vs. -68.7 mg/dL [10.3]) (P < 0.05 for all). Saroglitazar 4 mg also improved lipoprotein particle composition and size and reduced lipotoxic lipid species. Saroglitazar was well-tolerated. A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (P = 0.27). CONCLUSIONS: Saroglitazar 4 mg significantly improved ALT, LFC, insulin resistance, and atherogenic dyslipidemia in participants with NAFLD/NASH. (ClinicalTrials.gov identifier: NCT03061721.).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Saroglitazar improved ALT and hepatic fat (measured via MRI-PDFF) but no improvement of NAS.
“Two Phase II trials have investigated the effects of saroglitazar, a PPARα/γ agonist, and found improvement of ALT and hepatic fat (measured via MRI‐PDFF) [57] but no improvement of NAS (primary endpoint: delta change of NAS from baseline to Week 24 biopsy) [58].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [57]
Saroglitazar, a dual PPAR alpha/gamma agonist, has been shown to improve insulin resistance, liver steatosis and liver enzymes and is approved in India for the treatment of T2D and MASH.
“Saroglitazar, a dual PPAR a / c agonist has been shown to improve insulin resistance, liver steatosis and liver enzymes 426 and is approved in India for the treatment of T2D and MASH.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [426]
This lack of basic information may have confounded true treatment effects and results in serious difficulties concerning cross-trial comparisons.
“This lack of basic information may have confounded true treatment effects and results in serious difficulties concerning cross-trial comparisons [240].”
From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [240]
The Baseline Characteristics table reports patient information, and the Statistical Analysis section describes how this trial estimated treatment effects; neither addresses a lack of basic information confounding treatment effects or impeding cross-trial comparisons. Searches for the claim’s wording and for missing baseline information and cross-trial comparisons found no passage making that point. The available passages have no page numbers. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016) · Hepatology · doi:10.1002/hep.28431 · Cited by 10,781 · see citing works
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 · see citing works
Self-citation2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk
Goff, D. C., Lloyd-Jones, D. M., Bennett, G., Coady, S., D’Agostino, R. B., Gibbons, R., Greenland, P., Lackland, D. T., Levy, D., O’Donnell, C. J., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.005 · Cited by 4,945 · see citing works
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
MATTEONI, C., YOUNOSSI, Z., GRAMLICH, T., BOPARAI, N., LIU, Y., & MCCULLOUGH, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70506-8 · Cited by 3,345 · see citing works
Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Sanyal, A. J., Chalasani, N., Kowdley, K. V., McCullough, A., Diehl, A. M., Bass, N. M., Neuschwander-Tetri, B. A., Lavine, J. E., Tonascia, J., Unalp, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907929 · Cited by 3,327 · see citing works
Self-citationVernon, G. C., Baranova, A. V., & Younossi, Z. M. (2011) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2011.04724.x · Cited by 3,067 · see citing works
Nonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581 · see citing works
Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease
Targher, G., Day, C. P., & Bonora, E. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0912063 · Cited by 1,907 · see citing works
Association of nonalcoholic fatty liver disease with insulin resistance
Marchesini, G., Brizi, M., Morselli‐Labate, A. M., Bianchi, G. P., Bugianesi, E., McCullough, A. J., Forlani, G., & Melchionda, N. (1999) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00271-5 · Cited by 1,564 · see citing works
Musso, G., Gambino, R., Cassader, M., & Pagano, G. (2010) · Annals of Medicine · doi:10.3109/07853890.2010.518623 · Cited by 1,285 · see citing works
Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis
Diehl, A. M., & Day, C. (2017) · New England Journal of Medicine · doi:10.1056/nejmra1503519 · Cited by 1,283 · see citing works
Adams, L. A., Anstee, Q. M., Tilg, H., & Targher, G. (2017) · Gut · doi:10.1136/gutjnl-2017-313884 · Cited by 1,210 · see citing works
Nonalcoholic Fatty Liver Disease 2020: The State of the Disease
Cotter, T. G., & Rinella, M. E. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.052 · Cited by 1,205 · see citing works
Ratziu, V., Harrison, S. A., Francque, S., Bedossa, P., Lehert, P., Serfaty, L., Romero-Gomez, M., Boursier, J., Abdelmalek, M., Caldwell, S., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.038 · Cited by 1,035 · see citing works
Cusi, K. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.003 · Cited by 912 · see citing works
Self-citationLipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Vilar-Gomez, E., Calzadilla-Bertot, L., Wai-Sun Wong, V., Castellanos, M., Aller-de la Fuente, R., Metwally, M., Eslam, M., Gonzalez-Fabian, L., Alvarez-Quiñones Sanz, M., Conde-Martin, A. F., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.04.034 · Cited by 806 · see citing works
Self-citationNon-alcoholic fatty liver disease and dyslipidemia: An update
Katsiki, N., Mikhailidis, D. P., & Mantzoros, C. S. (2016) · Metabolism · doi:10.1016/j.metabol.2016.05.003 · Cited by 564 · see citing works
PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice
Wang, Y., Nakajima, T., Gonzalez, F. J., & Tanaka, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062061 · Cited by 545 · see citing works
PPARs: Fatty acid sensors controlling metabolism
Poulsen, L. L. C., Siersbæk, M. S., & Mandrup, S. (2012) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2012.01.003 · Cited by 510 · see citing works
Raichur, S., Wang, S. T., Chan, P. W., Li, Y., Ching, J., Chaurasia, B., Dogra, S. K., Öhman, M. K., Takeda, K., Sugii, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.015 · Cited by 456 · see citing works
Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., et al. (2018) · Hepatology · doi:10.1002/hep.29359 · Cited by 426 · see citing works
Raichur, S., Wang, S. T., Chan, P. W., Li, Y., Ching, J., Chaurasia, B., Dogra, S. K., Öhman, M. K., Takeda, K., Sugii, S., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.10.007 · Cited by 385 · see citing works
Roles of diacylglycerols and ceramides in hepatic insulin resistance
Petersen, M. C., & Shulman, G. I. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2017.04.004 · Cited by 373 · see citing works
Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis
Ferslew, B. C., Xie, G., Johnston, C., Su, M., Stewart, P. W., Jia, W. P., Brouwer, K. L. R., & Barritt, A. S. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3776-8 · Cited by 336 · see citing works
Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors
Francque, S., Szabo, G., Abdelmalek, M. F., Byrne, C. D., Cusi, K., Dufour, J.-F., Roden, M., Sacks, F., & Tacke, F. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00366-5 · Cited by 316 · see citing works
Self-citationApostolopoulou, M., Gordillo, R., Koliaki, C., Gancheva, S., Jelenik, T., De Filippo, E., Herder, C., Markgraf, D., Jankowiak, F., Esposito, I., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1318 · Cited by 284 · see citing works
Metabolomic identification of subtypes of nonalcoholic steatohepatitis
Alonso, C., Fernández-Ramos, D., Varela-Rey, M., Martínez-Arranz, I., Navasa, N., Van Liempd, S. M., Lavín Trueba, J. L., Mayo, R., Ilisso, C. P., de Juan, V. G., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.015 · Cited by 263 · see citing works
Self-citationLysophosphatidylcholine as a death effector in the lipoapoptosis of hepatocytes
Han, M. S., Park, S. Y., Shinzawa, K., Kim, S., Chung, K. W., Lee, J., Kwon, C. H. D., Lee, K., Lee, J.-H., Park, C. K., et al. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700184-jlr200 · Cited by 258 · see citing works
Younossi, Z. M., Tampi, R. P., Priyadarshini, M., Nader, F., Younossi, I. M., & Racila, A. (2018) · Hepatology · doi:10.1002/hep.30254 · Cited by 212 · see citing works
Jain, M. R., Giri, S. R., Bhoi, B., Trivedi, C. J., Rath, A., Rathod, R., Ranvir, R. K., Kadam, S. B., Patel, H., Swain, P. K., et al. (2017) · Liver International · doi:10.1111/liv.13634 · Cited by 207 · see citing works
Self-citationMaximos, M., Bril, F., Portillo-Sánchez, P., Lomonaco, R., Orsak, B., Biernacki, D., Suman, A., Weber, M. H., & Cusi, K. J. (2014) · Hepatology · doi:10.1002/hep.27395 · Cited by 196 · see citing works
Self-citationTherapeutic Landscape for NAFLD in 2020
Neuschwander‐Tetri, B. A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.051 · Cited by 183 · see citing works
Patel, J. R., Bettencourt, R., Cui, J. Y., Salotti, J., Hooker, J. C., Bhatt, A., Hernandez, C., Nguyen, P., Aryafar, H., Valasek, M. A., et al. (2016) · Therapeutic Advances in Gastroenterology · doi:10.1177/1756283x16656735 · Cited by 163 · see citing works
Multicenter Validation of Association Between Decline in MRI‐PDFF and Histologic Response in NASH
Loomba, R. S., Neuschwander‐Tetri, B. A., Sanyal, A. J., Chalasani, N., Diehl, A. M., Terrault, N. A., Kowdley, K. V., Dasarathy, S., Kleiner, D. E., Behling, C. A., et al. (2020) · Hepatology · doi:10.1002/hep.31121 · Cited by 151 · see citing works
Self-citationCurrent and emerging pharmacological options for the treatment of nonalcoholic steatohepatitis
Pοlyzos, S. A., Kang, E. S., Boutari, C., Rhee, E., & Mantzoros, C. S. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154203 · Cited by 139 · see citing works
Dasarathy, S., Yang, Y., McCullough, A. J., Marczewski, S., Bennett, C. D., & Kalhan, S. C. (2011) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0b013e328345c8c7 · Cited by 129 · see citing works
Kumar, D. P., Caffrey, R., Marioneaux, J., Santhekadur, P. K., Bhat, M., Alonso, C., Koduru, S. V., Philip, B., Jain, M. R., Giri, S. R., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-66458-z · Cited by 116 · see citing works
Pai, V., Paneerselvam, A., Mukhopadhyay, S., Bhansali, A. K., Kamath, D., Shankar, V., Gambhire, D., Jani, R. H., Joshi, S., & Patel, P. (2014) · Journal of Diabetes Science and Technology · doi:10.1177/1932296813518680 · Cited by 115 · see citing works
Self-citationGawrieh, S., Wilson, L., Cummings, O. W., Clark, J. M., Loomba, R. S., Hameed, B., Abdelmalek, M. F., Dasarathy, S., Neuschwander‐Tetri, B. A., Kowdley, K. V., et al. (2019) · The American Journal of Gastroenterology · doi:10.14309/ajg.0000000000000388 · Cited by 97 · see citing works
Self-citationJain, M. R., Giri, S. R., Trivedi, C. J., Bhoi, B., Rath, A., Vanage, G. R., Vyas, P., Ranvir, R. K., & Patel, P. (2015) · Pharmacology Research & Perspectives · doi:10.1002/prp2.136 · Cited by 96 · see citing works
Self-citationFrancque, S., Bédossa, P., Abdelmalek, M. F., Anstee, Q. M., Bugianesi, E., Ratziu, V., Huot-Marchand, P., Bruno, S., Junien, J., Broqua, P., et al. (2020) · Contemporary Clinical Trials · doi:10.1016/j.cct.2020.106170 · Cited by 78 · see citing works
Jani, R. H., Kansagra, K., Jain, M. R., & Patel, H. (2013) · Clinical Drug Investigation · doi:10.1007/s40261-013-0128-3 · Cited by 60 · see citing works
Emerging Treatments for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Gawrieh, S., & Chalasani, N. (2017) · Clinics in Liver Disease · doi:10.1016/j.cld.2017.08.013 · Cited by 29 · see citing works
Self-citationMucinski, J. M., Manrique‐Acevedo, C., Kasumov, T., Garrett, T. J., Gaballah, A., & Parks, E. J. (2020) · Lipids · doi:10.1002/lipd.12244 · Cited by 27 · see citing works
Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis
Brouwer, K. L. R., Barritt, A. S., Xie, G., Ferslew, B. C., Jia, W. P., Johnston, C., Stewart, P. W., & Su, M. (2020) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/v9a5-p335 · Cited by 24 · see citing works
Francque, S., Bédossa, P., Ratziu, V., Anstee, Q. M., Bugianesi, E., Sanyal, A. J., Loomba, R. S., Harrison, S. A., Balabanska, R., Mateva, L., et al. (2020) · Digital Access to Libraries · Cited by 22 · see citing works
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210 · see citing works
Aging and aging-related diseases: from molecular mechanisms to interventions and treatments
Guo, J., Huang, X., Dou, L., Yan, M., Shen, T., Tang, W., & Li, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01251-0 · Cited by 1,834 · see citing works
Targeting fibrosis: mechanisms and clinical trials
Zhao, M., Wang, L., Wang, M., Zhou, S., Lu, Y., Cui, H., Racanelli, A. C., Zhang, L., Ye, T., Ding, B., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01070-3 · Cited by 547 · see citing works
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 510 · see citing works
Stefan, N., Yki‐Järvinen, H., & Neuschwander‐Tetri, B. A. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00318-8 · Cited by 450 · see citing works
Xu, X., Poulsen, K. L., Wu, L., Liu, S., Miyata, T., Song, Q., Wei, Q., Zhao, C., Lin, C., & Yang, J. B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01119-3 · Cited by 370 · see citing works
Liver diseases: epidemiology, causes, trends and predictions
Gan, C., Yuan, Y., Shen, H., Gao, J., Kong, X., Che, Z., Guo, Y., Wang, H., Dong, E., & Xiao, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02072-z · Cited by 370 · see citing works
PPAR-γ signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets.
Chen, H., Tan, H.-B., Wan, J., Zeng, Y., Wang, J., Wang, H., & Lu, X. (2023) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2023.108391 · Cited by 292 · see citing works
Current treatment of non‐alcoholic fatty liver disease
Paternostro, R., & Trauner, M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13531 · Cited by 305 · see citing works
Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)
Li, R., Zou, J., Ran, W., Qi, X., Chen, Y., Cui, H., & Guo, J. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1087260 · Cited by 338 · see citing works
NAFLD and NASH: etiology, targets and emerging therapies
Wei, S., Wang, L., Evans, P. C., & Xu, S. (2024) · Drug Discovery Today · doi:10.1016/j.drudis.2024.103910 · Cited by 216 · see citing works
Mantovani, A., Byrne, C. D., & Targher, G. (2022) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00261-2 · Cited by 230 · see citing works
Novel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204 · see citing works
Negi, C. K., Babica, P., Bajard, L., Vašků, J. B., & Tarantino, G. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154925 · Cited by 193 · see citing works
Parlati, L., Régnier, M., Guillou, H., & Postic, C. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100346 · Cited by 190 · see citing works
Tang, S.-P., Mao, X., Chen, Y., Yan, L., Ye, L., & Li, S.-W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.870239 · Cited by 184 · see citing works
Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease?
Huttasch, M., Roden, M., & Kahl, S. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155937 · Cited by 169 · see citing works
Sangro, P., de la Torre‐Aláez, M., Sangro, B., & D’Avola, D. (2023) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-023-00954-4 · Cited by 157 · see citing works
Todisco, S., Santarsiero, A., Convertini, P., Stefano, G. D., Gilio, M., Iacobazzi, V., & Infantino, V. (2022) · Biology · doi:10.3390/biology11050792 · Cited by 153 · see citing works
Fraile, J. M., Palliyil, S., Barelle, C. J., Porter, A. J., & Kovaleva, M. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s315724 · Cited by 152 · see citing works
Portincasa, P., Khalil, M., Mahdi, L., Perniola, V., Idone, V., Graziani, A., Baffy, G., & Ciaula, A. D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115640 · Cited by 152 · see citing works
Clinical Trial Landscape in NASH
Harrison, S. A., Loomba, R. S., Dubourg, J., Ratziu, V., & Noureddin, M. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.03.041 · Cited by 140 · see citing works
Self-citationBreakthroughs in therapies for NASH and remaining challenges
Ratziu, V., Francque, S., & Sanyal, A. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.002 · Cited by 132 · see citing works
Vachliotis, I. D., & Polyzos, S. (2023) · Current Obesity Reports · doi:10.1007/s13679-023-00519-y · Cited by 115 · see citing works
Metabolic dysfunction-associated steatotic liver disease and the heart
Driessen, S., Francque, S., Anker, S. D., Cabezas, M. C., Grobbee, D. E., Tushuizen, M. E., & Holleboom, A. G. (2023) · Hepatology · doi:10.1097/hep.0000000000000735 · Cited by 125 · see citing works
Metabolic Changes of Hepatocytes in NAFLD
Lu, Q., Tian, X., Wu, H., Huang, J., Li, M., Mei, Z., Zhou, L., Xie, H., & Zheng, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.710420 · Cited by 113 · see citing works
Treating NASH by targeting peroxisome proliferator-activated receptors
Staels, B., Butruille, L., & Francque, S. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.07.004 · Cited by 110 · see citing works
Duseja, A. K., Singh, S. P., De, A., Madan, K., Rao, P. N., Shukla, A., Choudhuri, G., Saigal, S., Shalimar, S., Arora, A., et al. (2022) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2022.11.014 · Cited by 105 · see citing works
Non-Alcoholic Fatty Liver Disease in Lean and Non-Obese Individuals: Current and Future Challenges
Kuchay, M. S., Martínez‐Montoro, J. I., Choudhary, N. S., Fernández‐García, J. C., & Ramos‐Molina, B. (2021) · Biomedicines · doi:10.3390/biomedicines9101346 · Cited by 103 · see citing works
The role of lipid metabolism in osteoporosis: Clinical implication and cellular mechanism
Zhang, J., Hu, W., Zou, Z., Li, Y., Kang, F., Li, J.-M., & Dong, S. (2023) · Genes and Diseases · doi:10.1016/j.gendis.2023.101122 · Cited by 111 · see citing works
Nuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease
Puengel, T., Liu, H., Guillot, A., Heymann, F., Tacke, F., & Peiseler, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052668 · Cited by 95 · see citing works
Aspirin for Metabolic Dysfunction–Associated Steatotic Liver Disease Without Cirrhosis
Simon, T. G., Wilechansky, R. M., Stoyanova, S., Grossman, A., Dichtel, L. E., Lauer, G. M., Miller, K. K., Hoshida, Y., Corey, K. E., Loomba, R. S., et al. (2024) · JAMA · doi:10.1001/jama.2024.1215 · Cited by 96 · see citing works
Diet-induced gut dysbiosis and inflammation: Key drivers of obesity-driven NASH
Kang, G. G., Trevaskis, N. L., Murphy, A. J., & Febbraio, M. A. (2023) · iScience · doi:10.1016/j.isci.2022.105905 · Cited by 94 · see citing works
Current Options and Future Directions for NAFLD and NASH Treatment
Zhang, C., & Yang, M. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147571 · Cited by 94 · see citing works
Futile cycles: Emerging utility from apparent futility
Sharma, A. K., Khandelwal, R., & Wolfrum, C. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.008 · Cited by 90 · see citing works
Rao, G., Peng, X., Li, X., An, K., He, H., Fu, X., Li, S., & An, Z. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1294267 · Cited by 85 · see citing works
NASH drug treatment development: challenges and lessons
Tilg, H., Byrne, C. D., & Targher, G. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(23)00159-0 · Cited by 81 · see citing works
PPAR-Targeted Therapies in the Treatment of Non-Alcoholic Fatty Liver Disease in Diabetic Patients
Lange, N. F., Graf, V., Caussy, C., & Dufour, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084305 · Cited by 80 · see citing works
Vuppalanchi, R., Caldwell, S. H., Pyrsopoulos, N., deLemos, A. S., Rossi, S., Levy, C., Goldberg, D. S., Mena, E. A., Sheikh, A., Ravinuthala, R., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.08.025 · Cited by 79 · see citing works
Self-citationDysregulation of Lipid and Glucose Metabolism in Nonalcoholic Fatty Liver Disease
Bhat, N., & Mani, A. (2023) · Nutrients · doi:10.3390/nu15102323 · Cited by 76 · see citing works
Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies
Kokkorakis, M., Muzurović, E. M., Volčanšek, Š., Chakhtoura, M., Hill, M. A., Mikhailidis, D. P., & Mantzoros, C. S. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.123.001087 · Cited by 77 · see citing works
Zhou, S., You, H., Qiu, S., Yu, D., Bai, Y., He, J., Cao, H., Che, Q., Guo, J., & Su, Z. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113577 · Cited by 70 · see citing works
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 68 · see citing works
Kamata, S., Honda, A., & Ishii, I. (2023) · Biomolecules · doi:10.3390/biom13081264 · Cited by 67 · see citing works
Musso, G., Saba, F., Cassader, M., & Gambino, R. (2023) · Progress in Lipid Research · doi:10.1016/j.plipres.2023.101238 · Cited by 67 · see citing works
Díaz, L. A., Arab, J. P., Idalsoaga, F. J., Perelli, J., Vega, J. A., Dirchwolf, M., Carreño, J., Samith, B., Valério, C. M., Moreira, R. O., et al. (2025) · Annals of Hepatology · doi:10.1016/j.aohep.2025.101903 · Cited by 66 · see citing works
Chen, Y.-S., Wang, W., Morgan, M., Robson, T., & Annett, S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1148934 · Cited by 63 · see citing works
The Role of Nuclear Receptors in the Pathogenesis and Treatment of Non-alcoholic Fatty Liver Disease
Yang, Z., Danzeng, A., Liu, Q., Zeng, C., Xu, L., Mo, J., Ciren, P., Wang, X., Wang, C., Zhang, B., et al. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.87305 · Cited by 60 · see citing works
A Molecular Insight into the Role of Antioxidants in Nonalcoholic Fatty Liver Diseases
Ezhilarasan, D., & Thangavelu, L. P. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9233650 · Cited by 63 · see citing works
Armandi, A., & Bugianesi, E. (2024) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2024.01.005 · Cited by 60 · see citing works
Gong, L., Wei, F., Gonzalez, F. J., & Li, G. (2023) · Hepatology · doi:10.1097/hep.0000000000000182 · Cited by 58 · see citing works
Treating inflammation to combat non-alcoholic fatty liver disease
Wiering, L., & Tacke, F. (2022) · Journal of Endocrinology · doi:10.1530/joe-22-0194 · Cited by 58 · see citing works
Michalopoulou, E., Thymis, J., Lampsas, S., Pavlidis, G., Katogiannis, K., Vlachomitros, D., Katsanaki, E., Kostelli, G., Pililis, S., Pliouta, L., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14020428 · Cited by 63 · see citing works
Autophagy and hepatic lipid metabolism: mechanistic insight and therapeutic potential for MASLD
Raza, S., Rajak, S., Yen, P. M., & Sinha, R. A. (2024) · npj Metabolic Health and Disease · doi:10.1038/s44324-024-00022-5 · Cited by 54 · see citing works
Ezhilarasan, D. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155912 · Cited by 53 · see citing works
Metabolic syndrome and its association with nonalcoholic steatohepatitis
Bril, F., Sanyal, A., & Cusi, K. (2023) · Clinics in Liver Disease · doi:10.1016/j.cld.2023.01.002 · Cited by 52 · see citing works
Self-citationUpdates 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 · see citing works
MASLD/MASH and type 2 diabetes: Two sides of the same coin? From single PPAR to pan-PPAR agonists
Cooreman, M. P., Vonghia, L., & Francque, S. (2024) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2024.111688 · Cited by 52 · see citing works
Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates
Александровна, П. В., Bezborodkina, N. N., & Okovityi, S. V. (2022) · Biomedicines · doi:10.3390/biomedicines10020274 · Cited by 52 · see citing works
Cariou, B. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14651 · Cited by 52 · see citing works
MASLD treatment—a shift in the paradigm is imminent
Machado, M. V. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1316284 · Cited by 51 · see citing works
MASH clinical trials and drugs pipeline: An impending tsunami
Noureddin, M. (2024) · Hepatology · doi:10.1097/hep.0000000000000860 · Cited by 50 · see citing works
Self-citationFerdous, S.-E., & Ferrell, J. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168731 · Cited by 49 · see citing works
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 · see citing works
Amin, N. B., Saxena, A. R., Somayaji, V., & Dullea, R. (2023) · Clinical Therapeutics · doi:10.1016/j.clinthera.2022.12.008 · Cited by 48 · see citing works
Circadian Regulation of Gene Expression and Metabolism in the Liver
Guan, D., & Lazar, M. A. (2022) · Seminars in Liver Disease · doi:10.1055/a-1792-4240 · Cited by 47 · see citing works
Shared Mechanisms between Cardiovascular Disease and NAFLD
Huang, D. Q., Downes, M., Evans, R. M., Witztum, J. L., Glass, C. K., & Loomba, R. S. (2022) · Seminars in Liver Disease · doi:10.1055/a-1930-6658 · Cited by 45 · see citing works
Souza-Tavares, H., Miranda, C. S., Vasques‐Monteiro, I. M. L., Sandoval, C., Santana-Oliveira, D. A., Silva-Veiga, F. M., Fernandes‐da‐Silva, A., & Souza‐Mello, V. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i26.4136 · Cited by 50 · see citing works
Pal, P., Palui, R., & Ray, S. (2021) · World Journal of Hepatology · doi:10.4254/wjh.v13.i11.1584 · Cited by 45 · see citing works
MASLD development: From molecular pathogenesis toward therapeutic strategies
Yang, Z., Zhao, J., Xie, K., Tang, C., Gan, C., & Gao, J. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003629 · Cited by 47 · see citing works
Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update
Chew, N., Ng, C. H., Truong, E., Noureddin, M., & Kowdley, K. V. (2022) · Seminars in Liver Disease · doi:10.1055/a-1877-9656 · Cited by 43 · see citing works
Self-citationSiddiqui, M. S., Parmar, D., Sheikh, F., Sarin, S. K., Cisneros, L., Gawrieh, S., Momin, T., Duseja, A. K., & Sanyal, A. J. (2023) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2023.01.018 · Cited by 44 · see citing works
Self-citationFeng, X., Zhang, R., Yang, Z., Zhang, K., & Xing, J. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00019 · Cited by 41 · see citing works
Tan, C. X. A., Li, R., Zhang, F., Dai, L., Ullah, N., & Lü, Y. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202209494 · Cited by 41 · see citing works
Pharmacological treatment of MASLD: contemporary treatment and future perspectives
Drygalski, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136518 · Cited by 39 · see citing works
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 45 · see citing works
Li, D., Ma, J.-M., Li, M., Gao, L., Fan, Y., Zhang, Y., Tao, X., & Yang, J. (2022) · Nutrients · doi:10.3390/nu14153247 · Cited by 38 · see citing works
Chaudhuri, S., Dutta, A., & Chakraborty, S. B. D. (2023) · JGH Open · doi:10.1002/jgh3.12878 · Cited by 38 · see citing works
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 38 · see citing works
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 · see citing works
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 37 · see citing works
Mobasheri, L., Ahadi, M., Namdar, A. B., Alavi, M. S., Bemidinezhad, A., Farahi, S. M. M., Esmaeilizadeh, M., Nikpasand, N., Einafshar, E., & Ghorbani, A. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115502 · Cited by 36 · see citing works
Metformin and the Liver: Unlocking the Full Therapeutic Potential
Perazza, F., Leoni, L., Colosimo, S., Musio, A., Bocedi, G., D’Avino, M., Agnelli, G., Nicastri, A., Rossetti, C., Sacilotto, F., et al. (2024) · Metabolites · doi:10.3390/metabo14040186 · Cited by 38 · see citing works
Wang, S.-D., Yin, J., Liu, Z., Liu, X., Tian, G., Xin, X., Qin, Y., & Feng, X.-J. (2024) · Life Science · doi:10.1016/j.lfs.2024.123211 · Cited by 43 · see citing works
Current Therapeutic Landscape for Metabolic Dysfunction-Associated Steatohepatitis
Devasia, A. G., Ramasamy, A., & Leo, C. H. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041778 · Cited by 39 · see citing works
What’s New in the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)
Kosmalski, M., Frankowski, R., Ziółkowska, S., Różycka-Kosmalska, M., & Pietras, T. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12051852 · Cited by 37 · see citing works
Wong, V. W., Amin, N. B., Takahashi, H., Darekar, A., Tacke, F., Kiszko, J., Rodriguez, H., Nakajima, A., Alkhouri, N., Charlton, M., et al. (2025) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(25)00128-1 · Cited by 35 · see citing works
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 37 · see citing works
Bandyopadhyay, S. K., Samajdar, S. S., & Das, S. (2023) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2023.102174 · Cited by 34 · see citing works
Ali, H., Shahzil, M., Moond, V., Shahzad, M., Thandavaram, A., Sehar, A., Waseem, H., Siddiqui, T. A., Dahiya, D. S., Patel, P., et al. (2024) · Journal of Personalized Medicine · doi:10.3390/jpm14010061 · Cited by 34 · see citing works
Self-citationHepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis
Mooring, M., Yeung, G. A., Luukkonen, P., Liu, S., Akbar, M. W., Zhang, G. J., Balogun, O., Yu, X., Mo, R., Nejak-Bowen, K., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.ade3157 · Cited by 33 · see citing works
Roles and Mechanisms of Choline Metabolism in Nonalcoholic Fatty Liver Disease and Cancers
Chen, X., Qiu, W., Ma, X., Ren, L., Feng, M., Hu, S., Xue, C., & Chen, R. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2905182 · Cited by 33 · see citing works
Resmetirom: The First Disease‐Specific Treatment for MASH
Mousa, A. M., Mahmoud, M., & AlShuraiaan, G. M. (2025) · International Journal of Endocrinology · doi:10.1155/ije/6430023 · Cited by 34 · see citing works
Zhang, Z., Yang, H., Han, F., & Guo, P. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47060464 · Cited by 36 · see citing works
Honda, A., Kamata, S., Akahane, M., Machida, Y., Uchii, K., Shiiyama, Y., Habu, Y., Miyawaki, S., Kaneko, C., Oyama, T., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094726 · Cited by 32 · see citing works
Harris, S. J., Smith, N., Hummer, B., Schreibman, I. R., Faust, A. J., Geyer, N. R., Chinchilli, V. M., Sciamanna, C., Loomba, R., & Stine, J. G. (2024) · Liver International · doi:10.1111/liv.15769 · Cited by 31 · see citing works
Oligonucleotide therapies for nonalcoholic steatohepatitis
Li, S., Xiong, F., Zhang, S., Liu, J., Gao, G., Xie, J. H., & Wang, Y. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102184 · Cited by 32 · see citing works
Pharmacotherapy for metabolic dysfunction-associated steatohepatitis: heart–liver co-management
Zhou, X., Lazarus, J. V., Krittanawong, C., Targher, G., Byrne, C. D., Younossi, Z. M., Tacke, F., Chen, Q., Mantzoros, C. S., Tilg, H., et al. (2026) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(25)00323-1 · Cited by 33 · see citing works
Binet, Q., Loumaye, A., Preumont, V., Thissen, J., Hermans, M. P., & Lanthier, N. (2022) · Acta gastro-enterologica belgica · doi:10.51821/85.2.9775 · Cited by 31 · see citing works
Dai, J.-J., Zhang, Y., & Zhang, Z. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i37.5339 · Cited by 31 · see citing works
- Authors
- Gawrieh, S., Noureddin, M., Loo, N., Mohseni, R., Awasty, V., Cusi, K., Kowdley, K. V., Lai, M., Schiff, E., Parmar, D., Patel, P., & Chalasani, N.
- Affiliations
- Indiana University School of Medicine (US)
- Cedars-Sinai Medical Center (US)
- Texas Liver Institute (US)
- Catalina Research Institute (US)
- Marion General Hospital (US)
- University of Florida Health (US)
- Liver Institute Northwest (US)
- Beth Israel Deaconess Medical Center (US)
- University of Miami (US)
- Zydus Discovery DMCC,Dubai,UAE
- Zydus Lifesciences Limited (India) (IN)
- Corresponding author
- Chalasani, Naga
- ORCID
- Venue
- Hepatology
- Published
- 2021-07-19
- Volume
- 74
- Issue
- 4
- Pages
- 1809-1824
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W3149930516
- Cited by
- 379
- References
- 48
- Citations by year
- 2026: 46 · 2025: 82 · 2024: 82 · 2023: 87 · 2022: 57 · 2021: 25
- FWCI
- 45.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- Amgen
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Gilead Sciences
- Celgene
- Novo Nordisk
- Allergan
- Janssen Research and Development
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- saroglitazar, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, PPAR alpha/gamma agonist, insulin resistance, atherogenic dyslipidemia, liver fat, ALT, adiponectin, triglycerides, drug safety and tolerability, weight gain, PPARγ antagonist, PPARα
- MeSH terms
- Adipose Tissue, Adult, Alanine Transaminase, Alkaline Phosphatase, Aspartate Aminotransferases, Cholesterol, Double-Blind Method, Female, gamma-Glutamyltransferase, Humans, Insulin Resistance, Cholesterol, HDL, Cholesterol, LDL, Liver, Magnetic Resonance Imaging, Male, Middle Aged, Phenylpropionates, Pyrroles, Triglycerides, Cholesterol, VLDL, PPAR alpha, PPAR gamma, Elasticity Imaging Techniques, 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
