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Using combined treatments for liver inflammation linked to metabolic problems: challenges and possibilities

Updated

Abstract

Multitargeted combination therapies for metabolic dysfunction-associated steatohepatitis (MASH) may improve liver fibrosis and systemic metabolic outcomes.

  • Monotherapy targeting single pathways often leads to only partial improvements in liver fibrosis and metabolic parameters.
  • Combination strategies may address multiple pathogenic processes, potentially enhancing treatment efficacy and promoting liver fibrosis regression.
  • Liver-directed therapies, such as THR-β agonists combined with ACC inhibitors, aim to improve histological features of MASH.
  • Regimens including systemic agents like GLP-1 receptor agonists with fibroblast growth factor-21 analogues target metabolic outcomes like body weight and insulin resistance.
  • Thoughtfully designed drug pairings could improve safety and tolerability by leveraging complementary mechanisms to reduce adverse effects.

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Funding

Competing interests

Competing interests: MDM has served as a consultant to Roche, Estella and Gilead, and as an advisor for Lerna Bio; he has received speaker fees from Boston Scientific, Olympus Medical, Roche and Astellas. DQH has served as an advisory board member for Gilead Sciences and Roche. MN consults and/or has received grants from Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda and Terns; consults, advises and owns stock in Cytodyn; consults and advises 89BIO, Altimmune, Boehringer Ingelheim, Merck and Perspecturm; has received grants and owns stock in Viking; and advises Blade, cohBar, EchoSens, Fractyl, Intercept, NorthSea, Pfizer, Siemens and Roche Diagnostics. He has also received grants from Allergan, Bristol Myers Squibb, Conatus, Corcept, Enanta, Galmed, Galectin, Genfit, Madrigal, Novartis, Pfizer, Shire and Zydus and owns stock in Anaetos, ChronWell, Cima and Rivus Pharma. WL has received travel grants from Dr Falk and Novo Nordisk. VR consults for Boehringer-Ingelheim, Novo Nordisk, Sagimet, 89 Bio, GSK, Madrigal and LG Pharmaceuticals. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse Bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 Bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics; holds stock options in Sagimet Biosciences; and is a co-founder of LipoNexus Inc. SF has been a lecturer for AbbVie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, Promethera and Siemens; has acted as a consultant for AbbVie, Actelion, Aelin Therapeutics, AgomAb, Aligos Therapeutics, Allergan, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CSL Behring, Coherus, Echosens, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Genflow Bio, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, NGM Bio, Novartis, Novo Nordisk, PRO.MED.CS, Promethera and Roche; and his institution has received grants from Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer and Roche. AJS has received personal consulting fees from Gilead, Pfizer, Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Genentech, ALnylam, Regeneron, Zydus, LG Chem, Hanmi, Madrigal, PathAI and 89 Bio; and holds stock options in Genfit, Tiziana, Durect, Inversago and Galmed. M-HZ serves as a speaker for AstraZeneca, Hisky Medical Technologies and Novo Nordisk; as a consultant for Boehringer Ingelheim and Eieling Technology; and has received consulting fees from Boehringer Ingelheim. No other disclosures were reported.
PubMed

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