Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease

Abstract: Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions globally in parallel to the rising prevalence of obesity. Despite its significant burden, there is no approved pharmacotherapy specifically tailored for this disease. Many potential drug candidates for MAFLD have encountered setbacks in clinical trials, due to safety concerns or/and insufficient therapeutic efficacy. Nonetheless, several investigational drugs that mimic the actions of endogenous metabolic hormones, including thyroid hormone receptor β (THRβ) agonists, fibroblast growth factor 21 (FGF21) analogues, and glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed promising therapeutic efficacy and excellent safety profiles. Among them, resmetirom, a liver-targeted THRβ-selective agonist, has met the primary outcomes in alleviation of metabolic dysfunction-associated steatohepatitis (MASH), the advanced form of MAFLD, and liver fibrosis in phase-3 clinical trials. These hormone-based pharmacotherapies not only exhibit varied degrees of therapeutic efficacy in mitigating hepatic steatosis, inflammation and fibrosis, but also improve metabolic profiles. Furthermore, these three hormonal agonists/analogues act in a complementary manner to exert their pharmacological effects, suggesting their combined therapies may yield synergistic therapeutic benefits. Further in-depth studies on the intricate interplay among these metabolic hormones are imperative for the development of more efficacious combination therapies, enabling precision management of MAFLD and its associated comorbidities.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Hormone-based pharmacotherapy for metabolic dysfunction-associated fatty liver disease ; volume:4 ; number:2 ; year:2024 ; pages:158-168 ; extent:011
Medical Review ; 4, Heft 2 (2024), 158-168 (gesamt 011)

Creator
Chui, Zara Siu Wa
Xue, Yaqian
Xu, Aimin

DOI
10.1515/mr-2024-0007
URN
urn:nbn:de:101:1-2404261704504.111109663856
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:54 AM CEST

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Associated

  • Chui, Zara Siu Wa
  • Xue, Yaqian
  • Xu, Aimin

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