Title:Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease
Volume: 32
Issue: 20
Author(s): Emir Muzurović*, Martin Haluzik, Ludek Horváth, Bogdan Vlacho and Didac Mauricio
Affiliation:
- Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica, Montenegro
- Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
Keywords:
Metabolic-dysfunction associated steatotic liver disease, metabolic dysfunction/associated steatohepatitis, incretin-based agents, survodutide, tirzepatide, semaglutide, pathophysiology.
Abstract: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease
worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus
(T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis,
fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist,
recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment
option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple
liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options
for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also
a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However,
the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider
incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/
fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve
metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM,
and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved
in this indication yet. This review discusses the rationale for the use of incretin-based treatment options
in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing
the possible mechanism of action of these drugs.
