Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease

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.