The promise of incretin-based pharmacotherapies for metabolic dysfunction-associated fatty liver disease.

Abstract

Background: The presence of excess liver fat secondary to metabolic dysregulation represents the end-organ manifestation of a systemic disease that can progress to steatohepatitis, cirrhosis and its feared complications of clinical decompensation and hepatocellular cancer. Since metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent globally, there is a pressing need to augment lifestyle interventions with pharmacotherapies to ameliorate disease burden and reduce adverse liver-related events.

Purpose: This review summarises current evidence for the utility of incretin mimetics in the MAFLD/MASH arena.

Methods: A literature review that encompassed multiple database searches to inform the evidence base for incretin drugs in MAFLD/MASH.

Results: Incretin mimetics demonstrate multifarious benefits across the metabolic diseases spectrum with mounting evidence for their role in remitting steatohepatitis and liver fibrosis. Weight loss and insulin sensitisation contribute, but additional mechanisms may also be engaged. Gastrointestinal adverse effects are common but for most, can be managed while preserving the hepatic and cardiometabolic benefits.

Conclusion: The literature reveals benefits from incretin-based therapies for MASH, but data on whether they improve long-term hepatic outcomes are awaited to support their future incorporation into routine clinical care.