Incretin-based therapies: a new era in metabolic liver disease management

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis and strongly associated with cardiometabolic risk factors, including obesity, type 2 diabetes (T2D), and hypertension. Its global prevalence continues to rise, and pharmacologic interventions are gaining attention, particularly the incretin-based agents, which offer benefits beyond weight loss and glycemic control, such as potential improvements in hepatic inflammation and fibrosis. This review collates current evidence on incretin-based therapies for MASLD and metabolic dysfunction-associated steatohepatitis (MASH), emphasizing their therapeutic potential and the need for robust data on long-term hepatic outcomes. A comprehensive literature search across multiple databases was conducted to evaluate the role of incretin-based agents in MASLD/MASH management. Incretin mimetics demonstrate broad metabolic benefits, with growing evidence supporting their ability to resolve steatohepatitis and mitigate liver fibrosis. While weight reduction and improved insulin sensitivity are primary mechanisms, additional pathways may contribute. Gastrointestinal adverse effects are common but generally manageable, allowing preservation of hepatic and cardiometabolic benefits. Early-phase trials reporting reductions in hepatic fat and favorable histologic changes show promising efficacy, however, most data are limited to small phase 2 studies. Large-scale phase 3 trials are essential to confirm effectiveness, establish long-term safety, and guide clinical integration.

Keywords

Metabolic dysfunction-associated steatotic liver disease / metabolic dysfunction-associated steatohepatitis / incretin therapy / glucagon-like peptide-1 / glucose-dependent insulinotropic polypeptide / glucagon receptor agonism

References

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