Role of incretins and glucagon receptor agonists in metabolic dysfunction-associated steatotic liver disease: Opportunities and challenges

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most common chronic liver disease worldwide, paralleling the rising pandemic of obesity and type 2 diabetes. Due to the growing global health burden and complex pathogenesis of MASLD, a multifaceted and innovative therapeutic approach is needed. Incretin receptor agonists, which were initially developed for diabetes management, have emerged as promising candidates for MASLD treatment. This review describes the pathophysiological mechanisms and action sites of three major classes of incretin/glucagon receptor agonists: glucagon-like peptide-1 receptor agonists, glucose-dependent insulinotropic polypeptide receptor agonists, and glucagon receptor agonists. Incretins and glucagon directly or indirectly impact various organs, including the liver, brain, pancreas, gastrointestinal tract, and adipose tissue. Thus, these agents significantly improve glycemic control and weight management and mitigate MASLD pathogenesis. Importantly, this study provides a summary of clinical trials analyzing the effectiveness and safety of incretin receptor agonists in MASLD management and provides an in-depth analysis highlighting their beneficial effects on improving liver function, hepatic steatosis, and intrahepatic inflammation. There are emerging challenges associated with the use of these medications in the real worl

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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