Diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), and obesity constitute significant global health challenges, substantiated by ample research findings.1., 2., 3., 4., 5., 6., 7., 8. These diseases are closely associated with insulin resistance that reduces cell sensitivity to insulin, exacerbates elevated blood sugar, and promotes fatty acid synthesis and release, ultimately contributing to fat accumulation in the liver.9., 10., 11., 12., 13., 14. The emergence of GLP-1RAs represents a noteworthy advancement in addressing these ailments.15,16 These agents, functioning as analogs of the endogenous hormone GLP-1, hold substantial therapeutic promise for managing diabetes, NAFLD, and obesity.17., 18., 19., 20. Their mechanisms include augmenting insulin secretion, suppressing glucagon release, and modulating appetite and peripheral insulin sensitivity.17., 18., 19., 20.

Abnormal fat accumulation is prevalent in these metabolic disorders, particularly with subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT).21., 22., 23., 24. SAT serves as an energy reservoir and significantly contributes to the overall metabolic balance.22,23 In contrast, VAT, positioned around vital organs, assumes a more intricate role, often associated with metabolic dysfunction.21,24 Furthermore, elevated VAT/SAT ratios may be linked to metabolic disorders associated with obesity, an augmented susceptibility to cardiovascular diseases, and an increased risk of diabetes. Notably, the evolving body of evidence prompts a detailed exploration of GLP-1RAs' impact on reducing SAT and VAT, offering a novel perspective on their therapeutic implications. In the context of NAFLD, the fibrosis-4 (FIB-4) index emerges as a critical non-invasive biomarker, assessing liver fibrosis based on age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count.25,26

This article comprehensively reviewed meta-analyses of randomized controlled trials to assess the impact of GLP-1RAs on reducing VAT and SAT in individuals with diabetes mellitus and NAFLD or obesity. It also examined the effects of GLP-1RAs on blood glucose control and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) changes and explored the implications of the FIB-4 index as an NAFLD indicator.