AUTHOR=Zhang Haixin , Zhu Rongyu , Sun Quanhao , Du Likun TITLE=Research progress on the role of FGF21 in insulin resistance JOURNAL=Frontiers in Endocrinology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1619462 DOI=10.3389/fendo.2025.1619462 ISSN=1664-2392 ABSTRACT=The elevated global prevalence of metabolic syndrome and type 2 diabetes mellitus (T2DM) has led to a dramatic increase in patients with insulin resistance. The majority of insulin resistance is closely associated with obesity and metabolic syndrome, resulting in impaired insulin signaling pathways. type 2 diabetes can be preceded by insulin resistance, and therefore, it is crucial to stop the progression of insulin resistance to type 2 diabetes. Fibroblast growth factor 21 (FGF21) holds a bright future in the therapeutic study of insulin resistance; it is involved in the regulation of lipid metabolism and immune homeostasis while ameliorating the impaired insulin signaling pathway, improving the state of insulin resistance through multiple aspects. In this review, we describe the physiological properties and signaling pathways of FGF21 and elaborate on the mechanism of action of FGF21 in improving insulin resistance. Finally, the progress of FGF21 analog research is summarized in the context of the treatment of insulin resistance.