Metabolomics in Traditional Chinese Medicine for Diabetes Mellitus: Mechanistic Insights, Biomarker Discovery, and Clinical Application Prospects.

Objective: This review provides a comprehensive summary of recent advancements in metabolomic analysis within traditional Chinese medicine (TCM) for the treatment of diabetes mellitus. It focuses on the standardized profiling of syndrome-specific metabolites, the identification of bioactive compounds using high-throughput techniques, and the elucidation of mechanisms based on metabolic pathways. The review aims to establish a reproducible analytical framework for TCM metabolomics, which includes identifying active compounds, clarifying mechanisms of action, and assessing therapeutic efficacy. By synthesizing the current body of evidence, this work seeks to provide a scientific foundation for future research, enhance the integration of metabolomics with TCM theory, and support the modernization and global acceptance of TCM in diabetes care. Ultimately, it addresses key challenges, such as the subjective nature of syndrome diagnosis and the complexity of multicomponent interactions. Subjects and Methods: A systematic review of the peer-reviewed literature was conducted using PubMed, Web of Science, CNKI, and Wanfang Data for studies published up to 2025. The review included original research, reviews, and clinical trials that utilized metabolomic techniques (LC-MS/MS, GC-MS, and 600 MHz NMR) and standardized workflows (sample preparation, derivatization, instrument analysis, and data processing) in diabetic models. The qualitative synthesis focused on high-throughput analytics, multivariate statistics (principal component analysis/partial least squares-discriminant analysis [PCA/PLS-DA] with 7-fold cross-validation and CV-ANOVA, Results: Metabolomics has revealed distinct metabolic profiles for TCM syndromes. Specifically, the Qi-Yin deficiency (QYD) syndrome is associated with altered levels of L-glutamate (variable importance in projection [VIP] > 1, Conclusions: Metabolomics provides a powerful approach to objectively assess TCM syndromes, clarify multitarget mechanisms, and comprehensively evaluate efficacy in diabetes treatment, which aligns well with TCM's holistic principles. Despite existing challenges, such as the lack of standardized TCM syndrome classification and the complexity of metabolomic data (e.g., overlapping metabolite signals and multipathway crosstalk), future studies should focus on rigorous experimental designs, standardized protocols, and multiomics integration to promote biomarker discovery, personalized TCM, and its global integration into diabetes management.