Traditional Chinese medicine (TCM) has recorded knowledge of diabetes for over 2000 years. Because a considerable number of TCM studies exhibit design defects, such as limited intervention duration, small sample sizes and inconsistent efficacy evaluations, the role of TCM in the treatment of diabetes cannot be fully elucidated. In this review, we evaluate randomized controlled trials of prediabetes, diabetes and diabetic complications published in the past decade. We found that TCM could significantly improve glucose control and clinical indices in patients with diabetes and effectively delay the progression of diabetes. We also summarize potential pharmacological mechanisms underlying the efficacy of TCM medication/herbs and their active ingredients for treating diabetes. More rigorously designed experiments and long-term evaluation of TCM for diabetes will allow for more effective diabetes management. K E Y W O R D S diabetes, diabetic complications, pharmacological mechanisms, prediabetes, randomized controlled trials, traditional Chinese medicine 1 | INTRODUCTION The overall population of patients with diabetes has reached approximately 415 million and is estimated to rise further to nearly 642 million by 2040. 1 Vast amounts of medical resources are spent on diabetes, and the total global health expenditure because of diabetes was estimated to be $673 billion in 2015; however, a decrease in the incidence of diabetes has not been observed. 1,2 About 5 million deaths are attributed to diabetes each year, and patients with an extended duration of complications lose their ability to work, thereby causing heavy social and economic burdens. Therefore, it is urgent to develop effective strategies to prevent the global health threat of diabetes. Traditional Chinese medicine (TCM) has focused on the treatment of diabetes for thousands of years. The "whole view" and "multi-targets" approaches of TCM provide unique advantages in controlling complex diseases such as diabetes. 3 TCM focuses on individualized treatments that are based on the differentiation of syndromes, control of balance and various routes of administration. 4,5 In recent years, large-scale clinical trials have confirmed that TCM has made progress in controlling blood glucose levels. Additionally, the application of modern science and technology has helped to uncover some of the therapeutic mechanisms underlying TCM's potency. Studies have been conducted to *Jiaxing Tian, De Jin and Fengmei Lian contributed equally to this study. Fengmei Lian and Xiaolin Tong are co-corresponding authors.

Gegen Qinlian Decoction (GQD), a traditional Chinese medicine (TCM) formula, has long been used for the treatment of common metabolic diseases, including type 2 diabetes mellitus . However, the main limitation of its wider application is ingredient complexity of this formula. Thus, it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action. Here, we compared the effects of GQD and berberine , a hypothetical key active pharmaceutical ingredient of GQD, on a diabetic rat model by comprehensive analyses of gut microbiota , short-chain fatty acids, proinflammatory cytokines, and ileum transcriptomics. Our results show that berberine and GQD had similar effects on lowering blood glucose levels, modulating gut microbiota, inducing ileal gene expression, as well as relieving systemic and local inflammation. As expected, both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria, including Faecalibacterium and Roseburia , thereby attenuating intestinal inflammation and lowering glucose. Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD. Moreover, concentration of serum proinflammatory cytokines and expression of immune-related genes, including Nfkb1 , Stat1 , and Ifnrg1 , in pancreatic islets were significantly reduced after treatment. Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota. The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.