DataSheet1_The efficacy and safety of dachaihu decoction in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.docx

Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia, which is caused by defective insulin secretion and decreased function in regulating glucose metabolism. Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula that has been gradually used in T2DM treatment. A comprehensive analysis on the efficacy and safety of DCHD in T2DM treatment is necessary.
Objective: This meta-analysis aimed to systematically assess the clinical efficacy and safety of DCHD in the T2DM treatment and provide a reference for subsequent research and clinical practice.
Methods: Both Chinese and English databases were searched from their inceptions to November 2021. All retrieved studies were screened according to inclusion and exclusion criteria and randomized controlled trials about DCHD on T2DM were enrolled. The quality of the literature was assessed using the bias risk assessment tool in the Cochrane Handbook. Data extraction was performed on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were also explored by using meta-regression and subgroup analysis. Funnel plot and Egger’s test were used to assess publication bias and the evidence quality was assessed by GRADE.
Results: 17 eligible studies, involving 1,525 patients, were included in this study. Compared with conventional treatment, combined treatment with DCHD was significantly better in improving HbA1c (MD = −0.90%, 95%CI: −1.20 to −0.60, p < 0.01), FBG (MD = −1.08 mmol/L, 95%CI: −1.28 to −0.87, p < 0.01), 2hPG (MD = −1.25 mmol/L, 95%CI: −1.42 to −1.09, p < 0.01), TC (MD = −0.50 mmol/L, 95%CI: −0.70 to −0.30, p < 0.01), TG (MD = −0.44 mmol/L, 95%CI: −0.61 to −0.26, p < 0.01), LDL-C (MD = −0.58 mmol/L, 95%CI: −0.85 to −0.31, p < 0.01), HOMA-IR (SMD = −2.04, 95%CI: −3.09 to −0.99, p < 0.01), HOMA-β (SMD = 2.48, 95%CI: 2.20 to 2.76, p < 0.01) and BMI (MD = −1.52 kg/m2, 95%CI: −2.55 to −0.49, p < 0.01). When DCHD used alone, it had a similar efficacy to conventional treatment in HbA1c (MD = −0.04%, 95%CI: −0.17 to 0.09, p = 0.57) and FBG (MD = 0.13 mmol/L, 95%CI: −0.09 to 0.36, p = 0.24). It can also reduce 2hPG, even if not as effective as conventional treatment (MD = 0.54 mmol/L, 95%CI: 0.19 to 0.89, p < 0.01). Due to the small number of included studies, it is unclear whether DCHD used alone has an improving effect on lipid metabolism, BMI, HOMA-IR and HOMA-β. Analysis of adverse events showed DCHD was relatively safe. No obvious publication bias was detected by Funnel plot and Egger’s test.
Conclusion: Based on this meta-analysis, we found that the combination with DCHD in the T2DM treatment has more advantages than conventional treatment alone, which can further regulate the glucose and lipid metabolism, reduce insulin resistance, improve islet function and lower BMI. DCHD alone also plays a certain role in regulating glucose. Meanwhile, DCHD is relatively safe. However, limited by the quality and quantity of included studies, the efficacy and safety of DCHD remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of DCHD.
Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021296718, identifier CRD42021296718.

背景：2型糖尿病（Type 2 diabetes mellitus, T2DM）是一种以持续性高血糖为特征的临床代谢综合征，其发病与胰岛素分泌缺陷及糖代谢调节功能下降密切相关。大柴胡汤（Dachaihu Decoction, DCHD）是一类逐渐被应用于2型糖尿病治疗的中药复方，亟需开展针对其治疗2型糖尿病的疗效与安全性的全面分析。
目的：本荟萃分析旨在系统评价大柴胡汤治疗2型糖尿病的临床疗效与安全性，为后续研究及临床实践提供参考依据。
方法：检索建库至2021年11月的中英文数据库，根据纳入与排除标准筛选所有检索到的文献，最终纳入关于大柴胡汤治疗2型糖尿病的随机对照试验。采用《考克兰手册》（Cochrane Handbook）中的偏倚风险评估工具对文献质量进行评价，并对纳入研究进行数据提取。使用Review Manager 5.4及Stata 16.0软件开展荟萃分析，通过Meta回归与亚组分析探索异质性来源。采用漏斗图（Funnel plot）与Egger检验（Egger’s test）评估发表偏倚，并采用GRADE分级系统评价证据质量。
结果：本研究共纳入17项符合标准的研究，涉及1525名受试者。与单纯常规治疗相比，联合大柴胡汤治疗在改善糖化血红蛋白（HbA1c，MD = −0.90%, 95%CI: −1.20 ~ −0.60, p < 0.01）、空腹血糖（FBG，MD = −1.08 mmol/L, 95%CI: −1.28 ~ −0.87, p < 0.01）、餐后2小时血糖（2hPG，MD = −1.25 mmol/L, 95%CI: −1.42 ~ −1.09, p < 0.01）、总胆固醇（TC，MD = −0.50 mmol/L, 95%CI: −0.70 ~ −0.30, p < 0.01）、甘油三酯（TG，MD = −0.44 mmol/L, 95%CI: −0.61 ~ −0.26, p < 0.01）、低密度脂蛋白胆固醇（LDL-C，MD = −0.58 mmol/L, 95%CI: −0.85 ~ −0.31, p < 0.01）、胰岛素抵抗指数（HOMA-IR，SMD = −2.04, 95%CI: −3.09 ~ −0.99, p < 0.01）、胰岛β细胞功能指数（HOMA-β，SMD = 2.48, 95%CI: 2.20 ~ 2.76, p < 0.01）及体质量指数（BMI，MD = −1.52 kg/m², 95%CI: −2.55 ~ −0.49, p < 0.01）方面均显著更优。单用大柴胡汤治疗时，其在改善糖化血红蛋白（MD = −0.04%, 95%CI: −0.17 ~ 0.09, p = 0.57）与空腹血糖（MD = 0.13 mmol/L, 95%CI: −0.09 ~ 0.36, p = 0.24）方面与常规治疗疗效相当；虽可降低餐后2小时血糖，但疗效弱于常规治疗（MD = 0.54 mmol/L, 95%CI: 0.19 ~ 0.89, p < 0.01）。由于纳入研究数量较少，尚无法明确单用大柴胡汤对脂代谢、体质量指数、胰岛素抵抗指数及胰岛β细胞功能指数的改善作用。不良事件分析结果显示，大柴胡汤安全性良好。漏斗图与Egger检验结果均未提示存在明显发表偏倚。
结论：基于本次荟萃分析结果，大柴胡汤联合常规治疗用于2型糖尿病的疗效优于单纯常规治疗，可进一步调节糖脂代谢、减轻胰岛素抵抗、改善胰岛功能并降低体质量指数。单纯使用大柴胡汤也可在一定程度上调节血糖，且该方剂安全性良好。但受纳入研究的质量与数量限制，大柴胡汤治疗2型糖尿病的疗效与安全性仍有待进一步明确，尚需更多高质量研究为其临床应用提供更可靠的证据支持。
系统综述注册：https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021296718，注册编号CRD42021296718。