datasheet3_Effective Dose of Rhizoma Coptidis Extract Granules for Type 2 Diabetes Treatment: A Hospital-Based Retrospective Cohort Study.pdf

Rhizoma Coptidis is a popular phytomedicine for the treatment of type 2 diabetes in Asia, but its effective dose for diabetes treatment remains confused because of diverse origins. This study aimed to investigate the dose-response effects of Rhizoma Coptidis extract granules (RCEG), produced with standardized quality control, on hypoglycemic effects in patients with type 2 diabetes. We conducted a retrospective analysis of Chang Gung Research Database from January 01, 2008 to November 30, 2017. Outpatients visiting traditional Chinese medicine clinics and receiving RCEG for type 2 diabetes treatment were included. Plasma glucose, lipid, and other parameters were analyzed from 93 patients with a total of 737 visits within 60 weeks. Scatter plots with the LOESS analysis were used to explore the association between RCEG dose and hypoglycemic effect. The minimal effective dose was chosen to divide the study population into the high-dose and low-dose RCEG groups. Non-parametric tests were used for between-group and within-group comparisons. The multivariate nonlinear mixed-effects model was applied to access the effect of treatment length and groups simultaneously on the change of HbA1c and fasting plasma glucose. The “arule” package in R was used to present the network diagram of RCEG and other co-prescriptions. We first discovered a significant relationship between RCEG dose and HbA1c reduction when the dose reached 0.08 g/kg/day or higher. We thus defined 0.08 g/kg/day of RCEG as the minimum effective dose, and a threshold to separate patients into the high-dose (≥0.08 g/kg/d) and low-dose (<0.08 g/kg/d) RCEG groups. In the high-dose RCEG group, a significant decrease in total cholesterol and a trend toward triglyceride reduction were also noted. Patients more effectively responded to RCEG treatment if they had a higher initial HbA1c level, higher heart rates, better liver function tests, and better tolerance to the higher dose and treatment duration of RCEG. In addition, digestive/tonic/dampness draining formulas and blood regulation recipes were two of the most frequent co-prescriptions with RCEG. This study concluded that RCEG at a dose exceeding 0.08 g/kg/d had beneficial effects on glycemic and lipid control, without showing nephro- or hepatotoxicity, in patients with type 2 diabetes.

黄连（Rhizoma Coptidis）是亚洲地区用于治疗2型糖尿病的常用植物药，但由于其基原多样，其用于糖尿病治疗的有效剂量仍尚未明确。本研究旨在探讨采用标准化质量控制工艺制备的黄连提取物颗粒（RCEG）对2型糖尿病患者的降糖量效关系。本研究对2008年1月1日至2017年11月30日期间的长庚研究数据库（Chang Gung Research Database）进行回顾性分析，纳入就诊于中医门诊且因治疗2型糖尿病服用RCEG的门诊患者。研究共纳入93例患者，涵盖60周内共计737次就诊的血糖、血脂及其他相关指标数据。采用结合局部加权回归散点平滑法（LOESS）的散点图，探究RCEG剂量与降糖效应之间的关联。以最小有效剂量为界，将研究对象分为RCEG高剂量组与低剂量组。组间及组内比较采用非参数检验。通过多变量非线性混合效应模型，同时分析治疗时长与分组对糖化血红蛋白（HbA1c）及空腹血糖变化的影响。使用R语言中的"arule"包，绘制RCEG与其他联合用药的网络图。本研究首次发现，当RCEG剂量达到0.08g/kg/日及以上时，其剂量与HbA1c降幅之间存在显著相关性。据此，本研究将0.08g/kg/日的RCEG定义为最小有效剂量，并以此为阈值将患者分为RCEG高剂量组（≥0.08g/kg/日）与低剂量组（<0.08g/kg/日）。在RCEG高剂量组中，还观察到总胆固醇水平显著降低，甘油三酯亦呈下降趋势。初始HbA1c水平更高、心率更快、肝功能指标更佳，且对RCEG高剂量及较长治疗时长耐受性更好的患者，对RCEG治疗的应答更为有效。此外，消食、补益、利湿方剂与调血方药是与RCEG联用频率最高的两类联合用药。本研究最终得出结论：在2型糖尿病患者中，当RCEG剂量超过0.08g/kg/日时，可有效改善血糖与血脂控制，且未观察到肾毒性或肝毒性。