Safety and effectiveness of different herbal medicine dosage of Gegen Qinlian Decoction in Chinese patients with type 2 diabetes: a double-blind, two-part, randomised controlled trial

BackgroundGegen Qinlian Decoction, a Chinese herbal medicine, has been shown to be effective and safe for patients with type 2 diabetes, yet the roles of its main components, Radix Puerariae and Coptis chinensis, in diabetes is uncertain. We aimed to observe the relationship between dosage-changing of these herbal medicines of Gegen Qinlian Decoction and effectiveness in patients with type 2 diabetes.MethodsWe did a randomised, double-blind, two-part, parallel-dose controlled clinical trial. Patients with type 2 diabetes inadequately controlled by diet and exercise from Guang'anmen Hospital were enrolled in the phase 1 trial. Patients who had been treated for diabetes within 1 month were excluded from the trial. Patients were randomly allocated (1:1:1) via a computer-generated randomisation sequence to receive three different doses (24 g, 72 g, and 120 g) of Radix Puerariae of Gegen Qinlian Decoction for 12 consecutive weeks. Patients and clinicians were masked to group assignment. The primary outcomes were changes from baseline in HbA1c, fasting plasma glucose, and 2 h glucose after oral glucose tolerance test at week 12 in each group, and the outcomes were analysed in the per-protocol population who complied with the protocol and had no violations. Secondary endpoints included concentrations of fasting insulin and lipids, bodyweight, BMI, and waist circumference. If the relationship between dosage-changing in Radix Puerariae of Gegen Qinlian Decoction and HbA1c-decreasing was null, the new patients with diabetes were enrolled in the phase 2 trial, which had patients randomly allocated (1:1:1) to receive three different doses Coptis chinensis of Gegen Qinlian Decoction for 12 consecutive weeks. The efficacy evaluation was identical to the phase 1 trial. This study is registered with ClinicalTrials.gov, number NCT01219803.FindingsBetween Aug 8, 2011, and April 23, 2012, we enrolled 120 patients into the phase 1 trial. 97 patients were included in the per-protocol analysis (32 for high dose, 30 for middle dose, and 35 for low dose Radix Puerariae of Gegen Qinlian Decoction). At week 12, No significant difference among the groups was reported compared with week 0: the mean change in HbA1c was −0·58% in the high-dose group (SD 0·87), −0·28% in the middle-dose group (1·17), and −0·55% in the low-dose group (0·85; the difference between groups p=0·52, 95% CI −0·53 to 0·55). In the phase 2 trial, we enrolled another 122 patients between Nov 14, 2012, and Aug 29, 2013, and 103 of them were included in the per-protocol analysis. Compared with the HbA1c level from week 0, the mean change was −0·75% in the high-dose group (SD 0·82), −0·34% in the middle-dose group (0·71), and −0·26% in the low-dose group (0·79) at week 12. There was a significant HbA1c reduction in the groups after 12 weeks (p=0·0492, 95% CI −0·78 to −0·02). No cases of severe hypoglycaemia were reported in either trial.InterpretationChanging the dose of Coptis chinensis of Gegen Qinlian Decoction has a dose–effect relationship with glycaemic control. Coptis chinensis is the major drug of Gegen Qinlian Decoction for treating patients with type 2 diabetes.FundingNational Basic Research Program of China (973 Program).