The efficacy and safety of concentrated herbal extract granules, YH1, as an add-on medication in poorly controlled type 2 diabetes: A randomized, double-blind, placebo-controlled pilot trial

Abstract

Background: In Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes.

Methods: Forty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation.

Results: At week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial.

Conclusions: This pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

Fig 1. CONSORT flow diagram of enrollment, randomization, and treatment.

Two patients in the YH1 group and three patients in the placebo group were excluded from the study for the various reasons listed.

Fig 2. 3D-HPLC fingerprint of YH1.

The chemical composition of YH1 was analyzed using high-performance liquid chromatography (HPLC) with a photodiode array (PDA). Fourteen components, including allantoin, atractylenolide III, berberine, coptisine, ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, glycyrrhizin, liquiritin, pachymic acid, palmatine, platycodin D, magnoflorin and quercitrin, were detected.

Fig 3. Primary outcomes (HbA_1c) and secondary outcomes (2hPG) over 12 weeks.

The distribution of data (median, quartiles, range and outliers) for HbA_1c (A) and 2hPG (B) in the YH1 and placebo groups at week 0, week 4, and week 12 are displayed in the boxplot. To analyze the changes in parameters from their baseline values, Wilcoxon signed-rank test was applied. A value of p < 0.05 was considered significant. In the boxplot (Fig 3A), there was a significant reduction in the median HbA_1c value at week 4 (p = 0.003) and week 12 (p = 0.001) compared with the value at baseline in the YH1 group. In addition, the median 2hPG level from week 0 to week 12 declined significantly from 220 mg/dL to 172 mg/dL in the YH1 group (Fig 3B, p = 0.008). HbA_1c, glycated hemoglobin; 2hPG, 2-hour postprandial glucose.