Correspondence

Journal of Evidence-Based Integrative Medicine

Volume 23: 1-10
Chinese Herbal Medicine Versus Other ª The Author(s) 2018
Reprints and permission:

Interventions in the Treatment of sagepub.com/journalsPermissions.nav

DOI: 10.1177/2515690X18781519
journals.sagepub.com/home/cam
Type 2 Diabetes: A Systematic Review
of Randomized Controlled Trials

Ao Yu, MPH, BMed, BHSc, BHonHSc1, David Adelson, A.B, Ph.D.2,

and David Mills, MBBS, FRACGP DA, PRACOG MD2

Abstract
Diabetes affects 422 million people and directly caused 4.9 million deaths according to the global report on diabetes in 2014.
Type 2 diabetes accounts for 90% of people with diabetes around the world. Chinese herbal medicine treatment for diabetes
has more than 2000-year history in China. An increasing number of people around the world are trying to manage type 2
diabetes with Chinese herbal medicine. However, there is a lack of evidence to decide if Chinese herbal medicine is effective and
safe when compared with other interventions for the treatment of type 2 diabetes We identified 58 randomized controlled
trials involving 6637 participants with type 2 diabetes with trial periods lasting from 8 weeks to 1 year (average 12 weeks). We
extracted data following a predefined hierarchy. A total of 132 different Chinese herbal medicines were examined. We included
studies comparing Chinese herbal medicine with other interventions and excluded trials that did not satisfy the inclusion criteria.
We evaluated primary outcomes of trials in accordance with the Cochrane Handbook for Systematic Reviews of Intervention. Fifty-
six out of 58 studies reported evidence that Chinese herbal medicines were effective at controlling blood sugar, insulin
resistance, and traditional Chinese medicine clinical symptoms for patients with type 2 diabetes. And outcome variables are
summarized. However, the evidence is limited because of the quality of the studies. Well-designed long-term studies with large
samples and multiple centers as well as standardization and quality control will be required to determine if Chinese herbal
medicine treatment is effective and safe for type 2 diabetes.

Keywords
Chinese medicine, type 2 diabetes

Received November 16, 2017. Received revised April 20, 2018. Accepted for publication May 13, 2018.

Introduction or adult-onset diabetes, is described as a progressive condition

where the body becomes resistant to insulin and is associated
Description of the Condition with multiple lifestyle risk factors.5
As a group of chronic metabolic diseases, diabetes mellitus was Diabetes, predominantly type 2 diabetes, has been recog-
identified in 382 million people in 2013 worldwide and will nized as one of the enormous health care challenges for the
affect almost 600 million by 2035 based on the prediction from 21st century.1 Ninety percent of the people with diabetes are
the International Diabetes Foundation.1 About 5.8% of the recognized to have type 2 diabetes around the world.6 There is
world population was diagnosed with diabetes in 2014.2 Addi-
tionally, 1.5 million deaths were estimated as a direct result of
diabetes in 2012,2 and this number went up to 4.9 million in 1
Endeavour College of Natural Health, Adelaide, South Australia, Australia
2014 globally.3 The World Health Organization predicts that 2
The University of Adelaide, Adelaide, South Australia, Australia
diabetes will be the seventh leading cause of death in 2030.4
Corresponding Author:
There are 2 main types of diabetes: type 1 diabetes and type Ao Yu, Chinese Medicine Department, Endeavour College of Natural Health,
2 diabetes; gestational diabetes is a third form of diabetes.5 88 Currie Street, Adelaide, South Australia 5000, Australia.
Type 2 diabetes, which is also called non–insulin-dependent Email: ao.yu@endeavour.edu.au

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2 Journal of Evidence-Based Integrative Medicine

also an increasing prevalence of type 2 diabetes in children, mainly managed in public health care sectors as inpatient or
adolescents, and young adults.1 outpatient services.16
The economic burden of diabetes is remarkable and esti-
mated as US$376 billion, which was 12% of all global health
expenditure in 2010.1 It is predicted to rise to between US$490
How TCM Works
and US$893 billion by 2030.1 TCM has its own theory for disease mechanism, diagnostic
China has become the diabetes focus among all nations in techniques, and therapeutic principles. Generally speaking,
the world; there were 98.4 million diabetes patients diagnosed diseases are considered as interaction between both internal
in China in 2013 and this number will increase to 142.7 million and external causes and result in disturbance of Qi and blood,
in 2035.1 A total of 1.3 million Chinese with diabetes died in Zang-Fu, and imbalance between Yin and Yang.17 The diag-
2011.7 Direct health care expenditure of type 2 diabetes and its nostic system in TCM is 4 examinations: inspection, listening/
complications in China were estimated at US$26 billion in smelling, inquiry, and palpation.17 Tongue inspection and
2007 and is expected to increase to US$47.2 billion by 2030.1 pulse palpation are 2 unique diagnostic techniques of TCM
compared with Western medicine. The discussion of treatment
is based on syndrome differentiation. Syndrome differentiation
is an approach to make a comprehensive analysis of the data
Description of Intervention collected from the 4 examinations and decide the diagnosis
There is no cure for type 2 diabetes and the management is based on TCM theory.17 The major differentiating methods
through the control of blood glucose level by diet and exercise are developed as follows: 8 guiding principles syndrome dif-
alone or in combination with medications. These include phar- ferentiation, disease-cause syndrome differentiation, syndrome
maceuticals that are mainly Western hypoglycemic drugs and differentiation of qi, blood and body fluids, Zang-Fu organ
complementary therapy. Traditional Chinese medicine (TCM) syndrome differentiation, 6-channel syndrome differentiation,
is becoming increasingly popular in Western countries as an defense-qi-nutrient-blood syndrome differentiation, and triple-
alternative intervention for type 2 diabetes.8 burner syndrome differentiation.17 The therapeutic philosophy
Diabetes mellitus has been recognized since antiquity and and goals of TCM are focused on the overall functional state
TCM herbs have been used to treat diabetes in China for more of the patient, which can differ from those in Western medi-
than 2000 years.9 Xiaoke (wasting-thirst) is an ancient term for cine.18 Acupuncture and moxibustion, Chinese herbal medi-
diabetes, which was first recorded in The Yellow Emperor’s cine, Chinese dietary therapy, Chinese exercise therapy, and
Classic of Internal Medicine. 10 The recorded symptoms manual therapy are the 5 major branches of TCM treatment
describe 3 increases and 1 decrease (polydipsia, polyphagia, methods.17
polyuria, and weight loss) and probably equates to the term TCM usually concentrates on holistic treatment of the
“diabetes” in Western medicine.10 patient instead of focusing on treating a single disease.18 TCM
The treatment of diabetes with Chinese herbs is according to formulae often contain large numbers of active ingredients that
syndrome differentiation based on Qi (vital energy) and blood, are suitable for regulating several crucial targets based on indi-
Zang-Fu (5 viscera and 6 bowels), and Yin-Yang (representing vidualized treatment.18 Thus, the action of Chinese herbal med-
2 opposite principles in the body) theory, which is different icine is different due to the therapeutic principles and goals of
from Western medicine.11 TCM differing from those in Western medicine. And the mea-
The commonly recognized patterns of type 2 diabetes are Qi surement of intended effects of TCM herbs is also complicated
and Yin (body fluids) deficiency, heat, and stasis based on compared to Western medicine, which primarily consists of
TCM theory. Qi and Yin deficiency patterns may occur in single chemical compounds.18
initial stages and result in the heat of tissues and blood stasis.12 Although many of the antihyperglycemic components of
Alternatively, heat can occur earlier, or Yin deficiency and heat TCM herbs are unknown, Chang and colleagues summarized
may present simultaneously for relatively longer duration, the chemistry and biological action of 40 extracts and com-
while stasis may happen at any stage.13 Thus, frequently used pounds of plant origin.19 The mechanism of action of these
herbal formulae can be categorized into 4 groups: Qi invigor- herbal medicines involves improving insulin sensitivity, stimu-
ating, Yin nourishing, heat clearing, and stasis-reducing lating insulin secretion, protecting pancreatic islet cells, and
(improving blood circulation).12 The most frequently pre- inhibiting intake of intestinal carbohydrates.12
scribed herbs are Membranous Milkvetch Root (Huang qi),
Rehmannia Root (Di huang), Common Anemarrhena Rhizome
(Zhi mu), and Danshen Root (Dan shen), which respectively Adverse Effects of Chinese Herbal Medicine
belong to the above-mentioned groups.12 It has been widely acknowledged that medicinal herbs are
In China, government-owned health care delivery facilities normally nontoxic, while the consumption of herbs still has
are responsible for the treatment of most of patients and hos- risk due to incorrect prescribing, over dosage, improper pre-
pital delivery rates averaged 95% in 2011.14,15 The private paration, erroneous substitution, adulteration with Western
sector has grown more quickly than the public sector since the medicine, and inherent toxicity or contaminants. 8,20 The
mid-1990s, especially in rural areas.14 Diabetes in China is toxicity-related issues of herbal ingredients have been reported
Yu et al 3

earlier.8 The most commonly seen TCM-dependent clinical 1999, ADA 2003, China 1994, China 2007 and China 2012 were
complications are interactions between TCM herbs and con- used as the benchmark for type 2 diabetes in the inclusion criterion.
ventional drugs taken for diabetes.8 Another source of clinical Only studies of type 2 diabetes with Chinese herbal medicine treat-
concern is contamination of TCM preparations with impurities, ment were studied. The review included studies only if participants’
intervention duration was 8 weeks or more. Trials involving type 2
heavy metals, or bacteria, and heavy metals have been reported
diabetes treatment with acupuncture or other TCM modalities (alone
before as the main poison associated with the use of TCM
or combined with Chinese herbal medicine) were excluded.
products.8 Other causes of toxicity also involve intentional
adulteration of TCM with bioactive additives such as corticos-
teroids, hormones, salicylates, or antihistamines.8 Improper
prescription of herbal formulae and preparation of herbs, which Types of Interventions
relate to the regulation of herbal medicine and Chinese herbal Chinese herbal medicines including a compounded herbal formula or
medicine practitioners, is a cryptic underlying risk factor. For individualized prescriptions by Chinese medicine practitioner(s), pat-
example, if a doctor prescribed energy invigorating herbs rather ent herbs, single herb, Chinese herbal medicines combined with phar-
than heat clearing herbs to a diabetic patient with body heat macological intervention, and other intervention including diet
pattern, the symptoms could be worse in this patient. Identify- control, exercise therapy, and diabetes education, regardless of the
ing the active ingredients of herbs and their pharmacological dose, method of dosing, or duration of administration were compared
mechanism of actions are both time consuming and financially with other treatments (mainly pharmacological intervention). The fol-
expensive since one formula is often formed from many single lowing comparisons were included:
herbs, and a single herb usually has multiple compounds. 1. Chinese herbal medicines combined with other pharmaceuti-
Besides, the real efficacy and toxicity of herbal agents are cals versus other pharmaceuticals (mainly Western medicines)
difficult to test using the current evaluation paradigm for single 2. Chinese herbal medicines alone versus other pharmaceuticals
chemical compounds.18 (mainly Western medicines)
3. Chinese herbal medicines (alone or combined with other inter-
ventions or other pharmaceuticals) versus placebo
Why It Is Important to Conduct This Review
4. Chinese herbal medicines combined with other pharmaceuti-
An increasing number of type 2 diabetes patients choose to cals versus Chinese herbal medicines versus pharmaceuticals
manage their condition with TCM without consideration of the alone
potential toxic effects of medicinal herbs.8 There are limited 5. Chinese herbal medicines alone versus pharmaceuticals versus
studies in the English literature discussing both effectiveness other interventions (including diabetes education, diet control,
and adverse effects of Chinese herbs used to treat type 2 dia- and exercise therapy)
betes. This review evaluated the evidence for effectiveness,
explored adverse effects, and quality control according to the
Cochrane Handbook for Systematic Reviews of Interventions,
and also provides an English literature review of type 2 dia- Types of Outcome Measures
betes treatments with Chinese herbal medicines versus other Effectiveness of Intervention.
interventions based on the original Chinese literature. In prac-
tice, it should also provide valuable information of study  Glycemic control: glycated hemoglobin levels (HbA1C) and
designs for future research into diabetes treatment with TCM blood glucose levels (fasting blood glucose [FBG] or 2-hour
herbal medicines. postprandial blood glucose [2hPBG])
 Blood lipid profiles: total cholesterol [TC], triglycerides [TG],
low-density lipoprotein cholesterol [LDL-C], high-density
Methods lipoprotein cholesterol [HDL-C]
 Weight or body mass index (BMI)
Criteria for Considering Studies for This Review  Insulin resistance levels (HOMA-IR or ISI)
We did a systematic review and assessed the primary outcomes  TCM clinical symptom score
according to the Cochrane Handbook for Systematic Review of
Interventions. Scoring of TCM symptoms is a method of evaluating the symptoms of
diabetes including dry throat and mouth, lack of strength, polyphagia,
polydipsia, polyuria, shortness of breath, vexing heat in the chest,
Types of Studies
palms and soles, palpitation, insomnia, and so on.
Randomized controlled clinical trials with a minimum treatment
period of 8 weeks were included in this review. Only studies in the
English and Chinese literature were used in this review. Adverse Outcomes.

 Routine blood and urine test

Types of Participants  Liver and kidney function test
Adults diagnosed with type 2 diabetes mellitus based on documented  Electrocardiography (ECG)
diagnostic criteria were included. WHO 1999, WHO 2007, ADA  Clinical symptoms of adverse effects
4 Journal of Evidence-Based Integrative Medicine

Timing of Outcome Assessment obtain additional references. In addition, we contacted the

agency responsible for the regulation of reviewed Chinese her-
Studies with possible effective treatment duration from 8 weeks to 1
year were included for analysis. bal medicines—National Resource Centre for Chinese Materia
Medica and China Academy of Chinese Medical Science—in
order to retrieve information on published herb trials.
Search Methods for Identification of Studies
The following resources were searched to identify trials: Data Extraction and Management
 The Cochrane Library (Wiley Online Library) For studies that fulfilled the inclusion criteria, data of the relevant
 Web of Science population, intervention, and outcome characteristics were abstracted
 PubMed by using standard data extraction templates (for details, see “Table 2:
 Google Scholar Characteristics of Included Studies,” available as supplemental mate-
 The University of Adelaide Library Research rial in the online version of the article); any questions were resolved
 China Academic Journals Full-text Database (Basic Search) by discussion between the authors, referring back to the original arti-
 China Dissertation Database cle. When necessary, additional information was sought from the
 China Knowledge Resource Integrated (CNKI) Database authors of the primary studies.
 Baker Heart and Diabetes Institute
Assessment of Risk of Bias in Included Studies
We conducted extensive and ongoing electronic searches in the above-
described databases from 2004 until April 2016. All authors screened We assessed the risk of bias for each included study based on the
search results and identified the full texts of all relevant trials reports. criteria outlined in the Cochrane Handbook for Systematic Review of
Interventions. Any uncertainty was resolved by discussion between
We also detected additional keywords of relevance during any of
the 3 authors. The details of risk of bias are listed in “Table 2: Char-
electronic or other searches by modifying the search strategies to
acteristics of Included Studies” (available in the online version of the
incorporate the search terms. Studies published in English and Chi- article).
nese were included. We searched other resources as well, such as
reference lists of relevant trials and reviews from published studies
and used personal communication from the National Resource Centre Results
for Chinese Materia Medica for identification of additional relevant Description of Studies
studies. We did not search unpublished literature (the studies that have
558 clinical trials of type 2 diabetes with Chinese herbal med-
not been published due to negative results and the studies that were
icine treatment were identified, and 165 full-text articles were
not peer reviewed).
eligible for detailed review. 58 studies were included and 107
studies excluded based on the above-mentioned criteria.
Data Collection and Analysis
Selection of Studies. The abstract, title, or both of every record Results of the Search
retrieved were scanned by the authors to determine the studies to be A total of 558 references were identified by initial database
assessed further. The full texts of all potentially relevant articles was
searching up to April 8, 2016. 382 potentially eligible studies
studied, and inclusion in this review was based on the following
were kept for further assessment after duplicates were
criteria:
removed. 217 studies were excluded because they clearly did
 Compared Chinese herbal medicines (alone or combined with not fulfil the inclusion criteria. Full-text articles were explored
other intervention or other pharmaceuticals) with other phar- for clarification if the title and abstract did not provide clear
maceuticals (alone or combined with other intervention), pla- information. 165 full-text articles were assessed for eligibility.
cebo or other intervention (including diet control, exercise 58 full-text articles were included in our qualitative synthesis,
therapy and diabetes education) as treatment for type 2 diabetes and 107 full-text articles were excluded. The reasons for exclu-
 Included patients with type 2 diabetes mellitus; excluded pre- sion are listed in Figure 1 and “Table 3: Characteristics of
type 2 diabetes, diabetes complications
Excluded Studies” (available in the online version of the arti-
 Excluded herb extracts, Chinese herbal medicine combined
cle). Further investigation of the full articles retrieved included
with acupuncture and Tui Na (traditional Chinese medicine
remedial massage) treatment, comparison of different forms 5 studies that were initially excluded, and 9 studies were
of Chinese herbs excluded that were initially included. An adapted PRISMA
 Assessed more than one relevant outcome (Preferred Reporting Items for Systematic Reviews and
 Used random allocation to the comparison groups Meta-Analysis) flowchart of study selections is shown in Fig-
 Study duration not less than 8 weeks ure 1.

Where information was ambiguous or missing in the article

or there was differences of opinion, the decision to include the
Included Studies
trial was resolved by consensus. Authors of relevant identified 58 trials were included for effectiveness and safety assessment
studies and experts in relevant fields were contacted in order to and risk of bias analysis. For more information, see “Table 2:
Yu et al 5

Figure 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of study selection.

Characteristics of Included Studies” (available in the online 2013) provided very detailed information of the randomization
version of the artilce). methods. 1 trial (Ji 2013) had 4 arms (see Supplemental Mate-
rials for details of the studies).
Study Design
All the included studies stated they were randomized controlled
Participants
clinical trials, but only 13 trials reported the details of rando- All the study participants were hospital patients diagnosed with
mization methods, and 3 trials (Ji 2013; Chao 2009; Tong type 2 diabetes mellitus that were either receiving or not
6 Journal of Evidence-Based Integrative Medicine

receiving treatment before the study commenced. 55 studies Publication Details

were carried out in a single study center, mainly different pro-
See “Table 2: Characteristics of Included Studies” for detailed
vincial and municipal hospitals of main cities in mainland
information (available in the online version of the article).
China. 3 trials (Chao 2009; Tong 2013; Ji 2013) were carried
out in multiple study centers, with 2 studies using 2 and 10
centers, respectively, in China, and the other study using 20 Risk of Bias in Included Studies
centers (19 participant centers in China and 1 participant center Most participants in included studies were mainly Chinese
in Queensland, Australia). See Supplemental Materials for recruited from TCM hospitals, which led to selection bias
details of the studies. because the results might not be applicable to the general pop-
ulation. A general conclusion cannot be drawn because the
Diagnosis sample might not be representative of the whole population.
In addition, there was insufficient information to make a
The diagnostic criteria for type 2 diabetes mellitus were mainly formal assessment; most included studies were at an unclear
based on WHO criteria (43 trials by criteria in 1999, 1 trial by risk of bias for nearly all of the “Risk of Bias” domains apart
2007, 2 trials without specification), and 3 trials used the cri- from attrition bias. See “Table 2: Characteristics of Included
teria of ADA (1 trial by 1999, 1 trial by 2003, and 1 trial Studies” for more information.
without specification). 4 trials used their diagnostic criteria
based on textbook criteria, and 5 trials had no specification.
Allocation
Interventions and Comparisons 42 included studies reported that the participants were ran-
domly divided into 2 groups for respective treatments without
42 trials compared combined Chinese herbal medicines and giving further details. 11 included studies reported a further
other pharmaceuticals with other pharmaceutical. Ten trials randomization method: “By using random number table
compared Chinese herbal medicines with other pharmaceuti- method.” Moreover, 2 trials mention “by random file number
cals. 4 trials compared Chinese herbal medicines with placebo; method.” Only 3 trials reported a detailed randomization
2 trials compared 3 groups (one compared Chinese herbal method, “Statistics Analysis System software was used to ran-
medicines combined with pharmaceuticals to other pharmaceu- domly divide the subjects,”21 or “randomization was performed
ticals or to Chinese herbal medicines; the other compared Chi- centrally and was concealed and stratified in blocks of four,”22
nese herbal medicines to pharmaceuticals or to other or “randomization and blinding were conducted by personnel
interventions). Only 1 trial was a multiple-armed study that who did not participate in data acquisition and evaluation. A
compared Chinese herbal medicines combined with pharma- computer program was used to generate the subject assign-
ceuticals to other pharmaceutical between a drug naïve group ment; each subject was given a unique number and this number
and drug group. Most trials tested various Chinese herbal med- was used throughout the trial.”23 In addition, all 16 of these
icines including individual prescriptions modified from classi- trials were assessed as having a low risk of selection bias.
cal formulae. 3 trials only tested a single Chinese herb:
Huanglian (Coptidis Rhizoma) or Wuweizi (Fructus
Schisandrae). Blinding
The formulae of Chinese herbal medicines were different in 53 studies were assessed as unclear for performance bias and
each study. All recorded formulae, individual formulae, and detection bias because no information on blinding of partici-
patent herbal formulae were included in the studies and the pants and personnel or outcome assessors was provided in the
basic composition consisted of the 132 common Chinese her- trial reports. Only 5 studies reported detailed information of
bal medicines; for more details, see “Table 4: List of Chinese blinding methods: “double-blinded and placebo-controlled” or
Herbal Medicines Used as Treatment for Type 2 Diabetes” “All investigators were blinded from the study drug assign-
(available in the online version of the article). Pharmaceuticals ment, in which only a randomization code was disclosed.
included commonly used hypoglycemic Western medicines Unblinding was conducted only after all study data were col-
such as metformin, sulfonylureas (glibenclamide, glimepiride, lected.” Moreover, all 5 of these trials were assessed as having
and glipizide), α-glucosidase inhibitor (acarbose), thiazolidine- a low risk of performance bias and detection bias.
diones (rosiglitazone), and insulin. Other interventions mainly
included diet control, exercise therapy, diabetes health educa-
tion, and other lifestyle changes.
Incomplete Outcome Data
All 58 studies were assessed as having a low risk of attrition
bias. After checking the total number of participants and the
Follow-up patients included in each intervention group, there were no
All of the 58 included trials followed-up the participants until missing data in 53 studies. There were exclusions or losses
the end of the treatment. 24 trials studied and/or reported the to follow-up reported in 5 included studies. 1 trial lost
adverse effects of the intervention. follow-up in both groups before the start of the study. 2 trials
Yu et al 7

had missing outcome data balanced in numbers and with sim- general statistics for average change rate of primary outcomes
ilar reasons for missing data across groups. Another trial had in this review because insufficient information was available in
missing outcome data balanced in numbers across groups for many included studies to generate this summary. This is the
no reported reason. The last one had missing outcome data same reason that no meta-analysis was included in this review.
balanced in numbers across intervention groups, and the pro-
portion of missing data compared with the observed event risk
was not enough to have a clinically relevant impact on the
Summary of Main Results
intervention effect estimate.24 Effectiveness. The general results suggested that Chinese herbal
medicines used alone or in combination with other Western
Selective Reporting hypoglycemic agents or lifestyle changes was associated with
a decrease of glycated hemoglobin and blood glycemic level,
54 studies were assessed as having an unclear risk of reporting blood lipid profiles, BMI, and TCM clinical symptom score.
bias since their protocols were not available. 4 had clear pro- However, there was no clear description of how insulin resis-
tocols and were assessed as having a low risk of reporting bias. tance was measured. 14 trials recruited type 2 diabetes patients
with insulin resistance and used a combination of Chinese
Other Potential Sources of Bias herbal medicine with other pharmaceuticals or lifestyle inter-
ventions. The outcomes were associated with Chinese herbal
All 58 studies were assessed as unclear risk of other potential
medicine enhancing the therapeutic effects of other pharmaceu-
bias. All included studies followed-up the participants until the
ticals by improving insulin sensitivity in the treatment of type 2
end of treatment. Most of studies reported that there was no
diabetes.
significant difference among the groups before the interven-
42 trials showed statistically significant improvement of
tions, and were considered to have good baseline similarity.
blood glucose control by Chinese herbal medicines combined
However, other aspects of bias were still unclear, as most stud-
with Western hypoglycemic agents compared to Western med-
ies did not clearly report how diabetes had been controlled, and
icine alone for type 2 diabetes. 34 of the 42 trials indicated
for how long, before the studies.
improvement with statistical significance in both glycosylated
hemoglobin and glycemic control. 39 studies reported glycated
Effects of Interventions hemoglobin decreases, and the range of reduction was 0.02%
58 studies with 6637 patients diagnosed with type 2 diabetes to 2.81% for 34 trials and 0.2 to 1.6 mmol/L for 5 trials. 42
were included in the review. All included studies compared studies mentioned glycemic level decreases with 37 trials
Chinese herbal medicine with other interventions (pharmaceu- reporting measurable details: the range of reduction was 0.02
ticals, diet control, and exercise therapy and health education). to 1.75 mmol/L for fasting plasma glucose (37 trials) and −0.2
5 comparisons and summary of findings are available in Sup- to 7.2 mmol/L for postprandial plasma glucose (33 trials).
plemental Table 1 (available in the online version of the Except for one case of asymptomatic type 2 diabetes, 41 of
article). the 42 trials showed improvement of TCM clinical symptoms.
19 trials measured TCM symptoms scores of diabetes with the
range of reduction from 12% to 80%, indicating statistically
Discussion significant improvement. 26 studies included blood lipid pro-
This review aimed to evaluate the effectiveness and safety of files and 5 studies included BMI along with blood glycemic
Chinese herbal medicine as a treatment for type 2 diabetes level as primary outcomes. Most of these studies reported no
mellitus. The therapeutic effects of Chinese herbal medicine statistically significant difference with blood lipid profiles
on the control of glycated hemoglobin and glycemic level, changes between 2 groups. 20 studies measured insulin resis-
insulin resistant level, and TCM clinical symptoms score have tance level along with blood glycemic level as primary
been studied and reported mostly inside China, and very few outcomes.
English language studies were found outside of China. This 10 trials claimed improvement of glycemic control by Chi-
research included 55 studies from the Chinese literature and nese herbal medicines, alone or in combination with lifestyle
3 studies from the English literature (58 studies involving 6637 interventions compared to Western medicine for type 2 dia-
type 2 diabetes patients in total). All included studies from the betes. 8 of the 10 trials indicated statistically significant effec-
Chinese literature were translated into English and incorporated tiveness. 7 of 10 trials showed both glycated hemoglobin and
in “Table 2: Characteristics of Included Studies” (available in glycemic control improvement. The range of glycemic level
the online version of the article). There were 5 different com- reduction was 0.19 to 2.4 mmol/L for fasting plasma glucose
parisons with 132 herbal medicines involved in the 58 trials and 0.33 to 2.3 mmol/L for postprandial plasma glucose. 5
with trial periods lasting from 8 weeks to 1 year. Meta-analysis studies reported glycated hemoglobin reduction with a range
was not performed in this review because there was a mix of variation of 0.1% to 0.4%. All 10 trials showed improvement
comparisons of different treatments, the outcomes were too of TCM clinical symptoms, with 7 trials indicating statistically
diverse in most of the included studies, and bias was present significant improvement of TCM clinical symptoms score. The
in most of the individual studies.24 There was no picture of range of reduction is from 15% to 70%.
8 Journal of Evidence-Based Integrative Medicine

4 trials showed improvement at glycemic control of Chinese major limitation (selection bias of patients recruitment). Most
herbal medicines alone or in combination with other lifestyle clinical trials were not well designed, and the overall quality of
interventions compared to placebo for type 2 diabetes, with the studies was hard to determine because of the limited infor-
statistical significance for 2 of 4 trials. The range of the gly- mation reported in the studies. Overall, the quality of evidence
cated hemoglobin reduction was 0.1% to 0.4%, the range of was unsatisfactory and the risk of bias was unclear due to
glycemic level reduction was 0.1 to 0.3 mmol/L for fasting insufficient available information from most included studies.
plasma glucose, and 0.2 to 1.1 mmol/L for postprandial plasma Most participants were from the Chinese population and
glucose. All 4 trials claimed TCM symptom improvement but recruited from TCM hospitals, and this could influence the
only 2 trials had statistically significant (35% and 67%). applicability of the interventions to other populations. This is
For 2 trials with comparisons of 3 groups, effectiveness a major source of bias.
could not be evaluated based on the available data (one study
only reported effectiveness in the combination group compared
to single Chinese herbal medicine group and Western medicine
Quality of Methodology
group; another study reported the effectiveness in 2 treatment The general methodological quality of all selected trials was
groups compared to the no treatment group). unsatisfactory based on international standards for a well-
Most studies had average study durations of 8 to 12 weeks, conducted randomized controlled trial. All selected trials
which was too short to assess effectiveness in relation to gly- reported important demographic information and mentioned
cated hemoglobin and glycemic level control. that no significant difference was found between intervention
groups on baseline data at recruitment. Most studies provided
Adverse Effects. Chinese herbal medicines are generally regarded detailed information with baseline data before the recruitment
as safe to treat type 2 diabetes if used properly, and this is of the study. However, in terms of randomization, allocation,
supported by a long history of clinical practice. However, all and concealment methods, only 3 studies provided sufficient
medicines are associated with some risks and there is no excep- details. 13 trials reported limited details of randomization and
tion for Chinese herbal medicine. The adverse effects related to allocation concealment method. The remaining 42 trials only
type 2 diabetes treatment with Chinese herbal medicines might generally mentioned that randomization applied in their studies
be attributable to incorrect prescription, over dosage, improper without details of the randomization, allocation, and conceal-
preparation, erroneous substitution, adulteration with Western ment methods. Only 5 studies reported detailed information of
medicine, and inherent toxicity or contaminants.20 However, blinding methods. However, blinding is difficult with respect to
there was lack of universal reference for scientific evidence to Chinese medicine due to its taste. Furthermore, most studies
assess the safety of this intervention, and the data related to the that did not mention blinding might have avoided blinding
adverse effects of Chinese herbal medicine were insufficient. In because the patients were expected to receive only Chinese
addition, the chemical components of Chinese herbal medicines herbal treatment rather than Western medicines or placebo
are more complex than in Western medicine, and each formula since they had decided to see a traditional Chinese medicine
usually contains several herbs with each herb usually having practitioner.
multiple potentially active ingredients.
22 clinical trials out of the 58 included studies reported
adverse effects such as nausea, vomiting, bloating, diarrhea,
Study Design
or other stomach discomfort along with hypoglycemic epi- Most of the included studies provided information regarding
sodes. 19 trials out of 22 reported the examination details for the hypothesis to be tested, the baseline information of parti-
identifying adverse effects and certainly had no safety assess- cipants, their recruitment criteria, WHO diagnosis criteria of
ment comparable with Western medicines. 3 trials out of 22 type 2 diabetes mellitus, and diagnosis criteria by Chinese
reported no adverse effects observed and they did not mention medicine theory, clear information on study and control groups,
if and what kinds of examinations were performed for identify- the details of intervention medicines and treatment methods,
ing the adverse effects. There was no information reported in the duration of intervention, and the proper outcome measure-
terms of adverse effects in the other 36 included studies. There ments. However, only 22 clinical trials out of 58 reported
were no information reported of any serious adverse outcomes adverse effects, with 19 trials reporting the examination details
or deaths in the 58 included trials. for adverse effects. Most trials did not report potential side
effects as a study outcome. Adverse effects of Chinese herbal
Overall Completeness and Applicability of Evidence. There were 3 medicines may have been neglected in most clinical studies
main approaches of intervention for type 2 diabetes in all due to various reasons mentioned above. Meta-analysis could
included studies: pharmaceutical treatment, Chinese herbal not performed due to the limited information with respect to
medicine, and lifestyle (diet and exercise) control. In this study medicines and the different Chinese herbs used in each
review, all of these treatments were included for analysis. The study. Furthermore, there were only 4 placebo-controlled trials,
results suggest that Chinese herbal medicines combined with which were insufficient to draw any conclusion with respect to
other interventions (diet control, exercise therapy, and pharma- the effectiveness and safety of Chinese herbal medicine for
ceuticals) were more effective than pharmaceuticals but with a treating type 2 diabetes mellitus.
Yu et al 9

Result Report and Analysis In terms of duration of intervention, only 2 studies lasted 4
months, 5 studies lasted 6 months, 1 study 48 weeks, and 1
No exclusion or losses were reported in most of the included trials,
study 1 year. Most trials reported end-of-treatment outcomes
but the number of participants remained the same at the beginning
ranging from 8 to 12 weeks, which was too short to address
and the endpoint of studies. So apart from 5 trials that reported lost
long-term effectiveness and toxicity of the herbs. In particular,
follow-up data, all remaining 53 trials were assumed to have had
for Chinese herbal medicine, there is a lack of information
no dropouts by checking the numbers of participants from the
about the half-life of plant secondary metabolites to test
beginning and the end of the study. The 5 studies that reported the
long-term effectiveness and adverse effects, making it proble-
incomplete data were assessed as low risk based on the Cochrane
matic to determine if Chinese herbal medicine could be an
Collaboration’s tool for assessing risk of bias.24 The protocol of
effective and safe treatment for type 2 diabetes. Effectiveness
most included studies was not described in sufficient detail, so it
and safety issues should be a future research emphasis for
was not possible to carry out a meta-analysis.
Chinese herbal medicine used to treat chronic diseases such
as type 2 diabetes.
Conclusions of the Included Studies
All studies reported the therapeutic effects of the interventions,
Agreements and Disagreements With Other
but only 2 studies published outside of China recorded their Studies or Reviews
limitations in the discussion section of the trial report. The The findings in this review related to effectiveness of Chinese
approach to treating type 2 diabetes may differ according to herbal medicines to treat type 2 diabetes are similar to the
TCM syndrome differentiation. Many herbal formulae were conclusion of previous systematic reviews. The only previous
slightly modified compared to the classical prescription depend- Cochrane systematic review on Chinese herbal medicine to
ing on individual clinical presentation. Most studies described treat type 2 diabetes was in 2004 by Liu and others.11 Liu and
formulae with multiple herbs and only 3 studies reported single colleagues analyzed the effects of 66 randomized trials of 69
herb usage. Therefore, the conclusion with respect to effective- herbs involving 8302 patients with type 2 diabetes. The con-
ness in this review is only in general terms but not for specific clusion was that herbal medicines were effective on blood
formulae or individual Chinese herbal medicines. glucose control in people with type 2 diabetes mellitus. Nev-
All selected studies were eligible for this review but the ertheless, there was no mention of any adverse effects related to
overall quality of the methodology was inconclusive and unsa- type 2 diabetes with Chinese herbal medicine treatment.
tisfactory. The evidence of included studies was insufficient, so
the risk of bias of included studies was unclear. In addition, the
evidence of safety of Chinese herbal medicines as a treatment Conclusions
for type 2 diabetes was inadequate due to the variation in Implications for Practice
studies and methodology. Well-designed clinical trials with
A combination of Chinese herbal medicine and other pharma-
standard criteria are required for the study of safety of Chinese
ceuticals (mainly Western hypoglycemic agents) might be more
herbal medicines.
effective than pharmaceuticals in terms of glycated hemoglo-
bin, glycemia, and control of insulin resistance level in type 2
Potential Biases in the Review Process diabetes mellitus. However, there was limited evidence to
assess the effectiveness of Chinese herbal medicine alone for
We tried to include all relevant studies on type 2 diabetes treating type 2 diabetes (only 10 trials with small sample size).
treatment with Chinese herbal medicine. Most full-text articles The quality of evidence (data of study duration and outcome) is
were in Chinese with only English abstracts. However, not all insufficient to fully evaluate the effectiveness and adverse
literature are in all database. Some database could not be effects of the intervention.
accessed due to location and language limitation, as some Chi-
nese databases are not accessible from Australia. It is also
impossible to avoid publication bias, as negative studies were
Implications for Research
not reported. Alternatively, some articles were published but Long-term well-designed studies are required to compare Chi-
not peer reviewed. Meta-analysis could not be conducted due nese herbal medicines alone with pharmaceutical alone or pla-
to the reason mentioned above. cebo before drawing any conclusion about the effectiveness
Systematic bias could be possible since most of the included and safety of type 2 diabetes treatment with Chinese herbal
studies did not provide detailed protocol of administration of medicine. We suggest undertaking high-quality clinical trials
treatment and assessment of outcomes but only simply reported with multiple centers (large samples) and publication in Eng-
that randomization was performed for allocation of intervention lish as a way to rectify this. Adequate randomization methods
groups. Selection bias could not be avoided since most study need to be applied and clearly reported. Clear information
participants were Chinese recruited from TCM hospitals. should be provided about the management methods and their
Blinding of participants and personnel processes were duration before the study, along with other baseline character-
described with detailed information in most included studies. istics for the recruitment of patients. Evaluation of
10 Journal of Evidence-Based Integrative Medicine

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diabetes treatment. Future studies should address safety issues diction of toxicity related to herbs from traditional Chinese med-
by not only reporting adverse effects but also supplying details icine. Planta Med. 2010;76:2019–2025.
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TCM assessment and treatment variation based on syndrome J Clin Pharmacol. 2000;40:445–450.
differentiation, we suggest recruiting the same category of type 10. Zhang H, Tan C, Wang H, Xue S, Wang M. Study on the history
2 diabetes patients and treatment with similar Chinese herbal of traditional Chinese medicine to treat diabetes. Eur J Integr
medicines in future studies in order to reduce the information Med. 2010;2:41–46.
bias of studies as much as possible. We recommend multiple- 11. Liu JP, Zhang M, Wang WY, Grimsgaard S. Chinese herbal med-
center trials with type 2 diabetes patients recruited from different icines for type 2 diabetes mellitus. Cochrane Database Syst Rev.
sources (such as patients outside hospitals, patients outside 2004;(3):CD003642.
China, etc) in order to avoid selection bias. 12. Xie W, Zhao Y, Zhang Y. Traditional Chinese medicines in treat-
ment of patients with type 2 diabetes mellitus. Evid Based Com-
Authors’ Note
plement Alternat Med. 2011;2011:726723.
The work was carried out at the University of Adelaide with regular 13. Peng B. Traditional Chinese Internal Medicine. 2nd ed. Beijing,
meetings of the three authors.
China: People’s Medical Publishing House; 2007:516.
Author Contributions 14. Eggleston K, Ling L, Qingyue M, Lindelow M, Wagstaff A.
Health service delivery in China: a literature review. Health Econ.
Ao Yu - wrote the first draft of the manuscript, analyzed the data and
2008;17:149–165.
contributed to major revision.David Adelson and David Mills - con-
tributed to major revision, equally provided the support and mentor- 15. Meng Q, Xu L, Zhang Y, et al. Trends in access to health services
ship necessary for the success of the work. and financial protection in China between 2003 and 2011: a cross-
sectional study. Lancet. 2012;379:805–814.
Declaration of Conflicting Interests 16. Pan C, Yang W, Jia W, Weng J, Tian H. Management of Chinese
The authors declared no potential conflicts of interest with respect to patients with type 2 diabetes, 1998-2006: the Diabcare-China
the research, authorship, and/or publication of this article. surveys. Curr Med Res Opin. 2009;25:39–45.
17. Zhu B, Wang H. Diagnostics of Traditional Chinese Medicine
Funding (International Acupuncture Textbooks). 1st ed. Philadelphia, PA:
The authors disclosed receipt of the following financial support for the Singing Dragon; 2010.
research, authorship, and/or publication of this article: The University 18. Jiang WY. Therapeutic wisdom in traditional Chinese medicine: a
of Adelaide. perspective from modern science. Trends Pharmacol Sci. 2005;
Ethical Approval 26:558–563.
19. Chang CLT, Lin Y, Bartolome AP, Chen Y, Chiu S, Yang W.
None required.
Herbal therapies for type 2 diabetes mellitus: chemistry, biology,
Supplemental Material and potential application of selected plants and compounds. Evid
Based Complement Alternat Med. 2013;2013:378657.
Supplementary material for this article is available online. The list of
abbreviations is also available in supplementary material. 20. Zhao HL, Tong PCY, Chan JCN. Traditional Chinese medicine in
the treatment of diabetes. In: Bantle JP, Slama G, eds. Nutritional
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