Type 2 Diabetes
Conditions
Brief summary
Type 2 diabetes mellitus is a chronic metabolic disease that seriously affects patients worldwide, and it is always among the top 10 causes of death in Taiwan. To date, still many patients who take more than three kinds of oral hypoglycemic agents could not effectively control their glycohemoglobin levels in clinics. Hypoglycemia as well as weight gain are common side effect with insulin therapy, and many patients in Taiwan are not willing to receive insulin injection. It is common for diabetic patients treated with Chinese herbal medicine in China currently, and some therapeutic effects have been published in international journals. In this study, we will evaluate whether Chinese herbal medicine, YH1, enhances the glycemic control and is safe as add-on medication in poorly controlled type 2 diabetes patients. A total of 46 poorly controlled type 2 diabetes patients with glycohemoglobin ≥ 7% from Endocrinology and Metabolism clinics or Internal Chinese Medicine clinics will be enrolled in this randomized double-blind placebo-controlled trial. Subjects will be randomly assigned to receive either YH1 (6 g) or the placebo three times per day for 12 consecutive weeks. All subjects in both groups will also continuously receive their oral hypoglycemic agents without any dose or medicine change. During this 12-week period, the glycohemoglobin, fasting plasma glucose, 2h postprandial glucose, waist circumference, body weight, and body mass index will be assessed. In addition, insulin resistance, β -cell function, lipid profile, liver and renal function will also be evaluated. Independent statisticians will perform the data analysis at the end of the trial.
Detailed description
The YH1 in one batch number was used, manufactured by Sun Ten Pharmaceutical Co., LTD., a renowned GMP manufacturer of concentrated herbal extract granules conforming to international standards. The YH1 was prepared in small granules, including concentrated herbal extract granules of Rhizoma Coptidis (50%) and SLBZS (50%). Both medicines have already been approved by the Ministry of Health and Welfare in Taiwan as ethical drugs. YH1 granules were packed in aluminum foil packages. The placebo was also prepared as granules by Sun Ten Pharmaceutical Co., LTD., and the packaging of the placebo was identical to that of YH1. The chemical composition of YH1 was analyzed and profiled by using a high performance liquid chromatography (HPLC) with photodiode array (PDA) detection. Fourteen components, allantoin, atractylenolide III, berberine, coptisine, ginsenoside Rb1, ginsenoside Re, ginsenoside Rg1, glycyrrhizin, liquiritin, pachymic acid, palmatine, platycodin D, magnoflorin and quercitrin, were simultaneously used in the qualitative analysis under the developed HPLC-PDA method. As for the quantitative detection, each gram of YH1 contained 20.05 mg berberine.
Interventions
DRUGYH1 group
Participants were randomly assigned 1:1 to receive either YH1 or placebo for 12 consecutive weeks.
DRUGplacebo group
Participants were randomly assigned 1:1 to receive either YH1 or placebo for 12 consecutive weeks.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 20-75 years of age; 2. Diagnosed as type 2 diabetics based on World Health Organization criteria \[1\]; 3. Body mass index (BMI) ≥ 23 kg/m2; 4. Have been treated with ≥ 3 kinds of oral hypoglycemic agents (OHAs) with persistent (\> 6 months) high HbA1c (≥ 7.0 %).
Exclusion criteria
1. Type 1 diabetes, gestational diabetes, or other specific types of diabetes; 2. Have received insulin therapy in the past three months; 3. Have serious gastrointestinal (GI) tract diseases, such as peptic ulcers or GI tract bleeding; 4. Experience stressful situations, including diabetic ketoacidosis, nonketotic hyperosmolar diabetic coma, severe infection, or surgery in the previous one month; 5. Suffer from hepatic insufficiency with alanine aminotransferase (ALT) 2 times the upper limit of normal or renal insufficiency with estimated glomerular filtration rate (eGFR) \< 60; 6. Uncontrolled hypertension (blood pressure ≥ 160/100 mmHg); 7. Mental illness, abused or addicted to alcohol, psychoactive substances or other drugs; 8. Pregnant, lactating, or plan to become pregnant; 9. Hemoglobin disease or chronic anemia; 10. Have underlying conditions that could lead to poor compliance; 11. History of cerebrovascular disease or myocardial infarction; 12. Have undergone Chinese medicine treatment in the past two weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change in HbA1c Level From Baseline to 12 Weeks | 12 weeks | The primary efficacy endpoint was the percentage change in HbA1c levels from baseline to 12 weeks. The HbA1c level was measured by HPLC in the Department of Laboratory Medicine at Chang Gung Memorial Hospital. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage Change in 2hPG From Baseline to Week 12 | 12 weeks | The secondary efficacy endpoint was the percentage change in 2hPG level from baseline to 12 weeks by using enzymatic method in the Department of Laboratory Medicine at Chang Gung Memorial Hospital. |
Countries
Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| YH1 Group YH1 three times per day for 12 consecutive weeks. | 21 |
| Placebo Group placebo three times per day for 12 consecutive weeks. | 20 |
| Total | 41 |
Baseline characteristics
| Characteristic | YH1 Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 56 years | 52 years |
| HbA1c | 8.1 % | 8.7 % | 8.6 % |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 21 Participants | 20 Participants | 41 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 13 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 12 / 23 | 13 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
The Percentage Change in HbA1c Level From Baseline to 12 Weeks
The primary efficacy endpoint was the percentage change in HbA1c levels from baseline to 12 weeks. The HbA1c level was measured by HPLC in the Department of Laboratory Medicine at Chang Gung Memorial Hospital.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| YH1 Group | The Percentage Change in HbA1c Level From Baseline to 12 Weeks | -11.1 percentage change |
| Placebo Group | The Percentage Change in HbA1c Level From Baseline to 12 Weeks | 0.0 percentage change |
Secondary
The Percentage Change in 2hPG From Baseline to Week 12
The secondary efficacy endpoint was the percentage change in 2hPG level from baseline to 12 weeks by using enzymatic method in the Department of Laboratory Medicine at Chang Gung Memorial Hospital.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| YH1 Group | The Percentage Change in 2hPG From Baseline to Week 12 | -26.2 percentage change |
| Placebo Group | The Percentage Change in 2hPG From Baseline to Week 12 | 5.1 percentage change |