Diabetes Mellitus, Type 2
Conditions
Keywords
Pioglitazone, Metformin, Type 2 Diabetes Mellitus
Brief summary
Secondary failure of sulfonylureas (SUs) can occur in about 30%-40% of type 2 diabetic patients after treatment with SUs for 5 years, although SUs are widely used in type 2 diabetic patients. This study was designed to evaluate the effectiveness and safety of adding compound preparation of pioglitazone and metformin for type 2 diabetic patients who have bad glycemic control with the initial treatment of SUs.
Detailed description
Design of this clinical trial was multicenter, randomized, double-blind and placebo parallel controlled. Type 2 diabetic patients having bad glycemic control with the initial treatment of SUs were included. They were randomly divided into experiment group and control group, respectively taking compound preparation of pioglitazone and metformin (2mg/500mg) and placebo with identical shape immediately before a meal twice a day. Course of the treatment was 12 weeks.
Interventions
taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks
DRUGPlacebo
taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks
Sponsors
Wuhan Iron and Steel Workers' Hospital
Wuhan Pu-Ai Hospital
Hubei Xinhua Hospital
Huazhong University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetic patients (WHO criterion, 1999) * 19kg/m2 ≤ BMI ≤ 35kg/m2 * Subject with the initial treatment of SUs on the basis of controlling diet and sport; treatment lasting for no less than 3 months and stable dose for at least 1 month; HbA1c 7-11% * No insulin therapy during 6 months before being selected * Not involved in any drug test during 3 months before being selected * No serious heart, liver or kidney diseases * Must have effective contraception methods for women of child-bearing age * Willing to being informed consent
Exclusion criteria
* Type 1 diabetes or other specific types of diabetes * Pregnancy, preparation for pregnancy, lactation and women of child-bearing age incapable of effective contraception methods * Uncooperative subject because of various reasons * Abnormal liver function, glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) \> twice the upper limits of normal * Impairment of renal function, serum creatinine: ≥ 133mmol/L for female，≥ 135mmol/L for male * Serious chronic gastrointestinal diseases * Edema * Serious heart diseases, such as cardiac insufficiency (level III or more according to NYHA), acute coronary syndrome and old myocardial infraction * Blood pressure: Systolic blood pressure (SBP) ≥ 180mmHg and/or diastolic blood pressure (DBP) ≥ 110mmHg * White blood count (WBC) \< 4.0×109/L or platelet count (PLT) \< 90×109/L，or definite anemia (Hb：\< 120g/L for male, \< 110g/L for female), or other hematological diseases * Endocrine system diseases, such as hyperthyroidism and hypercortisolism * Experimental drug allergy or frequent hypoglycemia * Psychiatric disorders, drug or other substance abuse * Diabetic ketoacidosis and hyperosmolar nonketotic coma requiring insulin therapy * Stressful situations such as surgery, serious trauma and so on * Chronic hypoxic diseases such as pulmonary emphysema and pulmonary heart disease * Combined use of drugs effecting glucose metabolism such as glucocorticoid * Tumor, especially bladder tumor and/or family history of bladder tumor and/or long-term hematuria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of HbA1c From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of HbA1c at the start of the trail and at week 12 in all subjects, then using the natural logarithm of HbA1c to analyze the change in HbA1c from baseline at week 12 and compare that between experiment group and control group, since the HbA1c wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change of Fasting Insulin From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of fasting insulin at the start of the trail and at week 12 in all subjects, then using the natural logarithm of fasting insulin to analyze the change in fasting insulin from baseline at week 12 and compare that between experiment group and control group, since the fasting insulin wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level). |
| Change of TC From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of TC(Total Cholesterol) at the start of the trail and at week 12 in all subjects, then analyzing the change in TC from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of TG From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of TG(Triglyceride) at the start of the trail and at week 12 in all subjects, then analyzing the change in TG from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of HDL From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of HDL(High-Density Lipoprotein) at the start of the trail and at week 12 in all subjects, then analyzing the change in HDL from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of LDL From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of LDL(Low-Density Lipoprotein) at the start of the trail and at week 12 in all subjects, then using the natural logarithm of LDL to analyze the change in LDL from baseline at week 12 and compare that between experiment group and control group, since the LDL wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level). |
| Change of FPG From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of FPG(fasting plasma glucose) at the start of the trail and at week 12 in all subjects, then using the natural logarithm of FPG to analyze the change in FPG from baseline at week 12 and compare that between experiment group and control group, since the FPG wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level). |
| Change of 2hPPG From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of 2hPPG(2-hour postprandial glucose) at the start of the trail and at week 12 in all subjects, then analyzing the change in 2hPPG from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of 2-hour Postprandial Insulin From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of 2-hour postprandial insulin at the start of the trail and at week 12 in all subjects, then using the natural logarithm of 2-hour postprandial insulin to analyze the change in 2-hour postprandial insulin from baseline at week 12 and compare that between experiment group and control group, since the 2-hour postprandial insulin wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change of TBil From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of TBil(total bilirubin) at the start of the trail and at week 12 in all subjects, then analyzing the change in TBil from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of DBil From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of DBil(direct bilirubin) at the start of the trail and at week 12 in all subjects, then analyzing the change in DBil from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of ALT From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of ALT at the start of the trail and at week 12 in all subjects, then analyzing the change in ALT from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
| Change of AST From Baseline at Week 12 | Baseline, Week 12 | Measuring venous level of AST at the start of the trail and at week 12 in all subjects, then analyzing the change in AST from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level). |
Countries
China
Participant flow
Recruitment details
98 participants were recruited at 15 hospitals in Wuhan between March 2012 and September 2013.
Pre-assignment details
All participants were randomized to the two groups.They had a week for washout before the trial, during which they received diet and sport instructions, kept the sulfonylureas (SUs) unchanged and didn't use any drugs affecting blood glucose.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone and Metformin Type 2 diabetic patients only took SUs previously. During a week for washout before the trial, they received diet and sport instructions, kept the SUs unchanged and didn't use any drugs affecting blood glucose. All participants added 1 tablet of pioglitazone and metformin twice a day (before breakfast and before dinner) orally for 12 weeks. | 46 |
| Placebo Type 2 diabetic patients only took SUs previously. During a week for washout before the trial, they received diet and sport instructions, kept the SUs unchanged and didn't use any drugs affecting blood glucose. All participants added 1 tablet of placebo twice a day (before breakfast and before dinner) orally for 12 weeks. | 51 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Pioglitazone and Metformin | Total | Placebo |
|---|---|---|---|
| 2-hour Postprandial Glucose(2hPPG) | 16.47 mmol/L STANDARD_DEVIATION 3.96 | 16.02 mmol/L STANDARD_DEVIATION 3.86 | 15.59 mmol/L STANDARD_DEVIATION 3.81 |
| Age, Continuous | 54.65 years STANDARD_DEVIATION 9.91 | 54.61 years STANDARD_DEVIATION 8.54 | 54.51 years STANDARD_DEVIATION 7.23 |
| Diastolic Blood Pressure(DBP) | 76.24 mmHg STANDARD_DEVIATION 6.38 | 76.87 mmHg STANDARD_DEVIATION 7.86 | 77.83 mmHg STANDARD_DEVIATION 8.78 |
| Direct Bilirubin(DBil) | 3.91 mmol/L STANDARD_DEVIATION 1.79 | 3.92 mmol/L STANDARD_DEVIATION 1.96 | 3.92 mmol/L STANDARD_DEVIATION 2.11 |
| Duration of Type 2 Diabetes | 4.86 years STANDARD_DEVIATION 3.67 | 4.64 years STANDARD_DEVIATION 3.63 | 4.39 years STANDARD_DEVIATION 3.63 |
| Glutamic-oxaloacetic Transaminase(AST) | 20.47 U/L STANDARD_DEVIATION 6.92 | 21.42 U/L STANDARD_DEVIATION 7.43 | 22.25 U/L STANDARD_DEVIATION 7.82 |
| Glutamic-pyruvic Transaminase(ALT) | 21.98 U/L STANDARD_DEVIATION 8.57 | 23.75 U/L STANDARD_DEVIATION 10.6 | 25.35 U/L STANDARD_DEVIATION 12 |
| Height(Female) | 158.23 cm STANDARD_DEVIATION 6 | 159.33 cm STANDARD_DEVIATION 5.68 | 159.88 cm STANDARD_DEVIATION 5.54 |
| Height(Male) | 169.17 cm STANDARD_DEVIATION 5.03 | 169.49 cm STANDARD_DEVIATION 5.69 | 169.92 cm STANDARD_DEVIATION 6.44 |
| High Density Lipoprotein(HDL) | 1.22 mmol/L STANDARD_DEVIATION 0.25 | 1.17 mmol/L STANDARD_DEVIATION 0.24 | 1.13 mmol/L STANDARD_DEVIATION 0.22 |
| ln(2-hour Postprandial Insulin) | 3.49 ln(mU/L) STANDARD_DEVIATION 0.67 | 3.49 ln(mU/L) STANDARD_DEVIATION 0.66 | 3.48 ln(mU/L) STANDARD_DEVIATION 0.65 |
| ln(Fasting Insulin) | 2.21 ln(mU/L) STANDARD_DEVIATION 0.62 | 2.19 ln(mU/L) STANDARD_DEVIATION 0.6 | 2.17 ln(mU/L) STANDARD_DEVIATION 0.58 |
| ln(Fasting Plasma Glucose(FPG)) | 2.16 ln(mmol/L) STANDARD_DEVIATION 0.23 | 2.12 ln(mmol/L) STANDARD_DEVIATION 0.21 | 2.08 ln(mmol/L) STANDARD_DEVIATION 0.18 |
| ln(HbA1c) | 2.14 ln(percent) STANDARD_DEVIATION 0.12 | 2.12 ln(percent) STANDARD_DEVIATION 0.19 | 2.10 ln(percent) STANDARD_DEVIATION 0.14 |
| ln(Low Density Lipoprotein(LDL)) | 0.90 ln(mmol/L) STANDARD_DEVIATION 0.32 | 0.88 ln(mmol/L) STANDARD_DEVIATION 0.39 | 0.87 ln(mmol/L) STANDARD_DEVIATION 0.45 |
| Race/Ethnicity, Customized Han | 45 participants | 95 participants | 50 participants |
| Race/Ethnicity, Customized Other ethnicity | 1 participants | 2 participants | 1 participants |
| Region of Enrollment China | 46 participants | 97 participants | 51 participants |
| Sex: Female, Male Female | 13 Participants | 39 Participants | 26 Participants |
| Sex: Female, Male Male | 33 Participants | 58 Participants | 25 Participants |
| Systolic Blood Pressure(SBP) | 125.35 mmHg STANDARD_DEVIATION 9.46 | 126.86 mmHg STANDARD_DEVIATION 9.98 | 128.46 mmHg STANDARD_DEVIATION 10.38 |
| Total Bilirubin(TBil) | 15.26 mmol/L STANDARD_DEVIATION 5.87 | 14.64 mmol/L STANDARD_DEVIATION 5.42 | 14.09 mmol/L STANDARD_DEVIATION 5 |
| Total Cholesterol(TC) | 4.76 mmol/L STANDARD_DEVIATION 0.79 | 4.76 mmol/L STANDARD_DEVIATION 0.92 | 4.76 mmol/L STANDARD_DEVIATION 1.04 |
| Triglyceride(TG) | 1.76 mmol/L STANDARD_DEVIATION 0.93 | 1.74 mmol/L STANDARD_DEVIATION 0.91 | 1.71 mmol/L STANDARD_DEVIATION 0.9 |
| Weight(Female) | 64.85 Kg STANDARD_DEVIATION 5.49 | 63.62 Kg STANDARD_DEVIATION 5.49 | 63.00 Kg STANDARD_DEVIATION 5.49 |
| Weight(Male) | 71.18 Kg STANDARD_DEVIATION 8.03 | 72.05 Kg STANDARD_DEVIATION 9.39 | 73.37 Kg STANDARD_DEVIATION 10.89 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 46 | 5 / 51 |
| serious Total, serious adverse events | 1 / 47 | 0 / 51 |
Outcome results
Primary
Change of HbA1c From Baseline at Week 12
Measuring venous level of HbA1c at the start of the trail and at week 12 in all subjects, then using the natural logarithm of HbA1c to analyze the change in HbA1c from baseline at week 12 and compare that between experiment group and control group, since the HbA1c wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded. Intention to treat analysis and last observational carried forward(LOCF) imputation method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of HbA1c From Baseline at Week 12 | ln(HbA1c) at Baseline | 2.14 ln(percent) | Standard Deviation 0.12 |
| Pioglitazone and Metformin | Change of HbA1c From Baseline at Week 12 | ln(HbA1c) at Week 12 | 1.95 ln(percent) | Standard Deviation 0.12 |
| Pioglitazone and Metformin | Change of HbA1c From Baseline at Week 12 | Change from Baseline at Week 12 | 0.19 ln(percent) | Standard Deviation 0.14 |
| Placebo | Change of HbA1c From Baseline at Week 12 | ln(HbA1c) at Baseline | 2.10 ln(percent) | Standard Deviation 0.14 |
| Placebo | Change of HbA1c From Baseline at Week 12 | ln(HbA1c) at Week 12 | 2.02 ln(percent) | Standard Deviation 0.17 |
| Placebo | Change of HbA1c From Baseline at Week 12 | Change from Baseline at Week 12 | 0.07 ln(percent) | Standard Deviation 0.21 |
Comparison: Null hypothesis is that there was no difference in change of HbA1c between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.065Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of HbA1c between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of HbA1c between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0005Wilcoxon (Mann-Whitney)
Secondary
Change of 2-hour Postprandial Insulin From Baseline at Week 12
Measuring venous level of 2-hour postprandial insulin at the start of the trail and at week 12 in all subjects, then using the natural logarithm of 2-hour postprandial insulin to analyze the change in 2-hour postprandial insulin from baseline at week 12 and compare that between experiment group and control group, since the 2-hour postprandial insulin wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | ln(2-hour Postprandial Insulin) at Baseline | 3.49 ln(mU/L) | Standard Deviation 0.67 |
| Pioglitazone and Metformin | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | ln(2-hour Postprandial Insulin) at Week 12 | 3.33 ln(mU/L) | Standard Deviation 0.75 |
| Pioglitazone and Metformin | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | Change from Baseline at Week 12 | 0.19 ln(mU/L) | Standard Deviation 0.83 |
| Placebo | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | ln(2-hour Postprandial Insulin) at Baseline | 3.48 ln(mU/L) | Standard Deviation 0.65 |
| Placebo | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | ln(2-hour Postprandial Insulin) at Week 12 | 3.64 ln(mU/L) | Standard Deviation 0.74 |
| Placebo | Change of 2-hour Postprandial Insulin From Baseline at Week 12 | Change from Baseline at Week 12 | -0.15 ln(mU/L) | Standard Deviation 0.77 |
Comparison: Null hypothesis is that there was no difference in change of 2-hour postprandial insulin between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.1147Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of 2-hour postprandial insulin between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.4006Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of 2-hour postprandial insulin between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0614Wilcoxon (Mann-Whitney)
Secondary
Change of 2hPPG From Baseline at Week 12
Measuring venous level of 2hPPG(2-hour postprandial glucose) at the start of the trail and at week 12 in all subjects, then analyzing the change in 2hPPG from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of 2hPPG From Baseline at Week 12 | 2hPPG at Baseline | 16.47 mmol/L | Standard Deviation 3.96 |
| Pioglitazone and Metformin | Change of 2hPPG From Baseline at Week 12 | 2hPPG at Week 12 | 12.68 mmol/L | Standard Deviation 3.43 |
| Pioglitazone and Metformin | Change of 2hPPG From Baseline at Week 12 | Change from Baseline at Week 12 | 3.65 mmol/L | Standard Deviation 3.73 |
| Placebo | Change of 2hPPG From Baseline at Week 12 | 2hPPG at Baseline | 15.59 mmol/L | Standard Deviation 3.81 |
| Placebo | Change of 2hPPG From Baseline at Week 12 | 2hPPG at Week 12 | 15.23 mmol/L | Standard Deviation 3.8 |
| Placebo | Change of 2hPPG From Baseline at Week 12 | Change from Baseline at Week 12 | 0.45 mmol/L | Standard Deviation 3.94 |
Comparison: Null hypothesis is that there was no difference in change of 2hPPG between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of 2hPPG between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.2428Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of 2hPPG between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0003Wilcoxon (Mann-Whitney)
Secondary
Change of Fasting Insulin From Baseline at Week 12
Measuring venous level of fasting insulin at the start of the trail and at week 12 in all subjects, then using the natural logarithm of fasting insulin to analyze the change in fasting insulin from baseline at week 12 and compare that between experiment group and control group, since the fasting insulin wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of Fasting Insulin From Baseline at Week 12 | ln(Fasting Insulin) at Baseline | 2.21 ln(mU/L) | Standard Deviation 0.62 |
| Pioglitazone and Metformin | Change of Fasting Insulin From Baseline at Week 12 | ln(Fasting Insulin) at Week 12 | 1.90 ln(mU/L) | Standard Deviation 0.58 |
| Pioglitazone and Metformin | Change of Fasting Insulin From Baseline at Week 12 | Change from Baseline at Week 12 | 0.35 ln(mU/L) | Standard Deviation 0.58 |
| Placebo | Change of Fasting Insulin From Baseline at Week 12 | ln(Fasting Insulin) at Baseline | 2.17 ln(mU/L) | Standard Deviation 0.58 |
| Placebo | Change of Fasting Insulin From Baseline at Week 12 | ln(Fasting Insulin) at Week 12 | 2.26 ln(mU/L) | Standard Deviation 0.74 |
| Placebo | Change of Fasting Insulin From Baseline at Week 12 | Change from Baseline at Week 12 | -0.08 ln(mU/L) | Standard Deviation 0.79 |
Comparison: Null hypothesis is that there was no difference in change of fasting insulin between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of fasting insulin between before and after treatment in Placebo group.. The test was performed with a significance level of 0.05.p-value: 0.7353Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of fasting insulin between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0013Wilcoxon (Mann-Whitney)
Secondary
Change of FPG From Baseline at Week 12
Measuring venous level of FPG(fasting plasma glucose) at the start of the trail and at week 12 in all subjects, then using the natural logarithm of FPG to analyze the change in FPG from baseline at week 12 and compare that between experiment group and control group, since the FPG wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of FPG From Baseline at Week 12 | ln(FPG) at Baseline | 2.16 ln(mmol/L) | Standard Deviation 0.23 |
| Pioglitazone and Metformin | Change of FPG From Baseline at Week 12 | ln(FPG) at Week 12 | 1.91 ln(mmol/L) | Standard Deviation 0.22 |
| Pioglitazone and Metformin | Change of FPG From Baseline at Week 12 | Change from Baseline at Week 12 | 0.25 ln(mmol/L) | Standard Deviation 0.24 |
| Placebo | Change of FPG From Baseline at Week 12 | ln(FPG) at Baseline | 2.08 ln(mmol/L) | Standard Deviation 0.18 |
| Placebo | Change of FPG From Baseline at Week 12 | ln(FPG) at Week 12 | 2.05 ln(mmol/L) | Standard Deviation 0.29 |
| Placebo | Change of FPG From Baseline at Week 12 | Change from Baseline at Week 12 | 0.04 ln(mmol/L) | Standard Deviation 0.28 |
Comparison: Null hypothesis is that there was no difference in change of FPG between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of FPG between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0849Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of FPG between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0005Wilcoxon (Mann-Whitney)
Secondary
Change of HDL From Baseline at Week 12
Measuring venous level of HDL(High-Density Lipoprotein) at the start of the trail and at week 12 in all subjects, then analyzing the change in HDL from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of HDL From Baseline at Week 12 | HDL at Baseline | 1.22 mmol/L | Standard Deviation 0.25 |
| Pioglitazone and Metformin | Change of HDL From Baseline at Week 12 | HDL at Week 12 | 1.33 mmol/L | Standard Deviation 0.29 |
| Pioglitazone and Metformin | Change of HDL From Baseline at Week 12 | Change from Baseline at Week 12 | -0.09 mmol/L | Standard Deviation 0.19 |
| Placebo | Change of HDL From Baseline at Week 12 | HDL at Baseline | 1.13 mmol/L | Standard Deviation 0.22 |
| Placebo | Change of HDL From Baseline at Week 12 | HDL at Week 12 | 1.15 mmol/L | Standard Deviation 0.26 |
| Placebo | Change of HDL From Baseline at Week 12 | Change from Baseline at Week 12 | 0.00 mmol/L | Standard Deviation 0.17 |
Comparison: Null hypothesis is that there was no difference in change of HDL between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.0038Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of HDL between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.3812Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of HDL between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0108Wilcoxon (Mann-Whitney)
Secondary
Change of LDL From Baseline at Week 12
Measuring venous level of LDL(Low-Density Lipoprotein) at the start of the trail and at week 12 in all subjects, then using the natural logarithm of LDL to analyze the change in LDL from baseline at week 12 and compare that between experiment group and control group, since the LDL wasn't normal distribution and was logarithmic normal distribution. Change = ln(Baseline Level) - ln(Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of LDL From Baseline at Week 12 | ln(LDL) at Baseline | 0.90 ln(mmol/L) | Standard Deviation 0.32 |
| Pioglitazone and Metformin | Change of LDL From Baseline at Week 12 | ln(LDL) at Week 12 | 0.89 ln(mmol/L) | Standard Deviation 0.28 |
| Pioglitazone and Metformin | Change of LDL From Baseline at Week 12 | Change from Baseline at Week 12 | 0.02 ln(mmol/L) | Standard Deviation 0.2 |
| Placebo | Change of LDL From Baseline at Week 12 | ln(LDL) at Baseline | 0.87 ln(mmol/L) | Standard Deviation 0.45 |
| Placebo | Change of LDL From Baseline at Week 12 | ln(LDL) at Week 12 | 0.83 ln(mmol/L) | Standard Deviation 0.34 |
| Placebo | Change of LDL From Baseline at Week 12 | Change from Baseline at Week 12 | 0.03 ln(mmol/L) | Standard Deviation 0.42 |
Comparison: Null hypothesis is that there was no difference in change of LDL between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.5476Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of LDL between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.1248Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of LDL between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.362Wilcoxon (Mann-Whitney)
Secondary
Change of TC From Baseline at Week 12
Measuring venous level of TC(Total Cholesterol) at the start of the trail and at week 12 in all subjects, then analyzing the change in TC from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of TC From Baseline at Week 12 | TC at Baseline | 4.76 mmol/L | Standard Deviation 0.79 |
| Pioglitazone and Metformin | Change of TC From Baseline at Week 12 | TC at Week 12 | 4.74 mmol/L | Standard Deviation 0.88 |
| Pioglitazone and Metformin | Change of TC From Baseline at Week 12 | Change from Baseline at Week 12 | 0.06 mmol/L | Standard Deviation 0.6 |
| Placebo | Change of TC From Baseline at Week 12 | TC at Baseline | 4.76 mmol/L | Standard Deviation 1.04 |
| Placebo | Change of TC From Baseline at Week 12 | TC at Week 12 | 4.66 mmol/L | Standard Deviation 0.83 |
| Placebo | Change of TC From Baseline at Week 12 | Change from Baseline at Week 12 | 0.09 mmol/L | Standard Deviation 0.8 |
Comparison: Null hypothesis is that there was no difference in change of TC between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.3795Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TC between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.4236Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TC between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 1Wilcoxon (Mann-Whitney)
Secondary
Change of TG From Baseline at Week 12
Measuring venous level of TG(Triglyceride) at the start of the trail and at week 12 in all subjects, then analyzing the change in TG from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on the full analysis set: all participants who were eligible or drop-out, but eliminated participants were excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of TG From Baseline at Week 12 | TG at Baseline | 1.76 mmol/L | Standard Deviation 0.93 |
| Pioglitazone and Metformin | Change of TG From Baseline at Week 12 | TG at Week 12 | 1.66 mmol/L | Standard Deviation 0.94 |
| Pioglitazone and Metformin | Change of TG From Baseline at Week 12 | Change from Baseline at Week 12 | 0.09 mmol/L | Standard Deviation 0.77 |
| Placebo | Change of TG From Baseline at Week 12 | TG at Baseline | 1.71 mmol/L | Standard Deviation 0.9 |
| Placebo | Change of TG From Baseline at Week 12 | TG at Week 12 | 1.85 mmol/L | Standard Deviation 1.49 |
| Placebo | Change of TG From Baseline at Week 12 | Change from Baseline at Week 12 | -0.17 mmol/L | Standard Deviation 1.24 |
Comparison: Null hypothesis is that there was no difference in change of TG between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.3151Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TG between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.6963Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TG between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.3204Wilcoxon (Mann-Whitney)
Other Pre-specified
Change of ALT From Baseline at Week 12
Measuring venous level of ALT at the start of the trail and at week 12 in all subjects, then analyzing the change in ALT from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on safety set：all participants who received intervention at least once and had actual data of safety record.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of ALT From Baseline at Week 12 | ALT at Baseline | 21.98 U/L | Standard Error 8.57 |
| Pioglitazone and Metformin | Change of ALT From Baseline at Week 12 | ALT at Week 12 | 21.63 U/L | Standard Error 7.17 |
| Pioglitazone and Metformin | Change of ALT From Baseline at Week 12 | Change from Baseline at Week 12 | 0.40 U/L | Standard Error 9.14 |
| Placebo | Change of ALT From Baseline at Week 12 | ALT at Baseline | 25.35 U/L | Standard Error 12 |
| Placebo | Change of ALT From Baseline at Week 12 | ALT at Week 12 | 24.80 U/L | Standard Error 10.01 |
| Placebo | Change of ALT From Baseline at Week 12 | Change from Baseline at Week 12 | 0.47 U/L | Standard Error 13.88 |
Comparison: Null hypothesis is that there was no difference in change of ALT between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.5636Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of ALT between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.3681Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of ALT between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.2589Wilcoxon (Mann-Whitney)
Other Pre-specified
Change of AST From Baseline at Week 12
Measuring venous level of AST at the start of the trail and at week 12 in all subjects, then analyzing the change in AST from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on safety set：all participants who received intervention at least once and had actual data of safety record.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of AST From Baseline at Week 12 | AST at Baseline | 20.47 U/L | Standard Deviation 6.92 |
| Pioglitazone and Metformin | Change of AST From Baseline at Week 12 | AST at Week 12 | 21.12 U/L | Standard Deviation 5.58 |
| Pioglitazone and Metformin | Change of AST From Baseline at Week 12 | Change from Baseline at Week 12 | -0.41 U/L | Standard Deviation 7.35 |
| Placebo | Change of AST From Baseline at Week 12 | AST at Baseline | 22.25 U/L | Standard Deviation 7.82 |
| Placebo | Change of AST From Baseline at Week 12 | AST at Week 12 | 21.87 U/L | Standard Deviation 6.03 |
| Placebo | Change of AST From Baseline at Week 12 | Change from Baseline at Week 12 | 0.41 U/L | Standard Deviation 8.5 |
Comparison: Null hypothesis is that there was no difference in change of AST between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.7972Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of AST between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.7801Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of AST between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.8744Wilcoxon (Mann-Whitney)
Other Pre-specified
Change of DBil From Baseline at Week 12
Measuring venous level of DBil(direct bilirubin) at the start of the trail and at week 12 in all subjects, then analyzing the change in DBil from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on safety set：all participants who received intervention at least once and had actual data of safety record.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of DBil From Baseline at Week 12 | DBil at Baseline | 3.91 mmol/L | Standard Deviation 1.79 |
| Pioglitazone and Metformin | Change of DBil From Baseline at Week 12 | DBil at Week 12 | 3.69 mmol/L | Standard Deviation 2.08 |
| Pioglitazone and Metformin | Change of DBil From Baseline at Week 12 | Change from Baseline at Week 12 | 0.12 mmol/L | Standard Deviation 2.08 |
| Placebo | Change of DBil From Baseline at Week 12 | DBil at Baseline | 3.92 mmol/L | Standard Deviation 2.11 |
| Placebo | Change of DBil From Baseline at Week 12 | DBil at Week 12 | 3.32 mmol/L | Standard Deviation 1.15 |
| Placebo | Change of DBil From Baseline at Week 12 | Change from Baseline at Week 12 | 0.55 mmol/L | Standard Deviation 2.04 |
Comparison: Null hypothesis is that there was no difference in change of DBil between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.0339Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of DBil between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.0997Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of DBil between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.5015Wilcoxon (Mann-Whitney)
Other Pre-specified
Change of TBil From Baseline at Week 12
Measuring venous level of TBil(total bilirubin) at the start of the trail and at week 12 in all subjects, then analyzing the change in TBil from baseline at week 12 and comparing that between experiment group and control group. Change = (Baseline Level - Week 12 Level).
Time frame: Baseline, Week 12
Population: Based on safety set：all participants who received intervention at least once and had actual data of safety record.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pioglitazone and Metformin | Change of TBil From Baseline at Week 12 | TBil at Baseline | 15.26 mmol/L | Standard Deviation 5.87 |
| Pioglitazone and Metformin | Change of TBil From Baseline at Week 12 | TBil at Week 12 | 14.72 mmol/L | Standard Deviation 6.09 |
| Pioglitazone and Metformin | Change of TBil From Baseline at Week 12 | Change from Baseline at Week 12 | 0.31 mmol/L | Standard Deviation 6.53 |
| Placebo | Change of TBil From Baseline at Week 12 | TBil at Baseline | 14.09 mmol/L | Standard Deviation 5 |
| Placebo | Change of TBil From Baseline at Week 12 | TBil at Week 12 | 13.44 mmol/L | Standard Deviation 4.23 |
| Placebo | Change of TBil From Baseline at Week 12 | Change from Baseline at Week 12 | 0.57 mmol/L | Standard Deviation 4.65 |
Comparison: Null hypothesis is that there was no difference in change of DBil between before and after treatment in Pioglitazone and Metformin group. The test was performed with a significance level of 0.05.p-value: 0.8034Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TBil between before and after treatment in Placebo group. The test was performed with a significance level of 0.05.p-value: 0.7675Wilcoxon (Mann-Whitney)
Comparison: Null hypothesis is that there was no difference in change of TBil between Pioglitazone and Metformin group and Placebo group. The test was performed with a significance level of 0.05.p-value: 0.6918Wilcoxon (Mann-Whitney)