Trial | NCT02099838  Report issue

Title

Effectiveness and Safety of Adding Compound Preparation of Pioglitazone and Metformin for Type 2 Diabetic Patients
The Randomized Multiple Center Trial for 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 Sulfonylureas

  • Phase

    Phase 4

  • Study Type

    Interventional

  • Study Participants

    98
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.
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.
Study Started
Jan 31
2012
Primary Completion
Dec 31
2013
Study Completion
Dec 31
2013
Results Posted
Jun 10
2014
Estimate
Last Update
Jun 25
2014
Estimate

Drug Pioglitazone and Metformin

taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks

  • Other names: Compound Preparation of Pioglitazone and Metformin, Kashuangping, H20100180

Drug Placebo

taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks

Pioglitazone and Metformin Experimental

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.

Placebo Placebo Comparator

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.

Criteria 

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

Summary

Pioglitazone and Metformin

Placebo

All Events

Event Type Organ System Event Term Pioglitazone and Metformin Placebo

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.19
ln(percent) (Mean)
Standard Deviation: 0.14

ln(HbA1c) at Baseline

2.14
ln(percent) (Mean)
Standard Deviation: 0.12

ln(HbA1c) at Week 12

1.95
ln(percent) (Mean)
Standard Deviation: 0.12

Placebo

Change from Baseline at Week 12

0.07
ln(percent) (Mean)
Standard Deviation: 0.21

ln(HbA1c) at Baseline

2.1
ln(percent) (Mean)
Standard Deviation: 0.14

ln(HbA1c) at Week 12

2.02
ln(percent) (Mean)
Standard Deviation: 0.17

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.25
ln(mmol/L) (Mean)
Standard Deviation: 0.24

ln(FPG) at Baseline

2.16
ln(mmol/L) (Mean)
Standard Deviation: 0.23

ln(FPG) at Week 12

1.91
ln(mmol/L) (Mean)
Standard Deviation: 0.22

Placebo

Change from Baseline at Week 12

0.04
ln(mmol/L) (Mean)
Standard Deviation: 0.28

ln(FPG) at Baseline

2.08
ln(mmol/L) (Mean)
Standard Deviation: 0.18

ln(FPG) at Week 12

2.05
ln(mmol/L) (Mean)
Standard Deviation: 0.29

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).

Pioglitazone and Metformin

2hPPG at Baseline

16.47
mmol/L (Mean)
Standard Deviation: 3.96

2hPPG at Week 12

12.68
mmol/L (Mean)
Standard Deviation: 3.43

Change from Baseline at Week 12

3.65
mmol/L (Mean)
Standard Deviation: 3.73

Placebo

2hPPG at Baseline

15.59
mmol/L (Mean)
Standard Deviation: 3.81

2hPPG at Week 12

15.23
mmol/L (Mean)
Standard Deviation: 3.80

Change from Baseline at Week 12

0.45
mmol/L (Mean)
Standard Deviation: 3.94

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.35
ln(mU/L) (Mean)
Standard Deviation: 0.58

ln(Fasting Insulin) at Baseline

2.21
ln(mU/L) (Mean)
Standard Deviation: 0.62

ln(Fasting Insulin) at Week 12

1.9
ln(mU/L) (Mean)
Standard Deviation: 0.58

Placebo

Change from Baseline at Week 12

-0.08
ln(mU/L) (Mean)
Standard Deviation: 0.79

ln(Fasting Insulin) at Baseline

2.17
ln(mU/L) (Mean)
Standard Deviation: 0.58

ln(Fasting Insulin) at Week 12

2.26
ln(mU/L) (Mean)
Standard Deviation: 0.74

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.19
ln(mU/L) (Mean)
Standard Deviation: 0.83

ln(2-hour Postprandial Insulin) at Baseline

3.49
ln(mU/L) (Mean)
Standard Deviation: 0.67

ln(2-hour Postprandial Insulin) at Week 12

3.33
ln(mU/L) (Mean)
Standard Deviation: 0.75

Placebo

Change from Baseline at Week 12

-0.15
ln(mU/L) (Mean)
Standard Deviation: 0.77

ln(2-hour Postprandial Insulin) at Baseline

3.48
ln(mU/L) (Mean)
Standard Deviation: 0.65

ln(2-hour Postprandial Insulin) at Week 12

3.64
ln(mU/L) (Mean)
Standard Deviation: 0.74

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.06
mmol/L (Mean)
Standard Deviation: 0.60

TC at Baseline

4.76
mmol/L (Mean)
Standard Deviation: 0.79

TC at Week 12

4.74
mmol/L (Mean)
Standard Deviation: 0.88

Placebo

Change from Baseline at Week 12

0.09
mmol/L (Mean)
Standard Deviation: 0.80

TC at Baseline

4.76
mmol/L (Mean)
Standard Deviation: 1.04

TC at Week 12

4.66
mmol/L (Mean)
Standard Deviation: 0.83

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.09
mmol/L (Mean)
Standard Deviation: 0.77

TG at Baseline

1.76
mmol/L (Mean)
Standard Deviation: 0.93

TG at Week 12

1.66
mmol/L (Mean)
Standard Deviation: 0.94

Placebo

Change from Baseline at Week 12

-0.17
mmol/L (Mean)
Standard Deviation: 1.24

TG at Baseline

1.71
mmol/L (Mean)
Standard Deviation: 0.90

TG at Week 12

1.85
mmol/L (Mean)
Standard Deviation: 1.49

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

-0.09
mmol/L (Mean)
Standard Deviation: 0.19

HDL at Baseline

1.22
mmol/L (Mean)
Standard Deviation: 0.25

HDL at Week 12

1.33
mmol/L (Mean)
Standard Deviation: 0.29

Placebo

Change from Baseline at Week 12

HDL at Baseline

1.13
mmol/L (Mean)
Standard Deviation: 0.22

HDL at Week 12

1.15
mmol/L (Mean)
Standard Deviation: 0.26

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.02
ln(mmol/L) (Mean)
Standard Deviation: 0.20

ln(LDL) at Baseline

0.9
ln(mmol/L) (Mean)
Standard Deviation: 0.32

ln(LDL) at Week 12

0.89
ln(mmol/L) (Mean)
Standard Deviation: 0.28

Placebo

Change from Baseline at Week 12

0.03
ln(mmol/L) (Mean)
Standard Deviation: 0.42

ln(LDL) at Baseline

0.87
ln(mmol/L) (Mean)
Standard Deviation: 0.45

ln(LDL) at Week 12

0.83
ln(mmol/L) (Mean)
Standard Deviation: 0.34

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).

Pioglitazone and Metformin

ALT at Baseline

21.98
U/L (Mean)
Standard Error: 8.57

ALT at Week 12

21.63
U/L (Mean)
Standard Error: 7.17

Change from Baseline at Week 12

0.4
U/L (Mean)
Standard Error: 9.14

Placebo

ALT at Baseline

25.35
U/L (Mean)
Standard Error: 12.00

ALT at Week 12

24.8
U/L (Mean)
Standard Error: 10.01

Change from Baseline at Week 12

0.47
U/L (Mean)
Standard Error: 13.88

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).

Pioglitazone and Metformin

AST at Baseline

20.47
U/L (Mean)
Standard Deviation: 6.92

AST at Week 12

21.12
U/L (Mean)
Standard Deviation: 5.58

Change from Baseline at Week 12

-0.41
U/L (Mean)
Standard Deviation: 7.35

Placebo

AST at Baseline

22.25
U/L (Mean)
Standard Deviation: 7.82

AST at Week 12

21.87
U/L (Mean)
Standard Deviation: 6.03

Change from Baseline at Week 12

0.41
U/L (Mean)
Standard Deviation: 8.50

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.31
mmol/L (Mean)
Standard Deviation: 6.53

TBil at Baseline

15.26
mmol/L (Mean)
Standard Deviation: 5.87

TBil at Week 12

14.72
mmol/L (Mean)
Standard Deviation: 6.09

Placebo

Change from Baseline at Week 12

0.57
mmol/L (Mean)
Standard Deviation: 4.65

TBil at Baseline

14.09
mmol/L (Mean)
Standard Deviation: 5.00

TBil at Week 12

13.44
mmol/L (Mean)
Standard Deviation: 4.23

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).

Pioglitazone and Metformin

Change from Baseline at Week 12

0.12
mmol/L (Mean)
Standard Deviation: 2.08

DBil at Baseline

3.91
mmol/L (Mean)
Standard Deviation: 1.79

DBil at Week 12

3.69
mmol/L (Mean)
Standard Deviation: 2.08

Placebo

Change from Baseline at Week 12

0.55
mmol/L (Mean)
Standard Deviation: 2.04

DBil at Baseline

3.92
mmol/L (Mean)
Standard Deviation: 2.11

DBil at Week 12

3.32
mmol/L (Mean)
Standard Deviation: 1.15

Total

97
Participants

2-hour Postprandial Glucose(2hPPG)

16.02
mmol/L (Mean)
Standard Deviation: 3.86

Age, Continuous

54.61
years (Mean)
Standard Deviation: 8.54

Diastolic Blood Pressure(DBP)

76.87
mmHg (Mean)
Standard Deviation: 7.86

Direct Bilirubin(DBil)

3.92
mmol/L (Mean)
Standard Deviation: 1.96

Duration of Type 2 Diabetes

4.64
years (Mean)
Standard Deviation: 3.63

Glutamic-oxaloacetic Transaminase(AST)

21.42
U/L (Mean)
Standard Deviation: 7.43

Glutamic-pyruvic Transaminase(ALT)

23.75
U/L (Mean)
Standard Deviation: 10.60

Height(Female)

159.33
cm (Mean)
Standard Deviation: 5.68

Height(Male)

169.49
cm (Mean)
Standard Deviation: 5.69

High Density Lipoprotein(HDL)

1.17
mmol/L (Mean)
Standard Deviation: 0.24

ln(2-hour Postprandial Insulin)

3.49
ln(mU/L) (Mean)
Standard Deviation: 0.66

ln(Fasting Insulin)

2.19
ln(mU/L) (Mean)
Standard Deviation: 0.60

ln(Fasting Plasma Glucose(FPG))

2.12
ln(mmol/L) (Mean)
Standard Deviation: 0.21

ln(HbA1c)

2.12
ln(percent) (Mean)
Standard Deviation: 0.19

ln(Low Density Lipoprotein(LDL))

0.88
ln(mmol/L) (Mean)
Standard Deviation: 0.39

Systolic Blood Pressure(SBP)

126.86
mmHg (Mean)
Standard Deviation: 9.98

Total Bilirubin(TBil)

14.64
mmol/L (Mean)
Standard Deviation: 5.42

Total Cholesterol(TC)

4.76
mmol/L (Mean)
Standard Deviation: 0.92

Triglyceride(TG)

1.74
mmol/L (Mean)
Standard Deviation: 0.91

Weight(Female)

63.62
Kg (Mean)
Standard Deviation: 5.49

Weight(Male)

72.05
Kg (Mean)
Standard Deviation: 9.39

Race/Ethnicity, Customized

Region of Enrollment

Sex: Female, Male

Overall Study

Pioglitazone and Metformin

Placebo

Drop/Withdrawal Reasons

Pioglitazone and Metformin

Placebo