Effectiveness and Safety of Adding Compound Preparation of Pioglitazone and Metformin for Type 2 Diabetic Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Pioglitazone and Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone and Metformin<br>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. | Drug: Pioglitazone and Metformin<br>* taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks<br>* Other names: H20100180;|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* taking 1 tablet twice a day (before breakfast and before dinner) orally for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 
| 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). | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pioglitazone, Metformin, Type 2 Diabetes Mellitus