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

Phase 4

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Placebo
Drug: Pioglitazone and Metformin

Registration Number: NCT02099838

Lead Sponsor: Huazhong University of Science and Technology

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 98

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Pioglitazone and Metformin	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).
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 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 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 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 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).