Comparison of the Efficacy and Safety Between Pioglitazone and Placebo Added to Combination Therapy in Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this trial is to study the efficacy and safety of pioglitazone added to combination therapy of sulfonylurea plus metformin with placebo in patients with type 2 diabetes.

Detailed Description
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Pioglitazone hydrochloride, a thiazolidinedione compound, is a new therapeutic agent for the treatment of type 2 diabetes that reduces insulin resistance by enhancing insulin action in skeletal muscle, liver, and adipose tissue. In the study of diabetes, pioglitazone reduced the hyperglycemia, hyperinsulinemia, and hypertriglyceridemia characteristic of insulin-resistant states. The metabolic changes induced by pioglitazone result in increased responsiveness of insulin-dependent tissues and are observed in numerous models of insulin resistance. In the present randomized, double-blind, parallel study, we aim to compare the efficacy and safety of pioglitazone added to combination therapy of sulfonylurea plus metformin with those of sulfonylurea plus metformin for the treatment of type 2 diabetic patients.

Official Title
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To Compare the Efficacy and Safety Between Pioglitazone Added to Combination Therapy of Sulfonylurea Plus Metformin and Placebo Control Group in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, Aged > 25 years and had been diagnosed as type 2 diabetes for at least 3 months before study entry. Subjects have taken sulfonylurea plus metformin therapy for at least 3 months before study entry. Subjects have to take daily Metformin 500 2000mg tolerable dosages and sulfonylurea (such as the usage dose of glimepiride ≧4mg; dose of Gliclazide≧160mg; dose of Glipizide ≧20mg; dose of glyburide≧4mg) for at least 1 months. Those subjects with HbA1C historical levels between 7.0% and 11.0% within 3 month prior to study entry. BMI between 20-35 kg /m2. Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document. Subjects have been under stable diet control for at least 1 month before study entry. Subjects are willing to stick to current diet and sulfonylurea plus metformin treatment plan during this trial. Exclusion Criteria: Pregnant women or lactating mothers. Type 1 DM(IDDM), or diabetes caused by pancreas damage、secondary forms of diabetes, i.e., Cushing's syndrome or acromegaly. A history of acute metabolic complication within 3 months before study entry, i.e., ketoacidosis or hyperosmolar state (coma). There are significant macrovascular complications (i.e. unstable angina or acute myocardial infarction) or renal impairment (serum creatinine higher than 1.5 mg/dL). Have a known allergy to pioglitazone. Other medications can be taken if their use had been instituted before study entry, but agents that can interfere with study evaluations, including other oral antidiabetic agents and corticosteroids, were not allowed.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br> | Drug: Pioglitazone<br>* A total 16-week randomized, double-blind, controlled study to compare the efficacy and safety of pioglitazone 15mg once daily added to combination metformin plus sulfonylurea with those of placebo combining control group. (4-week run in period and 12-week pioglitazone 15mg added to combination therapy of sulfonylurea plus metformin and placebo control group in patients with type 2 diabetes)<br>|
| Placebo Comparator: Placebo<br> | Drug: Pioglitazone<br>* A total 16-week randomized, double-blind, controlled study to compare the efficacy and safety of pioglitazone 15mg once daily added to combination metformin plus sulfonylurea with those of placebo combining control group. (4-week run in period and 12-week pioglitazone 15mg added to combination therapy of sulfonylurea plus metformin and placebo control group in patients with type 2 diabetes)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in HbA1Cand FPG |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance (HOMA-IR index) |  | Week 12 |