Pioglitazone Versus Metformin in Type 2 Diabetes

Study Overview
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Brief Summary
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Type 2 diabetes is an epidemic. Its long-term consequences translate into enormous human suffering and economic costs; however, much of the morbidity associated with long-term microvascular and neuropathic complications can be substantially reduced by interventions that achieve glucose levels close to the nondiabetic range. However, none of the recent intervention studies has demonstrated a benefit of intensive glycemic control on their primary CVD outcomes. The investigators report the findings of a long-term randomized and comparator-controlled clinical trial conducted in patients with newly-diagnosed type 2 diabetes. The investigators compared the effect of pioglitazone with that of metformin on circulating endothelial cell-derived submicroscopic membranous vesicles, termed microparticles: because of their putative role in inflammatory processes and their ability to directly affect endothelial functions, they are gaining increasing popularity as a surrogate marker of cardiovascular outlook. Metformin was chosen as a comparator because the American Diabetes Association recommendations suggest to start therapy in newly-diagnosed type 2 diabetic subjects combining a drug (metformin) with lifestyle changes. Moreover, the mechanism of action of pioglitazone is distinct from that of metformin.

Official Title
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Effect of Pioglitazone Compared With Metformin on Endothelial Microparticles in Type 2 Diabetes. A Randomized Trial

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 30-75 years, with newly-diagnosed type 2 diabetes (according to the ADA criteria) and never treated with antihyperglycemic drugs, were selected for the study. Inclusion criteria also included a body mass index (BMI) >25 kg/m2, and HbA1c level <10%. Exclusion Criteria: Pregnancy or breast-feeding Any investigational drug within the previous 3 months Use of agents affecting glycemic control (systemic glucocorticoids, and weight-loss drugs) Presence of any clinically relevant somatic or mental diseases that anticipated poor adherence to diet regimens To minimize the likelihood of including subjects with late-onset type 1 diabetes, candidates with a positive test for anti-GAD antibody or with fasting plasma C-peptide less than 0.76 ng/L (<0.25 pmol/L) were excluded Also excluded were patients with abnormal laboratory tests, including liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase) greater than 3 times the upper limit of normal, and serum creatinine greater than 123.8 μmol/L (1.4 mg/dL).

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 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: 1<br> | Drug: Pioglitazone<br>* 15-45 mg/die<br>|
| Active Comparator: 2<br> | Drug: Metformin<br>* 500-2000 mg/die<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating Endothelial microparticles |  | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose profile, lipid profile, hemoglobin A1c, carotid intima-media thickness |  | six months |