Efficacy of Pioglitazone/Metformin Combination Therapy in Subjects With Type 2 Diabetes Mellitus and Dyslipidemia.

Effects of a Pioglitazone/Metformin Fixed Combination in Comparison to Metformin in Combination With Glimepiride on Diabetic Dyslipidemia

The purpose of this study is to compare pioglitazone and metformin combination therapy, twice daily (BID), to glimepiride and metformin combination therapy for treating diabetic subjects with dyslipidemia.

Insulin resistance is a major endocrinopathy preceding the development of hyperglycemia, diabetic dyslipidemia and cardiovascular disease in type 2 diabetes. The most common pattern of dyslipidemia in patients with type 2 diabetes are elevated triglyceride levels, decreased hih-density lipoprotein cholesterol and a predominance of small dense low-density lipoprotein particles. Each of these dyslipidemia features is associated with an increased risk of cardiovascular events.

Pioglitazone and Metformin are established drugs which can be used for the treatment of type 2 diabetes. This study will investigate the effects of treatment with fixed Pioglitazone/Metformin combination therapy of Metformin and Glimepiride in Metformin-pretreated type 2 diabetic patients with dyslipidemia.

Total participation time in this study is anticipated to be approximately 24 weeks.

Inclusion Criteria:

• Type 2 diabetes according to the American Diabetes Association Criteria.
• Treatment with individual maximal tolerated dose of metformin (850 - 2000 mg) as monotherapy within the last 12 weeks.
• Glycosylated Hemoglobin greater than or equal to 6.5% and less than or equal to 9%.
• Dyslipidemia defined as high-density lipoprotein cholesterol less than or equal to 1.03 mmol/l (40 mg/dL) and/or triglycerides greater than or equal to 1.7 mmol/l (150 mg/dL).
• Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.

Exclusion Criteria:

• Type 1 diabetes mellitus.

• Insulin-dependent type 2 diabetes mellitus.

• Treatment or history of treatment with any insulin formulation other than emergency for more than 2 weeks.

• Treatment with other oral antidiabetic drugs in addition to metformin within the last 12 weeks.

• Anamnestic history of hypersensitivity to the study drugs or to drugs with similar chemical structures.

• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

  • Heparin (and heparin-like drugs)

  • coumarin

  • phenprocoumon

  • hirudin

  • Protein C

  • Fondaparinux

  • antithrombin III

  • Peroxisome Proliferation Activating Receptor (gamma) agonists

  • Treatment within the last 12 weeks with:

    • fibrates
    • gemfibrozil
    • niacin
    • months
    • Rifampicin

  • Changes in dosage of any statin treatment to lower low-density lipoprotein within 2 weeks before study entry and during study participation interval.

  • Changes in dosage of any anticoagulant treatment with acetyl salicylic acid and/or clopidogrel within 2 weeks before study entry and during study participation interval.

  • Start of statin and/or anticoagulant treatment during study participation interval.

• History of severe or multiple allergies and/ or acute severe infections.

• Have had more than one unexplained episode of severe hypoglycemia (defined as requiring assistance of another person due to disabling hypoglycemia) within 6 months prior to screening visit.

• Progressive fatal disease.

• Any elective surgery during study participation.

• History of drug or alcohol abuse within the last 5 years.

• A history of significant cardiovascular (New York Heart Association stage I - IV), respiratory, gastrointestinal, hepatic (alanine aminotransferase and/or aspartate aminotransferase greater than 2.5 times the upper limit of the normal reference range), renal (serum creatinine greater than 1.2 mg/dL in women and greater than 1.5 mg/dL in men, glomerular filtration rate less than 60 ml/min as estimated by the Cockroft-Gault formula), neurological, psychiatric and/or hematological disease as judged by the investigator, history of macular edema.

• Blood donation within the last 30 days.