Effect of Ezetimibe or Simvastatin or Both on Low Densitiy Lipoprotein -Subfractions in Patients With Type 2 Diabetes

The Effect of Ezetimibe 10 mg, Simvastatin 20 mg and the Combination of Simvastatin 20 mg Plus 10 mg Ezetimibe on Low Density Lipoprotein (LDL)-Subfractions in Patients With Type 2 Diabetes

It is of interest how ezetimibe alone or in combination with statin may influence atherogenic dense Low Density Lipoprotein (dLDL) in patients with type 2 diabetes mellitus. The primary objective of this study will be whether there is a change of the concentrations of Apolipoprotein B (ApoB) in dLDL from baseline in each of the 3 treatment groups.

The selective cholesterol resorption inhibitor ezetimibe belongs to a new class of cholesterol lowering drugs. It is of interest how ezetimibe alone or in combination with statin may influence atherogenic dense Low Density Lipoprotein (dLDL) in patients with type 2 diabetes mellitus.

The primary objective of this study will be whether there is a change of the concentrations of Apolipoprotein B (ApoB) in dLDL from baseline in each of the 3 treatment groups. The comparison between treatment groups is exploratory due to insufficient power to detect any change between treatments.

Inclusion Criteria:

• men > 18 and ≤ 75 years
• post-menopausal women ≤ 75 years (follicle stimulating hormone (FSH) >30 mIU/ml, women > 60 years FSH > 20 mIU/ml )
• well controlled diabetes mellitus type II (glycohaemoglobin ≤ 8,0 %)
• LDL-cholesterol ≤ 160 mg/dl
• LDL-subfractions: concentration of apoB-100 in dLDL (LDL-5 und LDL-6) > 25 mg/dl
• written informed consent

Exclusion Criteria:

• participation in a clinical trial within the last 30 d before screening- visit
• patient is unable to give written informed consent
• Body mass index <15 kg/m² and > 35 kg/m²
• clinical atherosclerotic disease (coronary heart disease, peripheral artery disease, carotid artery disease)
• malignoma
• uncontrolled arterial hypertension (>160/>100 mmHg)
• clinically relevant disease of liver and/or kidneys
• clinically relevant endocrinally or hematologic problems
• allergy to study medication (Ezetimibe and/or Simvastatin)
• alcohol- or drug abuse
• laboratory: alanine aminotransferase, aspartate aminotransferase, total bilirubin > 3 x ULN, creatine kinase > 5 x ULN
• Concurrent treatment with potent CYP3A4-inhibitors (e.g. itraconazole, ketoconazole, HIV-protease-inhibitors, erythromycin, clarithromycin, telithromycin und nefazodone)
• other relevant diseases