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

• Change of the concentrations of Total Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
• Change of the concentrations of Low Densitiy Lipoprotein (LDL) -Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
• Change of the concentrations of High Density Lipoprotein (HDL) -Cholesterol [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]
• Change of the concentrations of triglycerides [ Time Frame: baseline and 6 weeks ] [ Designated as safety issue: No ]

• change of the concentrations of total cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• change of the concentrations of LDL-cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• change of the concentrations of HDL-cholesterol [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• change of the concentrations of triglycerides [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

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.

• Diabetes Mellitus Type 2
• Hypercholesterolemia

• Drug: ezetimibe
  ezetimibe 10 mg per day for six weeks
  Other Name: Ezetrol 10 mg
• Drug: simvastatin
  Simvastatin 20 mg per day for six weeks
  Other Name: Zocor MSD
• Drug: Ezetimibe 10/Simvastatin 20
  Ezetimibe 10mg/Simvastatin 20mg per day for six weeks
  Other Name: Inegy 10/20

• Active Comparator: Ezetimibe 10mg/d
  intake of ezetimibe 10mg per day for six weeks after wash-out
  Intervention: Drug: ezetimibe
• Active Comparator: Simvastatin 20 mg per day
  intake of simvastatin 20 mg per day for six weeks after wash-out
  Intervention: Drug: simvastatin
• Active Comparator: Ezetimibe 10 mg/d and Simvastatin 20mg/d
  intake of ezetimibe 10 mg and simvastatin 20 mg per day for six weeks after wash-out
  Intervention: Drug: Ezetimibe 10/Simvastatin 20

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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