Ezetimibe and Statins on Postprandial Lipemia in Type 2 Diabetes (EZE)

• Incremental AUC after a fat rich-meal of apo B48 concentration- marker of the number of intestinally derived lipoproteins- in chylomicron and VLDL [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Fasting LDL concentration [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Cholesterol/triglyceride ratio in postprandial chylomicrons and VLDL fractions. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Postprandial LDL size [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Concentration and Composition of different lipoprotein subclasses in the fasting condition. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

• incremental AUC after a fat rich-meal of apo B48 concentration- marker of the number of intestinally derived lipoproteins- in chylomicron and VLDL [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• fasting LDL concentration [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Cholesterol/triglyceride ratio in postprandial chylomicrons and VLDL fractions. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Postprandial LDL size. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Concentration and Composition of different lipoprotein subclasses in the fasting condition. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether ezetimibe in association with statins is more effective than statins alone on postprandial lipemia in type 2 diabetic patients.

• Postprandial Lipemia
• Type 2 Diabetes

• Drug: ezetimibe tablets
  ezetimibe tablets 10 mg/die
• Drug: simvastatin tablets
  simvastatin tablets 20 mg/die
• Drug: placebo
  placebo

• Experimental: 1
  ezetimibe tablets 10 mg/die + simvastatin tablets 20 mg/die six weeks
  Interventions:

  • Drug: ezetimibe tablets
  • Drug: simvastatin tablets
• Placebo Comparator: 2
  placebo + simvastatin tablets 20 mg/die six weeks
  Interventions:

  • Drug: simvastatin tablets
  • Drug: placebo

• Rivellese AA, De Natale C, Di Marino L, Patti L, Iovine C, Coppola S, Del Prato S, Riccardi G, Annuzzi G. Exogenous and endogenous postprandial lipid abnormalities in type 2 diabetic patients with optimal blood glucose control and optimal fasting triglyceride levels. J Clin Endocrinol Metab. 2004 May;89(5):2153-9.
• Annuzzi G, De Natale C, Iovine C, Patti L, Di Marino L, Coppola S, Del Prato S, Riccardi G, Rivellese AA. Insulin resistance is independently associated with postprandial alterations of triglyceride-rich lipoproteins in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2397-402. Epub 2004 Sep 30.
• Davidson MH, Toth PP. Combination therapy in the management of complex dyslipidemias. Curr Opin Lipidol. 2004 Aug;15(4):423-31. Review.

Inclusion Criteria:

• Type 2 diabetes since at least two years
• Stable metabolic control (HbA1c<8.0%) for at least six months on diet or diet+oral hypoglycemic drugs (insulin secretagogues or metformin), not to be changed during the study period.
• BMI<30 kg/m2 and body weight stable during the last six months.
• Both sexes; only post-menopausal women.
• LDL-cholesterol >130 mg/dl, plasma triglycerides <400 mg/dl.
• No use of hypolipidemic drugs in the last three months.

Exclusion Criteria:

• Patient with renal (serum creatinine >1.5 mg/dl) or hepatic (serum transaminases >three times upper normal values) impairment.
• Patients with history of cardiovascular disease.
• Pre-menopausal women.
• Any other acute or chronic degenerative disease.
• Anemia (Hb<12 g/dl).
• Uncontrolled blood pressure.
• Use of any drugs able to interfere with the study medications