@article {Gaudiani:January 2005:1462-8902:88, author = "Gaudiani, L. M.", author = "Lewin, A.", author = "Meneghini, L.", author = "Perevozskaya, I.", author = "Plotkin, D.", author = "Mitchel, Y.", author = "Shah, S.", title = "Efficacy and safety of ezetimibe coadministered with simvastatin in thiazolidinedione-treated type 2 diabetic patients", journal = "Diabetes, Obesity and Metabolism", volume = "7", year = "January 2005", abstract = "Aim: 

In patients with type 2 diabetes mellitus (T2DM), combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol (LDL-C) and other lipid parameters associated with cardiovascular risk. The thiazolidinediones (TZDs) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Ezetimibe, an intestinal cholesterol absorption inhibitor, has a mechanism of action that differs from that of statins, which inhibit hepatic cholesterol synthesis. We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin, vs. doubling the dose of simvastatin, in TZD-treated T2DM patients. Methods: 

This was a randomized, double-blind, parallel group, multicentre study in T2DM patients, 30–75 years of age, who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l (100 mg/dl) prior to study entry. Other antidiabetic medications were also allowed. Following 6 weeks of open-label simvastatin 20 mg/day, patients were randomized to the addition of either blinded ezetimibe 10 mg/day (n = 104) or an additional blinded simvastatin 20 mg/day (total simvastatin 40 mg/day; n = 110) for 24 weeks. Patients were stratified according to TZD type and dose (pioglitazone 15–30 vs. 45 mg/day; rosiglitazone 2–4 vs. 8 mg/day). Results: 

LDL-C was reduced more (p < 0.001) by adding ezetimibe 10 mg to simvastatin 20 mg (−20.8%) than by doubling the dose of simvastatin to 40 mg (−0.3%). Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C (p < 0.001), very low-density lipoprotein cholesterol (p < 0.05) and apolipoprotein B (p < 0.001) relative to simvastatin 40 mg. There were no differences between the groups with respect to changes in TG and HDL-C levels, and both treatments were well tolerated. Conclusions: 

Co-administration of ezetimibe with simvastatin, a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption, is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs.", pages = "88-97(10)", url = "http://www.ingentaconnect.com/content/bsc/dom/2005/00000007/00000001/art00012" doi = "doi:10.1111/j.1463-1326.2004.00420.x" }