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Efficacy and safety of ezetimibe co‐administered with simvastatin in thiazolidinedione‐treated type 2 diabetic patients
Author(s) -
Gaudiani L. M.,
Lewin A.,
Meneghini L.,
Perevozskaya I.,
Plotkin D.,
Mitchel Y.,
Shah S.
Publication year - 2005
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2004.00420.x
Subject(s) - simvastatin , ezetimibe , medicine , pioglitazone , thiazolidinedione , type 2 diabetes , endocrinology , pharmacology , type 2 diabetes mellitus , cholesterol , lipid profile , rosiglitazone , combination therapy , statin , diabetes mellitus , gastroenterology
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.