Durrington Paul N, Tuomilehto Jaakko, Hamann Andreas, Kallend David, Smith Karen
University of Manchester, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
Diabetes Res Clin Pract. 2004 May;64(2):137-51. doi: 10.1016/j.diabres.2003.11.012.
The aim of this study was to evaluate the effects of rosuvastatin and fenofibrate alone and in combination in type 2 diabetes associated with combined hyperlipidaemia. A total of 216 patients with total cholesterol >/=200 mg/dl (>/=5.17 mmol/l) and triglycerides >/=200 and <800 mg/dl (>/=2.26 and <9.03 mmol/l) were randomised to one of two placebo groups, rosuvastatin 5 mg or rosuvastatin 10 mg for 6 weeks (fixed-dose phase). During the subsequent 18-week dose-titration phase, one placebo group received titrated rosuvastatin 10, 20 and 40 mg (placebo/rosuvastatin); one placebo group received titrated fenofibrate 67 mg once, twice and three times daily (placebo/fenofibrate); and patients receiving 5 or 10 mg rosuvastatin received titrated fenofibrate as above (rosuvastatin 5mg/fenofibrate and rosuvastatin 10 mg/fenofibrate groups). Doses were increased at 6-week intervals if low-density lipoprotein (LDL) cholesterol remained >50 mg/dl (>1.3 mmol/l). At 24 weeks, the placebo/rosuvastatin group and placebo per fenofibrate group had triglyceride reductions of 30.3% versus 33.6%, respectively (P = NS), and LDL cholesterol was reduced by 46.7% in the rosuvastatin group and increased by 0.7% in the fenofibrate group (P < 0.001). The triglyceride reduction in the rosuvastatin 10 mg/fenofibrate group (47.1%) was significantly greater than in the placebo/rosuvastatin group (P = 0.001), with no significant differences in other lipid measures found between these two groups. No significant differences in effect on high-density lipoprotein (HDL) were observed among treatment groups. In the fixed-dose phase, rosuvastatin 5 and 10 mg reduced triglycerides by 24.5 and 29.5%, respectively, and decreased LDL cholesterol by 40.7 and 45.8%, respectively. All treatments were well tolerated. These results indicated that rosuvastatin produces marked reductions in triglycerides and LDL cholesterol when used alone or in combination with fenofibrate in type 2 diabetes patients with elevated cholesterol and triglyceride levels and may constitute a valuable treatment option in the diabetic population.
本研究旨在评估瑞舒伐他汀和非诺贝特单药及联合用药对伴有混合型高脂血症的2型糖尿病患者的影响。共有216例总胆固醇≥200mg/dl（≥5.17mmol/l）且甘油三酯≥200且<800mg/dl（≥2.26且<9.03mmol/l）的患者被随机分为两个安慰剂组、瑞舒伐他汀5mg组或瑞舒伐他汀10mg组，治疗6周（固定剂量期）。在随后的18周剂量滴定期，一个安慰剂组接受滴定剂量的瑞舒伐他汀10mg、20mg和40mg（安慰剂/瑞舒伐他汀）；一个安慰剂组接受滴定剂量的非诺贝特67mg，每日一次、两次和三次（安慰剂/非诺贝特）；接受5mg或10mg瑞舒伐他汀的患者接受如上滴定剂量的非诺贝特（瑞舒伐他汀5mg/非诺贝特组和瑞舒伐他汀10mg/非诺贝特组）。如果低密度脂蛋白（LDL）胆固醇仍>50mg/dl（>1.3mmol/l），则每隔6周增加剂量。在24周时，安慰剂/瑞舒伐他汀组和安慰剂/非诺贝特组的甘油三酯分别降低了30.3%和33.6%（P=无显著性差异），瑞舒伐他汀组的LDL胆固醇降低了46.7%，非诺贝特组升高了0.7%（P<0.001）。瑞舒伐他汀10mg/非诺贝特组的甘油三酯降低率（47.1%）显著高于安慰剂/瑞舒伐他汀组（P=0.001），两组之间在其他血脂指标上未发现显著差异。各治疗组在对高密度脂蛋白（HDL）的影响上未观察到显著差异。在固定剂量期，瑞舒伐他汀5mg和10mg分别使甘油三酯降低了24.5%和29.5%，使LDL胆固醇分别降低了40.7%和45.8%。所有治疗耐受性良好。这些结果表明，在胆固醇和甘油三酯水平升高的2型糖尿病患者中，瑞舒伐他汀单独使用或与非诺贝特联合使用时，可显著降低甘油三酯和LDL胆固醇，可能是糖尿病患者的一种有价值的治疗选择。
