Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: A multicenter, randomized, double-blind, controlled clinical trial
Effects of 1 year of treatment with pioglitazone or rosiglitazone added to glimepiride on lipoprotein (a) and homocysteine concentrations in patients with type 2 diabetes mellitus and metabolic syndrome: A multicenter, randomized, double-blind, controlled clinical trial
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DOI：
10.1016/j.clinthera.2006.05.012
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发表时间：
2006-05-01
影响因子：
3.2
通讯作者：
Ragonesi, Pietro D.
中科院分区：
文献类型：
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作者：
Derosa, Giuseppe;Cicero, Arrigo F. G.;Ragonesi, Pietro D.
背景：虽然噻唑烷二酮类药物的代谢影响已得到充分研究，但缺乏其对某些心血管危险因素影响的比较数据，例如血浆脂蛋白 (a) (Lp[a]) 和同型半胱氨酸 (Hcy) 水平升高。 目的：本研究比较了格列美脲中添加吡格列酮或罗格列酮对 2 型糖尿病患者的一系列血脂参数的影响，重点是 Lp(a) 和 Hey方法：这是一项针对 2 型糖尿病和代谢综合征（高血压 [ >= 130/85 mm Hg]）和甘油三酯血症（>= 150 mg/dL）患者的多中心、随机、对照、双盲研究。除了格列美脲 4 mg/d 外，患者还接受吡格列酮 15 mg QD 或罗格列酮 4 mg QD，为期 1 年。主要功效变量是体重指数 (BMI)、糖化血红蛋白 (HbA(1c))、Lp(a) 和 Hcy 相对于基线的变化。次要疗效指标是空腹血糖 (FPG) 和餐后血糖 (PPG) 浓度、空腹和餐后胰岛素浓度（分别为 FPI 和 PPI）、稳态模型评估指数和脂质谱（总胆固醇 [TC]、低密度脂蛋白胆固醇 [LDL-C]、高密度脂蛋白胆固醇 [HDL-C] 和甘油三酯）的变化。所有这些参数都是在一年内每 3 个月禁食 12 小时后测量一次。根据每次研究访视时报告的不良事件和实验室异常情况评估耐受性。结果：纳入了 91 名患有 2 型糖尿病和代谢综合征的白人患者，其中 87 名完成了研究（43 名男性，44 名女性；平均 [SD] 年龄，53 [6] 岁；平均体重，68.4 [3.3] kg）。 BMI 和 HbA(1c) 的平均基线值分别为 24.3 (0.8) kg/m(2) 和 8.1% (0.8%)。 1 年结束时，两个治疗组的 BMI 均较基线显着增加（4.9% 格列美脲 + 吡格列酮，6.2% 格列美脲 + 罗格列酮；P < 0.05）。格列美脲+吡格列酮与以下血糖控制指标较基线改善百分比相关：HbA(1c) -17.1%、FPG -19.3%、PPG -1.7.8%、FPI -40.1% 和 PPI -22.6%（全部，P < 0.01）。格列美脲 + 罗格列酮相对于基线的相应改善百分比分别为 -16.3%、-19.9%、-15.0%、-44.8% 和 -22.1%（全部，P < 0.01）。治疗组之间在任何这些参数上均没有显着差异。吡格列酮组的 TC (-11.1%)、LDL-C (-12.0%)、HDL-C (15.0%) 和甘油三酯 (22.4%) 较基线显着改善（全部，P < 0.05），而罗格列酮组的 TC (14.9%)、LDL-C (16.5%) 和甘油三酯显着增加(17.9%)（全部，P < 0.05）；吡格列酮与罗格列酮比较差异有统计学意义（P < 0.05）。吡格列酮组的 Lp(a) 相对于基线的变化显着，无论是相对于基线还是与罗格列酮组相比（分别为 -19.7% 与 0.5%；与基线相比和与罗格列酮组相比，P < 0.05）。吡格列酮组和罗格列酮组的 Hcy 相对于基线的变化均显着（分别为 -20.2% 和 -25.0%；P < 0.05），但组间无显着差异。两种治疗的耐受性良好，并且没有患者的转氨酶发生显着变化。结论：在这些患有 2 型糖尿病和代谢综合征的患者中，格列美脲与吡格列酮以及格列美脲与罗格列酮的组合在血糖控制、血脂和同型半胱氨酸血症方面产生了显着改善。与罗格列酮组合相比，吡格列酮组合治疗一年后血浆 Lp(a) 水平显着降低。
Background: Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy).Objective: This study compared the effects of pioglitazone or rosiglitazone added to glimepiride on a range of lipid parameters, focusing on Lp(a) and Hey, in patients with type 2 diabetes mellitus and the metabolic syndrome.Methods: This was a multicenter, randomized, controlled, double-blind study in patients with type 2 diabetes and the metabolic syndrome (hypertension [ >= 130/85 mm Hg]) and triglyceridemia ( >= 150 mg/dL). In addition to glimepiride 4 mg/d, patients received pioglitazone 15 mg QD or rosiglitazone 4 mg QD for 1 year. The primary efficacy variables were change from baseline in body mass index (BMI), glycosylated hemoglobin (HbA(1c)), Lp(a), and Hcy. Secondary efficacy measures were changes in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) concentrations, fasting and postprandial insulin concentrations (FPI and PPI, respectively), the Homeostasis Model Assessment index, and the lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides). All these parameters were measured after a 12-hour fast every 3 months for 1 year. Tolerability was assessed based on reported ad-verse events and laboratory abnormalities at each study visit.Results: Ninety-one white patients with type 2 diabetes and the metabolic syndrome were enrolled, and 87 completed the study (43 men, 44 women; mean [SD] age, 53 [6] years; mean weight, 68.4 [3.3] kg). Mean baseline values for BMI and HbA(1c) were 24.3 (0.8) kg/m(2) and 8.1% (0.8%), respectively. At the end of 1 year, both treatment groups had significant increases from baseline in BMI (4.9% glimepiride + pioglitazone, 6.2% glimepiride + rosiglitazone; P < 0.05). Glimepiride + pioglitazone was associated with the following percent improvements from baseline in measures of glycemic control: -17.1% in HbA(1c), -19.3% in FPG, -1.7.8% in PPG, -40.1% in FPI, and -22.6% in PPI (all, P < 0.01). The corresponding percent improvements from baseline with glimepiride + rosiglitazone were -16.3%, -19.9%, -15.0%, -44.8%, and -22.1% (all, P < 0.01). There were no significant differences between treatment groups in any of these parameters. The pioglitazone group had significant improvements from baseline in TC (-11.1%), LDL-C (-12.0%), HDL-C (15.0%), and triglycerides (22.4%) (all, P < 0.05), whereas the rosiglitazone group had significant increases in TC (14.9%), LDL-C (16.5%), and triglycerides (17.9%) (all, P < 0.05); the difference between pioglitazone and rosiglitazone was statistically significant (P < 0.05). The change from baseline in Lp(a) was significant in the pioglitazone group, both relative to baseline and compared with the rosiglitazone group (-19.7% vs 0.5%, respectively; P < 0.05 vs baseline and vs rosiglitazone). Changes from baseline in Hcy were significant in both the pioglitazone and rosiglitazone groups (-20.2% and -25.0%, respectively; P < 0.05), with no significant difference between groups. Both treatments were well tolerated, and no patients had significant changes in transaminases.Conclusions: In these patients with type 2 diabetes and the metabolic syndrome, the combinations of glimepiride with pioglitazone and glimepiride with rosiglitazone produced significant improvements in measures of glycemic control, plasma lipids, and homocysteinemia. One year of treatment with the pioglitazone combination was associated with significantly reduced plasma Lp(a) levels compared with the rosiglitazone combination.