Derosa Giuseppe, Cicero Arrigo F G, D'Angelo Angela, Ragonesi Pietro D, Ciccarelli Leonardina, Piccinni Mario N, Pricolo Fabio, Salvadeo Sibilla A T, Ferrari Ilaria, Gravina Alessia, Fogari Roberto
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Hypertens Res. 2006 Nov;29(11):849-56. doi: 10.1291/hypres.29.849.
The aim of our study was to investigate the metabolic effect of telmisartan and irbesartan in subjects treated with rosiglitazone, a well-known insulin-sensitizing drug, in order to clarify the direct metabolic effects of the two former drugs. Patients were enrolled, evaluated, and followed at 3 Italian centers. We evaluated 188 type 2 diabetic patients with metabolic syndrome (94 males and 94 females in total; 49 males and 46 females, aged 56+/-5, treated with telmisartan; and 45 males and 48 females, aged 55+/-4, treated with irbesartan). All had been diabetic for at least 6 months, and glycemic control by the maximum tolerated dietary changes and maximum tolerated dose of oral hypoglycemic agents had been attempted and failed in all cases. All patients took a fixed dose of rosiglitazone, 4 mg/day. We administered telmisartan (40 mg/day) or irbesartan (150 mg/day) in a randomized, controlled, double-blind clinical manner. We evaluated body mass index (BMI), glycemic control (HbA1c fasting plasma glucose and insulin levels [FPG, and FPI, respectively], and homeostasis model assessment [HOMA] index), lipid profile (total cholesterol [TC], low density lipoprotein-cholesterol [LDL-C], high density lipoprotein-cholesterol [HDL-C], and triglycerides [TG]), systolic and diastolic blood pressure (SBP and DBP), tumor necrosis factor-alpha (TNF-alpha), and leptin during the 12 months of this treatment. No BMI change was observed after 6 or 12 months in either group. Significant decreases in HbAlc and FPG were observed after 6 months in the telmisartan group, and after 12 months in both groups. The decrease in HbA1c and FPG at 12 months was statistically significant only in the telmisartan group. A significant decrease in FPI was observed at 12 months in both groups, and this decrease was significantly greater in the telmisartan group. Significant decreases in the HOMA index were observed at 6 and 12 months in both groups, and the decrease in the HOMA index after 12 months was significantly greater in the telmisartan group than in the irbesartan group. Significant changes in SBP, DBP, TC, and LDL-C were observed after 6 and 12 months in both groups. Significant decreases in TNF-alpha and leptin levels were observed after 6 months in the telmisartan group, and after 12 months in both groups. In conclusion, in this study of patients with type 2 diabetes mellitus and metabolic syndrome, telmisartan seemed to result in a greater improvement in glycemic and lipid control and metabolic parameters related to metabolic syndrome compared to irbesartan. These observed metabolic effects of different angiotensin type 1 receptor blockers could be relevant when choosing a therapy to correct metabolic derangement of patients affected by metabolic syndrome and diabetes.
我们研究的目的是调查替米沙坦和厄贝沙坦对使用罗格列酮（一种著名的胰岛素增敏药物）治疗的受试者的代谢影响，以阐明前两种药物的直接代谢作用。患者在3个意大利中心进行招募、评估和随访。我们评估了188例患有代谢综合征的2型糖尿病患者（共94例男性和94例女性；49例男性和46例女性，年龄56±5岁，接受替米沙坦治疗；45例男性和48例女性，年龄55±4岁，接受厄贝沙坦治疗）。所有患者糖尿病病程至少6个月，且通过最大耐受饮食改变和最大耐受剂量的口服降糖药进行血糖控制的尝试均失败。所有患者均服用固定剂量的罗格列酮，4mg/天。我们以随机、对照、双盲的临床方式给予替米沙坦（40mg/天）或厄贝沙坦（150mg/天）。在治疗的12个月期间，我们评估了体重指数（BMI）、血糖控制情况（糖化血红蛋白、空腹血糖和胰岛素水平[分别为FPG和FPI]以及稳态模型评估[HOMA]指数）、血脂谱（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[TG]）、收缩压和舒张压（SBP和DBP）、肿瘤坏死因子-α（TNF-α）和瘦素。两组在6个月或12个月后均未观察到BMI变化。替米沙坦组在6个月后观察到糖化血红蛋白和FPG显著下降，两组在12个月后均观察到下降。12个月时糖化血红蛋白和FPG的下降仅在替米沙坦组具有统计学意义。两组在12个月时均观察到FPI显著下降，且替米沙坦组的下降幅度更大。两组在6个月和12个月时均观察到HOMA指数显著下降，且12个月后替米沙坦组HOMA指数的下降幅度显著大于厄贝沙坦组。两组在6个月和12个月后均观察到SBP、DBP、TC和LDL-C有显著变化。替米沙坦组在6个月后观察到TNF-α和瘦素水平显著下降，两组在12个月后均观察到下降。总之，在这项对2型糖尿病和代谢综合征患者的研究中，与厄贝沙坦相比，替米沙坦似乎在血糖和血脂控制以及与代谢综合征相关的代谢参数方面带来更大改善。在选择治疗方法以纠正受代谢综合征和糖尿病影响患者的代谢紊乱时，观察到的不同血管紧张素1型受体阻滞剂的这些代谢作用可能具有相关性。
