Mohideen Pharis, Bornemann Michael, Sugihara Jared, Genadio Viola, Sugihara Valerie, Arakaki Richard
Department of Medicine of the John A. Burns School of Medicine, University of Hawaii-Manoa, Honolulu, USA.
Endocrine. 2005 Nov;28(2):181-6. doi: 10.1385/ENDO:28:2:181.
Thiazolidinediones (TZD) are effective agents for the treatment of hyperglycemia, and appear ideal in diabetic patients with progressive or end-stage renal disease because of its predominant hepatic clearance. Troglitazone, the first available TZD for clinical use, was withdrawn due to safety concerns; however, studies completed with this agent can provide a better understanding of the class effect of TZDs. This study was an open-label, controlled clinical trial examining the safety and efficacy of troglitazone in type 2 diabetic patients with end-stage renal disease (ESRD). Twelve subjects were randomized to parallel study groups and treated for 6 mo with or without troglita-zone at a maximum dose of 600 mg/d in addition to continuing their previous diabetes medications (insulin or sulfonylurea). The results showed no significant differences in glycemic control with or without troglit-azone treatment for 6 mo. However, there was a significant reduction in insulin dosage with troglitazone treatment (22.9 +/- 7.3 units/d) than without troglita-zone treatment (54 +/- 12.9 units/d) (p < 0.05), as well as the change in the insulin dosage from baseline between the two groups (troglitazone, -8.4 units vs control, +4.3 units, p < 0.05). Weight changes and aspartate amino-transferase levels greater than 1.5 times the upper limit of normal were not observed in participants of either treatment group. This study demonstrates that troglit-azone was safe and effective for the treatment of hyper-glycemia in patients requiring dialysis, and strongly supports the clinical use of currently available TZDs in diabetic patients with renal failure.
噻唑烷二酮类药物（TZD）是治疗高血糖的有效药物，因其主要通过肝脏清除，所以对于患有进展性或终末期肾病的糖尿病患者似乎是理想之选。曲格列酮是首个可供临床使用的TZD，但由于安全问题已被撤市；然而，用该药物完成的研究能够让人们更好地了解TZD的类效应。本研究是一项开放标签的对照临床试验，旨在检验曲格列酮在2型终末期肾病（ESRD）糖尿病患者中的安全性和疗效。12名受试者被随机分为平行研究组，除继续使用之前的糖尿病药物（胰岛素或磺脲类药物）外，接受或不接受曲格列酮治疗6个月，最大剂量为600mg/d。结果显示，接受或不接受曲格列酮治疗6个月，血糖控制情况无显著差异。然而，曲格列酮治疗组的胰岛素剂量（22.9±7.3单位/天）较未接受曲格列酮治疗组（54±12.9单位/天）显著降低（p<0.05），两组间胰岛素剂量相对于基线的变化也有显著差异（曲格列酮组为-8.4单位，对照组为+4.3单位，p<0.05）。两个治疗组的参与者均未观察到体重变化以及天冬氨酸氨基转移酶水平高于正常上限1.5倍的情况。本研究表明，曲格列酮对于需要透析的患者治疗高血糖是安全有效的，并有力地支持了目前可用的TZD在肾衰竭糖尿病患者中的临床应用。
