Long-term effects of troglitazone: open-label extension studies in type 2 diabetic patients.
Long-term effects of troglitazone: open-label extension studies in type 2 diabetic patients.
复制标题
曲格列酮的长期影响：2 型糖尿病患者的开放标签延伸研究。
作者：
Vivian Fonseca;H. Foyt;Katherine A. Shen;R. Whitcomb
目的
确定曲格列酮单药治疗或与磺脲类或胰岛素联合治疗对血糖和血脂指标的长期影响。
研究设计和方法
完成三项双盲研究（一项为期6个月的曲格列酮单药治疗研究、一项为期52周的曲格列酮联合微粉化格列本脲研究或一项为期6个月的曲格列酮联合胰岛素研究）之一的患者允许进入其各自双盲研究的开放标签扩展期。在曲格列酮单药治疗或磺酰脲类联合治疗的开放标签阶段，允许曲格列酮剂量滴定至最大600 mg，以应对血糖控制不佳，但不与胰岛素联合治疗。本文重点介绍了这些研究中使用的最高剂量曲格列酮（每日600 mg）的有效性。还列出了所有剂量下研究的所有患者的安全性数据。
结果
对于接受固定剂量600 mg曲格列酮治疗的患者，空腹血糖和HbA 1c水平从基线至开放标签期结束的平均变化分别为-57 mg/dl和-0.4%（单药治疗）; -49 mg/dl和-1.8%（磺脲类药物联合治疗）;-31 mg/dl和-1.0%（胰岛素联合治疗）。所有三项研究的合并队列中达到HbA 1c水平≤ 8%的患者比例为54%，而基线时仅为19%。三项研究中接受固定剂量600 mg曲格列酮治疗的所有患者中，甘油三酯从基线至开放标签期结束平均降低18%。在这三项开放标签研究中，曲格列酮的耐受性良好;在这三项研究中，共有758例患者完成了16，264患者月的曲格列酮总暴露，不良事件极少。
结论
长期单独使用曲格列酮或与磺脲类或胰岛素联合使用对维持2型糖尿病患者的血糖控制和降低高血糖是安全有效的。
OBJECTIVE
To determine the long-term effects of troglitazone as monotherapy or in combination with sulfonylureas or insulin regarding glycemic and lipid measures.
RESEARCH DESIGN AND METHODS
Patients who completed one of three double-blind studies (a 6-month troglitazone monotherapy study, a 52-week study of troglitazone in combination with micronized glyburide, or a 6-month study of troglitazone in combination with insulin) were allowed to enter open-label extensions of their respective double-blind studies. Troglitazone dose titrations were allowed to a maximum of 600 mg in response to inadequate glycemic control during the open-label phases of troglitazone monotherapy or sulfonylurea combination therapy but not with insulin combination therapy. This article focuses on the effectiveness of the highest dose of troglitazone used in these studies (600 mg daily). Safety data from all patients studied at all doses are also presented.
RESULTS
For patients who received a fixed dose of 600 mg troglitazone, mean changes in fasting serum glucose and HbA1c levels from baseline to the end of the open-label phase were -57 mg/dl and -0.4%, respectively (monotherapy); -49 mg/dl and -1.8%, respectively (sulfonylurea combination); and -31 mg/dl and -1.0%, respectively (insulin combination). The proportion of patients achieving an HbA1c level of < or =8% from the combined cohort of all three studies was 54% versus only 19% at baseline. The mean decrease in triglycerides from baseline to the end of the open-label phase was 18% among all patients in the three studies who received a fixed dose of 600 mg troglitazone. Troglitazone was well tolerated in these three open-label studies; a total of 758 patients completed a total exposure of 16,264 patient-months to troglitazone in these three studies with minimal adverse events.
CONCLUSIONS
Long-term use of troglitazone alone or in combination with sulfonylureas or insulin is safe and effective in sustaining glycemic control and in reducing hypertriglyceridemia in type 2 diabetic patients.