Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program.
Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program.
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DOI：
10.2337/diabetes.54.4.1150
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发表时间：
2005-04
期刊：
影响因子：
7.7
通讯作者：
W. Knowler;R. Hamman;S. Edelstein;E. Barrett-Connor;D. Ehrmann;E. Walker;S. Fowler;D. Nathan;S. Kahn
中科院分区：
文献类型：
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作者：
W. Knowler;R. Hamman;S. Edelstein;E. Barrett-Connor;D. Ehrmann;E. Walker;S. Fowler;D. Nathan;S. Kahn
糖尿病预防计划 (DPP) 是一项针对高危人群预防 2 型糖尿病的随机临床试验。曲格列酮是一种胰岛素增敏剂，最初使用，但在试验期间停用。将曲格列酮治疗与其他 DPP 干预措施进行比较，同时考虑短期“试验中”结果和停用曲格列酮后的长期结果。从 1996 年到 1998 年，参与者被随机分配接受二甲双胍 (n = 587)、曲格列酮 (n = 585)、双安慰剂 (n = 582) 或强化生活方式干预 (ILS) (n = 589) 治疗。由于担心其肝脏毒性，曲格列酮组于 1998 年 6 月停止使用，此后继续对所有参与者进行随访。在曲格列酮治疗的平均 0.9 年（范围 0.5-1.5 年）期间，糖尿病发病率为 3.0 例/100 人年，而安慰剂、二甲双胍和 ILS 参与者的糖尿病发病率为 12.0、6.7 和 5.1 例/100 人年（P < 0.001，曲格列酮与安慰剂；P = 0.02，曲格列酮与二甲双胍；P = 0.18，曲格列酮与 ILS）。曲格列酮的这种作用部分是由于改善胰岛素敏感性并维持胰岛素分泌。曲格列酮停药后3年内，糖尿病发病率与安慰剂组几乎相同。因此，曲格列酮在有限的使用期内显着降低了糖尿病的发病率，但这种作用并没有持续下去。长期使用其他噻唑烷二酮类药物是否可以安全地预防糖尿病仍有待确定。
The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in high-risk people. Troglitazone, an insulin-sensitizing agent, was used initially but was discontinued during the trial. Troglitazone therapy was compared with other DPP interventions, considering both the short-term "in-trial" results and the longer-term results after troglitazone were discontinued. From 1996 to 1998, participants were randomly assigned to treatment with metformin (n = 587), troglitazone (n = 585), double placebo (n = 582), or intensive lifestyle intervention (ILS) (n = 589). Because of concern regarding its liver toxicity, the troglitazone arm was discontinued in June 1998, after which follow-up of all participants continued. During the mean 0.9 year (range 0.5-1.5 years) of troglitazone treatment, the diabetes incidence rate was 3.0 cases/100 person-years, compared with 12.0, 6.7, and 5.1 cases/100 person-years in the placebo, metformin, and ILS participants (P < 0.001, troglitazone vs. placebo; P = 0.02, troglitazone vs. metformin; P = 0.18, troglitazone vs. ILS). This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion. During the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group. Troglitazone, therefore, markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist. Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined.