糖尿病预防计划中使用曲格列酮预防2型糖尿病

Abstract
Background:
The purpose of the Diabetes Prevention Program (DPP) was to determine whether type 2 diabetes could be prevented or delayed through lifestyle or medication interventions applied to a high-risk population. Troglitazone, an insulin-sensitizing agent, was initially used but was discontinued. Troglitazone therapy was compared with other DPP interventions, in terms of both the short-term, in-trial results and longer term results after troglitazone was discontinued.

Methods:
From 1996 to 1998, study participants were randomly assigned to treatment with metformin (587 participants), troglitazone (585 participants), double placebo (582 participants), or intensive lifestyle intervention (589 participants). Concerns over the liver toxicity of troglitazone and the death of 1 patient in the troglitazone-treated group forced its discontinuation in June 1998.

Results:
During the mean 0.9 year 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 intense lifestyle intervention groups. This effect of troglitazone was attributable in part to improved insulin sensitivity with maintenance of insulin secretion. In the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group (Fig 3).

 

Figure 3: A: Cumulative incidence of diabetes (%) from date of randomization in participants assigned to placebo or troglitazone. B: Cumulative incidence of diabetes (%) from date of discontinuation of troglitazone (4 June 1998) in participants assigned to placebo or troglitazone. C: Diabetes incidence rates (cases/100 person-years) from date of randomization, showing the date of discontinuation of troglitazone (4 June 1998), in participants assigned to placebo or troglitazone. (Courtesy of Knowler WC, Diabetes Prevention Program Research Group: Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes 54:1150–1156, 2005. Copyright 2005 American Diabetes Association.)

Conclusions:
Troglitazone produced a significant reduction in the incidence of diabetes in the limited period of use, but this effect did not persist after withdrawal of the drug because of concerns about liver toxicity. Additional studies are needed to determine whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes.