Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program - PubMed (original) (raw)

Clinical Trial

Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program

William C Knowler et al. Diabetes. 2005 Apr.

Abstract

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.

PubMed Disclaimer

Figures

FIG. 1

FIG. 1

Mean values of body weight, waist circumference, and FPG and 2-h postload glucose concentrations in response to treatment. Sample sizes are shown in Table 2.

FIG. 2

FIG. 2

A: Cumulative incidence of diabetes during the time when troglitazone was used, according to treatment assignment. B: Diabetes incidence rates (cases/100 person-years) with 95% CIs during the time when troglitazone was used, according to treatment assignment.

FIG. 3

FIG. 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.

Similar articles

Cited by

References

    1. The Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403. - PMC - PubMed
    1. The Diabetes Prevention Program Research Group. The Diabetes Prevention Program: design and methods for a clinical trial in the prevention of type 2 diabetes mellitus. Diabetes Care. 1999;22:623–634. - PMC - PubMed
    1. The Diabetes Prevention Program Research Group. The Diabetes Prevention Program (DPP): description of the lifestyle intervention. Diabetes Care. 2002;25:2165–2171. - PMC - PubMed
    1. Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med. 1994;331:1188–1193. - PubMed
    1. The Diabetes Prevention Program Research Group. The Diabetes Prevention Program: recruitment methods and results. Control Clin Trials. 2002;23:157–171. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources