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

William C Knowler1, Richard F Hamman, Sharon L Edelstein

  • 1George Washington University Biostatistics Center, Rockville, Maryland, USA.

Diabetes
|March 29, 2005
PubMed

Insights

Troglitazone effectively reduced type 2 diabetes incidence during its use in the Diabetes Prevention Program trial. However, this protective effect on diabetes prevention did not persist after the drug was discontinued.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Clinical Trials

Background:

  • The Diabetes Prevention Program (DPP) investigated interventions for type 2 diabetes prevention in high-risk individuals.
  • Troglitazone, an insulin-sensitizing agent, was evaluated as a potential preventative therapy.
  • Concerns about liver toxicity led to the early discontinuation of the troglitazone arm.

Purpose of the Study:

  • To compare the efficacy of troglitazone with metformin and intensive lifestyle intervention (ILS) in preventing type 2 diabetes.
  • To assess both the short-term (during treatment) and long-term (after withdrawal) effects of troglitazone on diabetes incidence.

Main Methods:

  • A randomized clinical trial involving 2352 participants assigned to metformin, troglitazone, placebo, or ILS.
  • Troglitazone treatment was administered from 1996 to 1998 before its discontinuation due to safety concerns.
  • Follow-up continued for all participants after troglitazone withdrawal to assess long-term outcomes.

Main Results:

  • During troglitazone treatment (mean 0.9 years), diabetes incidence was significantly lower compared to placebo (3.0 vs. 12.0 cases/100 person-years) and metformin (P=0.02).
  • The benefit of troglitazone was partly attributed to improved insulin sensitivity and maintained insulin secretion.
  • In the 3 years post-withdrawal, the diabetes incidence rate in the troglitazone group was similar to the placebo group, indicating a lack of persistent effect.

Conclusions:

  • Troglitazone demonstrated a significant, albeit temporary, reduction in type 2 diabetes incidence during its administration.
  • The diabetes-preventive action of troglitazone did not extend beyond the period of its use.
  • Further research is needed to determine if other thiazolidinediones can safely prevent diabetes with sustained use.

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