Article Summary Pharmacological Treatment of Insulin Resistance at Two Different Stages in the Evolution of Type 2 Diabetes: Impact on Glucose Tolerance and ß-Cell Function. Xiang AH, Peters RK, Kjos SL, Goico J, Ochoa C, Marroquin A, Tan S, Hodis HN, Azen SP, Buchanan TA. J Clin Endocrinol Metab. 2004;89:2846-2851. Objective: To evaluate the effect of troglitazone treatment on ß-cell function and blood glucose (BG) levels in Hispanic women with previous gestational diabetes mellitus (GDM) before developing and at the onset of diabetes. Note that although this abstract summarizes results of the Troglitazone in Prevention of Diabetes (TRIPOD) study as published, the trial was stopped 5 months before originally planned, as a result of the removal of troglitazone from the market. However, the study drug appeared to reduce endogenous insulin requirements and insulin resistance. The authors therefore suggest that treatment with other insulin sensitizers may have similar beneficial effects without the adverse events linked to troglitazone. Methods: Over a 3-year period, 266 nondiabetic Hispanic women with a history of GDM in the prior 4-year period were randomized to placebo or to 400-mg troglitazone in this double-blind study. Fasting plasma glucose was measured quarterly, and 75-g oral glucose tolerance tests were administered annually. Results: Only 236 women returned for at least 1 follow-up visit: 122 randomized to placebo (late intervention) and 114 randomized to study drug (early intervention). BG and insulin values rose significantly between baseline and end-of-trial testing in the late intervention group but remained stable in the early intervention arm. Treatment that was designed to ameliorate insulin resistance was superior in the early intervention group and appeared to preserve pancreatic ß-cell function. A decrease in ß-cell function characterized by progression to diabetes in the placebo arm was arrested when treatment with study drug was initiated at disease onset. Conclusion: Delaying treatment of insulin resistance until patients develop type 2 diabetes may be inferior to earlier pharmacologic intervention in at-risk populations.