The effect of troglitazone on coagulation markers among individuals with prediabetes

The present work is focused on coagulation defects associated with prediabetes, which are reflected in laboratory abnormalities of coagulation markers, such as fibrinogen and tPA. These markers are associated with increased risks of thrombosis which are associated with increased risks of cardiovascular (CV) events, including myocardial infarction (MI), coronary heart disease (CHD), and other forms of atherosclerosis. The Diabetes Prevention Program (DPP) trial was designed to study the effect of four different interventions (Intensive Lifestyle (ILS) modifications, metformin, troglitazone, and placebo) on the development and progression of diabetes in subjects with Impaired glucose tolerance (IGT). In this study we analyzed the effect of troglitazone on coagulation markers including fibrinogen and tPA in the DPP population. Materials and Methods: Our analysis selected a subgroup (n= 3,171) from the original DPP population. The effect of troglitazone on coagulation markers was measured by analyzing its effects on the levels of fibrinogen and tPA at baseline and at 12 months and compared to the other three interventions (ILS, metformin, and placebo). Results: Troglitazone reduced fibrinogen levels, median percent change of - 6.65% (p <0.001) for all between group analysis: troglitazone vs. lifestyle, troglitazone vs. metformin, and troglitazone vs. placebo). This change revealed the highest change among all other interventions as reported in the previous DPP studies. Troglitazone also produced the highest median percent reduction in tPA levels (-21.39%) comparted to -20.41% in the lifestyle, -18.00% in the metformin, and -6.25% in the placebo intervention. Discussion and Conclusions: Our study demonstrated the benefits of the TZDs in reducing certain CV surrogate risk markers due to the treatment with troglitazone for 12 months. These benefits appeared as a decrease in the levels of coagulation markers including fibrinogen and tPA. These benefits are of special value especially in such a population already at increased risk for CV morbidity and mortality. The effects of troglitazone on these markers exceed that of metformin. Our analysis was unable to associate the effect of changes in weigh and waist circumference, and changes in measures of glycemia and insulin resistance with the main effect of troglitazone on coagulation markers.