The objective of this study was to determine if treatment of non-insulin-dependent diabetes mellitus (NIDDM) patients with the "insulin sensitizer" troglitazone, both as monotherapy and in combination with insulin, corrects the impaired fibrinolysis and activated coagulation associated with NIDDM. Patients participating in two clinical trials comparing troglitazone and placebo in patients with NIDDM were studied at the time of randomization and after 26 weeks of treatment. Eighteen patients were treated with troglitazone (ten in combination with insulin and eight as monotherapy) and eight were treated with placebo (four in each trial). Plasma concentrations of plasminogen activator inhibitor (PAI-1), prothrombin fragment F1+2, fibrinogen, and von Willebrand Factor (vWF) activity were measured. Plasma PAI-1 concentrations fell significantly from a mean of 68.8 +/- 32.3 ng/mL to 40.4 +/- 20.4 in the troglitazone treated group, but did not change significantly in the placebo treated group. Plasma PAI-1 concentrations were elevated in 15 patients treated with troglitazone and fell to normal in eight of them. There was no significant change in plasma F1+2, vWF, and fibrinogen, but plasma C-peptide and triglyceride concentrations fell significantly with troglitazone. This study demonstrates that troglitazone treatment is associated with a significant fall in plasma PAI-1 antigen concentrations in patients with NIDDM and, therefore, may have a beneficial effect on fibrinolysis.