OBJECTIVE To investigate the clinical efficacy of troglitazone, a newly developed oral hypoglycemic agent, in patients with NIDDM. METHODS There were 284 NIDDM patients (20-82 years of age) whose glycemic control while on a diet was judged stable but was judged unsatisfactory (fasting plasma glucose [FPG] > or = 8.3 mmol/l) when entered into a multicenter and double-blind study with parallel groups study. They were randomly allocated into two groups, the troglitazone group (the T group: 400 mg/day p.o.) and the placebo group (the P group), and were treated with test drugs for 12 weeks. RESULTS We evaluated efficacy in 136 patients of the T group and 126 patients of the P group. There was no significant difference in any of baseline characteristics between the T and P groups. In the T group, FPG and HbA1c decreased significantly after treatment (before versus after, FPG 10.1 +/- 1.6 vs. 8.8 +/- 1.9 mmol/l, P < 0.001; HbA1c: 8.6 +/- 1.5 vs 8.1 +/- 1.7%, P < 0.001). FPG and HbA1c did not change after treatment in the P group (before versus after, FPG 10.1 +/- 1.8 vs. 9.9 +/- 2.1 mmol/l; HbA1c 8.5 +/- 1.5 vs. 8.6 +/- 1.6%). Of 136 patients in the T group, 62 (45.6%) were classified as responders. Serum triglyceride level also decreased in the T group but not in the P group. Body weight increased slightly only in the T group. There were no differences in changes in blood pressure between the two groups. No serious adverse events occurred in either group. CONCLUSIONS Troglitazone at 400 mg/day decreased FPG and HbA1c significantly in NIDDM patients who had failed to respond to diet therapy. Troglitazone, developed as a drug to enhance insulin action, can be a useful hypoglycemic agent for the treatment of NIDDM.