Objective: To evaluate the efficacy of pioglitazone for the prevention of macrovascular outcomes in Japanese patients with type 2 diabetes, without a recent history of macrovascular morbidity.
Research design and methods: This 2.5-4 year, prospective, randomized, open-label, blinded-endpoint study was conducted in 20 Japanese centers. Patients received pioglitazone +/- other oral glucose-lowering drugs (excluding another thiazolidinedione) [n = 293] or oral glucose-lowering drugs excluding thiazolidinediones (n = 294). Treatment was adjusted to achieve HbA(1c) < 6.5%. The primary endpoint was the time to onset of a macrovascular event.
Results: Pioglitazone delayed the time to onset of macrovascular events and was associated with a lower cumulative incidence of such events (3.56% vs. 4.49% for controls). Neither finding achieved statistical significance. This was likely because of the type of patient included in the study (i.e. no recent history of cardiovascular events) and the high use of concomitant anti-diabetic agents. Reductions in HbA(1c), fasting blood glucose and fasting blood insulin levels, and an increase in HDL-C were significantly greater with pioglitazone throughout most of the study (p < 0.05). Fewer patients in the pioglitazone group commenced permanent treatment with insulin (3.3% vs. 13.7% in the control group). Adverse events were reported by 97.6% of the pioglitazone group and 96.9% of the control group (serious adverse events, including deaths, were 20.1 vs. 22.2%, respectively). The only notable difference between the two groups was a higher incidence of edema in the pioglitazone group. The main limitation of this study was that too few patients were included to identify statistically significant differences in the primary endpoint.
Conclusions: Pioglitazone produced good glycemic control in Japanese patients with type 2 diabetes, and significantly fewer patients treated with pioglitazone needed long-term insulin therapy. These changes were associated with a trend towards delayed onset of macrovascular events.
Clinical trial registration: UMIN000001363.