Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

Aim: No previous studies have evaluated the long-term anti-atherosclerotic effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the present study investigated the protective effects of pioglitazone on the progression of carotid intima-media thickness (IMT), an established surrogate marker of cardiovascular events in Japanese type 2 diabetic patients without a recent history of cardiovascular morbidity. Methods: This 2.5-4-year, randomized, open-label, blinded endpoint study was conducted in 6 centers across Japan. Patients received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione) (n = 89) or oral glucose-lowering drugs, excluding thiazolidinediones (n = 97). Treatment was adjusted to achieve HbA(1c) < 6.5%. The primary endpoints of the study were the absolute changes from the baseline to final visit in max- and mean-IMT in the average of bilateral common carotid arteries. Results: Pioglitazone induced carotid IMT regression compared to baseline measurements (from 1.060 +/- 0.2368 to 0.992 +/- 0.1921 mm; p = 0.0042 in max-IMT and from 0.839 +/- 0.1873 to 0.780 +/- 0.1571 mm; p = 0.0019 in mean-IMT). Although the between-group difference did not reach statistical significance, the regression of carotid IMT values was greater in the pioglitazone-treatment group than in the non-pioglitazone group, (max-IMT: -0.069 +/- 0.2199 mm vs -0.031 +/- 0.2327 mm, respectively; p = NS, mean-IMT: -0.058 +/- 0.1718 mm vs -0.043 +/- 0.1644 mm, respectively; p = NS). Conclusions: Pioglitazone induced and maintained the long-term regression of carotid IMT in Japanese type 2 diabetic patients. This suggests that pioglitazone may inhibit the progression of atherosclerosis in this patient group. Further studies are required to verify these findings.