Pioglitazone treatment and cardiovascular event and death in subjects with type 2 diabetes without established cardiovascular disease (JDDM 36)

AimsThe protective association of pioglitazone with cardiovascular events and death was investigated over 6-years in large-scale type 2 diabetic subjects without established cardiovascular disease in a primary care setting.MethodsA six-year observational cohort study including 2864 subjects with type 2 diabetes without established cardiovascular disease was performed. The primary endpoint was a composite of first occurrence of cardiovascular disease or death. The effect of pioglitazone use at a baseline year with a Cox proportional hazard model and the time-dependent use in each one-year examination interval with a pooled logistic regression model were analyzed.ResultsBaseline use of pioglitazone (n = 493) did not show a statistically protective effect on the primary endpoint (n = 175), although it tended to reduce the risk (adjusted hazard ratio 0.67 [95% CI: 0.43–1.05]). However, pooled logistic regression analysis indicated a significant protective association of pioglitazone with the primary endpoint (0.58 [0.38 to 0.87] and cardiovascular disease (0.54 [0.33–0.88]), independent of concurrent levels of blood glucose, blood pressure, lipids, albuminuria, and renal function. In particular, this protective association was observed in those with diabetic nephropathy regardless of the daily dose of pioglitazone. Among a total of 898 subjects who took pioglitazone during the period, 43% experienced a discontinuation at least once; however, serious adverse effects were rare.ConclusionsThis observational study indicated a protective association of pioglitazone with cardiovascular disease and death in type 2 diabetic subjects without established vascular disease, particularly those with nephropathy.