Effect of pioglitazone on metabolic syndrome risk factors: results of double-blind, multicenter, randomized clinical trials

OBJECTIVE: To evaluate the effect of pioglitazone, metformin, and/or sulfonylurea on metabolic syndrome and its component parameters after a year of treatment. METHODS: Adult patients with poorly controlled type 2 diabetes were enrolled in 4 multicenter, double-blind studies and received pioglitazone, sulfonylurea, metformin, or a combination of any 2 agents. Post hoc analyses were performed on data from patients with evaluations at baseline and week 52, and treatment groups were compared to determine change from baseline in metabolic syndrome status and its component variables by using the McNemar test and analysis of covariance, respectively. RESULTS: Most patients (72.1%) had metabolic syndrome at baseline. Change in the proportion of patients with metabolic syndrome status was significant in each monotherapy and the pioglitazone plus metformin combination groups. Pioglitazone alone or in combination with metformin resulted in a significantly greater percent decrease from baseline in triglycerides (pioglitazone vs. metformin, 10.3%; pioglitazone vs. sulfonylurea, 6.5%; pioglitazone plus metformin vs. sulfonylurea plus metformin, 13.4%; P < 0.05) and a greater percent increase from baseline in high-density lipoprotein (HDL) cholesterol (pioglitazone vs. metformin, 9.1%; pioglitazone vs. sulfonylurea, 12.6%; pioglitazone plus metformin vs. sulfonylurea plus metformin, 17.8%; P < 0.001) at week 52 than did the respective comparison groups. A significant decrease from baseline in the ratio of urinary albumin to creatinine was found only with pioglitazone monotherapy (-1.764 mg/ mmol; P < 0.001), which was significantly greater than the change in the metformin monotherapy group (2.1%; P < 0.05). Significant decrease in blood pressure was observed in the pioglitazone monotherapy and pioglitazone plus sulfonylurea groups, with no significant treatment group differences. CONCLUSIONS: Treatment with pioglitazone as monotherapy or combination therapy led to sustained, positive effects on important components of metabolic syndrome in patients with type 2 diabetes, independent of effects on blood glucose control and, as such, could be translated to potential for reducing the risk of cardiovascular disease.