Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus

Pioglitazone, a peroxisome proliferator–activated receptor γ agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 ± 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A1c and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.