Atherosclerosis is the major cause of morbidity and mortality in patients with type 2 diabetes, and pioglitazone has been reported to have anti-inflammatory and potential antiatherogenic effects. The aim of the present study was to determine whether pioglitazone, glibenclamide, or voglibose affects carotid intima-media thickness (IMT), pulse wave velocity (PWV), and urinary albumin excretion (UAE) in normotensive type 2 diabetic nephropathy patients. Forty-five normotensive type 2 diabetes patients with microalbuminuria were randomized to 12-month treatment with pioglitazone (30 mg/d, n = 15), glibenclamide (5 mg/d, n = 15), or voglibose (0.6 mg/d, n = 15). Pre- and posttreatment UAE, PWV, and IMT values were compared between treatment groups and a group of age-matched healthy control subjects (n = 30). Pretreatment PWV, IMT, and UAE values differed little between the 3 groups, but UAE was greater in the 45 type 2 diabetes patients (132.5 +/- 36.4 microg/min) than in the control subjects (6.2 +/- 1.8 microg/min, P < .001). IMT (0.76 +/- 0.12 mm) was significantly greater in the diabetics than in the controls (0.60 +/- 0.08 mm, P < .01). PWV (1,840 +/- 320 cm/s) was also significantly greater in the diabetics than in the controls (1,350 +/- 225 cm/s, P < .01). After 6 and 12 months, UAE, IMT, and PWV in the pioglitazone treatment group were significantly lower than those in the glibenclamide treatment group and voglibose treatment group (UAE: 6 months, P < .05 and 12 months, P < .01; IMT and PWV: 6 months, P < .05 and 12 months, P < .05). Pioglitazone, but not glibenclamide or voglibose, appears to be effective in reducing UAE, IMT, and PWV in normotensive type 2 diabetes patients with microalbuminuria.