Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed Type 2 diabetes


Toshikazu Yamanouchi MD, Department of Internal Medicine, University of Teikyo, Kaga, Itabashi-ku, Tokyo 173-0003, Japan. E-mail:


Aims  To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes.

Methods  A total of 114 patients with Type 2 diabetes who had never used oral hypoglycaemic drugs were studied for 12 months. Patients were randomly assigned to pioglitazone (30–45 mg/day, n = 38), metformin (750 mg/day, n = 39), or glimepiride (1.0–2.0 mg/day, n = 37). The effect of treatment on fasting plasma glucose (FPG), glycated haemoglobin (HbA1c), 1,5-anhydroglucitol (1,5AG), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, free fatty acids (FFA), and fasting plasma insulin levels was monitored monthly. Body weight and safety data were also collected.

Results  Eight patients withdrew from the study (three in the pioglitazone group, two in the metformin group, and three in the glimepiride group). The rate of reduction of HbA1c was fastest in patients receiving glimepiride and slowest in patients receiving pioglitazone. Although there were no significant differences among the three groups in HbA1c levels at the end of the study, patients taking pioglitazone had relatively lower FPG and 1,5AG levels than patients taking the other two drugs. These results suggest that pioglitazone acts predominantly on nocturnal metabolism rather than at mealtimes. FFA were reduced significantly in those taking pioglitazone (542.2 µEq/l vs. 237.3 µEq/l; P < 0.01) before a decrease in HbA1c was apparent. The change in FFA levels correlated with the change in HbA1c (r = 0.409, P < 0.01). There were no significant differences in other lipid parameters among the groups.

Conclusions  Pioglitazone, metformin, and glimepiride are equally effective in reducing blood glucose in patients with newly diagnosed Type 2 diabetes. However, their specific characteristics, such as the rapid action on blood glucose levels of glimepiride and the favourable action on FPG and FFA of pioglitazone, should be considered when choosing an appropriate agent.