Differential Regulations of Lipid Profiles between Japanese Responders and Nonresponders Treated with Pioglitazone

Abstract

The aim of this study was to evaluate the effects of pioglitazone on lipid profiles in relation to glycemic control. Eighty-one treatment-naïve patients with type 2 diabetes mellitus received pioglitazone monotherapy. Subjects who had ≥ 1% reduction in hemoglobin A1c (HbA_1c) levels were defined as responders (n = 47) and those with > 1% reduction as nonresponders (n = 34). At 3 months, the _HbA1c levels and several lipid parameters were compared with baseline values. Because it is known that the response to some antihyperglycemic agents is proportional to baseline _HbA1c levels, the changes (Δ) in these parameters were compared for 2 groups based on their ΔHbA1c/baseline _HbA1c ratio. The lowest tertile was called super-responders (n = 25) and highest tertile was called extreme nonresponders (n = 24). At baseline, HbA1c levels and body mass index (BMI) were significantly higher in responders; no significant differences were observed in total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, or non–HDL-C between the 2 groups. At 3 months, significant decreases in TGs and increases in HDL-C were observed in both groups. In contrast, TC, non–HDL-C, and LDL-C/HDL-C ratio significantly decreased in responders. Low-density lipoprotein cholesterol had a tendency to decrease in responders. However, these parameters were nonsignificantly increased in nonresponders. Body mass index significantly increased in responders, while it slightly increased in nonresponders. Analysis of covariance revealed that significant intergroup differences existed with TC, LDL-C, non–HDL-C, and LDL-C/HDL-C ratio, while no such differences were observed with TGs, HDL-C, and BMI. Very similar results were obtained with super-responders and extreme nonresponders. These results suggest that approximately 40% of the treatment-naïve Japanese subjects with type 2 diabetes mellitus were nonresponders to pioglitazone, and differential regulations of lipid parameters exist between responders and nonresponders treated with pioglitazone. Bad cholesterols (eg, TC, LDL-C, and non–HDL-C) were reduced only in responders. Irrespective of its efficacy on glycemic control, pioglitazone can significantly downregulate TGs and upregulate HDL-C levels.

Keywords:

• diabetes
• pioglitazone
• dyslipidemia
• cholesterol
• lipid levels
• insulin resistance