Pioglitazone lowers plasma CETP mass and hepatic triglyceride content while raising HDL cholesterol in type 2 diabetes, confirming prior mouse findings (Diabetes Care 2010)

Original title: Pioglitazone decreases plasma cholesteryl ester transfer protein mass, associated with a decrease in hepatic triglyceride content, in patients with type 2 diabetes

Diabetes Care · 11 February 2010 · 7

Jonker JT, Wang Y, de Haan W, Diamant M, Rijzewijk LJ, van der Meer RW, Lamb HJ, Tamsma JT, de Roos A, Romijn JA, Rensen PC, Smit JW

In mice with human-like lipoprotein metabolism, a decrease in hepatic triglyceride content was previously associated with decreased plasma cholesteryl ester transfer protein (CETP) mass and increased HDL levels. To test this in humans, 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years, HbA1c 7.1 +/- 0.1%) were randomized to pioglitazone (30 mg/day) or metformin (2000 mg/day) plus matching placebo, added to glimepiride, for 24 weeks. Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P < 0.05), decreased plasma CETP mass (2.33 +/- 0.10 versus 2.06 +/- 0.10 microg/ml, P < 0.05), and increased plasma HDL cholesterol (1.22 +/- 0.05 versus 1.34 +/- 0.05 mmol/l, P < 0.05); metformin produced no significant change in these parameters.

Original abstract

Objective: Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes.

Research Design And Methods: We included 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P < 0.05), decreased plasma CETP mass (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P < 0.05), and increased plasma HDL cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P < 0.05). Metformin did not significantly change any of these parameters.

Conclusions: A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mice.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.