Pioglitazone and rosiglitazone move CETP activity in opposite directions despite similar glucose control (Diabetes Metab Res Rev 2007)

Original title: Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study

Diabetes Metab Res Rev · 1 July 2007 · 7

Chappuis B, Braun M, Stettler C, Allemann S, Diem P, Lumb PJ, Wierzbicki AS, James R, Christ ER

In a prospective randomized crossover trial, seventeen patients with type 2 diabetes received pioglitazone (PGZ) or rosiglitazone (RGZ) for 12 weeks each. Both drugs similarly improved fasting glucose, HbA1c, and insulin resistance, but fasting and postprandial triglycerides were significantly lower with PGZ (fasting: -0.35 vs 0.44 mmol/L, p < 0.04), while fasting cholesterol, particularly in VLDL subfractions, rose more with RGZ (0.06 vs 0.59 mmol/L, p < 0.04). Fasting apoB, apoA-I, apoC-II/C-III ratio, and lipoprotein lipase activity did not differ between drugs, but CETP activity decreased after RGZ and increased after PGZ (-6.2 vs 4.2 p/mol/mL/min, p < 0.002). The authors attribute PGZ's additional lipid benefit partly to its distinct effects on insulin-independent VLDL production and CETP activity.

Original abstract

Background: Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.

Methods: Seventeen patients with T2Dm were randomized to RGZ or PGZ for 12 weeks, with an 8-week wash-out period. Fasting blood samples were taken for glucose (FPG), insulin, HbA(1c), lipids, apolipoproteins (apo), lipoprotein (LPL) and hepatic lipase (HL), and cholesterol ester transfer protein (CETP) activity. A standardized breakfast was served and postprandial glucose, insulin, and lipid subfraction profiles were determined.

Results: RGZ and PGZ treatment resulted in a similar improvement in FPG, HbA(1c) and homeostasis model assessment. Fasting and postprandial triglyceride (TG) levels were significantly lower following PGZ therapy (fasting: -0.35 vs 0.44 mmol/L; p < 0.04; postprandial AUC-TG: -195.6 vs 127.9 mmol/L/min; p < 0.02) associated with changes in VLDL-2-TG (-0.10 vs 0.21 mmol/L; p = 0.23) and VLDL-3-TG (0.0 vs 0.34 mmol/L; p < 0.04). Fasting cholesterol increased with RGZ compared to PGZ (0.06 vs 0.59 mmol/L; p < 0.04), particularly in VLDL-2-C (-0.30 vs 0.59 mmol/L; p < 0.03) and VLDL-3-C (-0.85 vs 2.11 mmol/L; p < 0.02). Postprandial VLDL lipid and protein content increased after RGZ and decreased after PGZ. Fasting apoB, apoA-I, apoC-II/C-III-ratio, and LPL activity did not differ. CETP activity decreased after RGZ and increased after PGZ (-6.2 vs 4.2 p/mol/mL/min; p < 0.002).

Conclusions: Both the glitazones had similar effects on glucose metabolism. The additional beneficial effect of PGZ on lipid metabolism may be related to its effects on insulin-independent VLDL production and CETP activity.

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