Long-term lipid effects of pioglitazone by baseline anti-hyperglycemia medication therapy and statin use from the PROactive experience (PROactive 14)

Am J Cardiol. 2009 Jul 15;104(2):234-9. doi: 10.1016/j.amjcard.2009.03.023. Epub 2009 Jun 3.


Studies have shown that pioglitazone treatment in patients with type 2 diabetes mellitus can improve parameters of diabetic dyslipidemia. The aim of this study was to examine the effect of pioglitazone on triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels in patients from the Prospective Pioglitazone Clinical Trial in Macrovascular Events (PROactive) to determine whether pioglitazone-induced lipid effects were altered by different baseline antihyperglycemia medication or statin use. PROactive was a long-term, randomized, double-blind, cardiovascular outcomes study in patients with type 2 diabetes at high cardiovascular risk who had pioglitazone or placebo added to existing treatment. The present post hoc study analyzed lipid results from patients who received different baseline antihyperglycemia regimens and the presence or absence of baseline statin use. Independent of antihyperglycemia medication and statin use, triglyceride levels decreased in all subgroups treated with pioglitazone (-9.9% to -12.3%), whereas little change was observed in placebo groups. High-density lipoprotein cholesterol increased nearly twice as much with pioglitazone (18.1% to 20.3%) as with placebo (8.1% to 11.8%) across all subgroups. Low-density lipoprotein cholesterol increased moderately with pioglitazone (5.2% to 9.6%) compared with placebo (3.3% to 7.6%) (placebo-adjusted range 1.11% to 4.37%). In conclusion, long-term pioglitazone therapy led to durable improvements in triglyceride and high-density lipoprotein cholesterol levels, irrespective of baseline antihyperglycemia therapy or statin use.

Trial registration: ClinicalTrials.gov NCT00174993.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypoglycemic Agents / therapeutic use*
  • Lipids / blood*
  • Male
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Time Factors
  • Triglycerides / blood


  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Fibrinolytic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • Lipids
  • Thiazolidinediones
  • Triglycerides
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT00174993