Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance

Study Questions:

What is the effect of pioglitazone on diabetes risk and cardiovascular risk factors in adults with impaired glucose tolerance?


The investigators conducted a randomized, double-blind, placebo-controlled study to examine whether pioglitazone can reduce the risk of type 2 diabetes mellitus in adults with impaired glucose tolerance. A total of 602 patients were randomly assigned to receive pioglitazone or placebo. The median follow-up period was 2.4 years. Fasting glucose was measured quarterly, and oral glucose tolerance tests were performed annually. Conversion to diabetes was confirmed on the basis of the results of repeat testing.


Annual incidence rates for type 2 diabetes mellitus were 2.1% in the pioglitazone group and 7.6% in the placebo group, and the hazard ratio for conversion to diabetes in the pioglitazone group was 0.28 (95% confidence interval, 0.16-0.49; p < 0.001). Conversion to normal glucose tolerance occurred in 48% of the patients in the pioglitazone group and 28% of those in the placebo group (p < 0.001). Treatment with pioglitazone as compared with placebo was associated with significantly reduced levels of fasting glucose (a decrease of 11.7 mg/dl vs. 8.1 mg/dl [0.7 mmol/L vs. 0.5 mmol/L], p < 0.001), 2-hour glucose (a decrease of 30.5 mg/dl vs. 15.6 mg/dl [1.6 mmol/L vs. 0.9 mmol/L], p < 0.001), and glycated hemoglobin (a decrease of 0.04 percentage points vs. an increase of 0.20 percentage points, p < 0.001). Pioglitazone therapy was also associated with a decrease in diastolic blood pressure (by 2.0 mm Hg vs. 0.0 mm Hg, p = 0.03), a reduced rate of carotid intima-media thickening (31.5%, p = 0.047), and a greater increase in the level of high-density lipoprotein cholesterol (by 7.35 mg/dl vs. 4.5 mg/dl [0.4 mmol/L vs. 0.3 mmol/L], p = 0.008). Weight gain was greater with pioglitazone than with placebo (3.9 kg vs. 0.77 kg, p < 0.001), and edema was more frequent (12.9% vs. 6.4%, p = 0.007).


The authors concluded that pioglitazone reduced the risk of conversion of impaired glucose tolerance to type 2 diabetes mellitus by 72%.


This study suggests that treatment with pioglitazone in patients with impaired glucose tolerance reduced the risk of diabetes, although pioglitazone was associated with significant weight gain and edema. The influence of these effects on long-term diabetic complications needs to be determined in future studies. It should be noted that lifestyle interventions effectively reduce the conversion of impaired glucose tolerance to diabetes, and should remain the primary approach to prevention of type 2 diabetes mellitus.

Clinical Topics: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet

Keywords: Cholesterol, Follow-Up Studies, Glucose Tolerance Test, Diabetes Mellitus, Type 2, Edema, Risk Factors, Blood Pressure, Fasting, Thiazolidinediones, Glucose

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