Comparison of Pioglitazone vs. Glimepiride on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes

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No antidiabetic regimen has demonstrated the ability to reduce progression of coronary atherosclerosis. Commonly used oral glucose-lowering agents include sulfonylureas, which are insulin secretagogues, and thiazolidinediones, which are insulin sensitizers.
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<p>The objectives of the study were to compare the effects of an insulin sensitizer, Pioglitazone, with an insulin secretagogue, Glimepiride, on the progression of coronary atherosclerosis in patients with type 2 diabetes. </p>
<p>The study was a double-blind, randomized, multicenter trial at 97 academic and community hospitals in North and South America (enrollment August 2003-March 2006) in 543 patients with coronary disease and type 2 diabetes. A total of 543 patients underwent coronary intravascular ultrasonography and were randomized to receive Glimepiride, 1 to 4 mg, or Pioglitazone, 15 to 45 mg, for 18 months with titration to maximum dosage, if tolerated. Atherosclerosis progression was measured by repeat intravascular ultrasonography examination in 360 patients at study completion. </p>
<p>Least squares mean PAV increased 0.73% (95% CI, 0.33% to 1.12%) with Glimepiride and decreased 0.16% (95% CI, –0.57% to 0.25%) with Pioglitazone (P = .002). An alternative analysis imputing values for noncompleters based on baseline characteristics showed an increase in PAV of 0.64% (95% CI, 0.23% to 1.05%) for Glimepiride and a decrease of 0.06% (–0.47% to 0.35%) for Pioglitazone (between-group P = .02). </p>
<p>Mean (SD) baseline HbA1c levels were 7.4% (1.0%) in both groups and declined during treatment an average 0.55% (95% CI, –0.68% to –0.42%) with Pioglitazone and 0.36% (95% CI, –0.48% to –0.24%) with Glimepiride (between-group P = .03). In the Pioglitazone group, compared with Glimepiride, high-density lipoprotein levels increased 5.7 mg/dL (95% CI, 4.4 to 7.0 mg/dL; 16.0%) vs 0.9 mg/dL (95% CI, –0.3 to 2.1 mg/dL; 4.1%), and median triglyceride levels decreased 16.3 mg/dL (95% CI, –27.7 to –11.0 mg/dL; 15.3%) vs an increase of 3.3 mg/dL (95% CI, –10.7 to 11.7 mg/dL; 0.6%) (P &lt; .001 for both comparisons). </p>
<p>Median fasting insulin levels decreased with Pioglitazone and increased with Glimepiride (P &lt; .001). Hypoglycemia was more common in the Glimepiride group and edema, fractures, and decreased hemoglobin levels occurred more frequently in the Pioglitazone group. </p>
<p>In patients with type 2 diabetes and coronary artery disease, treatment with Pioglitazone resulted in a significantly lower rate of progression of coronary atherosclerosis compared with Glimepiride. <br /><br /><strong>Source: JAMA. 2008;299(13):1561-1573</strong></p>