Pioglitazone vs glimepiride: Differential effects on vascular endothelial function in patients with type 2 diabetes

Objective: The aim of this study was to compare the effect of glimepiride and pioglitazone on endothelial function in patients with type 2 diabetes already on metformin. Methods: Twenty-eight patients with type 2 diabetes already on metformin without known cardiovascular disease, were randomized in 2 groups; glimepiride (4 mg od) was added in group A (n = 14) and pioglitazone (30 mg od) in group B (n = 14) for 6 months. Flow-mediated dilation (FMD) in the brachial artery was assessed in all patients, at baseline and at follow-up. Results: The 2 groups did not differ in age (mean +/- S.D., 63.6 +/- 7.3 years vs 62.8 +/- 7.2 years respectively), or any measured variable at baseline. Fasting glucose and glycated haemoglobin improved similarly in both groups. There were significant differences between the 2 groups in the absolute changes observed at follow-up in waist circumference, +1.86 +/- 3.11 cm vs -1.86 +/- 1.88 cm in groups A and B respectively; fasting insulin levels, +14.79 +/- 12.56 pmol/L vs -25.84 +/- 28.09 pmol/L; homeostasis model assessment (HOMA), +0.66 +/- 1.01 vs -1.83 +/- 1.38; HDL cholesterol levels, -0.07 +/- 0.22 mmol/L vs +0.14 +/- 0.20 mmol/L and FMD, +0.14 +/- 1.09% vs +2.02 +/- 2.05% (p<0.05 for all). The only independent predictor factor of the FMD improvement was treatment-induced changes in HOMA (R-2: 0.488, slope: -0.782, [95% Cl: -1.128, -0.436], p=0.0001). Conclusions: In patients with type 2 diabetes already on metformin, addition of pioglitazone as compared to glimepiride, improved endothelial function despite similar glycemic control. The improvement in endothelial function was mainly due to a reduction in insulin resistance. (C) 2008 Elsevier Ireland Ltd. All rights reserved.