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

Papathanassiou, Katerina; Naka, Katerina K.; Kazakos, Nikolaos; Kanioglou, Chryssanthi; Makriyiannis, Demetrios; Pappas, Konstantinos; Katsouras, Christos S.; Liveris, Konstantinos; Kolettis, Theofilos; Tsatsoulis, Agathocles; Michalis, Lampros K.

doi:10.1016/j.atherosclerosis.2008.11.027

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Volume 205, Issue 1 , Pages 221-226, July 2009

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

Katerina Papathanassiou
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
Katerina K. Naka
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
- Department of Cardiology, University of Ioannina, Ioannina, Greece
Nikolaos Kazakos
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
- Intensive Care Unit, Arta General Hospital, Arta, Greece
Chryssanthi Kanioglou
- Department of Endocrinology, University of Ioannina, Ioannina, Greece
Demetrios Makriyiannis
- Department of Endocrinology, Hatzikosta General Hospital, Ioannina, Greece
Konstantinos Pappas
- Department of Cardiology, University of Ioannina, Ioannina, Greece
Christos S. Katsouras
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
- Department of Cardiology, University of Ioannina, Ioannina, Greece
Konstantinos Liveris
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
- Department of Cardiology, Zakynthos General Hospital, Zakynthos, Greece
Theofilos Kolettis
- Department of Cardiology, University of Ioannina, Ioannina, Greece
Agathocles Tsatsoulis
- Department of Endocrinology, University of Ioannina, Ioannina, Greece
Lampros K. Michalis
- Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece
- Department of Cardiology, University of Ioannina, Ioannina, Greece
- Corresponding author at: University of Ioannina Medical School, Department of Cardiology, University Campus, Ioannina GR 45 110, Greece. Tel.: +30 26510 97533/97710; fax: +30 26510 97017/97865.

Received 21 July 2008; received in revised form 24 November 2008; accepted 25 November 2008. published online 12 January 2009.

Abstract

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 (4mg od) was added in group A (n=14) and pioglitazone (30mg 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±3.11cm vs −1.86±1.88cm in groups A and B respectively; fasting insulin levels, +14.79±12.56pmol/L vs −25.84±28.09pmol/L; homeostasis model assessment (HOMA), +0.66±1.01 vs −1.83±1.38; HDL cholesterol levels, −0.07±0.22mmol/L vs +0.14±0.20mmol/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 (R²: 0.488, slope: −0.782, [95% CI: −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.

Keywords: Endothelial function, Diabetes, Pioglitazone, Glimepiride, Insulin resistance, Atherosclerosis