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Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

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Abstract

Objective

To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

Methods

In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

Results

Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

Conclusions

Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

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Acknowledgement

We are grateful to the Ministry of Science and Technology and Environment, the Government of Malaysia, for supporting this project [Intensification of Research in Priority Areas (IRPA) Grant no. 305/PPSP/6112215]. We are also thankful to GlaxoSmithKline and Avantis for supporting the medication facilities and to all study participants for their cooperation and support.

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Authors and Affiliations

  1. Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

    Sayeeda Rahman

  2. Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

    Aziz Al-Shafi Ismail

  3. Department of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

    Shaiful Bhari Ismail

  4. Unit of Biostatistics and Research Methodology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

    Nyi Nyi Naing

  5. Advanced Medical and Dental Institute, Universiti Sains Malaysia, 11800, Penang, Malaysia

    Abdul Rashid Abdul Rahman

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  1. Sayeeda Rahman
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  2. Aziz Al-Shafi Ismail
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  5. Abdul Rashid Abdul Rahman
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Correspondence to Sayeeda Rahman.

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Rahman, S., Ismail, A.AS., Ismail, S.B. et al. Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study. Eur J Clin Pharmacol 63, 733–741 (2007). https://doi.org/10.1007/s00228-007-0315-3

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  • DOI: https://doi.org/10.1007/s00228-007-0315-3

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