Effect of rosiglitazone and ramipril on macrovasculopathy in patients with type 2 diabetes: needs longer treatment and/or higher doses?

Abstract

Introduction: The aim of the study is to investigate whether standard doses of rosiglitazone (4 mg/daily) and ramipril (5 mg/daily) can reverse pre-clinical macrovasculopathy in newly diagnosed never treated type 2 diabetes (T2DM) patients.

Methods: In this randomized, double-blind, placebo-controlled study, 33 T2DM patients were randomized to rosiglitazone (4 mg/daily) or ramipril (5 mg/daily) or placebo for 1 year. Hemodynamic variables were measured at 3 treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

Result: In diabetic patients, PWV (P = 0.037) and AI (P = 0.005) with ramipril and AI (P < 0.001) with rosiglitazone were significantly reduced during overall treatment period from the baseline; however, these differences were not significant in comparison to placebo.

Discussion and conclusion: The present study showed that treatment with standard doses of rosiglitazone and ramipril are not adequate to reverse pre-clinical vasculopathy in T2DM. The lack of benefit in newly diagnosed T2DM may be because of the relatively short-term intervention and/or the use of lower doses of rosiglitazone/ramipril. Further trials are needed for a longer period of time, possibly with higher doses, to show whether rosiglitazone/ramipril can reverse pre-clinical vasculopathy in T2DM (ClinicalTrials.gov number, NCT00489229).

Keywords: diabetic vasculopathy; ramipril; rosiglitazone.

Figure 1

Estimated marginal means of PWV and AI in type 2 diabetes between treatment with rosiglitazone, ramipril and placebo from base line overtime. With ramipril PWV (P = 0.037) and AI (P = 0.005) and with rosiglitazone AI (P < 0.001) were significantly reduced during overall treatment period from the baseline. Abbreviations: AI, augmentation index; PWV, pulse wave velocity.