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Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study
  1. D A Stakos1,
  2. D P Schuster2,
  3. E A Sparks1,
  4. C F Wooley1,
  5. K Osei2,
  6. H Boudoulas3
  1. 1Division of Cardiology, The Ohio State University, Columbus, Ohio, USA
  2. 2Division of Endocrinology, The Ohio State University
  3. 3Centre for Clinical Research, Foundation of Biomedical Research, Academy of Athens, Athens, Greece
  1. Correspondence to:
    Dr Harisios Boudoulas
    Centre for Clinical Research, Foundation of Biomedical Research, Academy of Athens, 4 Soranou Ephessiou St, 11527, Athens, Greece; boudoulasbioacademy.gr

Abstract

Objective: To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance.

Patients: 181 African American subjects with insulin resistance and normal glucose tolerance test were randomised to receive glipizide 5 mg/day (n  =  25), metformin 500 mg/day (n  =  59), or placebo (n  =  97) for 24 months. Insulin sensitivity, glucose tolerance, lipid profile, left ventricular mass (echocardiography), aortic distensibility (echocardiography, blood pressure), aortic pulse wave velocity (PWV, carotid to femoral artery, Doppler) were measured at baseline and at 12 and 24 months after randomisation.

Results: A significant increase in PWV was observed in both glipizide (mean (SEM) change at 24 months 2.8 (2.7) m/s, p  =  0.012) and metformin (2.2 (0.7) m/s, p  =  0.01) groups during the follow up period. In contrast, PWV remained unchanged in the placebo group. The increase in PWV in the treatment groups was significant compared with placebo (analysis of variance p < 0.05). Other cardiovascular or metabolic variables did not change significantly compared with placebo during follow up.

Conclusions: The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta. The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated.

  • HDL, high density lipoprotein
  • LDL, low density lipoprotein
  • LV, left ventricular
  • NIDDM, non-insulin dependent diabetes mellitus
  • PWV, pulse wave velocity
  • SI, insulin sensitivity index
  • insulin resistance
  • glipizide
  • metformin
  • aorta
  • pulse wave velocity
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