CARDIOVASCULAR MEDICINE

Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study

D A Stakos¹, D P Schuster², E A Sparks¹, C F Wooley¹, K Osei², H Boudoulas³

¹ Division of Cardiology, The Ohio State University, Columbus, Ohio, USA
² Division of Endocrinology, The Ohio State University
³ Centre for Clinical Research, Foundation of Biomedical Research, Academy of Athens, Athens, Greece

Correspondence to:
Correspondence to:
Dr Harisios Boudoulas
Centre for Clinical Research, Foundation of Biomedical Research, Academy of Athens, 4 Soranou Ephessiou St, 11527, Athens, Greece; boudoulas{at}bioacademy.gr

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.

Abbreviations: HDL, high density lipoprotein; LDL, low density lipoprotein; LV, left ventricular; NIDDM, non-insulin dependent diabetes mellitus; PWV, pulse wave velocity; S_I, insulin sensitivity index

Keywords: insulin resistance; glipizide; metformin; aorta; pulse wave velocity

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• Stakos, D. A, Schuster, D. P, Sparks, E. A, Meis, S. B., Wooley, C. F, Osei, K., Boudoulas, H. (2007). Association between glycosylated hemoglobin, left ventricular mass and aortic function in nondiabetic individuals with insulin resistance. Eur J Endocrinol 157: 63-68 [Abstract] [Full Text]  
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Do the Conclusions Fit the Results?

John A Kao

Online, 20 Jun 2005 [Full text]