The effects of rosiglitazone on atherosclerotic progression in patients with Type 2 diabetes at high cardiovascular risk.

Aims: Cardiovascular mortality remains high despite intensive treatment of people with Type 2 diabetes mellitus. Meta-analyses on rosiglitazone have raised concerns regarding its cardiovascular safety. We studied the effects of rosiglitazone on ultrasonic indices of carotid arterial disease and inflammatory markers in a group of Type 2 diabetic patients at high cardiovascular risk.

Methods: A trial of rosiglitazone in Type 2 diabetic patients with high cardiovascular risk and internal carotid artery plaque compared changes in carotid ultrasound intima-media thickness (IMT), plaque thickness, arterial stiffness and compliance, and inflammatory markers at baseline, 26 and 52 weeks.

Results: In the rosiglitazone group (n=28), carotid artery plaque thickness was reduced by 0.08 mm, compared with an increase of 0.19 mm (P=0.075) in the placebo group (n=29). There were no significant differences in changes of IMT, carotid wall compliance and stiffness between the two groups. Glycated haemoglobin reduced by -0.9 vs. 0.1% (-7 vs. 2 mmol/mol), (P<0.001); insulin resistance (HOMA-IR) reduced by -37.6 vs. -1.1% (P=0.016); and B cell function (HOMA-B) increased by 36.8 vs. 0.7% (P=0.009). Non-esterified fatty acids reduced by -23.5 vs. 7.9% (P=0.005); tissue plasminogen activator reduced by -25.0 vs. 0.6% (P=0.001); and plasminogen activator inhibitor activity reduced by -57.4 vs. -34.6% (P=0.052).

Conclusions: Rosiglitazone reduced carotid artery plaque thickness, though not significantly, and there was no significant change in intima media thickness or other ultrasonic indices of carotid arterial disease. There were significant improvements in glycaemic control, insulin sensitivity and fibrinolytic, but not inflammatory, markers. There was no evidence in this study of any adverse effects on progression of carotid arterial disease.