Rosiglitazone and carotid IMT progression rate in a mixed cohort of patients with type 2 diabetes and the insulin resistance syndrome: main results from the Rosiglitazone Atherosclerosis Study

J Intern Med. 2007 Mar;261(3):293-305. doi: 10.1111/j.1365-2796.2007.01767.x.

Abstract

Objective: Insulin resistance is associated with progression of atherosclerosis. We assessed the effect of 12 months of treatment with rosiglitazone (RSG) on the progression of carotid intima-media thickness (IMT) in people with type 2 diabetes mellitus (T2DM) or the insulin resistance syndrome (IRS).

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Malmö University Hospital, Malmö, Sweden.

Subjects: 555 subjects (200 with T2DM and 355 nondiabetics with IRS according to EGIR criteria), aged 35-80 years. 447 subjects (165 T2DM and 282 IRS) completed the study.

Intervention: Participants were allocated to placebo or RSG 4 mg for 2 months and then 8 mg daily.

Main outcome measure: Change in composite IMT [mean IMT in the common carotid artery (CCA) and maximal IMT in the bulb] was the primary and various other IMT measures were secondary outcome variables.

Results: There was no effect of RSG treatment in the mixed population. In T2DM patients there was a reduced progression of the composite IMT (mean change: 0.041 vs. 0.070 mm, P = 0.07), and of the mean IMT CCA (mean change: -0.005 mm vs. 0.021 mm, P = 0.007). RSG treatment led to significant reductions of HOMA-IR, fasting plasma glucose, HbA1c, PAI-1 activity, fibrinogen, C-reactive protein and matrix metalloproteinase-9.

Conclusions: In a mixed study population of patients with T2DM and IRS RSG treatment was not associated with a statistically significant reduction of carotid IMT progression rate. Separate analyses of these two patient groups indicated, however, a significant beneficial effect on CCA IMT in T2DM patients but no similar effect in subjects with IRS.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Atherosclerosis / drug therapy*
  • Carotid Artery Diseases / drug therapy*
  • Carotid Artery Diseases / pathology
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / pathology
  • Disease Progression
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Rosiglitazone
  • Sweden
  • Thiazolidinediones / therapeutic use*
  • Tunica Intima / pathology

Substances

  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone