Favorable Effects of Insulin Sensitizers Pertinent to Peripheral Arterial Disease in Type 2 Diabetes

Results from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial

  1. for the BARI 2D Study Group
  1. 1Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
  2. 2Division of Cardiology, Rhode Island Hospital, Providence, Rhode Island
  3. 3Mid-America Heart Institute, Kansas City, Missouri
  4. 4Instituto Méxicano del Seguro Social, Mexico City, Mexico
  5. 5New York University School of Medicine, New York, New York
  6. 6Montreal Heart Institute and l’Université de Montréal, Montreal, Quebec, Canada
  1. Corresponding author: Andrew D. Althouse, ada25{at}


OBJECTIVE The aim of this manuscript was to report the risk of incident peripheral arterial disease (PAD) in a large randomized clinical trial that enrolled participants with stable coronary artery disease and type 2 diabetes and compare the risk between assigned treatment arms.

RESEARCH DESIGN AND METHODS The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomly assigned participants to insulin sensitization (IS) therapy versus insulin-providing (IP) therapy for glycemic control. Results showed similar 5-year mortality in the two glycemic treatment arms. In secondary analyses reported here, we examine the effects of treatment assignment on the incidence of PAD. A total of 1,479 BARI 2D participants with normal ankle-brachial index (ABI) (0.91–1.30) were eligible for analysis. The following PAD-related outcomes are evaluated in this article: new low ABI ≤0.9, a lower-extremity revascularization, lower-extremity amputation, and a composite of the three outcomes.

RESULTS During an average 4.6 years of follow-up, 303 participants experienced one or more of the outcomes listed above. Incidence of the composite outcome was significantly lower among participants assigned to IS therapy than those assigned to IP therapy (16.9 vs. 24.1%; P < 0.001). The difference was significant in time-to-event analysis (hazard ratio 0.66 [95% CI 0.51–0.83], P < 0.001) and remained significant after adjustment for in-trial HbA1c (0.76 [0.59–0.96], P = 0.02).

CONCLUSIONS In participants with type 2 diabetes who are free from PAD, a glycemic control strategy of insulin sensitization may be the preferred therapeutic strategy to reduce the incidence of PAD and subsequent outcomes.

  • Received November 2, 2012.
  • Accepted April 5, 2013.

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  1. Diabetes Care
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