Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: ORIGIN-GRACE

Lonn EM, Bosch J, Diaz R, et al; for the GRACE and ORIGIN Investigators. Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: the Glucose Reduction and Atherosclerosis Continuing Evaluation Study (ORIGIN-GRACE). Diabetes Care. 2013;36(9):2466-2474.

Findings from ORIGIN-GRACE showed no statistically significant difference in annualized change in maximum carotid intima-media thickness (CIMT) for 12 carotid artery segments, the study's primary outcome, with insulin glargine or omega-3 fatty acid treatment. ORIGIN-GRACE, a substudy of the ORIGIN trial, examined the effects of insulin glargine and omega-3 fatty acids on CIMT in patients with dysglycemia and additional risk factors for atherosclerosis progression.

Rates of the primary outcome were as follows; there was a statistically nonsignificant 11% reduction in the slope of CIMT progression in the glargine arm:

  • Insulin glargine: 0.0234 ± 0.0015 mm/year vs standard care, 0.0264 ± 0.0015 mm/year (P=0.145)
  • Omega-3 fatty acid: 0.0254 ± 0.0015 mm/year vs placebo, 0.0244 ± 0.0015 mm/year (P=0.650)

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Slide05 - ORIGIN-GRACE No Difference Max CIMT  

With regard to secondary outcomes, statistically significant changes in maximum CIMT were seen for the glargine arm only. For the secondary outcome of maximum CIMT for four common coronary artery segments, there was a statistically significant 20% reduction in slope of CIMT progression in the glargine arm. 
  • Insulin glargine: 0.0126 ± 0.0012 mm/year vs standard care, 0.0158 ± 0.0012 mm/year (P=0.049)
  • Omega-3 fatty acid: 0.0140 ± 0.0012 mm/year vs placebo, 0.0144 ± 0.0012 mm/year (P=0.812)
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Slide06 - ORIGIN-GRACE Glargine Not Omega-3  
For the secondary outcome of maximum CIMT for eight common carotid and bifurcation segments, there was a statistically significant 18% reduction in slope of CIMT progression in the glargine arm. 
  • Insulin glargine: 0.0209 ± 0.0015 mm/year vs standard care, 0.0254 ± 0.0015 mm/year (P=0.032)
  • Omega-3 fatty acid: 0.0243 ± 0.0015 mm/year vs placebo, 0.0221 ± 0.0015 mm/year (P=0.288) 
 Click on slide to view larger. 
Slide06 - ORIGIN-GRACE Glargine Not Omega-3  
No statistically significant differences in annualized change in maximum far-wall CIMT were seen in either treatment arm, although a 15% reduction in the slope of CIMT progression was seen in the glargine arm. No differences were seen in major cardiovascular events between groups.
 
 
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 Slide07 - ORIGIN-GRACE No Difference Max Far Wall  Slide08 - ORIGIN-GRACE Major Cardiovascular  
 
ORIGIN-GRACE was a substudy of  ORIGIN. ORIGIN was a randomized, double-blind trial enrolling 12,537 patients at high risk for cardiovascular events and who had impaired fasting glucose, impaired glucose tolerance, or newly diagnosed diabetes. Subjects in ORIGIN-GRACE were randomized in a 2x2 factorial design to open-label insulin glargine (targeting fasting glucose  ≤95 mg/dL) or standard glycemic care or double-blind omega-3 fatty acid (1-g capsule) or placebo.

 Click on slides to view larger. 
Slide01 - ORIGIN-GRACE Design  Slide02 - ORIGIN-GRACE Primary and Secondary  Slide03 - ORIGIN-GRACE Eligibility CriteriaSlide04 - ORIGIN-GRACE Select Baseline  Slide09 - ORIGIN-GRACE Summary  

ORIGIN=Outcome Reduction with an Initial Glargine Intervention
ORIGIN-GRACE=Glucose Reduction and Atherosclerosis Continuing Evaluation

 

Related content: 

Expert Commentary: Vivian A. Fonseca on the omega-3 fatty acid arm of the ORIGIN trial
Expert Commentary:
Silvio E. Inzucchi on the glargine arm of the ORIGIN trial  

 

The pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

May 2013 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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Last Modified: 8/4/2014