Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention)

Am Heart J. 2008 Jan;155(1):26-32, 32.e1-6. doi: 10.1016/j.ahj.2007.09.009. Epub 2007 Nov 26.


Aims: Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes arise due to insufficient insulin secretion and are risk factors for cardiovascular (CV) events. Thus, targeting normal fasting glucose levels with insulin may reduce CV events. Previous studies suggest that omega-3 fatty acid supplements may reduce CV death; however, their effect in high-risk dysglycemic individuals is not known.

Methods: People aged > or = 50 years with evidence of CV disease and with IFG, IGT, newly detected or established diabetes (on 0 or 1 oral agent), and a local glycated hemoglobin < 150% of the upper limit of normal for that assay were recruited and allocated to (a) either 1 daily injection of insulin glargine with the dose titrated to achieve a fasting plasma glucose < or = 5.3 mmol/L (95 mg/dL), or standard glycemic care; and (b) either omega-3-acid ethyl esters 90 (1 g consisting of EPA 465 mg and DHA 375 mg) or identical placebo, according to a 2 x 2 factorial design. The 2 different primary outcomes for the insulin and omega-3 fatty acid arms are CV events and CV death, respectively.

Results: A total of 12,612 (mean age 64, 35% women) people in 40 countries were randomized during a 2-year period ending December 2005. Eighty-two percent had established diabetes, 6% had new diabetes, and 12% had IGT or IFG; the mean fasting plasma glucose was 7.3 mmol/L (131 mg/dL).

Conclusions: The ORIGIN trial will determine whether or not either or both of these interventions can reduce CV events.

Trial registration: ClinicalTrials.gov NCT00069784.

Publication types

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

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Blood Glucose / drug effects*
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Glucose Tolerance Test
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / drug effects*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Insulin / analogs & derivatives*
  • Insulin Glargine
  • Insulin, Long-Acting
  • International Cooperation
  • Male
  • Middle Aged
  • Patient Selection
  • Probability
  • Proportional Hazards Models
  • Reference Values
  • Research Design
  • Severity of Illness Index
  • Survival Analysis
  • Treatment Outcome


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin, Long-Acting
  • Insulin Glargine

Associated data

  • ClinicalTrials.gov/NCT00069784