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).
OBJECTIVE
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.
Gerstein
Hertzel
H
Yusuf
Salim
S
Riddle
Matthew C
MC
Ryden
Lars
L
Bosch
Jackie
J
D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011336:Probability; D016016:Proportional Hazards Models; D012016:Reference Values; D012107:Research Design; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting