title: Long-term effects of intensive glucose lowering on cardiovascular outcomes.
abstract: BACKGROUND
  Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events.
  
  
  METHODS
  We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial.
  
  
  RESULTS
  Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P=0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups.
  
  
  CONCLUSIONS
  As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.).
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Michael E
authors.initials: ME
authors.lastname: Miller
authors.forename: Saul
authors.initials: S
authors.lastname: Genuth
authors.forename: Faramarz
authors.initials: F
authors.lastname: Ismail-Beigi
authors.forename: John B
authors.initials: JB
authors.lastname: Buse
authors.forename: David C
authors.initials: DC
authors.lastname: Goff
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Henry N
authors.initials: HN
authors.lastname: Ginsberg
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Bigger
authors.forename: Richard H
authors.initials: RH
authors.lastname: Grimm
authors.forename: Robert P
authors.initials: RP
authors.lastname: Byington
authors.forename: Yves D
authors.initials: YD
authors.lastname: Rosenberg
authors.forename: William T
authors.initials: WT
authors.lastname: Friedewald
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D016016:Proportional Hazards Models; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents