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 glucoselowering
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.
