Epidemiologic studies have shown a relationship between glycated hemoglobin levels
and cardiovascular events in patients with type 2 diabetes. We investigated whether
intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular
events in patients with type 2 diabetes who had either established cardiovascular
disease or additional cardiovascular risk factors.
In this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated
hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated
hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%).
Of these patients, 38% were women, and 35% had had a previous cardiovascular event.
The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke,
or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy
group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up.
At 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved
in the intensive-therapy group and the standard-therapy group, respectively. During
follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group,
as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence
interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy
group died, as compared with 203 patients in the standard-therapy group (hazard ratio,
1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight
gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001).
As compared with standard therapy, the use of intensive therapy to target normal glycated
hemoglobin levels for 3.5 years increased mortality and did not significantly reduce
major cardiovascular events. These findings identify a previously unrecognized harm
of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov
2008 Massachusetts Medical Society