"Intensive blood glucose control and vascular outcomes in patients
with type 2
diabetes," by the ADVANCE Collaborative Group (A. Patel,
et al.), New England Journal of Medicine, 358(24):
2560-72, 12 June 2008.
Abstract:Background: In patients with
type 2 diabetes, the effects of intensive glucose control on vascular
outcomes remain uncertain. Methods: We randomly assigned
11,140 patients with type 2 diabetes to undergo either standard glucose
control or intensive glucose control, defined as the use of gliclazide
(modified release) plus other drugs as required to achieve a glycated
hemoglobin value of 6.5% or less. Primary end points were composites of
major macrovascular events (death from cardiovascular causes, nonfatal
myocardial infarction, or nonfatal stroke) and major microvascular events
(new or worsening nephropathy or retinopathy), assessed both jointly and
separately. Results: After a median of 5 years of
follow-up, the mean glycated hemoglobin level was lower in the
intensive-control group (6.5%) than in the standard-control group (7.3%).
Intensive control reduced the incidence of combined major macrovascular and
microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio,
0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that
of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI,
0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of
nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93;
P=0.006), with no significant effect on retinopathy (P=0.50). There were no
significant effects of the type of glucose control on major macrovascular
events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06;
P=0.32), death from cardiovascular causes (hazard ratio with intensive
control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause
(hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28).
Severe hypoglycemia, although uncommon, was more common in the
intensive-control group (2.7%, vs. 1.5% in the standard-control group;
hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).
Conclusions: A strategy of intensive glucose control,
involving gliclazide (modified release) and other drugs as required, that
lowered the glycated hemoglobin value to 6.5% yielded a 10% relative
reduction in the combined outcome of major macrovascular and microvascular
events, primarily as a consequence of a 21% relative reduction in
nephropathy.
This 2008 report from the New England Journal of Medicine was
cited 52 times in current journal articles
indexed by Clarivate during March-April 2009. Only two other medicine
papers published in the last two years, aside from reviews, collected
higher citation totals during that two-month period. Prior to the most
recent bimonthly count, citations to the paper have accrued as follows:
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