Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
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. (ClinicalTrials.gov number, NCT00145925.)
Anushka
A
Patel
Stephen
S
MacMahon
John
J
Chalmers
Bruce
B
Neal
Laurent
L
Billot
Mark
M
Woodward
Michel
M
Marre
Mark
M
Cooper
Paul
P
Glasziou
Diederick
D
Grobbee
Pavel
P
Hamet
Stephen
S
Harrap
Simon
S
Heller
Lisheng
L
Liu
Giuseppe
G
Mancia
Carl Erik
CE
Mogensen
Changyu
C
Pan
Neil
N
Poulter
Anthony
A
Rodgers
Bryan
B
Williams
Severine
S
Bompoint
Bastiaan E
BE
de Galan
Rohina
R
Joshi
Florence
F
Travert
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000517:prevention & control; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005907:Gliclazide / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors
D001786:Blood Glucose; D005907:Gliclazide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents