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.)
Patel
Anushka
A
MacMahon
Stephen
S
Chalmers
John
J
Neal
Bruce
B
Billot
Laurent
L
Woodward
Mark
M
Marre
Michel
M
Cooper
Mark
M
Glasziou
Paul
P
Grobbee
Diederick
D
Hamet
Pavel
P
Harrap
Stephen
S
Heller
Simon
S
Liu
Lisheng
L
Mancia
Giuseppe
G
Mogensen
Carl Erik
CE
Pan
Changyu
C
Poulter
Neil
N
Rodgers
Anthony
A
Williams
Bryan
B
Bompoint
Severine
S
de Galan
Bastiaan E
BE
Joshi
Rohina
R
Travert
Florence
F
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