Background In patients with type 2 diabetes, the effects ofintensive glucose control on vascular outcomes remain uncertain.
Methods We randomly assigned 11,140 patients with type 2 diabetesto undergo either standard glucose control or intensive glucosecontrol, defined as the use of gliclazide (modified release)plus other drugs as required to achieve a glycated hemoglobinvalue of 6.5% or less. Primary end points were composites ofmajor macrovascular events (death from cardiovascular causes,nonfatal myocardial infarction, or nonfatal stroke) and majormicrovascular events (new or worsening nephropathy or retinopathy),assessed both jointly and separately.
Results After a median of 5 years of follow-up, the mean glycatedhemoglobin level was lower in the intensive-control group (6.5%)than in the standard-control group (7.3%). Intensive controlreduced the incidence of combined major macrovascular and microvascularevents (18.1%, vs. 20.0% with standard control; hazard ratio,0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), aswell 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), primarilybecause 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 wereno significant effects of the type of glucose control on majormacrovascular 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 to1.04; P=0.12), or death from any cause (hazard ratio with intensivecontrol, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia,although uncommon, was more common in the intensive-controlgroup (2.7%, vs. 1.5% in the standard-control group; hazardratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001).
Conclusions A strategy of intensive glucose control, involvinggliclazide (modified release) and other drugs as required, thatlowered the glycated hemoglobin value to 6.5% yielded a 10%relative reduction in the combined outcome of major macrovascularand microvascular events, primarily as a consequence of a 21%relative reduction in nephropathy. (ClinicalTrials.gov number,NCT00145925
[ClinicalTrials.gov]
.)
Source Information
The members of the Writing Committee of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Collaborative Group are listed in the Appendix. This article (10.1056/NEJMoa0802987) was published at www.nejm.org on June 6, 2008.
Address reprint requests to Dr. Anushka Patel at the Cardiovascular Division, George Institute for International Health, University of Sydney, P.O. Box M201, Missenden Rd., Sydney, NSW 2050, Australia, or at apatel{at}george.org.au.
Intensive Glucose Control in Type 2 Diabetes
Jenny-Avital E. R., Luan F. L., Nguyen K., Tobey T. A., Parashar A., Byington R. P., Gerstein H. C., Friedewald W. T., Patel A., MacMahon S., Chalmers J.
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N Engl J Med 2008;
359:1519-1521, Oct 2, 2008.
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