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Previous Volume 358:2560-2572 June 12, 2008 Number 24 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set CME Exam Supplementary Material Perspective by Krumholz, H. M. Editorial by Dluhy, R. G. Editorial by Cefalu, W. T. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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. (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.

Full Text of this Article

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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.
Extract | Full Text | PDF  
N Engl J Med 2008; 359:1519-1521, Oct 2, 2008. Correspondence

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