Type 2 Diabetes and Glycated Hemoglobin (HbA1c)
Where Have We Been and Where Are We Going?
December 2020
Volume 1, Issue 1

A Summary of Dr. Robert G. Dluhy and Dr. Graham T. McMahon’s Editorial “Intensive Glycemic Control in the ACCORD and ADVANCE Trials”

N Engl J Med. 2008;358(24):2630-2633

This editorial appeared in the same issue of The New England Journal of Medicine as the previous editorial; it’s also the same issue (June 12, 2008) that published the results of the ACCORD and ADVANCE trials.

Dr. Dluhy and Dr. McMahon write a thoughtful analysis of the two trials, pointing out issues to take into consideration when interpreting the results.


The authors note that the primary outcome in the ADVANCE trial was a composite end point of macrovascular and microvascular events, and they say that these end points should not have been combined since they most likely have a different pathophysiological base.  They also point out that it’s already accepted that intensive glucose therapy lowers microvascular risks, so perhaps this study should’ve focused exclusively on the role of intensive glucose therapy in preventing cardiovascular events.

It is also noted that nonglycemic cardiovascular risk factors were not optimally controlled.


The authors express interest in the unexpected, excess deaths in the ACCORD trial—the reason that the intensive blood glucose control patients were transitioned to standard blood glucose control before the end of the study period.  They explain that 19 of the 41 excess deaths from cardiovascular causes were attributed to “unexpected or presumed cardiovascular disease,” and they go on to say that those deaths could’ve been caused by hypoglycemia but misclassified as cardiovascular-related death.

The authors explain that combination therapies, such as the ones used in the ACCORD trial, have been known to increase the risk of hypoglycemia.  If, then, hypoglycemia was a contributing cause of death, the authors recommend further studies on cardiovascular risk reduction by using strategies and therapies that lower the risk of hypoglycemia.

Interpretation of the Studies

The authors make several key points about the implications of the studies.  They write, “The results of the ACCORD and ADVANCE studies should be interpreted in the context of comprehensive care of patients with diabetes.”  They recommend individualized glycated hemoglobin (HbA1c) targets, as well as implementing programs to help more patients reach the currently recommended goals.  As an example, they note that clinicians need to continue to focus on smoking cessation, dietary and exercise counseling, blood pressure control, and providing aspirin and a statin.

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Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes
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