Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes

By H. Gerstein, Michael E. Miller, Saul Genuth, Faramarz Ismail-Beigi, J. Buse, David C. Goff, J. Probstfield, William C Cushman, Henry N. Ginsberg, J. T. Bigger and 4 more. New England Journal of Medicine, 2011

1,024 citations recorded by the source corpus.

BACKGROUND Intensive glucose lowering has previously been shown to increase mortality among persons with advanced type 2 diabetes and a high risk of cardiovascular disease. This report describes the 5-year outcomes of a mean of 3.7 years of intensive glucose lowering on mortality and key cardiovascular events. METHODS We randomly assigned participants with type 2 diabetes and cardiovascular disease or additional cardiovascular risk factors to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level of 7 to 7.9%). After termination of the intensive therapy, due to higher mortality in the intensive-therapy group, the target glycated hemoglobin level was 7 to 7.9% for all participants, who were followed until the planned end of the trial. RESULTS Before the intensive therapy was terminated, the intensive-therapy group did not differ significantly from the standard-therapy group in the rate of the primary outcome (a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) (P = 0.13) but had more deaths from any cause (primarily cardiovascular) (hazard ratio, 1.21; 95% confidence interval [CI], 1.02 to 1.44) and fewer nonfatal myocardial infarctions (hazard ratio, 0.79; 95% CI, 0.66 to 0.95). These trends persisted during the entire follow-up period (hazard ratio for death, 1.19; 95% CI, 1.03 to 1.38; and hazard ratio for nonfatal myocardial infarction, 0.82; 95% CI, 0.70 to 0.96). After the intensive intervention was terminated, the median glycated hemoglobin level in the intensive-therapy group rose from 6.4% to 7.2%, and the use of glucose-lowering medications and rates of severe hypoglycemia and other adverse events were similar in the two groups. CONCLUSIONS As compared with standard therapy, the use of intensive therapy for 3.7 years to target a glycated hemoglobin level below 6% reduced 5-year nonfatal myocardial infarctions but increased 5-year mortality. Such a strategy cannot be recommended for high-risk patients with advanced type 2 diabetes. (Funded by the National Heart, Lung and Blood Institute; ClinicalTrials.gov number, NCT00000620.)

Subfields: Endocrinology, Diabetes and Metabolism

View Paper: https://www.semanticscholar.org/paper/8cd87c5bb89c643921b2b1bb53f24da334ba8ced

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

1. R. Bergenstal
2. V. Basevi

Citations in the corpus

• Standards of Medical Care in Diabetes—2012 (2011, background): “group, due to a reduction in nonfatal MI, both when the glycemic control intervention was halted (81) and at completion of the planned follow-up (85).”
• The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. (2013, neutral): “The appropriate target for a glycaemic control has been explored recently in the ADVANCE [664], ACCORD [665], and Veterans’ Affairs Diabetes Trial (VADT) [666] studies, which randomized one study arm to very low HbA1c targets (<6.”
• Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2012, background): “aged patients—threefold that associated with conventional therapy [129].”
• CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. (2016, background): “Severe hypoglycemia occurs more frequently with intensive glycemic control (72,75,77,79).”
• Standards of Medical Care in Diabetes—2013 (2012, background): “The primary outcome of ACCORD (nonfatal MI, nonfatal stroke, or cardiovascular death) was nonsignificantly lower in the intensive glycemic control group due to a reduction in nonfatal MI, both when the glycemic control comparison was halted and all participants transitioned to the standard glycemic ”