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Intensive Glucose Control in Type 2 Diabetes Mellitus Reduces CV Events, but Not Mortality, After 10 Years


Clinical question: Are there long-term benefits to more intensive glycemic control in patients with type 2 diabetes mellitus?

Bottom line: After approximately 10 years of follow-up, this study found 1 fewer cardiovascular event per 116 person-years among a group of patients (97% men) randomized to receive tight glycemic control, but found no reduction in mortality. This result must be balanced against the results from other trials, which saw a mixed bag of benefits and harms with long-term follow-up. It is important to note that even the intensive glycemic control group had a mean hemoglobin A1c of 6.9%, not 6% or 6.5% as some guidelines advocate.

Reference: Hayward RA, Reaven PD, Wiitala WL, et al, for the VADT Investigators. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;372(23):2197-2206.

Study design: Cohort (prospective); (LOE: 2b)

Setting: Outpatient (any)

Synopsis: The Veteran's Affairs Diabetes Trial (VADT) originally randomized 1791 veterans with type 2 diabetes mellitus to receive intensive or usual glycemic control, and achieved mean hemoglobin A1C levels of 6.9% and 8.4%, respectively, after a median of 5.6 years. The original trial found a nonsignificant trend toward fewer cardiovascular events in the intensive therapy group, but no change in mortality. Two other large, similar trials reported similar findings, although one found increased mortality in the intensive glycemic control group. Follow-up studies for these 2 other trials have had mixed results, one finding increased mortality and no change in events, with the other finding fewer events but no change in mortality.

The current study linked patients in the original VADT to national disease registries (92% of participants) and also to regular record reviews and surveys (77% agreed to participte). The median follow-up was 9.8 years for cardiovascular events and 11.8 years for assessment of total mortality. They found a small but statistically significant reduction in the primary combined outcome of myocardial infarction , stroke, new or worsening heart failure, cardiovascular death, or amputation (44.1 vs 52.7 per 1000 person-years; P = .04). There was no significant difference between groups in the likelihood of cardiovascular death or all-cause mortality. The greatest contribution to the reduction in cardiovascular events was fewer nonfatal myocardial infarctions.

Mark H. Ebell, MD, MS, is an associate professor at the University of Georgia in Athens, editor-in-chief of Essential Evidence, and deputy editor of the American Family Physician journal.

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