Tight glycemic control modestly reduced the rate of major cardiovascular events but didn’t improve mortality in an extended follow-up of a clinical trial involving 1,791 veterans with type 2 diabetes, which was published online June 3 in the New England Journal of Medicine.
At the conclusion of the treatment phase of the Veteran Affairs Diabetes Trial in 2008, the primary outcome – the rate of a first major CV event – was nonsignificantly lower with intensive glycemic control than with standard glycemic control. Researchers now report the findings after an additional 7.5 years of follow-up of 92% of the participants in that multicenter unblended randomized controlled trial.
During the treatment phase of the study, median glycated hemoglobin level differed by 1.5 percentage points between patients who received intensive therapy (6.9%) and patients who received standard therapy (8.4%). During follow-up, this difference declined to only 0.2-0.3 percentage points. “Even with the support of a dedicated research team, only approximately half the participants [achieved] a glycated hemoglobin level of less than 7%,” said Dr. Rodney A. Hayward of the VA Center for Clinical Management Research, VA Ann Arbor (Mich.) Healthcare System, and his associates.
During extended follow-up, there were 253 major CV events in the group randomly assigned to intensive therapy and 288 in the group assigned to standard therapy. Tight glycemic control using a multidrug regimen was associated with a significant, though modest, 17% relative reduction in a the primary composite outcome of heart attack, stroke, new or worsening congestive heart failure, death from CV causes, or amputation due to ischemic gangrene. This represents 8.6 CV events prevented per 1,000 person-years.
However, there was no evidence of any reduction in either cardiovascular or all-cause mortality. In addition, treatment effects were no different between patients at high and those at low cardiovascular risk, the investigators said (N. Engl. J. Med. 2015 June 3 [doi:10.1056/NEJMoa1414266]).
“In the absence of a reduction in total mortality, a small to moderate reduction in the rate of CV events needs to be weighed against potential harm due to overly aggressive care and the burden, long-term safety profile, and side effects of treatment, including weight gain and hypoglycemia,” they added.