Final observational follow-up data from the Veterans Administration Diabetes Trial (VADT) will be reported on Sunday, June 24, at the Scientific Sessions.
There will almost certainly be more subanalyses of the VADT findings published in the next few years, but this is the final preplanned observational follow-up report, according to Peter Reaven, MD, an endocrinologist at VA Health Care System in Phoenix and co-principal investigator of the VADT follow-up study.
“We know from the 10-year follow-up data that intensive glycemic control during the active treatment portion of VADT showed a statistically and clinically significant improvement in cardiovascular outcomes,” Dr. Reaven said. “Now that we have another five years of follow-up, key questions that remain are: What’s the trajectory of that benefit? Is there a legacy benefit to good glucose control? And is there evidence, one way or another, about the impact of glucose control on mortality?”
Dr. Reaven will be one of four featured speakers at the Scientific Sessions symposium The Veterans Affairs Diabetes Trial (VADT) at 15 Years. The presenters will review the intervention and follow-up study design and analysis approach; report the 15-year findings on cardiovascular disease and other microvascular complications, including renal disease and eye complications; and address the key clinical implications of the findings.
VADT, which was funded by the VA Cooperative Studies Program, randomized 1,791 mostly older military veterans with poor glycemic control to a mean of 5.6 years of intensive glycemic therapy versus standard treatment. The goal was to reduce A1C below 8 percent from a mean starting A1C of 9.5 percent. Patients in the trial had a mean age of 60 and had been diagnosed with type 2 diabetes for a mean of 11.5 years.
At the end of active treatment, patients in the intensive arm had a mean A1C of 6.9 percent compared to 8.4 percent in the standard treatment arm. The active treatment portion of the trial showed a trend toward fewer cardiovascular events in the intensive control arm, Dr. Reaven noted, but the difference was not statistically significant.
Patients returned to usual care after the active treatment portion of the trial, though expectations of care had changed for both patients and providers.
“Not surprisingly, if you have been getting lots of intensive glucose lowering care, you tend not to change that right away,” Dr. Reaven said. “Most patients likely continued with intensive care for some time while standard care patients were likely treated a bit more aggressively to improve their A1C. After approximately 10 years—five years of active treatment and five years of follow-up—we saw a merging of A1C levels. Thereafter, both the intensive treatment and standard care arm A1C levels essentially equalized.”
Even though A1C levels in the two groups eventually merged, the effects of tighter glycemic control became more pronounced over time, Dr. Reaven continued. What had been a trend toward fewer cardiovascular events in the intensive control arm after 5.6 years of active treatment had solidified into a 17 percent reduction in cardiovascular events after another five years of follow-up. But there was no difference in cardiovascular mortality or overall mortality between the two groups.
Another five years of observational follow-up may answer some of the remaining questions about tighter glycemic control and the long-term benefits on complications, mortality, and quality of life.
“This 15-year assessment is trying to further elucidate the long-term cardiovascular and overall benefits that result from intensive glucose lowering,” Dr. Reaven said. “This symposium will provide a fairly definitive assessment of the long-term benefits of intensive glycemic control in more advanced type 2 diabetes patients. This should provide evidence-based guidance for clinicians in the care of similar patients.”