Long-term results from the Veterans Administration Diabetes Trial will be reported Sunday afternoon during the two-hour session The Veterans Affairs Diabetes Trial (VADT) at 15 Years, which begins at 4:30 p.m. in room W414. VADT is the longest-running type 2 diabetes trial and observational follow-up.
“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,” said Peter Reaven, MD, Director of the Diabetes Research Program at Phoenix VA Health Care System. “Now that we have another five years of follow-up, key questions that remain are: What is 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 was co-principal investigator of the VADT follow-up study (VADT-F) and will discuss macrovascular events in VADT-F during the symposium. Nicholas V. Emanuele, MD, of Hines VA Hospital/Loyola University of Chicago Stritch School of Medicine, will review renal and other microvascular outcomes in the study. Specifically, he will discuss whether good blood glucose control has a long-term impact on kidney function and eye complications in patients with advanced type 2 diabetes.
Hertzel C. Gerstein, MD, from the Department of Endocrinology and Metabolism at McMaster University in Hamilton, Canada, will review the study’s clinical implications. And Wyndy L. Wiitala, PhD, of VA Center for Clinical Management Research, will open the symposium by describing the design of the VADT and VADT-F studies.
VADT randomized 1,791 people with poor glycemic control to a mean of 5.6 years of intensive glycemic therapy versus standard treatment. The study group was mostly older military veterans (mean age 60) who were diagnosed with type 2 diabetes for a mean of 11.5 years. The goal was to reduce A1C from a mean starting point of nearly 9.5 percent to below 7 percent in the intensive treatment arm.
Patients in the intensive arm had a median A1C of 6.9 percent compared to 8.4 percent in the standard treatment arm at the conclusion of active treatment. There was a trend toward fewer cardiovascular events in the intensive control arm, Dr. Reaven said, 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.”
After almost 10 years of follow-up, researchers found that even though A1C levels in the two groups eventually merged, tighter glycemic control cardiovascular effects became more pronounced over time. What had been a trend toward fewer cardiovascular events in the intensive control arm after 5.6 years of active treatment became a 17 percent reduction in cardiovascular events after another five years of follow-up. There was, however, no difference in cardiovascular mortality or overall mortality between the two groups.
Another five years of follow-up may answer some of the residual questions about tighter glycemic control and long-term benefits on complications, mortality, and quality of life.
“This symposium will provide a fairly definitive assessment of the long-term benefits of intensive glycemic control in more advanced type 2 diabetes patients,” Dr. Reaven said. “This should provide evidence-based guidance for clinicians in the care of similar patients.”
Many more sub-analyses of the VADT population are expected in the coming years, but VADT-F is the final preplanned observational follow-up report. The study was conducted with long-term funding support by the VA Cooperative Study Program.