Reaven PD, et al. – The authors of this study previously reported a median of 5.6 years of intensive vs standard glucose lowering in nearly 1,800 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) following 10 years of combined intervention and observational follow-up. In the current work, they report the full 15-year follow-up study findings. Overall, the investigators noted a lower risk of cardiovascular events among participants randomized to intensive glucose control for 5.6 years vs participants who received standard therapy only during the prolonged period in which the glycated hemoglobin curves were separated. They did not uncover any evidence of a legacy effect or a mortality benefit with intensive glucose control.

Methods

• Following the conclusion of the original clinical trial, enrolled participants (complete cohort) were observationally followed by using central databases for the incidence of cardiovascular events, hospitalizations, and deaths.
• Participants were asked to provide additional data via surveys and chart reviews (survey cohort).
• A composite of major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, and death from cardiovascular causes comprised the prespecified primary outcome.
• The prespecified secondary outcome was death from any cause.

Results

• The complete cohort consisted of 1,655 participants, with the survey cohort comprised of 1,391 participants.
• The separation of the glycated hemoglobin curves averaged 1.5 percentage points during the trial (which originally enrolled 1,791 participants) between the intensive-therapy group (892 participants) and the standard-therapy group (899 participants); 3 years following the end of the trial, the difference declined to 0.2 to 0.3 percentage points.
• Over a period of 15 years of follow-up (active treatment plus post-trial observation), the intensive-therapy group vs the standard-therapy group displayed no lower risks of major cardiovascular events or death.
• The investigators, however, did note a reduction in the risk of major cardiovascular disease during an extended interval of separation of the glycated hemoglobin curves, but this benefit did not continue post-equalization of the glycated hemoglobin levels.