Cardiovascular Benefits of Intensive Glucose Control in Veterans with Type 2 Diabetes Did Not Persist in Long-term Post-Trial Follow-Up
Observational cohort studies have demonstrated increasing risk for both macrovascular and microvascular events with increasing average blood glucose levels. Trials conducted in type 1 diabetes patients and in new onset type 2 diabetes patients demonstrated that improving glucose control reduced microvascular complications. Long-term follow-up of glucose lowering in patients with type 2 diabetes may help clarify the duration of any potential cardiovascular disease (CVD) benefit. In an interim analysis of the Veterans Affairs Diabetes Trial (VADT) follow-up study, investigators reported a significant 17% reduction in major CVD events resulting from 5.6 years of intensive vs. standard glucose lowering in 1,791 Veterans. In the current study, VADT investigators report on the full 15-year follow-up. The original VADT trial included 1,791 Veterans with type 2 diabetes who were randomly assigned to receive either intensive or standard glucose control. The 15-year follow-up study included 1,391 Veterans from the original VADT trial. The primary outcome was a composite of major CVD events, including non-fatal heart attack, non-fatal stroke, new or worsening congestive heart failure, amputation for ischemic gangrene, or CVD-related death. Secondary outcomes included CVD death, all-cause death, any major diabetes outcome, and health-related quality of life.
- Veterans with type 2 diabetes at high CVD risk, with 5.6 years of intensive glucose lowering to a HbA1c of 6.9%, did not experience reduced major cardiovascular events over 13.6 years of follow-up or reduced total mortality or improved quality of life over 15 years of total follow-up.
- Although there was a 17% reduction in major CVD events during the approximate 10-year period when HbA1c levels were separated between the intensive and standard therapy groups, there was no evidence of a beneficial legacy effect in the subsequent 5-year period once levels equalized among the groups.
- Results suggest there are modest long-term cardiovascular benefits of intensive glucose lowering therapy in patients with more advanced diabetes, but that long-term maintenance of lower levels may be required to maintain these improvements.
- Variables not well captured by medical records could have differed between groups and influenced outcomes during the observational follow-up.
- Although the duration of glucose lowering in the original VADT study was substantial, it is possible that more sustained efforts may have led to greater long-term benefits.
This study was funded by VA's Cooperative Studies Program. Drs. Wiitala and Hayward are part of HSR&D's Center for Clinical Management Research (CCMR), in Ann Arbor, MI.
Reaven P, Emanuele N, Wiitala W, Bahn G, Reda D, McCarren M, Duckworth W, and Hayward R, on behalf of investigators in the VA Diabetes Trial. Intensive Glucose Control in Patients with Type 2 Diabetes – 15-Year Follow-up. The New England Journal of Medicine. June 6, 2019;380(23):2215-2224.