Challenges to hemoglobin A1c as a therapeutic target for type 2 diabetes mellitus.

Glycated hemoglobin (HbA1c) is widely accepted as the most reliable measure of long-term glycemia. However, there is disagreement among professional medical societies on a proper glycemic target for long-term benefits in type 2 diabetes (T2D). The use of some glucose-lowering drugs was associated with heart failure despite substantial lowering of HbA1c. The failure of intensive glycemic control to reduce cardiovascular risk in some trials again brought into question the usefulness of HbA1c as a therapeutic target in T2D. In large cardiovascular outcome trials, some newer glucose-lowering drugs were associated with higher risks of heart failure or amputation despite comparable glycemic control between the test and placebo groups. Here, we provide evidence that variation in hemoglobin glycation between individuals is responsible for these inconsistencies. We suggest that further research be conducted in this area and that the findings be applied to clinical trials and practice.