Abstract
Hemoglobin A1C (HbA1c) is used as an index of average blood glucose measurement over a period of months and is a mainstay of blood glucose monitoring. This metric is easy to measure and relatively inexpensive to obtain, and it predicts diabetes-related microvascular complications. However, HbA1c provides only an approximate measure of glucose control; it does not address short-term glycemic variability (GV) or hypoglycemic events. Continuous glucose monitoring (CGM) is a tool which helps clinicians and people with diabetes to overcome the limitations of HbA1c in diabetes management. Time spent in the glycemic target range and time spent in hypoglycemia are the main CGM metrics that provide a more personalized approach to diabetes management. Moreover, the glucose management indicator (GMI), which calculates an approximate HbA1c level based on the average CGM-driven glucose level, facilitates individual decision-making when the laboratory-measured HbA1c and estimated HbA1c are discordant. GV, on the other hand, is a measure of swings in blood glucose levels over hours or days and may contribute to diabetes-related complications. In addition, addressing GV is a major challenge during the optimization of glycemia. The degree of GV is associated with the frequency, duration, and severity of the hypoglycemic events. Many factors affect GV in a patient, including lifestyle, diet, the presence of comorbidities, and diabetes therapy. Recent evidence supports the use of some glucose-lowering agents to improve GV, such as the new ultra-long acting insulin analogs, as these agents have a smoother pharmacodynamic profile and improve glycemic control with fewer fluctuations and fewer nocturnal hypoglycemic events. These newer glucose-lowering agents (such as incretin hormones or sodium-glucose cotransporter 2 inhibitors) can also reduce the degree of GV. However, randomized trials are needed to evaluate the effect of GV on important diabetes outcomes. In this review, we discuss the role of HbA1c as a measure of glycemic control and its limitations. We also explore additional glycemic metrics, with a focus on time (duration) in glucose target range, time (duration) in hypoglycemia, GV, GMI, and their correlation with clinical outcomes.