Glycated Haemoglobin (HbA1c)

HbA1c is haemoglobin with glucose attached non-enzymatically to the N-terminal valine of the beta chain, a stable Amadori product. The reaction rate is proportional to glucose concentration and the product persists for the life of the red cell, so the fraction integrates exposure over roughly one hundred and twenty days. The weighting is uneven: roughly half the value comes from the most recent month, which is why it responds to a change in control within weeks rather than after a full lifespan. It is reported as a percentage on the NGSP scale and as mmol per mol on the IFCC scale.

Thresholds are 5.7 to 6.4 percent for prediabetes and 6.5 or above for diabetes, and the link to microvascular complications was established by DCCT and UKPDS. Typical treatment effects give the scale: metformin lowers it by roughly one to one and a half percentage points, DPP-4 inhibitors by half to eight tenths, semaglutide by well over a point in SUSTAIN, and the higher tirzepatide doses in SURPASS exceeded two points from elevated baselines.

As an endpoint it is a validated surrogate for microvascular outcomes and a weaker one for macrovascular. ACCORD, which drove HbA1c below six percent with intensive therapy, was stopped early for excess mortality, and that remains the argument against reading a lower number as automatically better. HbA1c justifies a comparison of glucose exposure; it does not by itself justify a claim about cardiovascular events.

The analytical caveats bite. Anything that shortens red cell survival, such as haemolysis, transfusion or advanced kidney disease, lowers the value spuriously, iron deficiency raises it, and haemoglobin variants interfere with some assay methods and not others. Comparing a drop from a high baseline with one from near target is also unsound, since the achievable fall scales with the starting point.