HbA1c (Glycated Haemoglobin)
A blood test reflecting average blood sugar over 2-3 months by measuring the percentage of haemoglobin with attached glucose. Normal is below 5.7%, diabetes is diagnosed at ≥6.5%, and treatment targets are typically below 7.0%. HbA1c is the standard primary endpoint in diabetes clinical trials.
Technical Context
HbA1c is formed by non-enzymatic glycation — glucose binds irreversibly to the N-terminal valine of the haemoglobin beta chain. The rate of glycation is proportional to average glucose concentration over the preceding 2-3 months (reflecting the ~120-day red blood cell lifespan). HbA1c assays: standardised to DCCT/NGSP reference method (reported as percentage) or IFCC reference method (reported as mmol/mol; conversion: IFCC = [DCCT-2.15] × 10.929). Conditions affecting HbA1c accuracy: haemoglobin variants (HbS, HbC, HbE — can interfere with some assay methods), conditions altering RBC lifespan (haemolytic anaemia, recent transfusion — shorter lifespan underestimates average glucose; iron deficiency, B12 deficiency — longer lifespan overestimates), and pregnancy (haemodilution). In GLP-1 RA trials, HbA1c reductions of 1.0-2.0 percentage points are typical at therapeutic doses.