Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A(1c), anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA(1c) and then assigned to three target categories, based on whether HbA(1c) was <= 0.5% below or above (on-target), >0.5% below (below-target) or >0.5% above (above-target) their HbA(1c) goal, personalized according to the number of potential risks among age > 70 years, diabetes duration > 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA(1c) category (>= 8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22-1.47), p < 0.001) and those above-target (1.42 (1.29-1.57), p < 0.001). Risk was increased among individuals in the lowest HbA(1c) category (<6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03-1.29), p = 0.01 and 1.10 (1.01-1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA(1c) goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia.