Intensive glycemic control with certain drugs is known to increase risk of hypoglycemia which is associated with risk of mortality. The aim of this study was to evaluate the association between all-cause mortality and HbA1c levels in patients with type 2 diabetes. Two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database. One group included patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents (n=27,965) and the other group included patients who had changed to regimens that included insulin (n=20,005). The results showed that an HbA1c of approximately 7.5% was associated with the lowest all-cause mortality and the lowest progression to large-vessel disease events. In both regimens, an increase or decrease from this mean HbA1c value was associated with heightened risk of adverse outcomes. However, mortality risk between the two treatment cohorts differed, showing that insulin treatment was associated with increased mortality. Results confirmed a weak association between HbA1c and reduced risk of macrovascular events at an HbA1c higher than 7.5% but, showed a rise in mortality at an HbA1c of less than 6.5% in patients both with and without recorded macrovascular disease. Thus, these findings suggest a revision in diabetes guidelines concerning HbA1c targets with consideration for the type of pharmacotherapy used. In their comment, Balkau B et al. emphasized the epidemiological nature of this study which cannot be used as evidence of a causal relationship. However, they pointed out that these observations are representative of the real world practice. They recognised the contribution of this large and statistically powerful study to provide a rationale for recommending an HbA1c threshold of 7.5%.
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