Objective: To examine the effects of change in glycaemic control on clinical outcomes in patients with type 2 diabetes.

Research Design and Methods: Data were obtained from 9981 participants of the ADVANCE trial and ADVANCE-ON follow-up. Participants were categorized into 3 groups by glycated haemoglobin (HbA1c) change from baseline to 6 months, >0.25% decrease, >0.25% increase and minimal change (±0.25%). Adjusted Cox and logistic regression analyses examined relationships between HbA1c change and all-cause mortality, macrovascular events, microvascular events and severe hypoglycaemia.

Results: Mean (±SD) age was 65.8±6.4 years, diabetes duration 7.9±6.4 years and HbA1c 7.5±1.6% at baseline. In the first 6 months, 48%, 22% and 30% of participants had an HbA1c decrease, minimal change or increase respectively. Median (IQR) follow-up was 9.4 (5.1-10.4) years. Compared to those with minimal HbA1c change at 6 months, participants with an HbA1c increase at 6 months had greater risk of risk of all-cause mortality [1.26 (1.11-1.43)], macrovascular events [1.26 (1.10-1.44)] and microvascular disease [1.36 (1.09-1.70) whereas participants with an HbA1c decrease did not have greater risk of all-cause mortality [0.99 (0.87-1.12)], macrovascular events [1.06 (0.93-1.21)] or microvascular disease [0.97 (0.77-1.21)]. Neither HbA1c increase [1.05 (0.83-1.33)] or decrease [1.16 (0.91-1.47)] was associated with greater risk of severe hypoglycaemia. These effects were similar when HbA1c change at 3 months was considered and in subgroup analyses by age, gender, diabetes duration, or baseline HbA1c.

Conclusions: Increased rather than decreased HbA1c at 6 months was associated with increased risks of death and vascular events in type 2 diabetes.


N. Nanayakkara: None. T. Ohkuma: None. M. Woodward: Consultant; Self; Amgen Inc., Kirin. J. Chalmers: Research Support; Self; Idorsia. S. Zoungas: None.

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