In the original ADVANCE study, participants were randomised to either intensive glycaemic control (target HbA1c, <48 mmol/mol [6.5%]) or standard therapy (target HbA1c defined by local guidelines). Mean HbA1c at the study’s end (median follow-up, 5.0 years) was lower in the intensive therapy group (48 mmol/mol vs 56 mmol/mol [6.5% vs 7.3%]). Mortality risk was not significantly reduced (hazard ratio [HR], 0.93; P=0.3), but there was a significant reduction in the risk of ESRD (seven vs 20 events; HR, 0.35; P=0.02).
A total of 8494 participants were then followed for a median of 5.4 additional years after the study end. Any difference in HbA1c between the groups had disappeared by the first post-trial visit, an average of 2.9 years after the study end. The in-trial reductions in ESRD risk persisted in ADVANCE-ON after a total median follow-up of 9.9 years (29 vs 53 events; HR, 0.54; P<0.01). The benefits were greater in people with preserved kidney function and those with well-controlled blood pressure. There was no significant effect on all-cause or cardiovascular mortality.
The role of intensive glycaemic control in people with diabetes has been questioned in recent years since the publication of ADVANCE and ACCORD (Action to Control Cardiovascular Risk in Diabetes), the latter of which suggested that intensive control actually increased the risk of death. However, the long-term follow-up of ADVANCE suggests that intensive control has beneficial effects in terms of kidney disease that persist long after the intensive treatment has stopped, without increasing the risk of death. The results echo studies in people with type 1 diabetes, such as EDIC (Epidemiology of Diabetes Interventions and Control), which also show long-term benefits of early intensive control.
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