UKPDS was originally designed to identify optimal management in type 2 diabetes by assessing interventions such as tight blood pressure and tight blood glucose management. The original randomised studies found reductions in macrovascular events were associated with tight blood pressure control but there were only limited reductions on microvascular events with tight blood glucose control.
These new analyses are based on 10-year observational follow up of the same patient cohorts. Assessments were initially conducted in a clinic setting but towards the end of the study with an annual questionnaire.
The follow up of the blood pressure study found that the differences between the two original study arms disappeared within 2 years and unsurprisingly the observed benefits in diabetes-related death, stroke and microvascular outcomes disappeared too.
The follow up of the blood glucose study found that differences in HbA1c disappeared after the first year. Despite this the benefits seen in diabetes-related end points and microvascular disease persisted. Additionally, benefits were seen to emerge over time in terms of myocardial infarction and all-cause mortality. The macrovascular benefits observed with metformin were also seen to persist. This has given rise to a theory of "legacy effects'' or "metabolic memory".
Any conclusions based on these studies should be made with caution. The data are observational and therefore more prone to bias. They also contradict recently published randomised study data that found no macrovascular benefit with tight blood glucose control. It is also worth noting that 'tight control' for the UKPDS was defined as an HbA1c of 7% while recent studies have set tighter targets of approximately 6.5%.
Action: Clinicians should continue to manage all aspects of cardiovascular risk in patients with type 2 diabetes. This includes controlling blood pressure and blood glucose to National targets.
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