UKPDS

UKPDS Legacy Effect

Background

• United Kingdom Prospective Diabetes Study (UKPDS) 10-year follow-up

- Mean HbA1c levels identical in groups previously randomized to intensive or conventional glucose control

- Intensive vs conventional control group remained at significantly lower risk of complications - All-cause mortality: HR=0.87; p=0.006- MI: HR=0.85; p=0.014

- This continuing benefit has been termed T2DM legacy effect

UKPDS

Objectives

• Determine the degree to which historic HbA1c values contribute to later reduced risk of MI and all-cause mortalityDetermine time-dependent impact of earlier HbA1c values on year-to-year basis

Methods• 3849 UKPDS patients examined

• Analyses restricted to period for which HbA1c measurements available

• Continuous hazard functions estimated over 0-20 years for death and MI in relation to HbA1c, age, sex, and treatment group

UKPDS

Results

• HbA1c, older age, and male sex, but not treatment group, significantly associated with MI and death (p<0.001 for all)

• Reduction in risk of all-cause mortality almost 3X stronger with early HbA11c reduction (based on modeled impact of 1% HbA1c reduction on death)

• Early HbA1c reduction also reduced risk of MI (based on modeled impact of 1% HbA1c reduction on MI)

UKPDS

Conclusions

• Despite absence of glycemic difference during 10-year post-UKPDS observational follow-up, there was continued reduction in risk of complications with emergent risk reductions for MI and death

• Statistical modeling confirmed that earlier HbA1c levels continue to contribute to risk of diabetic complications, as seen in the Diabetes Control and Complications Trial (DCCT) [N Engl J Med 1993]

• Waiting years after diagnosis of T2DM to minimize glycemia is unlikely to achieve full benefits of immediate intervention

• Achieving and maintaining optimal glycemic control is essential to minimize long-term risk of diabetic complications