The UKPDS was designed and run by the late Prof. Robert Turner and Prof. Rury Holman. When the intervention trial finished in September 1997, all surviving UKPDS patients were entered into a 10-year, post-trial monitoring programme. Since that time, 116 manuscripts have been published using data from UKPDS. One of the initial, landmark findings from UKPDS was that progressive hyperglycaemia is a feature of T2D, despite continued treatment with metformin, sulphonylurea, or insulin, and that β-cell function continues to decline over time. The trial assessed the relationship between glycaemic exposure and the rate of microvascular and myocardial infarction (MI) complications, documenting a significant increase over time. In 1998, UKPDS had 5 simultaneous publications that demonstrated the benefits of intensive or tight glycaemic control on complications as well as a cost analysis of improved blood pressure control in hypertensive patients with T2D. Reducing glucose exposure (HbA1c 7.0 % versus 7.9 % over median 10.0 years), with sulphonylurea or insulin therapy, reduced the risk of “any diabetes-related endpoint” by 12% and microvascular disease by 25%, with a 16% trend to a reduced risk of MI. In the metformin study, a 0.6% difference in HbA1c was found to correlate with a 32% reduction in any-diabetes related endpoint, while the blood pressure study showed that a 10/5 mmHg mean difference in blood pressure reduced the risk of any diabetes-related endpoint by 24%, fatal and non-fatal stroke by 44%, microvascular disease by 37% and retinopathy progression by 34%. Following publication of this data from the UKPDS, due to changes in the management of patients, age-standardised diabetes complication rates for stroke and acute MI decreased dramatically.
In later studies, UKPDS reported on a ‘legacy’ effect that early glucose control has on all-cause mortality. Indeed, despite an early loss of glycaemic differences, a continued reduction in microvascular risk and emergent risk reductions for MI and death from any cause were observed during 10 years of post-trial follow-up. Today, it is taken for granted that increased survival is associated with earlier glycaemic reduction. The results of the UKPDS have highlighted that complications in T2D need to be identified and treated early, and that hyperglycaemia is an independent risk factor for coronary heart disease, progressive and secondary to declining β-cell function. Importantly, improved glucose control can substantially reduce the risk of microvascular disease. Given the legacy effect of glycaemic control, glucose-lowering therapies need to be introduced as early as possible to maximise their benefit. Foundation therapy with metformin can substantially reduce cardiovascular risk and all-cause mortality. These findings paved the way for later trials on the benefits of early glucose control and earlier introduction of combination therapy.