The UK Prospective Diabetes Study (UKPDS) is the longest trial of patients with diabetes. Initiated in the 70s, it has been keeping track of the participants for over four decades and continues to yield productive information about glycemic control in patients with type 2 diabetes.

The latest data from the UKPDS, presented in a symposium at the ongoing 58th annual meeting of the European Association for the Study of Diabetes (EASD) 2022 in Stockholm, which showcase the “legacy effects” of early intensive control of blood glucose, reaffirm its clout as a seminal trial in diabetes, which changed the management of diabetes.

According to the new results, after 44 years of follow-up, there were 26% fewer microvascular complications such as diabetic retinopathy, diabetic nephropathy following early intensive blood glucose control with sulfonylureas or insulin. Deaths also reduced by 11%. Early intensive blood glucose control with metformin also reduced heart attacks by 31% and deaths by 25% suggesting a legacy effect for metformin too.^1,2

The UKPDS was launched in the UK in 1977 as a multicenter trial of over 5000 patients with newly diagnosed type 2 diabetes. The participants were randomized to an intensive blood glucose control strategy with sulfonylureas, insulin or metformin, or to a conventional blood glucose control strategy, mainly with diet. The results, published in 1998, conclusively established the beneficial effects of intensive blood glucose control with sulfonylureas/insulin/metformin on the risk of complications of type 2 diabetes, including mortality, both diabetes-related and all-cause. With its advantages of fewer hypoglycemic attacks and weight loss, metformin went on to become the first-line treatment for patients with diabetes, particularly the overweight patients. Though this coveted position is now being challenged by the advent of an array of newer antidiabetic drugs.^2,3 Controlling BP also significantly improved the outcomes in these patients.

The UKPDS, along with the DCCT, was the first to introduce the concept of legacy effect in patients with diabetes, which became apparent with the publication of 10-year, post-trial monitoring results, which showed that the benefits observed earlier had persisted for up to 30 years. The reduction in risk of macrovascular complications also became evident.

Legacy effect has been defined as “a phenomenon of continuous beneficial effect of the intensive control on disease outcomes or complications even after a long duration of cessation of the intervention”.⁴

The 44-year follow-up results of the UKPDS show that the benefits of intensive glycemic control in patients with type 2 diabetes were persistent and did not wear off or disappear with time. They also place back metformin as the first-choice drug. However, for these beneficial effects, treatment has to be started early on in the course of the disease, preferably just after the diagnosis. ⁴ Early diagnosis of type 2 diabetes and timely initiation of intensive treatment are therefore important to ward off the diabetes-related complications and improve quality of life of the patients.

References

1. https://www.rdm.ox.ac.uk/news/intensive-blood-glucose-control-for-people-with-type-2-diabetes-when-they-are-first-diagnosed-reduces-diabetic-complications-and-prolongs-life.
2. https://www.dtu.ox.ac.uk/generic/article.php?ArticleID=350.
3. https://diabetes.medicinematters.com/ukpds/sulfonylureas/what-we-learned-from-the-ukpds/16146264.
4. Wander GS, et al. Legacy effect in medicine-the expanding horizon! Indian Heart J. 2018;70(6):769-771.