The 20-year UK Prospective Diabetes Study revealed incomparable clinical benefits for people with newly diagnosed type 2 diabetes randomized to intensive glycaemic control with sulfonylurea or insulin therapy or metformin therapy, compared with conventional glycaemic control. The 10-year post-trial follow-up identified emerging and persisting glycaemic and metformin legacy treatment effects in the cohort. This finding ushered researchers to determine whether these effects would wane by extending follow-up for another 14 years.

      The cohort for the extended trial included survivors of the 10-year post-trial monitoring period. The follow-up of these participants was carried out by linking them to their routinely collected National Health Service (NHS) data for another 14 years. Clinical outcomes were derived from records of deaths, hospital admissions, outpatient visits, and accident and emergency unit attendances. The investigating team examined seven pre-specified aggregate clinical outcomes such as any diabetes-related endpoint, diabetes-related death, death from any cause, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease by the randomised glycaemic control strategy with an intention-to-treat basis using Kaplan–Meier time-to-event and log-rank analyses.

      Findings from the study revealed that the mean age of the survivors as of 2021 was 79.9 years. Interestingly, for up to 24 years after trial end, the glycaemic and metformin legacy effects showed no signs of waning. Early intensive glycaemic control with sulfonylurea or insulin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 10% for death from any cause, 17% for myocardial infarction, and 26% for microvascular disease. Early intensive glycaemic control with metformin therapy, compared with conventional glycaemic control, showed overall relative risk reductions of 20% for death from any cause and 31% for myocardial infarction. No significant risk reductions during or after the trial for stroke or peripheral vascular disease were observed for both intensive glycaemic control groups, and no significant risk reduction for microvascular disease was observed for metformin therapy.

      Compared to traditional glycaemic control, early intensive glycaemic control with sulfonylurea, insulin, or metformin appears to provide a nearly lifetime decreased risk of death and myocardial infarction. It may be crucial to achieve near normoglycemia as promptly as possible after diagnosis in order to reduce the lifetime risk of complications from diabetes to the highest degree possible.

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