After 24 years, patients who received early treatment still had lower risk for mortality and other adverse events.

In the UK Prospective Diabetes Study (UKPDS) between 1977 and 1991, 5000 patients with newly diagnosed type 2 diabetes were randomised to early intensive glycaemic control with sulfonylurea or insulin (or, if overweight, with metformin) or to conventional care (diet alone). After 20 years, patients who were randomised to medication had significantly lower risk for a variety of diabetes-related endpoints and for clinically evident microvascular disease (NEJM JW Gen Med Oct 15 1998 and Lancet 1998; 352: 837-853; 854-865).

In year one of a post-trial monitoring study, survivors from both groups had reached similar treatment and glycaemic-control goals. However, after 10 years, those who received early medication still had significantly lower risk for all-cause mortality and myocardial infarction (MI) compared with patients who initially had received conventional care – a so-called ‘legacy effect’ (NEJM JW Gen Med Nov 1 2008 and N Engl J Med 2008; 359: 1577-1589).

Researchers now present data on clinical outcomes that were collected for 24 years after the conclusion of the interventional phase of the UKPDS. After a median 18 years of follow up, patients who initially received sulfonylureas or insulin had significantly lower risk for all- cause mortality (hazard ratio [HR], 0.90), MI (HR, 0.83) and microvascular disease (HR, 0.74) than those who received conventional care. Patients who initially received metformin had significantly lower risk for all-cause mortality (HR, 0.90) and MI (HR, 0.69).

Comment: The exact mechanism of this ‘legacy effect’ is unclear, but early hyperglycaemia might induce pathophysiological changes that are irreversible, despite improved glycaemic control later. This study suggests a lifelong value for diagnosing type 2 diabetes early and treating patients promptly. However, persistent differences in treatment of the two groups after the end of the randomised trial – and not simply a legacy effect – might explain some of the outcomes.

Bruce Soloway, MD, Associate Professor Emeritus of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

Adler AI, et al. Post-trial monitoring of a randomised controlled trial of intensive glycaemic control in type 2 diabetes extended from 10 years to 24 years (UKPDS 91). Lancet 2024 May 17; e-pub (https://doi. org/10.1016/S0140-6736(24)00537-3).

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine.