medwireNews: The legacy treatment benefits of intensive glycemic control with sulfonylurea, insulin, or metformin in people with newly diagnosed type 2 diabetes at the 10-year follow-up of the UKPDS trial show no signs of waning, suggest findings a further 14 years on.
Compared with conventional glycemic control, primarily diet restrictions, early intensive glycemic control “appears to confer a near-lifelong reduced risk of death and myocardial infarction,” say Rury Holman (Churchill Hospital, Oxford, UK) and colleagues in The Lancet.
They continue: “Achieving near normoglycaemia immediately following diagnosis might be essential to minimise the lifetime risk of diabetes-related complications to the greatest extent possible.”
The UKPDS spanned 20 years and showed significant relative risk reductions with intensive glucose control strategies versus conventional strategies that “endured or emerged anew as statistically significant,” at the 10-year follow-up after the trial ended in 1997.
Among individuals originally randomly assigned to receive sulfonylurea or insulin the risks for death from any cause, myocardial infarction (MI), and microvascular disease were reduced by a significant 13%, 15%, and 24%, respectively, relative to those receiving conventional glycemic control. For those assigned to receive metformin (BMI >27 kg/m2), the relative risk reductions were a significant 21% for any diabetes-related endpoint, 27% for death from any cause, and 33% for MI.
These legacy effects occurred despite all the participants returning to community- or hospital-based diabetes care and no attempts made to maintain patients on their allocated treatment strategies, the team points out.
Indeed, mean glycated hemoglobin levels were similar between the two groups within a year of the trial ending and they became progressively lower over the subsequent 4 years, while the number and intensity of glucose-lowering therapies increased in both groups.
In the current UKPDS 91 analysis – up to 24 years after the original trial ended – routinely collected NHS administrative data were available for 1489 (97.6%) of 1525 patients alive at the end of the 10-year post-trial follow-up. Their mean age at randomization to treatment in the UPDS as 50.2 years and 41.3% were women.
These individuals were aged 70.9 years at the start of the administrative follow-up, and the mean age of those still alive (33%) by the end was 79.9 years. The median follow-up from randomization was 17.5 years.
Among the 984 people originally assigned to receive sulfonylurea or insulin, the overall risks for death from any cause, MI, and microvascular disease were reduced by a significant 10%, 17%, and 26%, respectively, compared with the 370 assigned to receive conventional therapy. The corresponding absolute risk reductions were 3.7, 3.3, and 3.5 percentage points.
For the 135 individuals who received metformin, the relative risk reductions were 20% for death from any-cause and 31% for MI, with absolute risk reductions of 4.9 and 6.2 percentage points, respectively.
“UKPDS has shown that establishing and maintaining near normoglycaemia from the time of diagnosis of type 2 diabetes minimises the risk of complications and prolongs life,” say Holman et al.
They acknowledge that modern management of type 2 diabetes now includes new glucose-lowering agents, and they support their use, but emphasize that “the therapies used in the UKPDS are off patent, have been shown previously to be cost-effective or indeed cost-saving, are widely available globally at low cost, and are on the WHO list of Essential Medicines.”
The glycemic legacy effect shown in this analysis is therefore “likely to strengthen the economic case for the use of these therapies in low-income settings.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group
