Normalising blood glucose in patients with prediabetes may reduce heart disease risk

By Rebecca Jenkins

Normalising blood glucose in people with prediabetes is associated with a halving of the long-term risk of cardiovascular (CV) death or hospitalisation for heart failure, according to an observational post-hoc analysis of two large studies.

It was known that lifestyle interventions, including diet and exercise to target weight loss, could reduce the risk of people with prediabetes developing type 2 diabetes, but the long-term impact on CV outcomes remained unclear, researchers wrote in The Lancet Diabetes & Endocrinology.

They hypothesised that CV benefits might be restricted to the people who achieved normoglycaemia, making prediabetes remission a potential therapeutic goal.

To assess this idea, the researchers analysed findings from two trials: the US Diabetes Prevention Program Outcomes Study (DPPOS), which included 2402 adults with prediabetes randomised to lifestyle interventions, metformin or control groups; and the Chinese DaQing Diabetes Prevention Outcomes Study (DaQingDPOS), which included 540 adults with prediabetes who were randomised to diet, exercise or diet and exercise.

Prediabetes remission was defined as a fasting plasma glucose less than 5.6 mol/L (<100 mg/dL), 2-hour plasma glucose less than 7.8 mol/L (<140 mg/dL) and HbA_1c less than 39 mmol/mol (<5.7%).

The original findings from the DPPOS did not show statistically significant reductions in major adverse CV events (MACE) or mortality after 21 years when analysed according to the original randomisation groups.

But in this analysis, the event rate for CV death or hospitalisation from heart failure after a median follow up of 20 years was 1.74 per 1000 person-years among the 275 participants who reached remission after one year, compared with 4.17 in the remaining  2127 participants without remission, with a fully adjusted hazard ratio (HR) of 0.41.

The results remained robust after adjustment, were confirmed in the DaQingDPOS (primary endpoint: HR, 0.49) and were supported by a pooled meta-analysis, the researchers reported.

‘For individuals with prediabetes, treatment goals should prioritise achieving remission from hyperglycaemia to normoglycaemia alongside promoting weight loss,’ they concluded.

Commenting on the findings, Professor Jonathan Shaw, Deputy Director (Clinical and Population Health) of the Baker Heart and Diabetes Institute, Melbourne, said the study asked a good question about whether attempting to normalise blood sugar should be the real target for people with prediabetes, instead of focusing on preventing progression to type 2 diabetes.

‘The challenge is how confident we can be about making causal inferences from this analysis,’ he told Medicine Today.

‘This is an observational analysis (some of those who achieved remission will have come from the control not the intervention study arm of the trial), in which it’s hard to be certain that all confounding factors have been accounted for.’

Ultimately, a randomised controlled trial testing an intervention that could be expected to lead to remission of prediabetes was needed to demonstrate a causal link.

‘The problem is that the original trial component of the DPPOS already did that and found no CV benefit, which questions the ability to make a causal conclusion from the current paper,’ Professor Shaw said.

For now, the established benefits of intensive lifestyle interventions and metformin for the prevention of diabetes among people with prediabetes should continue to be pursued, as should appropriate management of CV risk factors, he said.

Lancet Diabetes Endocrinol 2026; https://doi.org/10.1016/S2213­8587(25)00295­5.