Association of Prediabetes Remission with Reduced Cardiovascular Mortality and Heart Failure

Article Impact Level: HIGH
Data Quality: STRONG
Summary of  the Lancet Diabetes & Endocrinology https://doi.org/10.1016/S2213-8587(25)00295-5 
Dr. Elsa Vazquez Arreola  et al.

Points

Researchers analyzed data from two major longitudinal trials to determine if normalizing blood glucose levels in prediabetic patients reduces the long-term risk of severe cardiovascular events.
The study found that patients who achieved prediabetes remission experienced a fifty-eight percent lower risk of cardiovascular death or hospitalization for heart failure compared to non-remission groups.
Data from the US cohort showed an adjusted hazard ratio of 0.41 for the primary endpoint which indicates a substantial protective benefit lasting decades after the intervention.
Results were consistent across diverse populations with the Chinese cohort demonstrating a similarly reduced hazard ratio of 0.49 for cardiovascular death and heart failure hospitalization events.
The findings suggest that clinicians should view glucose normalization as a primary prevention tool alongside blood pressure and cholesterol management to effectively mitigate future cardiac risks.

Summary

This post-hoc analysis investigated the long-term cardiovascular impact of achieving prediabetes remission using data from the Diabetes Prevention Program Outcomes Study (DPPOS) and the DaQing Diabetes Prevention Outcomes Study (DaQingDPOS). While lifestyle interventions are standard for management, their direct effect on cardiovascular mortality remains debated. The researchers assessed remission based on American Diabetes Association criteria after one year in the DPPOS cohort (n=2,402) and six years in the DaQingDPOS cohort (n=540), with primary endpoints defined as cardiovascular death or hospitalization for heart failure over 20- and 30-year follow-up periods respectively.

In the DPPOS cohort, 11.5% of participants achieved remission after one year of intervention. After a median follow-up of 20 years, the event rate for the primary composite endpoint was 1.74 (95% CI 0.87–3.48) per 1,000 person-years for the remission group, compared to 4.17 (95% CI 3.55–4.89) for non-remission participants (p=0.013). This translated to a fully adjusted hazard ratio (HR) of 0.41 (95% CI 0.20–0.84; p=0.014), indicating a significant reduction in risk that persisted independent of baseline differences.

These findings were corroborated by the DaQingDPOS data, which showed a similar hazard ratio of 0.49 (95% CI 0.28–0.84; p=0.010) for the primary endpoint. A pooled meta-analysis further supported these results, demonstrating a robust association between remission and reduced cardiovascular risk. Furthermore, analysis of the composite endpoint for those achieving remission at least once during follow-up yielded a hazard ratio of 0.43 (95% CI 0.29–0.63; p<0.0001). The study suggests that restoring normal glucose regulation constitutes a critical primary prevention target for mitigating fatal cardiac events and heart failure.

Link to the article: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(25)00295-5/fulltext

References

Vazquez Arreola, E., Gong, Q., Hanson, R. L., Wang, J., Sandforth, L., He, S., Sandforth, A., Qian, X., Giacca, M., Bornstein, S. R., Fritsche, A., Stefan, N., Preissl, H., Gregg, E. W., Marx, N., Jumpertz-von Schwartzenberg, R., Li, G., & Birkenfeld, A. L. (2025). Prediabetes remission and cardiovascular morbidity and mortality: Post-hoc analyses from the Diabetes Prevention Program Outcome study and the DaQing Diabetes Prevention Outcome study. The Lancet Diabetes & Endocrinology, S2213858725002955. https://doi.org/10.1016/S2213-8587(25)00295-5