Prediabetes: Impact on cardiovascular risk and emerging therapeutic strategies

Prediabetes is an umbrella term which refers to a collection of blood parameters related to glucose regulation exceeding their normal threshold, but not meeting the criteria for overt diabetes. Its prevalence is rising worldwide, largely driven by overweight/obesity, diet, lack of exercise and familiarity.

To provide a state-of-the-art overview of epidemiology, pathophysiology, cardiovascular (CV) implications, and emerging therapeutic strategies in prediabetes.

Narrative review with structured discussion of randomized controlled trials (RCTs) and meta-analyses addressing progression to T2DM and cardiovascular outcomes.

The risk of prediabetes progressing to T2DM is well established, with modest differences across phenotypes (impaired fasting glucose, impaired glucose tolerance, elevated HbA1c). In contrast, whether prediabetes independently increases CV risk remains debated. Observational studies and meta-analyses suggest a mild but statistically significant increase in CV events and mortality; however, randomized evidence demonstrating CV benefit from treating prediabetes is limited and methodologically heterogeneous. Current management of prediabetes primarily relies on lifestyle interventions, while metformin is recommended only in selected high-risk individuals. Glucagon-like peptide receptor-1 agonists and sodium-glucose cotransporter-2 inhibitors have shown disease-modifying effects in T2DM and related cardiometabolic conditions. Emerging data suggest potential benefits in individuals with prediabetes, although dedicated adequately powered CV outcome trials are lacking.

Prediabetes is a clinically relevant cardiometabolic state. While progression to T2DM is well documented, its role as an independent CV therapeutic target remains uncertain. Future trials should address phenotype-specific risk stratification and evaluate contemporary cardiometabolic therapies in appropriately powered populations.