A comprehensive post-hoc analysis of the ADVANCE trial has demonstrated that intensive glucose lowering therapy significantly reduces mortality and cardiovascular risks in patients with type 2 diabetes, regardless of their age at diagnosis or disease duration.
The study, published in Diabetes Care, analyzed data from 11,140 high-risk type 2 diabetes patients, with a mean age of 65.8 years, examining the effects of intensive glucose control across different patient subgroups. The research team, led by Dr. Toshiaki Ohkuma from The George Institute for Global Health, sought to address the question of whether treatment effectiveness varied based on age of diabetes onset or disease duration.
Key Clinical Findings
The intensive glucose lowering intervention, which targeted HbA1c levels of 6.5% or lower using gliclazide, demonstrated several significant benefits over standard glucose control:
- 10% reduction in composite risk for vascular events (HR = 0.9; 95% CI, 0.82-0.98)
- 12% reduction in cardiovascular death risk (95% CI, -4 to 26)
- 14% reduction in major microvascular events risk (95% CI, 3-23)
- 6% reduction in all-cause mortality risk (95% CI, -6 to 17)
Patient Subgroup Analysis
Researchers stratified participants into subgroups based on:
- Age at diagnosis: ≤50 years, 50-60 years, ≥60 years
- Disease duration: ≤5 years, 5-10 years, ≥10 years
The analysis revealed that patients diagnosed at younger ages typically had longer diabetes duration and higher rates of microvascular disease. However, the beneficial effects of intensive glucose control remained consistent across all subgroups, challenging previous assumptions about treatment efficacy variations.
Safety Considerations
While the treatment showed significant benefits, researchers observed an important safety signal: the risk of hypoglycemia increased substantially across all subgroups under intensive glucose control (HR = 1.86; 95% CI, 1.42-2.44). This finding underscores the need for careful monitoring and individualized treatment approaches.
Clinical Implications
Dr. Ohkuma and colleagues suggest that younger-onset patients and those with longer disease duration may require more intensive glucose-lowering approaches. However, they emphasize the importance of carefully selecting combination therapies to minimize hypoglycemia risk.
The study's findings provide valuable insights for clinical practice, though researchers acknowledge that contemporary diabetes treatment regimens may differ from those used in the ADVANCE trial. The results support a more aggressive approach to glucose control while highlighting the need for balanced consideration of benefits and risks.
