Identifying subgroups benefiting from intensive glycaemic treatment to improve renal outcomes in type 2 diabetes: Insights from the ACCORD trial

Aims

The ACCORD trial showed that intensive glucose-lowering therapy has a limited impact on renal function decline. We aimed to identify subgroups in the ACCORD population that might derive renal benefits from intensive glucose-lowering therapy.

Materials and Methods

The primary renal outcome included a ≥50% decline in baseline estimated glomerular filtration rate or end-stage renal disease (ESRD). Using the causal tree model, we employed internal cross-validation to identify five pivotal variables influencing the renal efficacy of intensive glycaemic control. These variables were integrated into the model-based recursive partitioning approach, yielding a visualizable tree model that depicted benefitting subgroups.

Results

Node 4, characterized by no cardiovascular history, systolic blood pressure (SBP) ≤142.67 mm Hg, and triglycerides ≤172 mg/dL, showed significantly reduced hazards of the composite renal outcome (fully adjusted hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.49–0.89; p = 0.006) and doubling of serum creatinine (fully adjusted HR 0.59, 95% CI 0.36–0.98; p = 0.041). Node 7 (no cardiovascular history and SBP 142.67–154 mm Hg) showed reduced hazards of the primary renal outcome (fully adjusted HR 0.67, 95% CI 0.49–0.93; p = 0.016) and ESRD (fully adjusted HR 0.35, 95% CI 0.17–0.74; p = 0.0057). Encouragingly, neither node 4 nor node 7 displayed elevated cardiovascular risk or hypoglycaemic events.

Conclusions

Through innovative machine learning, we identified ACCORD subgroups benefitting significantly from intensive glycaemic therapy for renal outcomes, without increased cardiovascular or hypoglycaemic risks.