1144-P: Patient Phenotypes and SGLT2 Inhibition in Type 2 Diabetes Mellitus: Insights from the EMPA-REG OUTCOME Trial

In EMPA-REG OUTCOME, empagliflozin (EMPA) reduced risk of cardiovascular (CV) death by 38% and hospitalization for heart failure (HHF) by 35% in patients with type 2 diabetes (T2D) and CV disease. We aimed to identify phenotypes of patients with different risk of outcomes and to explore treatment effects across these groups. Overall, 7020 patients were treated with EMPA 25, 10 mg or placebo (PBO). For this post-hoc analysis, patients were randomly separated into training (2/3) and validation sets (1/3 of patients). Latent class analysis identified 3 clusters using 6639 patients with complete data. The association of clusters to CV death and CV death/HHF, and treatment effect of EMPA vs. PBO across clusters was explored by Cox regression. Cluster 1 included younger patients with shorter T2D duration. Cluster 2 included more women with non-coronary atherosclerotic disease (CAD), and Cluster 3 older patients with advanced CAD. In the training set, risk of CV death varied across clusters (Cluster 2 vs. 1 HR 1.83 [95% CI 1.23, 2.71], Cluster 3 vs. 1 HR 1.86 [1.30, 2.67]) with similar pattern for CV death/HHF. Treatment effect of EMPA was consistent across clusters (Figure). Results were replicated in the validation set. We identified 3 phenotypes of patients with varying risk of outcomes. The consistent treatment effect across clusters reaffirms the robustness of CV death/HHF reduction with EMPA.

Duke Scholars

Author Robert John Mentz Medicine, Cardiology