Reduction in cardiovascular death with empagliflozin is consistent across categories of baseline HbA1c and change in HbA1c: Results from EMPA-REG OUTCOME

Aim: In the EMPA-REG OUTCOME trial, empagliflozin given in addition to standard of care significantly reduced cardiovascular (CV) death vs. placebo (HR 0.62; 95% CI 0.49, 0.77) in patients with type 2 diabetes (T2DM) and established CV disease. We investigated whether baseline HbA1c or change in HbA1c influenced the effect of empagliflozin on CV death. Methods: Patients were randomised to empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Background glucose-lowering therapy was to remain unchanged for 12 weeks, then adjusted to achieve glycaemic control according to local guidelines. CV death was analysed in the pooled empagliflozin group vs. placebo by categories of baseline HbA1c and change in HbA1c from baseline to the last value in the trial, using a Cox proportional hazards model. Results: A total of 7020 patients were treated. Median observation time was 3.1 years. In patients with baseline HbA1c < 7%, 7.0 to < 8.0%, 8.0 to < 9.0% and ≥9.0%, HRs for CV death were 0.30 (95% CI 0.12, 0.80), 0.59 (0.42, 0.83), 0.67 (0.45, 0.99) and 0.76 (0.44, 1.31), respectively (p = 0.4104 for treatment by subgroup interaction). In patients with reduction in HbA1c from baseline of ≥0.3% and < 0.3%, HRs for CV death were 0.58 (95% CI 0.42, 0.79) and 0.65 (0.47, 0.90) respectively (p = 0.5996 for interaction). Conclusion: In patients with T2DM and established CV disease, the reduction in the risk of CV death with empagliflozin vs. placebo was not affected by baseline HbA1c or the change in HbA1c from baseline to the last value in the trial.