Interrelationship between Reduction in Weight and Adiposity Indices and Improvement in Cardiovascular (CV) Death and Heart Failure (HF) Outcomes with Empagliflozin in Patients with Type 2 Diabetes (T2D) in EMPA-REG OUTCOME®

Aim:

In the EMPA-REG OUTCOME® trial, empagliflozin reduced CV death by 38% and hospitalisation for HF (HHF) or HF death by 39% vs. placebo in patients with T2D and CV disease. We explored whether reductions in weight and indices of adiposity with empagliflozin were related to its beneficial effects on CV outcomes.

Methods:

Patients were randomised to placebo, empagliflozin 10 mg, or empagliflozin 25 mg in addition to standard of care. CV death and HHF/HF death were assessed in the placebo vs. pooled empagliflozin groups by the median change (above/below) in weight, waist circumference (WC), and estimated total body fat (eTBF) at week 12.

Results:

Baseline median weight, WC, and eTBF were similar in the placebo and empagliflozin groups. At week 12, greater reductions in all parameters were observed with empagliflozin vs. placebo. The reduction in CV death with empagliflozin appeared to be greater in patients with greater weight reductions (HR 0.84 [95% CI 0.62, 1.14] vs. HR 0.46 [95% CI 0.32, 0.65]; p-value for interaction = 0.0114). The effect on CV death was similar by degree of change in WC or eTBF. HR for HHF/HF death was similar regardless of magnitude of change in adiposity indices.

Conclusion:

Empagliflozin may have a more robust effect on CV death with greater weight loss at week 12; effects did not differ by degree of reduction in WC or eTBF. Weight reduction (potentially related to volume loss), rather than fat reduction, may have contributed to the CV benefit seen with empagliflozin in EMPA-REG OUTCOME®.