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®.
