The EMPEROR study: MOA of Empagliflozin in heart failure patients

In a landmark drug mode of action (MOA) study of over 1100 heart failure patients from the EMPEROR program, Professor Faiez Zannad and colleagues used Olink Explore 1536 to measure ~1500 plasma proteins longitudinally over the course of a 52-week trial of the SGLT2 inhibitor, empagliflozin. Comparing empagliflozin and placebo-treated patients, 32 proteins were differentially expressed (>10% change at an FDR of <1%).

The 9 proteins showing the largest treatment effect (>15% change at an FDR of <1%) were IGFBP1, TfR1, CA2, EPO, TGM2, TMSB10, uMtCK, IGFBP4 & AFABP4. The functions of these proteins were most commonly related to the promotion of autophagic flux in the heart, kidney or endothelium, along with others linked to important biological processes in the heart and kidney. These findings in the clinical setting are consistent with those from previous experimental studies on the effects of SGLT2 inhibitors.