Photo Credit: Ekaterina Chizhevskaya
The following is a summary of “Reaffirmation of Mechanistic Proteomic Signatures Accompanying SGLT2 Inhibition in Patients With Heart Failure: A Validation Cohort of the EMPEROR Program,” published in the November 2024 issue of Cardiology by Packer et al.
Inhibitors of sodium-glucose cotransporter 2 (SGLT2) produce direct biological effects on the heart and kidneys in experimental models. Still, the relevance of these effects in patients with heart failure (HF) is not fully understood.
Researchers conducted a prospective study to validate large-scale proteomic changes in patients with HF treated with inhibitors of SGLT2.
They assessed the effects of randomized treatment with either placebo or empagliflozin on 1,283 circulating proteins in 1,134 patients with HF from the EMPEROR (Empagliflozin Outcome Trial in Patients with Chronic HF and Reduced Ejection Fraction) program. In a separate validation cohort of 1,120 patients in the EMPEROR program, the protein assessment was expanded to 2,155 proteins to confirm findings.
The results showed that 25 proteins were significantly enriched by empagliflozin (≥15% between-group difference and false discovery rate <1% at 12 weeks). Among them, 13 proteins promoted autophagy and cellular quality control (e.g., IGFBP1, OTUB1, DNAJB1, IST1, HSPA8, H-FABP, EPO), 12 enhanced mitochondrial health and ATP production (e.g., UMtCK, TBCA, H-FABP, ATPIFI), 7 improved iron mobilization or erythropoiesis (e.g., TfR1, ERMAP, SNCA), 3 influenced renal sodium handling, and 9 restored cardiac and renal function, with several proteins impacting multiple domains. Lowering the threshold to a 10% between-group difference identified 58 additional enriched proteins with effects on the heart and kidneys, supporting consistent biological signatures across both cohorts.
They concluded that inhibitors of SGLT2 effects—promoting autophagy, enhancing mitochondrial health and ATP production, supporting iron mobilization, influencing renal sodium handling, and restoring cardiac and renal function—were likely relevant for patients with HF.
Source: jacc.org/doi/10.1016/j.jacc.2024.07.013
