Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme

• Published in: European heart journal 2022-12, Vol.43 (48), p.4991-5002
• Main Authors: Zannad, Faiez, Ferreira, João Pedro, Butler, Javed, Filippatos, Gerasimos, Januzzi, James L, Sumin, Mikhail, Zwick, Matthias, Saadati, Maral, Pocock, Stuart J, Sattar, Naveed, Anker, Stefan D, Packer, Milton
• Format: Article
• Language: English
• Subjects: Diabetes Mellitus, Type 2 - drug therapy; Fast Track Clinical Research; Heart Failure - drug therapy; Heart Failure - metabolism; Humans; Inflammation - drug therapy; Proteomics; Sodium; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use; Somatomedins - therapeutic use
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehac495

Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in diverse patient populations, but their mechanism of action requires further study. The aim is to explore the effect of empagliflozin on the circulating levels of intracellular proteins in patients with heart failure, using large-scale proteomics. Over 1250 circulating proteins were measured at baseline, Week 12, and Week 52 in 1134 patients from EMPEROR-Reduced and EMPEROR-Preserved, using the Olink® Explore 1536 platform. Statistical and bioinformatical analyses identified differentially expressed proteins (empagliflozin vs. placebo), which were then linked to demonstrated biological actions in the heart and kidneys. At Week 12, 32 of 1283 proteins fulfilled our threshold for being differentially expressed, i.e. their levels were changed by ≥10% with a false discovery rate