The early metabolic cardiac targets of empagliflozin during the development of heart failure, independent of SGLT2 inhibition
The early, SGLT2-independent, metabolic mechanism marking HF protection by SGLT2i entail 1) decreases in metabolic intermediates that drive hypertrophy (G6P, malate), 2) boosting glycolysis (GLUT4, distal part glycolysis, lactate release) without shifting glucose/fatty acid oxidation ratio, and 3) activating ERRα/SIRT3 pathway associated with increased gene expression of mitochondrial energy pathways and improved cardiac ATP levels.
Authors
- Michael Pieper (ORCID: https://orcid.org/0000-0003-1348-5927)
- Nina C. Weber (ORCID: https://orcid.org/0000-0003-1111-9042)
- Diane Bakker
- Bauke V. Schomakers (ORCID: https://orcid.org/0000-0002-0242-9113)
- Coert J. Zuurbier (ORCID: https://orcid.org/0000-0001-8361-2448)
- Esther E. Creemers (ORCID: https://orcid.org/0000-0002-9001-3854)
- Inge van der Made
- Rubén Cuenca Coronel
- Anna M. Tebbens
- Sha Chen
- Markus W. Hollmann
- Myrto Lykidou
- Qian Wang
- Xin Hu
- Femke K.J. van Goor
- Yingyin Guan
Institutions
- Boehringer Ingelheim (Germany) (DE)
- Amsterdam Neuroscience (NL)
- University of Amsterdam (NL)
Publication Details
- Journal
- Metabolism
- Published
- 2026-02-17
- DOI
- https://doi.org/10.1016/j.metabol.2026.156568
- Primary Topic
- Cardiovascular Function and Risk Factors
- Type
- article
- Field-Weighted Citation Impact
- 0.00