Introduction Beyond their initial approvement for treating diabetic conditions, Sodium-Glucose co-transporter 2 (SGLT-2) inhibitors have recently been found to also offer cardioprotective properties. Since cardiovascular problems are one of the major complications that diabetic patients face, this finding was groundbreaking. Meanwhile it was shown that the cardioprotective effects are not limited to diabetic patients and the inhibitors’ approvements have been expanded respectively. Observations from clinical studies hint in the direction that those effects exceed the glucose lowering effect without offering an explanation for the underlying mechanisms. Since the drug’s target protein SGLT-2 is exclusively expressed in the early proximal tubule where it is responsible for the reabsorption of glucose it remains inconclusive why the positive effects are observed in the heart. Methods To investigate what kind of an effect those drugs have on the proteome of cardiac cells, the human cardiac cell lines AC16 (cardiomyocytes derived from left ventricular heart tissue) and HCM (human cardiac myocytes) have been treated with Dapa-, Cana- and Empagliflozin in a physiological and a higher concentration. Besides classical proteomics also redox-proteomics and Glutathione as well as its dimer have been measured as marker for oxidative stress. Results Changes in Glutathione metabolism have been observed. This is among others reflected by changed ratios of reduced to oxidized Glutathione variants, as well as changes in abundance and oxidation state of proteins. Furthermore, proteomics data reveal upregulation of DNA replication and translation, additionally to changes in different mitochondria associated proteins. Discussion All drug treatments seem to strive to maintain oxidative metabolism. Furthermore the data indicate that observed effects on the proteome do not strongly correlate with the concentration level used for treatment. Innovative aspects • Solid dataset for cardiac cells having been treated with Gliflozins, incl. further aspects as oxidative stress