Analysis of the SGLT2-independent off-target dapagliflozin activity using model organism Caenorhabditis elegans

Beyond their primary glucose-lowering mechanism, flozins exhibit significant benefits for heart failure and chronic kidney disease. This expanded therapeutic utility is noteworthy, particularly given the absence of SGLT2 expression in the cardiac tissue.

Hereby we utilized Caenorhabditis elegans as a model organism to analyze flozin off-target activity, specifically by dapagliflozin treatment. Although C. elegans lacks direct SGLT2 orthologue, dapagliflozin remarkably mirrored observations in murine models, specifically demonstrating prolonged longevity in glucose-fed conditions. Furthermore, transcriptomic analysis of glucose- and dapagliflozin-treated worms, compared to glucose-only treated controls, revealed a gene expression profile reminiscent of mammalian systems.