Analysis of Adverse Events Associated with SGLT2 Inhibitors and Molecular Mechanisms Using FAERS Database and Transcriptome Data
Abstract
In this thesis, we explored the differential effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on cardiovascular and renal health, utilizing both clinical data and molecular insights. Focusing on three commonly prescribed SGLT2 inhibitors—Dapagliflozin, Canagliflozin, and Empagliflozin—we employed the Food and Drug Administration Adverse Event Reporting System (FAERS) database to assess adverse events, including myocardial infarction, cardiac failure, tachycardia, acute kidney injury (AKI), renal failure, urinary tract infections, and fungal infections. This analysis was complemented by transcriptomic data from kidney cell lines treated with these drugs, processed through NCBI’s GEO2R and Limma programs, to reveal the gene expression profiles linked to these adverse outcomes. Together, this approach provided an integrative view of the cellular mechanisms and clinical risks associated with SGLT2 inhibitors, uncovering potential biomarkers and therapeutic targets such as interleukin-6 (IL-6) and hypoxia-inducible factor-1α (HIF-1α). FAERS data revealed distinct adverse event patterns among the three drugs, suggesting that Dapagliflozin may pose a higher risk of myocardial infarction compared to Canagliflozin and Empagliflozin, raising considerations for cardiovascular safety in patient selection. On the other On the other hand, Canagliflozin showed a comparatively lower risk of cardiac failure and hypotension, but an elevated risk of AKI and renal failure,…
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