Safety of dapagliflozin and empagliflozin in cases with diabetes mellitus or/and heart failure: a retrospective pharmacovigilance study conducted on the eudravigilance database

Introduction: Dapagliflozin and empagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors initially approved for the treatment of type 2 diabetes mellitus (DM), and later for heart failure (HF). Considering this differential therapeutic use, we decided to evaluate cases related to these agents by comparing those with DM, HF, or both (DM and HF). Methods: A retrospective, pharmacovigilance study was conducted by using data contained in the EudraVigilance from January 1st, 2021, to December 31st, 2023. Cases were classified into those with DM, HF, or both diseases. The Reporting Odds Ratio (ROR), and its 95% confidence interval (95%CI) were computed to compare the reporting probability of the four most reported adverse events. The following comparisons were performed: DM vs. HF; both DM and HF vs. HF; both DM and HF vs. DM. Analyses were adjusted for age, sex, and time between the approval date of the SGLT2 inhibitor and the reporting date. Results: A total of 14,594 (50.5%) cases were classifiable for DM (N = 11,962; 82.0%), HF (N = 2,100; 14.4%), or both DM and HF (N = 532; 3.64%). The empagliflozin was the most reported SGLT2 inhibitor (60.1%), and only 15 cases (0.1%) reported both empagliflozin and dapagliflozin. Cases with DM and both DM and HF were associated with a higher reporting probability of ketoacidosis (ROR: 5.95, 95%CI: 4.87-7.26; ROR: 3.05, 95%CI: 2.27-4.09) and Fournier's gangrene (ROR: 2.30, 95%CI: 1.65-3.20; ROR: 2.30, 95%CI: 1.38-3.82) than HF. These results were also confirmed by adjusted analyses. Conclusion: We found that ketoacidosis and Fournier's gangrene had a higher reporting in cases with DM. Further studies are warranted.