Mascolo Annamaria, Zinzi Alessia, Gaio Mario, Ruggiero Donatella, Scavone Cristina, Rossi Francesco, Capuano Annalisa
Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology - Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Via Costantinopoli 16, Naples, 80138, Italy.
Department of Experimental Medicine, Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy.
Pharmacol Rep. 2025 Feb;77(1):274-286. doi: 10.1007/s43440-024-00668-4. Epub 2024 Oct 23.
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).
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.
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.
We found that ketoacidosis and Fournier's gangrene had a higher reporting in cases with DM. Further studies are warranted.
达格列净和恩格列净是钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂，最初被批准用于治疗2型糖尿病（DM），后来也用于治疗心力衰竭（HF）。考虑到这种不同的治疗用途，我们决定通过比较患有DM、HF或两者兼有的患者（DM和HF）来评估与这些药物相关的病例。
利用欧洲药物警戒数据库（EudraVigilance）中2021年1月1日至2023年12月31日的数据进行了一项回顾性药物警戒研究。病例被分为患有DM、HF或两种疾病的患者。计算报告比值比（ROR）及其95%置信区间（95%CI），以比较四种报告最多的不良事件的报告概率。进行了以下比较：DM与HF；DM和HF与HF；DM和HF与DM。分析对年龄、性别以及SGLT2抑制剂批准日期与报告日期之间的时间进行了校正。
共有14594例（50.5%）病例可分类为患有DM（N = 11962；82.0%）、HF（N = 2100；14.4%）或DM和HF两者兼而有之（N = 532；3.64%）。恩格列净是报告最多的SGLT2抑制剂（60.1%），只有15例（0.1%）报告了同时使用恩格列净和达格列净。患有DM以及患有DM和HF的患者发生酮症酸中毒（ROR：5.95，95%CI：4.87 - 7.26；ROR：3.05，95%CI：2.27 - 4.09）和福尼埃坏疽（ROR：2.30，95%CI：1.65 - 3.20；ROR：2.30，95%CI：1.38 - 3.82）的报告概率高于患有HF的患者。校正分析也证实了这些结果。
我们发现酮症酸中毒和福尼埃坏疽在患有DM的病例中报告率更高。有必要进行进一步研究。
