Background. The U.S. Food and Drug Administration (FDA) released a safety warning of Fournier gangrene (FG), a rare but serious adverse effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors in August 2018. However, existing studies have focused mainly on individual FG case reports. Although several previous studies conducted reviews of cases, objective scientific analysis was not applied, and the prognosis data were inadequate. Objective. This study is aimed at presenting data supplementary to existing studies by analysing postmarketing adverse event reports in the FDA Adverse Events Reporting System (FAERS) database. Multiple statistical analysis methods were applied to evaluate the potential association between SGLT2 inhibitors and FG, thus providing reliable and professionalized medication usage recommendations for SGLT2 inhibitors in clinical practice. Methods. Disproportionality analysis and Bayesian analysis were applied for data mining among the suspected adverse event reports of FG associated with SGLT2 inhibitors recorded in the FAERS database during the period from January 2004 to September 2019. Results. There were 542 FG cases identified in the FAERS database in patients receiving SGLT2 inhibitors. Among all SGLT2 inhibitor therapies, empagliflozin was associated with the highest number of FG reports (232 in total), while empagliflozin plus metformin had the strongest association with FG occurrence with the reporting odds ratio (ROR 54.79, 95% two-sided CI 31.56 to 95.12) and proportional reporting ratio (PRR 53.36, χ2 666.70). There were 391 patients who underwent initial or prolonged hospitalization (72.14%), and 26 patients died (4.81%). Three new FG cases caused by ertugliflozin were found in 2019. Conclusion. The analysis of SGLT2 inhibitor-associated FG reports in the FAERS database identified signals between the drug and adverse events of interest. It also provides comprehensive information on the characteristics of FG onset and prognosis. Clinicians should pay more attention to this rare but severe adverse event when prescribing SGLT2 inhibitors in clinical practice.

PurposeThe neurocognitive disorder is a rare adverse event associated with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in the randomized controlled trail (RCTs), there was limited evidence to prove their relation. This study aimed to assessing their association by detecting adverse signal in the FDA Adverse Event Reporting System (FAERS).MethodsThe disproportionality analysis was conducted to detect the potential adverse signal between neurocognitive disorders and PCSK9 inhibitors. The adverse event reports from the first quarter of 2004 to the second quarter of 2020 were extracted from the FAERS database.ResultsThere were 81,272 adverse reports correlated with the usage of the PCSK9 inhibitors, of which 152 reports corresponded with our inclusion criteria. Among them, there were 106 and 46 neurocognitive disorder reports related to the usage of Evolocumab and Alirocumab, respectively. The total ROR value presented negative disproportionality, however, Alirocumab has generated a positive signal with a higher ROR value in comparison with Evolocumab. Moreover, there were 61.19% of adverse reports were submitted by healthcare professionals. As for the outcome events, 7.79% of patients had initial or prolonged hospitalization and 3.90% suffered a disability.ConclusionThe pharmacovigilance research helps to find out more about PCSK9 inhibitor-related neurocognitive disorders. Although the positive signal was identified in Alirocumab in this study, it still required further research to prove the association between neurocognitive disorder and PCSK9 inhibitors. In addition, the tenable mechanism should be explored, which can improve the insight of this neotype lipid-lowering medicine.