RESUMO
BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have acquired a foothold in managing type 2 diabetes mellitus, but few concerns have arisen regarding their overall safety profile. The aim of this study is to assess the potential risk of DPP-4 inhibitors by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: This is a retrospective study which explored the FAERS database till March 2023 for the collection of safety reports. The disproportionality analysis was performed using signal detection algorithms (SDAs) incorporating frequentist-based data mining approach such as relative reporting ratio (RRR), reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence interval (CI). RESULTS: A total of 14,573 adverse event reports were reported in the FAERS public dashboard associated with all the included DPP-4 inhibitors. The computed PRR, ROR, and RRR indicated positive signals for DPP-4 inhibitors with cardiac failure, pancreatitis, pemphigoid, hypoglycemia, acute kidney injury and lactic acidosis. Saxagliptin showed a higher signal score for cardiac failure, while sitagliptin was more associated with pancreatitis. Moreover, alogliptin exhibited an elevated signal score associated with pancreatic carcinoma. CONCLUSION: Several significant disproportionality signals were observed with DPP-4 inhibitors. However, clinicians have to consider the comorbidities and concomitant drugs while prescribing these drugs.
RESUMO
Concerns persist about venetoclax's long-term safety in larger populations, with limited evidence of infrequent and delayed adverse events (AEs). The study integrated safety data on venetoclax in leukemia patients from randomized controlled trials (RCTs) and FDA adverse event monitoring system (FAERS). We systematically reviewed RCTs reporting safety outcomes of venetoclax in adult leukemia patients of any gender, either monotherapy or in combination, applying advanced search on databases like PubMed, EMBASE, and ClinicalTrial.gov. The quality assessment was done using the Cochrane Risk of Bias Tool. We utilized a random effect meta-analysis to calculate risk ratio (RR) with 95% confidence intervals (CI). The Open Vigil 2.1 MedDRAv24 was used to search the FAERS database, with data available until September 2023. The disproportionality was calculated using the proportional reporting ratio and the reporting odds ratio. The study protocol for meta-analysis was registered with PROSPERO; CRD42022378006. For the safety meta-analysis, seven RCTs with available AEs were examined. A total of 942 AEs were found associated with the venetoclax group; 79% of them were in grade three or above. Venetoclax significantly increased the risk of neutropenia grade three or above (RR = 1.34, 95% CI: 1.10-1.64, p: 0.0033) compared with the control group. In FAERS, 26,436 patients were reported with AEs associated with venetoclax. Significant signal scores were observed in hematological, cardiac, vascular, and gastrointestinal disorders. 11 out of 30 generated signals, failed to meet the signal criteria upon refinement. The current study updated and improved the safety profile of venetoclax in the post-marketing period, assisting in risk evaluation and mitigation for the best possible patient health care.
