Multifaceted safety concerns of glibenclamide in managing type 2 diabetes: Evidence from real-world adverse event...

Glibenclamide (Gli), a second-generation sulfonylurea, has been widely used for managing type 2 diabetes mellitus (T2DM) due to its potent glucose-lowering effect and affordability. Recently, renewed scientific interest has emerged due to its potential anti-aging effects, mediated through mitochondrial function modulation and epigenetic regulation. Despite its longstanding clinical use, Gli's comprehensive real-world safety profile remains incompletely understood. This study aimed to systematically evaluate adverse event (AE) signals associated with Gli based on data from the U.S. FDA Adverse Event Reporting System (FAERS) between Q1 2004 and Q4 2023.

We performed a disproportionality analysis using four established signal detection algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). AEs were analyzed at both the system organ class (SOC) and preferred term (PT) levels, with additional sex-stratified assessments.

A total of 1,758 Gli-related reports were included. The strongest signal was identified in "metabolism and nutrition disorders" (ROR = 8.07; IC025 = 2.8), with hypoglycemia and its neurological sequelae being particularly prominent. Other elevated signals were noted for hepatobiliary, renal, and cardiac disorders. Sex-specific analysis revealed a stronger hepatic and metabolic signal in males, while some neurological and cardiovascular PTs were more prominent in females. Unexpected signals such as counterfeit product exposure and abnormal insulin C-peptide levels also emerged.

Our findings highlight Gli's multifaceted safety concerns, reinforcing known risks while identifying novel AE signals. This evidence supports the need for continued pharmacovigilance and individualized risk assessment in Gli prescribing.