Metabolic Disturbances Associated with Beta-Blocker Therapy: New Insights from a Large-Scale Pharmacovigilance Study.

Background: Beta-blockers (BBs) remain a foundation of cardiovascular therapy. However, cumulative evidence suggests that metabolic adverse effects may differ significantly between individual sub-classes. While conventional BBs have been associated with changes in glucose and lipid metabolism, the comparative real-world reporting patterns of these events have not been comprehensively evaluated. Objective: We investigated the association between selected BBs and metabolic diseases using a large pharmacovigilance database and compared the reporting profiles of metoprolol (MET), carvedilol (CAR), bisoprolol (BIS), and nebivolol (NEB). Methods: A descriptive and disproportionality analysis was performed using Individual Case Safety Reports (ICSRs) submitted to the EudraVigilance database up to 26 April 2026. Metabolic adverse events were grouped into pathophysiological categories, including dysglycemia and type 2 diabetes mellitus (T2DM), lipid disorders, obesity-related disorders, inflammatory biomarkers, and hepatic steatosis. Reporting odds ratios (RORs) with 95% confidence intervals (CI) were calculated to identify disproportional reporting signals. To improve clinical reliability, a stratified analysis restricted to healthcare professional (HP)-submitted reports was conducted. Results: A total of 63.744 ICSRs were identified for the four BBs, including 27.169 for MET, 21.860 for BIS, 9487 for CAR, and 5228 for NEB. Dysglycemic events represented the most frequently reported metabolic category, with hyperglycemia and T2DM accounting for 155 reports each. MET was associated with the highest number of reports for T2DM, obesity, hepatic steatosis, and elevated triglycerides. In HP-submitted reports, MET showed significantly higher reporting odds of increased triglycerides, obesity, inflammation, and T2DM than BIS and/or CAR. CAR showed higher reporting odds for hyperglycemia and obesity compared with BIS, whereas BIS and, particularly, NEB presented comparatively lower reporting frequencies for metabolic diseases. No significant differences were observed for hepatic steatosis, decreased high density lipoprotein cholesterol (HDL-C), or impaired glucose tolerance. Conclusions: This large-scale pharmacovigilance study highlights substantial heterogeneity in the reporting of metabolic adverse events among commonly prescribed BBs. MET and to a lesser extent CAR were associated with higher reporting odds of metabolic diseases, whereas BIS and especially NEB demonstrated more favorable reporting profiles. Although causality cannot be established from spontaneous reporting data, these findings support individualized BB selection and closer metabolic monitoring in patients with cardiometabolic risk factors.