{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:29:27Z","timestamp":1785403767893,"version":"3.56.0"},"reference-count":85,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015999","name":"\u201cLucian Blaga\u201d University of Sibiu","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100015999","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/026gdz537","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ph19081150","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:38:41Z","timestamp":1784889521000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Disturbances Associated with Beta-Blocker Therapy: New Insights from a Large-Scale Pharmacovigilance Study"],"prefix":"10.3390","volume":"19","author":[{"given":"Crina Cristina","family":"Solomon","sequence":"first","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9913-1750","authenticated-orcid":false,"given":"Carmen Maximiliana","family":"Dobrea","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1540-641X","authenticated-orcid":false,"given":"Anca","family":"Butuca","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4874-0430","authenticated-orcid":false,"given":"Adina","family":"Frum","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5395-2333","authenticated-orcid":false,"given":"Nastaca Alina","family":"Palade","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina Liliana","family":"Pintea","sequence":"additional","affiliation":[{"name":"County Emergency Clinical Hospital Sibiu, 550025 Sibiu, Romania"},{"name":"Department of Dental Medicine and Nursing, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drago\u0219 Anton","family":"D\u0103d\u00e2rlat","sequence":"additional","affiliation":[{"name":"Department of Dental Medicine and Nursing, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-4613","authenticated-orcid":false,"given":"Steliana","family":"Ghibu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, \u201cIuliu Ha\u0163ieganu\u201d University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5281-5004","authenticated-orcid":false,"given":"Ioana Rada Popa","family":"Ilie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 3-5 Louis Pasteur Street, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2730-8729","authenticated-orcid":false,"given":"Claudiu","family":"Morgovan","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Cornelia","family":"Tilinca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of T\u00e2rgu-Mures, 540142 T\u00e2rgu Mure\u0219, Romania"},{"name":"Clinical Compartment of Diabetes Mellitus, Nutrition and Metabolic Diseases, Emergency Clinical County Hospital of Targu Mures, 540136 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-9864","authenticated-orcid":false,"given":"Felicia Gabriela","family":"Gligor","sequence":"additional","affiliation":[{"name":"Preclinical Department, Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1573403X19666230111143901","article-title":"Smritigandha Role of \u03b2-Blockers in Preventing Heart Failure and Major Adverse Cardiac Events Post Myocardial Infarction","volume":"19","author":"Johri","year":"2023","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_2","first-page":"e91371","article-title":"Effectiveness of Beta-Blockers in Reducing Mortality and Recurrence After Myocardial Infarction: A Systematic Review of Contemporary and Foundational Evidence","volume":"17","author":"Popraya","year":"2025","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Religioni, U., Barrios-Rodr\u00edguez, R., Requena, P., Borowska, M., and Ostrowski, J. (2025). Enhancing Therapy Adherence: Impact on Clinical Outcomes, Healthcare Costs, and Patient Quality of Life. Medicina, 61.","DOI":"10.3390\/medicina61010153"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/03007995.2024.2318058","article-title":"\u03b2-Blockers Are Not All the Same: Pharmacologic Similarities and Differences, Potential Combinations and Clinical Implications","volume":"40","author":"Taddei","year":"2024","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1152\/ajpendo.00175.2003","article-title":"Effect of \u03921- and \u03922-Adrenergic Stimulation on Energy Expenditure, Substrate Oxidation, and UCP3 Expression in Humans","volume":"285","author":"Hoeks","year":"2003","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41598-020-79837-3","article-title":"Do Beta-Adrenergic Blocking Agents Increase Asthma Exacerbation? A Network Meta-Analysis of Randomized Controlled Trials","volume":"11","author":"Huang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Schena, G., and Caplan, M.J. (2019). Everything You Always Wanted to Know about \u03923-AR * (* But Were Afraid to Ask). Cells, 8.","DOI":"10.3390\/cells8040357"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1177\/2042018810390259","article-title":"\u03b2(3) Receptors: Role in Cardiometabolic Disorders","volume":"2","author":"Bhadada","year":"2011","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Quagliariello, V., Berretta, M., Bisceglia, I., Giacobbe, I., Iovine, M., Barbato, M., Maurea, C., Canale, M.L., Paccone, A., and Inno, A. (2025). In the Era of Cardiovascular\u2013Kidney\u2013Metabolic Syndrome in Cardio-Oncology: From Pathogenesis to Prevention and Therapy. Cancers, 17.","DOI":"10.3390\/cancers17071169"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1161\/01.CIR.0000066912.58385.DE","article-title":"Third-Generation Beta-Blockers Stimulate Nitric Oxide Release from Endothelial Cells through ATP Efflux: A Novel Mechanism for Antihypertensive Action","volume":"107","author":"Kalinowski","year":"2003","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.amjhyper.2007.01.019","article-title":"Effects of Carvedilol versus Metoprolol on Endothelial Function and Oxidative Stress in Patients with Type 2 Diabetes Mellitus","volume":"20","author":"Bank","year":"2007","journal-title":"Am. J. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s11906-017-0716-3","article-title":"Differential Metabolic Effects of Beta-Blockers: An Updated Systematic Review of Nebivolol","volume":"19","author":"Marketou","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.amjmed.2006.10.017","article-title":"Body Weight Changes with \u03b2-Blocker Use: Results from GEMINI","volume":"120","author":"Messerli","year":"2007","journal-title":"Am. J. Med."},{"key":"ref_14","first-page":"1938","article-title":"Beta-Blockers and Their Impact on Metabolic Processes","volume":"2024","year":"2024","journal-title":"World J. Adv. Res. Rev."},{"key":"ref_15","first-page":"71","article-title":"The Impact of Cardiovascular Drugs on Hyperglycemia and Diabetes: A Review of \u2018unspoken\u2019 Side Effects","volume":"83","author":"Widiarti","year":"2025","journal-title":"Hell. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100375","DOI":"10.1016\/j.metop.2025.100375","article-title":"Obesity: Prevalence, Causes, Consequences, Management, Preventive Strategies and Future Research Directions","volume":"27","author":"Ahmed","year":"2025","journal-title":"Metab. Open"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Dryga\u0142a, S., Radzikowski, M., and Maciejczyk, M. (2024). \u03b2-Blockers and Metabolic Modulation: Unraveling the Complex Interplay with Glucose Metabolism, Inflammation and Oxidative Stress. Front. Endocrinol., 15.","DOI":"10.3389\/fphar.2024.1489657"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/j.1524-6175.2004.03704.x","article-title":"Metabolic Properties of Vasodilating Beta Blockers: Management Considerations for Hypertensive Diabetic Patients and Patients with the Metabolic Syndrome","volume":"6","author":"Jacob","year":"2004","journal-title":"J. Clin. Hypertens."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/j.2040-4603.2020.tb00136.x","article-title":"Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake","volume":"10","author":"Merz","year":"2020","journal-title":"Compr. Physiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s43044-020-00099-5","article-title":"Effect of Carvedilol versus Nebivolol on Insulin Resistance among Non-Diabetic, Non-Ischemic Cardiomyopathy with Heart Failure","volume":"72","author":"Metwally","year":"2020","journal-title":"Egypt. Heart J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102837","DOI":"10.1016\/j.ebiom.2020.102837","article-title":"Machine Learning Guided Association of Adverse Drug Reactions with in Vitro Target-Based Pharmacology","volume":"57","author":"Ietswaart","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/ijo.2010.284","article-title":"Metabolic Sequelae of \u03b2-Blocker Therapy: Weighing in on the Obesity Epidemic?","volume":"35","author":"Lee","year":"2011","journal-title":"Int. J. Obes."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s13679-016-0237-4","article-title":"Changes in Energy Expenditure with Weight Gain and Weight Loss in Humans","volume":"5","author":"Enderle","year":"2016","journal-title":"Curr. Obes. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/clc.22304","article-title":"Modern Obesity Pharmacotherapy: Weighing Cardiovascular Risk and Benefit","volume":"37","author":"Cunningham","year":"2014","journal-title":"Clin. Cardiol."},{"key":"ref_25","unstructured":"Herink, M., and Ito, M.K. (2025). Medication Induced Changes in Lipids and Lipoproteins. Endotext, MDText.com, Inc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Pitanupong, J., Chang, A., and Wattanapisit, A. (2025). Association Between Ratio of Triglyceride to High-Density Lipoprotein Cholesterol and Cardiovascular and All-Cause Mortality in Non-Diabetic Hemodialysis Patients. Med. Sci., 13.","DOI":"10.3390\/medsci13040272"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Nasoufidou, A., Bantidos, M.G., Fyntanidou, B., Kofos, C., Stachteas, P., Arvanitaki, A., Karakasis, P., Sagris, M., Kassimis, G., and Fragakis, N. (2025). Cardioprotective Mechanisms of Beta-Blockers in Myocardial Ischemia and Reperfusion: From Molecular Targets to Clinical Implications. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26209843"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.apsb.2019.10.001","article-title":"Current Trends in Drug Metabolism and Pharmacokinetics","volume":"9","author":"Li","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101330","DOI":"10.1016\/j.conctc.2024.101330","article-title":"Global Trends in Clinical Trials and Interventions for the Metabolic Syndrome: A Comprehensive Analysis of the WHO International Clinical Trials Platform","volume":"40","author":"Muvhulawa","year":"2024","journal-title":"Contemp. Clin. Trials Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jacbts.2023.12.005","article-title":"The Imperative to Enhance Cost-Effectiveness for Cardiovascular Therapeutic Development","volume":"9","author":"Davidson","year":"2024","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1524-6175.2005.04679.x","article-title":"Do the Metabolic Effects of Beta Blockers Make Them Leading or Supporting Antihypertensive Agents in the Treatment of Hypertension?","volume":"8","author":"Sarafidis","year":"2006","journal-title":"J. Clin. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/pds.5548","article-title":"Methods for Drug Safety Signal Detection Using Routinely Collected Observational Electronic Health Care Data: A Systematic Review","volume":"32","author":"Coste","year":"2023","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tcm.2018.08.001","article-title":"Metabolic Effects of Cardiovascular Drugs","volume":"29","author":"Fragasso","year":"2019","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"van den Boogaard, B., van de Lavoir, M., Robeyns, R., Gys, C., Covaci, A., and Loof, H. (2026). De Beta Blocker Intoxications in Belgium: A Data Analysis with Focus on Propranolol. Pharmacy, 14.","DOI":"10.3390\/pharmacy14020043"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/jch.14819","article-title":"Physicians\u2019 Attitudes toward Beta-Blockers for the Treatment of Hypertension in Italy, Poland, and Turkey","volume":"26","author":"Prejbisz","year":"2024","journal-title":"J. Clin. Hypertens."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"862","DOI":"10.3399\/bjgp08X376195","article-title":"Trends and Inequities in Beta-Blocker Prescribing for Heart Failure","volume":"58","author":"Shah","year":"2008","journal-title":"Br. J. Gen. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hafiz, N., Hyun, K., Tu, Q., Manandi, D., Shi, W., Usherwood, T., and Redfern, J. (2025). Effectiveness of Quality Improvement Interventions in Improving Cardiovascular Disease-Related Outcomes in Primary and Tertiary Care: A Systematic Review and Meta-Analyses. BMC Prim. Care, 26.","DOI":"10.1186\/s12875-025-03006-6"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s11940-019-0556-3","article-title":"Beta-Blockers for Migraine Prevention: A Review Article","volume":"21","author":"Danesh","year":"2019","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102669","DOI":"10.1016\/j.cpcardiol.2024.102669","article-title":"Practice Patterns of Rate Control in Atrial Fibrillation and Clinical Outcomes from a Nationwide Cohort","volume":"49","author":"Frick","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103340","DOI":"10.1016\/j.cpcardiol.2026.103340","article-title":"Beta-Blocker Therapy and All-Cause Mortality after a Coronary Event: A Matched Nested Case-Control Study Using the Victorian Cardiac Outcomes Registry Linked Data","volume":"51","author":"Koh","year":"2026","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.tips.2011.02.010","article-title":"Evolution of \u03b2-Blockers: From Anti-Anginal Drugs to Ligand-Directed Signalling","volume":"32","author":"Baker","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1016\/j.jacc.2009.05.066","article-title":"Nebivolol: The Somewhat-Different Beta-Adrenergic Receptor Blocker","volume":"54","author":"Gori","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.clinthera.2009.03.007","article-title":"Nebivolol: A Third-Generation \u03b2-Blocker for Hypertension","volume":"31","author":"Cheng","year":"2009","journal-title":"Clin. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/eurheartj\/16.suppl_F.38","article-title":"Carvedilol, a Novel Multiple Action Antihypertensive Agent with Antioxidant Activity and the Potential for Myocardial and Vascular Protection","volume":"16","author":"Feuerstein","year":"1995","journal-title":"Eur. Heart J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2165\/00003495-197714050-00001","article-title":"Metoprolol: A Review of Its Pharmacological Properties and Therapeutic Efficacy in Hypertension and Angina Pectoris","volume":"14","author":"Brogden","year":"1977","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1177\/02698811251349190","article-title":"\u03b2-Blockers and Risk of Neuropsychiatric Adverse Events: An Active-Comparator Restricted Disproportionality on the FAERS","volume":"39","author":"Omrani","year":"2025","journal-title":"J. Psychopharmacol."},{"key":"ref_47","first-page":"18","article-title":"When Not to Use Beta-Blockers in Seniors with Hypertension","volume":"57","author":"Schumann","year":"2008","journal-title":"J. Fam. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1111\/bcp.12717","article-title":"Social Media and Pharmacovigilance: A Review of the Opportunities and Challenges","volume":"80","author":"Sloane","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Adisa, R., and Omitogun, T.I. (2019). Awareness, Knowledge, Attitude and Practice of Adverse Drug Reaction Reporting among Health Workers and Patients in Selected Primary Healthcare Centres in Ibadan, Southwestern Nigeria. BMC Health Serv. Res., 19.","DOI":"10.1186\/s12913-019-4775-9"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kalibala, J., Pech\u00e8re-Bertschi, A., and Desmeules, J. (2020). Gender Differences in Cardiovascular Pharmacotherapy\u2014The Example of Hypertension: A Mini Review. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00564"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Eugene, A.R. (2016). Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations. Med. Sci., 4.","DOI":"10.3390\/medsci4040018"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.amjcard.2012.11.031","article-title":"Meta-Analysis of Carvedilol versus Beta 1 Selective Beta-Blockers (Atenolol, Bisoprolol, Metoprolol, and Nebivolol)","volume":"111","author":"Dinicolantonio","year":"2013","journal-title":"Am. J. Cardiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cardfail.2011.05.009","article-title":"Carvedilol for the Treatment of Benign Prostatic Hypertrophy in Patients with Heart Failure?","volume":"17","author":"Rohrer","year":"2011","journal-title":"J. Card. Fail."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1161\/HYPERTENSIONAHA.120.16402","article-title":"Comprehensive Comparative Effectiveness and Safety of First-Line \u03b2-Blocker Monotherapy in Hypertensive Patients: A Large-Scale Multicenter Observational Study","volume":"77","author":"You","year":"2021","journal-title":"Hypertension"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/HYPERTENSIONAHA.124.22821","article-title":"Rationale for the Inclusion of \u03b2-Blockers among Major Antihypertensive Drugs in the 2023 European Society of Hypertension Guidelines","volume":"81","author":"Mancia","year":"2024","journal-title":"Hypertension"},{"key":"ref_56","unstructured":"Grand View Research (2025). Beta-Blocker Market Size, Growth Forecast 2026\u20132035, Grand View Research."},{"key":"ref_57","unstructured":"(2026, June 22). Most Prescribed Beta Blockers in US|Common Beta Blockers. Available online: https:\/\/www.definitivehc.com\/blog\/beta-blocker-prescription-patterns."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1007\/s40264-023-01355-8","article-title":"Comparative Analysis of Information Provided in German Adverse Drug Reaction Reports Sent by Physicians, Pharmacists and Consumers","volume":"46","author":"Christ","year":"2023","journal-title":"Drug Saf."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e70164","DOI":"10.1002\/prp2.70164","article-title":"Comparison of the Completeness of Spontaneously Reported Adverse Drug Reactions by Consumers, Healthcare Professionals, and Pharmaceutical Companies: An Evaluation of Databases From Two High-Income Countries","volume":"13","author":"Dedefo","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Popa Ilie, I.R., Ghibu, S., Butuca, A., Dobrea, C.M., Frum, A., Homorodean, C., Chis, A.A., and Morgovan, C. (2026). Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions\u2014A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data. Pharmaceuticals, 19.","DOI":"10.3390\/ph19060876"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/B978-0-12-824315-2.00525-X","article-title":"Beta-blockers","volume":"Volume 2","author":"Overbeek","year":"2024","journal-title":"Encyclopedia of Toxicology"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Yan, Y., An, W., Mei, S., Zhu, Q., Li, C., Yang, L., Zhao, Z., and Huo, J. (2024). Real-World Research on Beta-Blocker Usage Trends in China and Safety Exploration Based on the FDA Adverse Event Reporting System (FAERS). BMC Pharmacol. Toxicol., 25.","DOI":"10.1186\/s40360-024-00815-w"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"83","DOI":"10.59556\/japi.72.0715","article-title":"Position of Beta-Blockers in the Treatment of Hypertension Today: An Indian Consensus","volume":"72","author":"Mohan","year":"2024","journal-title":"J. Assoc. Physicians India"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1001\/jama.292.18.2227","article-title":"Metabolic Effects of Carvedilol vs Metoprolol in Patients with Type 2 Diabetes Mellitus and Hypertension: A Randomized Controlled Trial","volume":"292","author":"Bakris","year":"2004","journal-title":"JAMA"},{"key":"ref_65","unstructured":"(2026, June 22). Differential Effect of Chronic Treatment with Two Beta-Blocking Agents on Insulin Sensitivity: The Carvedilol-Metoprolol Study\u2014PubMed, Available online: https:\/\/pubmed.ncbi.nlm.nih.gov\/8761899\/."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/HYPERTENSIONAHA.111.189589","article-title":"Differential Effects of Nebivolol and Metoprolol on Insulin Sensitivity and Plasminogen Activator Inhibitor in the Metabolic Syndrome","volume":"59","author":"Ayers","year":"2012","journal-title":"Hypertension"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1681\/ASN.20223311S1528b","article-title":"Comparison of Beta Blocker Outcomes Among CKD Patients With Cardiorenal Syndrome","volume":"33","author":"Yu","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.2147\/COPD.S438930","article-title":"Efficacy and Safety of Bisoprolol in Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis","volume":"18","author":"Feng","year":"2023","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.2165\/00003495-200767080-00001","article-title":"Metabolic Profile of Nebivolol, a Beta-Adrenoceptor Antagonist with Unique Characteristics","volume":"67","author":"Rosei","year":"2007","journal-title":"Drugs"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1046\/j.1365-2796.1996.473824000.x","article-title":"Acute Administration of Metoprolol and Enalaprilat Reduces Insulin-Stimulated Thermogenesis and Skin Blood Flow","volume":"239","author":"Tuominen","year":"1996","journal-title":"J. Intern. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/j.1524-6175.2006.05247.x","article-title":"Metoprolol Succinate, a Selective Beta-Adrenergic Blocker, Has No Effect on Insulin Sensitivity","volume":"8","author":"Falkner","year":"2006","journal-title":"J. Clin. Hypertens."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1463-1326.2008.00927.x","article-title":"Comparison of Carvedilol and Metoprolol on Serum Lipid Concentration in Diabetic Hypertensive Patients","volume":"11","author":"Bell","year":"2009","journal-title":"Diabetes. Obes. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/pds.5303","article-title":"Risk of Clinically Relevant Hyperglycemia with Metoprolol Compared to Carvedilol in Older Adults with Heart Failure and Diabetes","volume":"30","author":"Dave","year":"2021","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1475-2840-9-21","article-title":"Metoprolol Compared to Carvedilol Deteriorates Insulin-Stimulated Endothelial Function in Patients with Type 2 Diabetes\u2014A Randomized Study","volume":"9","author":"Kveiborg","year":"2010","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1345\/aph.10239","article-title":"Hepatotoxicity Associated with Carvedilol","volume":"35","author":"Hagmeyer","year":"2001","journal-title":"Ann. Pharmacother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000490205","article-title":"Carvedilol-Induced Liver Injury, a Rare Cause of Mixed Hepatitis: A Clinical Case","volume":"26","author":"Rua","year":"2019","journal-title":"GE Port. J. Gastroenterol."},{"key":"ref_77","first-page":"1","article-title":"Early Detection of Nebivolol-Induced Hepatotoxicity","volume":"13","author":"Torunova","year":"2026","journal-title":"Eur. J. Case Rep. Intern. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e00273","DOI":"10.14309\/crj.0000000000000273","article-title":"\u03b2-Blocker-Induced Liver Injury: A Class Effect With Incidental Rechallenge","volume":"6","author":"Mitchell","year":"2019","journal-title":"ACG Case Rep. J."},{"key":"ref_79","unstructured":"(2026, May 23). European Database of Suspected Adverse Drug Reaction Reports\u2014Search. Available online: https:\/\/www.adrreports.eu\/en\/search.html."},{"key":"ref_80","unstructured":"(2026, February 10). Introductory Guide MedDRA Version 28.1. Available online: https:\/\/alt.meddra.org\/files_acrobat\/intguide_28_1_English.pdf."},{"key":"ref_81","unstructured":"(2024, April 11). European Medicines Agency Guideline on Good Pharmacovigilance Practices (GVP): Product-or Population-Specific Considerations IV: Paediatric Population. Available online: www.ema.europa.eu."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Butuca, A., Dobrea, C.M., Arseniu, A.M., Frum, A., Chis, A.A., Rus, L.L., Ghibu, S., Juncan, A.M., Muntean, A.C., and Laz\u0103r, A.E. (2024). An Assessment of Semaglutide Safety Based on Real World Data: From Popularity to Spontaneous Reporting in EudraVigilance Database. Biomedicines, 12.","DOI":"10.20944\/preprints202404.1954.v1"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Vintila, B.I., Arseniu, A.M., Morgovan, C., Butuca, A., B\u00eerlu\u021biu, V., Dobrea, C.M., Rus, L.L., Ghibu, S., Bereanu, A.S., and Arseniu, R. (2024). A Real-World Study on the Clinical Characteristics, Outcomes, and Relationship between Antibiotic Exposure and Clostridioides Difficile Infection. Antibiotics, 13.","DOI":"10.3390\/antibiotics13020144"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Morgovan, C., Dobrea, C.M., Butuca, A., Arseniu, A.M., Frum, A., Rus, L.L., Chis, A.A., Juncan, A.M., Gligor, F.G., and Georgescu, C. (2024). Safety Profile of the Trastuzumab-Based ADCs: Analysis of Real-World Data Registered in EudraVigilance. Biomedicines, 12.","DOI":"10.3390\/biomedicines12050953"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Popa Ilie, I.R., Dobrea, C.M., Butuca, A., Homorodean, C., Morgovan, C., Vonica-Tincu, A.L., Gligor, F.G., Ghibu, S., and Frum, A. (2024). Real-Life Data on the Safety of Pasireotide in Acromegaly: Insights from EudraVigilance. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121631"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1150\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:27:56Z","timestamp":1785040076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":85,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ph19081150"],"URL":"https:\/\/doi.org\/10.3390\/ph19081150","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}