Multi-database pharmacovigilance assessment of GLP-1 receptor agonist-related ophthalmic risks using advanced signal detection in FAERS and vigibase

Schernthaner G, Shehadeh N, Ametov AS, Bazarova AV, Ebrahimi F, Fasching P, Janež A, Kempler P, Konrāde I, Lalić NM, Mankovsky B, Martinka E, Rahelić D, Serafinceanu C, Škrha J, Tankova T, Visockienė Ž (2020) Worldwide inertia to the use of cardiorenal protective glucose-lowering drugs (SGLT2i and GLP-1 RA) in high-risk patients with type 2 diabetes. Cardiovasc Diabetol 19(1):185

Article  PubMed  PubMed Central  Google Scholar 

Sardà H, Genua I, Miñambres I (2025) GLP-1 receptor agonists in obesity treatment: effects on cardiometabolic variables and cardiovascular disease. Med Clin (Barc) 165(1):106951 English, Spanish

Article  PubMed  Google Scholar 

Lakhani M, Kwan AT, Mihalache A, Popovic MM, Nanji K, Xie JS, Feo A, Rabinovitch D, Shor R, Sadda S, Sarraf D, Hurley B, Margolin EA, Kertes PJ, Chaudhary V, Muni RH Association of Glucagon-like Peptide-1 Receptor Agonists with Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries. Am J Ophthalmol. 2025 May 16:S0002-9394(25)00239-9

Cai CX, Hribar M, Baxter S, Goetz K, Swaminathan SS, Flowers A, Brown EN, Toy B, Xu B, Chen J, Chen A, Wang S, Lee C, Leng T, Ehrlich JR, Barkmeier A, Armbrust KR, Boland MV, Dorr D, Boyce D, Alshammari T, Swerdel J, Suchard MA, Schuemie M, Bu F, Sena AG, Hripcsak G, Nishimura A, Nagy P, Falconer T, DuVall SL, Matheny M, Viernes B, O’Brien W, Zhang L, Martin B, Westlund E, Mathioudakis N, Fan R, Wilcox A, Lai A, Stocking JC, Takkouche S, Lee LH, Xie Y, Humes I, McCoy DB, Adibuzzaman M, Areaux RG Jr, Rojas-Carabali W, Brash J, Lee DA, Weiskopf NG, Mawn L, Agrawal R, Morgan-Cooper H, Desai P, Ryan PB (2025) Semaglutide and nonarteritic anterior ischemic optic neuropathy. JAMA Ophthalmol 143(4):304–314

Article  PubMed  PubMed Central  Google Scholar 

Katz BJ, Lee MS, Lincoff NS, Abel AS, Chowdhary S, Ellis BD, Najafi A, Nguyen J, Seay MD, Warner JEA (2025) Ophthalmic complications associated with the antidiabetic drugs semaglutide and Tirzepatide. JAMA Ophthalmol 143(3):215–220

Article  PubMed  Google Scholar 

Yao H, Zhang A, Li D, Wu Y, Wang CZ, Wan JY, Yuan CS (2024) Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. BMJ 384:e076410

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou Q, Li G, Hang K, Li J, Yang D, Wang MW (2025) Weight loss blockbuster development: a role for unimolecular polypharmacology. Annu Rev Pharmacol Toxicol 65(1):191–213

Article  CAS  PubMed  Google Scholar 

Nauck MA, Petrie JR, Sesti G, Mannucci E, Courrèges JP, Lindegaard ML, Jensen CB, Atkin SL (2016) A phase 2, randomized, dose-finding study of the novel once-weekly human GLP-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes. Diabetes Care 39:231–241

Article  CAS  PubMed  Google Scholar 

Centers for Disease Control and Prevention (CDC) (2022) National diabetes statistics Report, 2022. CDC, Atlanta, GA

Google Scholar 

Brookhart MA, Stürmer T, Glynn RJ, Rassen J, Schneeweiss S (2010) Confounding control in healthcare database research: challenges and potential approaches. Med Care 48(6 Suppl):S114–S120

Article  PubMed  PubMed Central  Google Scholar 

Klein R, Klein BE, Moss SE (2008) The Wisconsin epidemiologic study of diabetic retinopathy: XVII. the 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 115(10):1859–1868

Article  PubMed  Google Scholar 

Rentzeperi E, Pegiou S, Koufakis T, Grammatiki M, Kotsa K (2022) Sex differences in response to treatment with Glucagon-like peptide 1 receptor agonists: opportunities for a tailored approach to diabetes and obesity care. J Pers Med 12(3):454

Article  PubMed  PubMed Central  Google Scholar 

Richard JE, Anderberg RH, López-Ferreras L, Olandersson K, Skibicka KP (2016) Sex and estrogens alter the action of glucagon-like peptide-1 on reward. Biol Sex Differ 7:6

Article  PubMed  PubMed Central  Google Scholar 

Campesi I, Seghieri G, Franconi F (2021) Type 2 diabetic women are not small type 2 diabetic men: sex-and-gender differences in antidiabetic drugs. Curr Opin Pharmacol 60:40–45

Article  CAS  PubMed  Google Scholar 

Mollan SP (2024) Semaglutide and nonarteritic anterior ischemic optic neuropathy. JAMA Ophthalmol 142(8):740–741

Article  PubMed  Google Scholar 

Montastruc JL, Bondon-Guitton E, Abadie D et al (2019) Pharmacovigilance, Risks, and adverse effects: focus on methodological challenges in international databases. Drug Saf 42(12):1373–1385

Google Scholar 

Plueschke K, McGettigan P, Pacurariu A et al (2021) Regional differences in spontaneous adverse drug reaction reporting: A comparative analysis of the WHO vigibase and the U.S. FAERS. Drug Saf 44(3):295–306

Google Scholar 

Bate A, Evans SJW (2009) Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf 18(6):427–436

Article  CAS  PubMed  Google Scholar 

Davies EC, Chandler RE, de Vries ST et al (2015) Lixisenatide: A review of its use in the management of type 2 diabetes mellitus. Drugs 75(14):1643–1658

Google Scholar 

Chung YR, Park SW, Choi SY et al (2022) Association of GLP-1 receptor agonists with diabetic retinopathy: A pharmacovigilance study. Diabetes Care 45(8):e123–e125

Google Scholar 

Zhou J, Wang X, Zhang S (2023) Long-term use of GLP-1 receptor agonists and risk of cataract formation: a meta-analysis. J Clin Endocrinol Metab 108(4):890–898

Google Scholar 

Nguyen J, Chowdhary S, Warner JEA et al (2025) Ischemic optic neuropathy following GLP-1 receptor agonist therapy: A case series and literature review. Ophthalmol Ther 14(1):45–58

Google Scholar 

Simó R, Hernández C (2022) GLP-1 receptor agonists and neurovascular protection in diabetic retinopathy: mechanistic insights and therapeutic potential. Diabetes 71(6):1123–1135

Google Scholar 

Osumili B, Sapin H, Yang Z, Ranta K, Paik JS, Blüher M (2025) Efficacy and safety of Tirzepatide compared with GLP-1 RAs in patients with type 2 diabetes treated with basal insulin: a network meta-analysis. Diabetes Ther 16(6):1279–1311

Article  CAS  PubMed  PubMed Central  Google Scholar 

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