| アブストラクト | PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for type 2 diabetes and obesity; however, concerns about ophthalmic safety persist. This study examined associations between GLP-1 RAs and ocular adverse events (AEs). DESIGN: Global observational pharmacovigilance study. METHODS: We searched the US FAERS database (via OpenVigil 2.1) and WHO's VigiBase (via VigiAccess) for optic nerve and retinal AEs associated with semaglutide and tirzepatide, covering the period from their respective approval dates-December 2017 for semaglutide and May 2022 for tirzepatide-through September 2024. In FAERS, all other drugs were compared, while in VigiBase, metformin, empagliflozin, dulaglutide, and insulin served as controls. Disproportionality metrics included reporting odds ratios (RORs) with 95% confidence intervals. RESULTS: Semaglutide and tirzepatide accounted for 76 444 cases (0.59%) in FAERS (n = 12 936 341) and 118 639 cases (0.34%) in VigiBase (n > 35 000 000). Semaglutide showed significantly higher odds of ischemic optic neuropathy (ION) (FAERS: ROR = 11.12, 95% CI = 8.15-15.16; VigiBase: ROR = 68.58, 95% CI = 16.75-280.67), diabetic retinopathy (DR) (FAERS: ROR = 17.28, 95% CI = 13.62-21.91; VigiBase: ROR = 7.81, 95% CI = 5.60-10.90), as well as retinal/vitreous detachment, retinal/vitreous hemorrhage, and retinal tear (FAERS: ROR = 2.44-5.89, 95% CI = 1.70-8.97, all P < .001, IC(025) = 0.49, compared to all other drugs. VigiBase: ROR = 5.49-20.91, 95% CI = 2.71-90.11, all P </= .0001, IC(025) >/= 0.53, compared to metformin). Unique to VigiBase were macular edema (ROR = 3.87, 95% CI = 1.89-7.92), macular hole (ROR = 20.90, 95% CI = 2.65-165.01), and papilledema (ROR = 6.97, 95% CI = 2.53-19.17) (all P </= .004, IC(025) >/= 0.27, compared to metformin). Sensitivity analyses using empagliflozin and dulaglutide revealed significant associations with ION and DR, while vitreous detachment and hemorrhage were significant when compared to dulaglutide. Additionally, when insulin was used as a comparator, semaglutide showed a higher ROR for ION (ROR = 9.84, 95% CI = 4.25-22.81, P < .0001, IC(025) = 0.42). However, tirzepatide was only significantly associated with DR in FAERS. CONCLUSIONS: Given the widespread use of semaglutide, its association with ocular AEs highlight the need for global pharmacovigilance and post-marketing surveillance. |
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| 組織名 | From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa,;Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.),;Department of Ophthalmology, Ottawa, Ontario, Canada.;Temerty Faculty of Medicine (A.M., R.H.M.), University of Toronto, Toronto,;Ontario, Canada.;Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of;Medicine at University of California - Los Angeles (UCLA), Los Angeles,;California, USA; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X.,;R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada.;Department of Surgery (K.N., V.C.), Division of Ophthalmology, McMaster;University, Hamilton, Ontario, Canada.;Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M.,;P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada.;California, USA.;Faculty of Medicine (D.R.), Tel Aviv University, Tel Aviv, Israel.;P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of;Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health Toronto,;Toronto, Ontario, Canada.;California, USA; Doheny Eye Institute (S.S.), University of California - Los;Angeles (UCLA), Pasadena, California, USA.;California, USA; Stein Eye Institute (D.S.), University of California - Los;Angeles (UCLA), Los Angeles, California, USA.;The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of;Ophthalmology, Ottawa, Ontario, Canada.;P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; John and Liz;Tory Eye Centre (P.J.K.), Sunnybrook Health Sciences Centre, Toronto, Ontario,;Canada.;University, Hamilton, Ontario, Canada; Department of Health Research Methods;(V.C.), Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.;Ontario, Canada; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X.,;R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada;;Department of Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health;Toronto, Toronto, Ontario, Canada; Kensington Eye Institute (R.H.M.), Kensington;Vision and Research Centre, Toronto, Ontario, Canada. Electronic address:;rajeev.muni@gmail.com. |
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