Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes

Abstract Background Nonarteritic anterior ischemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evalua...

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Main Authors: Jakob Grauslund, Andreas Abou Taha, Laleh Dehghani Molander, Ryo Kawasaki, Sören Möller, Kurt Højlund, Lonny Stokholm
Format: Article
Language:English
Published: BMC 2024-12-01
Series:International Journal of Retina and Vitreous
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Online Access:https://doi.org/10.1186/s40942-024-00620-x
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author Jakob Grauslund
Andreas Abou Taha
Laleh Dehghani Molander
Ryo Kawasaki
Sören Möller
Kurt Højlund
Lonny Stokholm
author_facet Jakob Grauslund
Andreas Abou Taha
Laleh Dehghani Molander
Ryo Kawasaki
Sören Möller
Kurt Højlund
Lonny Stokholm
author_sort Jakob Grauslund
collection DOAJ
description Abstract Background Nonarteritic anterior ischemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evaluate this risk prospectively in all persons with type 2 diabetes (T2D) in Denmark. Methods In a five-year longitudinal cohort study, we identified all persons with T2D in Denmark (n = 424,152) between 2018 and 2024. Patients were stratified according to exposure (n = 106,454) or non-exposure (n = 317,698) to once-weekly semaglutide, and incidence rates and hazard ratios (HR) of NAION were estimated in a multivariable Cox proportional hazard regression model. Results At baseline, median age and hemoglobin A1c were 65 years and 50 mmol/mol, and 54·5% were male. During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide exposure was associated with a higher incidence rate (0·228 vs. 0·093 per 1000 person-years, p < 0·001) and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 1·54 − 3·12), even when multiple other factors were taken into account. Overall, 67 persons exposed to semaglutide developed NAION with a median time from first prescription to event of 22·2 months (interquartile range 10·2–37·8 months). Conclusions During five years of observation of all persons with T2D in Denmark, use of once-weekly semaglutide independently more than doubled the risk of NAION. Given the irreversible nature of NAION, it is important to acknowledge this risk, and upcoming studies should aim to identify high-risk subgroups.
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spelling doaj-art-d3bc1a41430c4f6caaaf51b01e581a8c2025-01-26T12:46:33ZengBMCInternational Journal of Retina and Vitreous2056-99202024-12-011011810.1186/s40942-024-00620-xOnce-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetesJakob Grauslund0Andreas Abou Taha1Laleh Dehghani Molander2Ryo Kawasaki3Sören Möller4Kurt Højlund5Lonny Stokholm6Department of Ophthalmology, Odense University HospitalDepartment of Ophthalmology, Odense University HospitalDepartment of Ophthalmology, Odense University HospitalDepartment of Clinical Research, University of Southern DenmarkDepartment of Clinical Research, University of Southern DenmarkDepartment of Clinical Research, University of Southern DenmarkDepartment of Clinical Research, University of Southern DenmarkAbstract Background Nonarteritic anterior ischemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evaluate this risk prospectively in all persons with type 2 diabetes (T2D) in Denmark. Methods In a five-year longitudinal cohort study, we identified all persons with T2D in Denmark (n = 424,152) between 2018 and 2024. Patients were stratified according to exposure (n = 106,454) or non-exposure (n = 317,698) to once-weekly semaglutide, and incidence rates and hazard ratios (HR) of NAION were estimated in a multivariable Cox proportional hazard regression model. Results At baseline, median age and hemoglobin A1c were 65 years and 50 mmol/mol, and 54·5% were male. During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide exposure was associated with a higher incidence rate (0·228 vs. 0·093 per 1000 person-years, p < 0·001) and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 1·54 − 3·12), even when multiple other factors were taken into account. Overall, 67 persons exposed to semaglutide developed NAION with a median time from first prescription to event of 22·2 months (interquartile range 10·2–37·8 months). Conclusions During five years of observation of all persons with T2D in Denmark, use of once-weekly semaglutide independently more than doubled the risk of NAION. Given the irreversible nature of NAION, it is important to acknowledge this risk, and upcoming studies should aim to identify high-risk subgroups.https://doi.org/10.1186/s40942-024-00620-xCohort studyNonarteritic anterior ischemic optic neuropathyRegistry basedSemaglutideType 2 diabetes
spellingShingle Jakob Grauslund
Andreas Abou Taha
Laleh Dehghani Molander
Ryo Kawasaki
Sören Möller
Kurt Højlund
Lonny Stokholm
Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
International Journal of Retina and Vitreous
Cohort study
Nonarteritic anterior ischemic optic neuropathy
Registry based
Semaglutide
Type 2 diabetes
title Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
title_full Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
title_fullStr Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
title_full_unstemmed Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
title_short Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes
title_sort once weekly semaglutide doubles the five year risk of nonarteritic anterior ischemic optic neuropathy in a danish cohort of 424 152 persons with type 2 diabetes
topic Cohort study
Nonarteritic anterior ischemic optic neuropathy
Registry based
Semaglutide
Type 2 diabetes
url https://doi.org/10.1186/s40942-024-00620-x
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