{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:02:20Z","timestamp":1791450140837,"version":"4.3.3"},"reference-count":40,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Foundation for Innovation"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To estimate the effect of initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase 4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) among adults with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>This active-comparator, new-user cohort emulated a pragmatic target trial using the U.K. Clinical Practice Research Datalink. Patients aged \u226518 years with a physician diagnosis of type 2 diabetes who newly initiated a GLP-1 RA or a DPP-4 inhibitor were included. DPP-4 inhibitors were selected as the comparator because they may be used as second-line treatment, like GLP-1 RAs, and have no established association with NAION. We estimated risks, risk differences (RDs), and risk ratios (RRs) of incident NAION, adjusted using propensity-score fine-stratification weighting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>At 1 year, there were 14 NAION events among 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 among 416,369 DPP-4 inhibitor initiators (7.2 per 100,000). GLP-1 RAs were associated with an increased risk of NAION compared with DPP-4 inhibitors (RR 2.56; 95% CI 1.44\u20134.86; RD 11.3 per 100,000). The risk of NAION was higher during the first 6 months of use, diminishing with longer duration of use, and was higher in patients aged &amp;lt;50 years, men, ever-smokers, and those with \u22651% hemoglobin A1c reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>GLP-1 RAs were associated with an increased 1-year risk of NAION compared with DPP-4 inhibitors among adults with type 2 diabetes, particularly in younger patients, men, ever-smokers, and patients with a marked hemoglobin A1c reduction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-2577","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:43:34Z","timestamp":1771350214000},"page":"763-771","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":9,"title":["Glucagon-Like Peptide 1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients With Type 2 Diabetes"],"prefix":"10.2337","volume":"49","author":[{"given":"Yunha","family":"Noh","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chonnam National University 1 , Gwangju, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yin","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital 2 , Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Ben Ghezala","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University 3 , Montreal, Canada"},{"name":"Department of Ophthalmology, Dijon University Hospital 4 , Dijon, France"},{"name":"Clinical Investigation Center 1432, Clinical Epidemiology\/Clinical Trials Unit, INSERM, Dijon University Hospital 5 , Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriana H.Y.","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital 2 , Montreal, Canada"},{"name":"Division of Endocrinology, Jewish General Hospital 6 , Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samy","family":"Suissa","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital 2 , Montreal, Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University 3 , Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5162-3556","authenticated-orcid":false,"given":"Laurent","family":"Azoulay","sequence":"additional","affiliation":[{"name":"Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital 2 , Montreal, Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University 3 , Montreal, Canada"},{"name":"Gerald Bronfman Department of Oncology, McGill University 7 , Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"2026061812464433100_B1","doi-asserted-by":"crossref","first-page":"S181","DOI":"10.2337\/dc25-S009","article-title":"9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes\u20142025","volume":"48","author":"American Diabetes Association Professional Practice Committee","year":"2025","journal-title":"Diabetes Care"},{"key":"2026061812464433100_B2","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.2337\/dci24-0003","article-title":"Efficacy and safety of GLP-1 medicines for type 2 diabetes and obesity","volume":"47","author":"Drucker","year":"2024","journal-title":"Diabetes Care"},{"key":"2026061812464433100_B3","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1001\/jamaophthalmol.2024.2296","article-title":"Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide","volume":"142","author":"Hathaway","year":"2024","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B4","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1001\/jamaophthalmol.2024.6058","article-title":"Ophthalmic complications associated with the antidiabetic drugs semaglutide and tirzepatide","volume":"143","author":"Katz","year":"2025","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B5","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3390\/vision7040072","article-title":"Non-arteritic anterior ischemic optic neuropathy (NA-AION): a comprehensive overview","volume":"7","author":"Salvetat","year":"2023","journal-title":"Vision (Basel)"},{"key":"2026061812464433100_B6","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.orcp.2025.03.001","article-title":"Disproportionality analysis on semaglutide and nonarteritic anterior ischemic optic neuropathy in the FDA adverse event reporting system: an emerging pharmacovigilance signal?","volume":"19","author":"Procacci","year":"2025","journal-title":"Obes Res Clin Pract"},{"key":"2026061812464433100_B7","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1111\/dom.16316","article-title":"Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: a Danish-Norwegian cohort study","volume":"27","author":"Simonsen","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"2026061812464433100_B8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s40942-024-00620-x","article-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","volume":"10","author":"Grauslund","year":"2024","journal-title":"Int J Retina Vitreous"},{"key":"2026061812464433100_B9","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1001\/jamaophthalmol.2024.6555","article-title":"Semaglutide and nonarteritic anterior ischemic optic neuropathy","volume":"143","author":"Cai","year":"2025","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B10","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1001\/jamaophthalmol.2025.0349","article-title":"Semaglutide and nonarteritic anterior ischemic optic neuropathy risk among patients with diabetes","volume":"143","author":"Hsu","year":"2025","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B11","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1177\/19322968241268050","article-title":"Real-world evidence assessment of the risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide","volume":"18","author":"Klonoff","year":"2024","journal-title":"J Diabetes Sci Technol"},{"key":"2026061812464433100_B12","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ajo.2025.02.025","article-title":"The effect of semaglutide and GLP-1 RAs on risk of nonarteritic anterior ischemic optic neuropathy","volume":"274","author":"Abbass","year":"2025","journal-title":"Am J Ophthalmol"},{"key":"2026061812464433100_B13","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1001\/jamaophthalmol.2025.2299","article-title":"GLP-1 RAs and risk of nonarteritic anterior ischemic optic neuropathy in older patients with diabetes","volume":"143","author":"Fung","year":"2025","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B14","doi-asserted-by":"crossref","first-page":"e2526321","DOI":"10.1001\/jamanetworkopen.2025.26321","article-title":"GLP-1 receptor agonists and sight-threatening ophthalmic complications in patients with type 2 diabetes","volume":"8","author":"Ramsey","year":"2025","journal-title":"JAMA Netw Open"},{"key":"2026061812464433100_B15","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/dom.16076","article-title":"Glucagon-like peptide 1 (GLP1) receptor agonists and risk for ischemic optic neuropathy: a meta-analysis of randomised controlled trials","volume":"27","author":"Silverii","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"2026061812464433100_B16","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1111\/dom.15529","article-title":"Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: a meta-analysis and meta-regression","volume":"26","author":"Rivera","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"2026061812464433100_B17","unstructured":"European Medicines Agency\n          . PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy. Accessed 12 February 2026. Available from https:\/\/www.ema.europa.eu\/en\/news\/prac-concludes-eye-condition-naion-very-rare-side-effect-semaglutide-medicines-ozempic-rybelsus-wegovy"},{"key":"2026061812464433100_B18","unstructured":"U.S. Food and Drug Administration\n          . Potential signals of serious risks\/new safety information identified by the FDA Adverse Event Reporting System (FAERS). Accessed 12 February 2026. Available from https:\/\/www.fda.gov\/drugs\/fdas-adverse-event-reporting-system-faers\/october-december-2024-potential-signals-serious-risksnew-safety-information-identified-fda-adverse"},{"key":"2026061812464433100_B19","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/ije\/dyv098","article-title":"Data Resource profile: Clinical Practice Research Datalink (CPRD)","volume":"44","author":"Herrett","year":"2015","journal-title":"Int J Epidemiol"},{"key":"2026061812464433100_B20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1365-2125.2009.03537.x","article-title":"Validation and validity of diagnoses in the General Practice Research Database: a systematic review","volume":"69","author":"Herrett","year":"2010","journal-title":"Br J Clin Pharmacol"},{"key":"2026061812464433100_B21","doi-asserted-by":"crossref","first-page":"e296","DOI":"10.1371\/journal.pmed.0040296","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies","volume":"4","author":"von Elm","year":"2007","journal-title":"PLoS Med"},{"key":"2026061812464433100_B22","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1136\/jech.2004.029496","article-title":"Estimating causal effects from epidemiological data","volume":"60","author":"Hern\u00e1n","year":"2006","journal-title":"J Epidemiol Community Health"},{"key":"2026061812464433100_B23","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.survophthal.2025.01.010","article-title":"An update on ocular effects of antidiabetic medications","volume":"70","author":"Sadeghi","year":"2025","journal-title":"Surv Ophthalmol"},{"key":"2026061812464433100_B24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/EDE.0000000000000595","article-title":"A propensity-score-based fine stratification approach for confounding adjustment when exposure is infrequent","volume":"28","author":"Desai","year":"2017","journal-title":"Epidemiology"},{"key":"2026061812464433100_B25","doi-asserted-by":"crossref","first-page":"101664","DOI":"10.1016\/j.diabet.2025.101664","article-title":"What the diabetologist needs to know about the risk of non-arteritic anterior ischaemic optic neuropathy and GLP-1 receptor agonist use in patients with type 2 diabetes","volume":"51","author":"Feldman-Billard","year":"2025","journal-title":"Diabetes Metab"},{"key":"2026061812464433100_B26","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/psp4.12790","article-title":"A quantitative approach to the choice of number of samples for percentile estimation in bootstrap and visual predictive check analyses","volume":"11","author":"Jonsson","year":"2022","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"2026061812464433100_B27","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1111\/j.0006-341X.2000.00779.x","article-title":"Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests","volume":"56","author":"Robins","year":"2000","journal-title":"Biometrics"},{"key":"2026061812464433100_B28","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity analysis in observational research: introducing the E-value","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann Intern Med"},{"key":"2026061812464433100_B29","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1111\/dom.70200","article-title":"GLP-1RA and the risk of non-arteritic anterior ischaemic optic neuropathy in patients with type 2 diabetes: a population-based study","volume":"28","author":"Tesfaye","year":"2026","journal-title":"Diabetes Obes Metab"},{"key":"2026061812464433100_B30","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ajo.2025.05.007","article-title":"Association of glucagon-like peptide-1 receptor agonists with optic nerve and retinal adverse events: a population-based observational study across 180 countries","volume":"277","author":"Lakhani","year":"2025","journal-title":"Am J Ophthalmol"},{"key":"2026061812464433100_B31","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ophtha.2024.10.030","article-title":"Association between semaglutide and nonarteritic anterior ischemic optic neuropathy","volume":"132","author":"Chou","year":"2025","journal-title":"Ophthalmology"},{"key":"2026061812464433100_B32","doi-asserted-by":"crossref","first-page":"e2526327","DOI":"10.1001\/jamanetworkopen.2025.26327","article-title":"Semaglutide or tirzepatide and optic nerve and visual pathway disorders in type 2 diabetes","volume":"8","author":"Wang","year":"2025","journal-title":"JAMA Netw Open"},{"key":"2026061812464433100_B33","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1001\/jamaophthalmol.2024.4530","article-title":"Considerations regarding association of semaglutide and nonarteritic anterior ischemic optic neuropathy","volume":"142","author":"Etminan","year":"2024","journal-title":"JAMA Ophthalmol"},{"key":"2026061812464433100_B34","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1007\/s13300-018-0424-2","article-title":"A systematic literature review and network meta-analysis comparing once-weekly semaglutide with other GLP-1 receptor agonists in patients with type 2 diabetes previously receiving 1-2 oral anti-diabetic drugs","volume":"9","author":"Witkowski","year":"2018","journal-title":"Diabetes Ther"},{"key":"2026061812464433100_B35","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.ajo.2007.07.031","article-title":"Anterior ischemic optic neuropathy in patients younger than 50 years","volume":"144","author":"Preechawat","year":"2007","journal-title":"Am J Ophthalmol"},{"key":"2026061812464433100_B36","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/dom.13538","article-title":"Worsening of diabetic retinopathy with rapid improvement in systemic glucose control: a review","volume":"21","author":"Bain","year":"2019","journal-title":"Diabetes Obes Metab"},{"key":"2026061812464433100_B37","doi-asserted-by":"crossref","first-page":"172","DOI":"10.2337\/db15-0443","article-title":"Topical administration of GLP-1 receptor agonists prevents retinal neurodegeneration in experimental diabetes","volume":"65","author":"Hern\u00e1ndez","year":"2016","journal-title":"Diabetes"},{"key":"2026061812464433100_B38","doi-asserted-by":"crossref","first-page":"e41562","DOI":"10.1371\/journal.pone.0041562","article-title":"Diabetes care provision in UK primary care practices","volume":"7","author":"Hawthorne","year":"2012","journal-title":"PLoS One"},{"key":"2026061812464433100_B39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/pds.3726","article-title":"Evaluating the validity of clinical codes to identify cataract and glaucoma in the UK Clinical Practice Research Datalink","volume":"24","author":"Kang","year":"2015","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2026061812464433100_B40","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12963-023-00302-0","article-title":"Completeness, agreement, and representativeness of ethnicity recording in the United Kingdom\u2019s Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES)","volume":"21","author":"Shiekh","year":"2023","journal-title":"Popul Health Metr"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/5\/763\/857119\/dc252577.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/5\/763\/857119\/dc252577.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:46:52Z","timestamp":1781801212000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/49\/5\/763\/164499\/Glucagon-Like-Peptide-1-Receptor-Agonists-and-Risk"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,17]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,2,17]]},"published-print":{"date-parts":[[2026,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc25-2577","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,17]]}}}