{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T14:18:14Z","timestamp":1792505894647,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pmed.1005064","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for Polish Science START"},{"name":"Foundation for Polish Science START"},{"name":"Medical University of Lodz BRaIN P1 programme"},{"name":"Medical University of Lodz BRaIN P1 programme"},{"name":"National Science Centre PRELUDIUM BIS","award":["4 (2022\/47\/O\/NZ5\/00683)"],"award-info":[{"award-number":["4 (2022\/47\/O\/NZ5\/00683)"]}]},{"DOI":"10.13039\/501100008813","name":"International Society for Pediatric and Adolescent Diabetes","doi-asserted-by":"publisher","award":["ISPAD-Breakthrough T1D"],"award-info":[{"award-number":["ISPAD-Breakthrough T1D"]}],"id":[{"id":"10.13039\/501100008813","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001870","name":"Foundation for Polish Science","doi-asserted-by":"crossref","award":["CRIDO \u201cKorzenie Przysz\u0142o\u015bci"],"award-info":[{"award-number":["CRIDO \u201cKorzenie Przysz\u0142o\u015bci"]}],"id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Polish Ministry of Science and Education","award":["\u201cPer\u0142y Nauki 1\u201d (PN\/01\/0025\/2022)"],"award-info":[{"award-number":["\u201cPer\u0142y Nauki 1\u201d (PN\/01\/0025\/2022)"]}]},{"name":"Ko\u00c5\u203aciuszko Foundation"},{"name":"Diabetes Poland"},{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"crossref","award":["PRELUDIUM 22 (2023\/49\/N\/NZ5\/02321)"],"award-info":[{"award-number":["PRELUDIUM 22 (2023\/49\/N\/NZ5\/02321)"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical University of Lodz\u00e2\u20ac\u201dDigital Medicine Center","award":["(2023\/ABM\/02\/00009)"],"award-info":[{"award-number":["(2023\/ABM\/02\/00009)"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Semaglutide, a glucagon-like peptide-1 receptor agonist, is widely used for the management of type 2 diabetes (T2DM). Recent case reports have raised concerns about a potential association between semaglutide use and the development of nonarteritic anterior ischemic optic neuropathy (NAION), a rare but vision-threatening condition. We aimed to evaluate whether semaglutide use is associated with an increased risk of NAION in patients with T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta-analysis of observational studies comparing patients with T2DM aged \u226512 years treated with semaglutide to those receiving other glucose-lowering therapies. We searched PubMed, Scopus, and Web of Science databases from January 2023 to November 2025. Two reviewers independently extracted data on study design, population characteristics, and outcomes. Risk of bias was assessed using the Newcastle\u2013Ottawa Scale, and ROBINS-I v.2. Certainty of the evidence was graded according to the GRADE framework. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models; sensitivity analyses included crude and subgroup HRs, and overlapping study replacement. Leave-one-out analysis was conducted to assess small-study effects and publication bias. Results were contextualized within other meta-analyses, systematic reviews, consensus statements, and regulatory communications on the topic.<\/jats:p>\n                    <jats:p>\n                      Five eligible observational studies met the inclusion criteria, and 7 additional studies were included in the sensitivity analysis. Semaglutide use was associated with a significantly increased hazard of NAION compared with nonsemaglutide glucose-lowering regimens (HR 2.17, 95% CI [1.73, 2.74];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), regimens excluding other GLP-1 receptor agonists (HR 2.13, 95% CI [1.60, 2.83];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) users (HR 1.96, 95% CI [1.28, 2.99];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002). Despite the increased relative risk, the absolute risk remained low at 0.014% (95% CI [0.005%, 0.023%];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), corresponding to approximately 1 additional case of NAION per 7,000 semaglutide-treated patients annually. The results were consistent with meta-analyses of observational studies and corroborated decisions presented in regulatory communications. Due to exclusive focus on retrospective, registry-based observational studies, the evidence synthesis was limited and could be biased by study-level outcome misclassification and confounding.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest a possible association between semaglutide use and an increased risk of NAION in patients with T2DM. Although the absolute risk is low, clinicians should be aware of this potential adverse event, particularly in individuals at increased baseline risk for optic neuropathies. While these findings support current recommendations to discontinue semaglutide in patients diagnosed with NAION, the certainty of the available evidence is low, underscoring the need for further high-quality studies to clarify this association.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1005064","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T17:37:56Z","timestamp":1779385076000},"page":"e1005064","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6204-8622","authenticated-orcid":true,"given":"J\u0119drzej","family":"Chrzanowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Walicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-8376","authenticated-orcid":true,"given":"Jacek","family":"Burzy\u0144ski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9030-9601","authenticated-orcid":true,"given":"Ma\u0142gorzata","family":"Zara\u015b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiusz","family":"Michalak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-9168","authenticated-orcid":true,"given":"Wojciech","family":"Fendler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"pmed.1005064.ref001","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(21)00213-0","article-title":"Semaglutide 2\u00b74\u2009mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial","volume":"397","author":"M Davies","year":"2021","journal-title":"Lancet"},{"issue":"19","key":"pmed.1005064.ref002","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"375","author":"SP Marso","year":"2016","journal-title":"N Engl J Med"},{"issue":"12","key":"pmed.1005064.ref003","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1093\/eurheartj\/ehae613","article-title":"Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial","volume":"46","author":"KW Mahaffey","year":"2025","journal-title":"Eur Heart J"},{"key":"pmed.1005064.ref004","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and cardiovascular outcomes in obesity without diabetes","volume":"389","author":"AM Lincoff","year":"2023","journal-title":"N Engl J Med"},{"key":"pmed.1005064.ref005","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1056\/NEJMoa2501006","article-title":"Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes","volume":"392","author":"DK McGuire","year":"2025","journal-title":"N Engl J Med"},{"issue":"1","key":"pmed.1005064.ref006","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1186\/s12872-025-05278-3","article-title":"Cardiovascular benefits of semaglutide: a systematic review and meta-analysis of randomized controlled trials","volume":"25","author":"S Sadraei","year":"2025","journal-title":"BMC Cardiovasc Disord"},{"issue":"1","key":"pmed.1005064.ref007","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1186\/s12916-025-04486-0","article-title":"The adverse effects associated with semaglutide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis","volume":"23","author":"CDB Sillassen","year":"2025","journal-title":"BMC Med"},{"key":"pmed.1005064.ref008","article-title":"Effect of semaglutide on insulin sensitivity and cardiometabolic risk factors in adolescents with obesity: the STEP TEENS study","author":"S Arslanian","year":"2025","journal-title":"Diabetes Care"},{"issue":"24","key":"pmed.1005064.ref009","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1056\/NEJMoa2208601","article-title":"Once-weekly semaglutide in adolescents with obesity","volume":"387","author":"D Weghuber","year":"2022","journal-title":"N Engl J Med"},{"key":"pmed.1005064.ref010","article-title":"8. 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