madman
Super Moderator
* NAION cases have been reported for all currently marketed GLP-1 RA products. FDA concluded that there is a potential increased risk of rare NAION events in patients taking GLP-1 RAs. Based on these findings, FDA is requiring that application holders add information about the risk for NAION to the Warnings and Precautions section of labeling of all GLP-1 RAs.
* NAION is a rare condition that can result in acute, painless, decreased vision in one eye, including permanent vision loss.
www.fda.gov
FDA conducted a detailed review of reports of NAION in patients treated with GLP-1 RAs that were received through the FDA Adverse Event Monitoring System (AEMS), formerly the FDA Adverse Event Reporting System (FAERS). These reports were challenging to interpret because the risk factors for NAION often overlap with conditions common in patients treated with GLP-1 RAs. Therefore, FDA evaluated other data sources, described below, to further assess for a potential relationship between GLP-1 RA use and NAION.
FDA review of the available animal data did not identify a mechanism for how GLP-1 RA use could increase the potential risk of NAION.
FDA performed a meta-analysis of clinical trials across GLP-1 RA development programs because of the small number or absence of cases of NAION observed in individual trials. The primary objective of the meta-analysis was to assess the incidence of NAION events in patients treated with GLP-1 RAs compared to the incidence in patients treated with a comparator (a placebo or a non-GLP-1 RA glucose-lowering medication). There were 126 such trials for GLP-1 RAs included in the meta-analysis, including a total of 134,253 patients (78,217 GLP-1 RA users and 56,036 patients receiving a comparator) with 288,879 PY of exposure (156,947 PY for the GLP-1 RA users and 131,932 PY for the patients receiving a comparator). We identified 15 probable NAION events, 10 in patients treated with GLP-1 RAs, 5 in patients receiving placebo, and none in patients who received other non-GLP-1 RA glucose-lowering medication. Overall, the results showed a NAION incidence rate of 6.4 events per 100,000 PY in patients treated with GLP-1 RAs compared to 3.8 events per 100,000 PY in comparator-treated patients.
In addition, FDA conducted a retrospective cohort study in FDA’s Sentinel Real-World Evidence Data Enterprise (RWE-DE) Commercial Network. This study assessed the NAION incidence rate among adults with type 2 diabetes mellitus who started a GLP-1 RA or another common diabetes medication – either a sodium glucose co-transporter-2 (SGLT-2) inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor – between 2019 and 2024. The NAION incidence rates ranged from 26 to 32 events per 100,000 PY (GLP-1 RA: 30-32 events; SGLT-2 inhibitor: 31 events; DPP-4 inhibitor: 26 events). There was no statistically significant increase in the risk for NAION with GLP1-RAs compared to SGLT-2 inhibitors (hazard ratio (HR) 1.19, 95% confidence interval (CI) 0.91, 1.54). In contrast, an increased risk of NAION was observed with GLP1-RAs compared to DPP-4 inhibitors (HR: 1.43, 95% CI: 1.02, 2.01).
FDA also reviewed published observational studies evaluating the association between GLP-1 RAs and NAION. Methodologically rigorous studies consistently reported an increased risk of NAION in patients with type 2 diabetes mellitus who initiated GLP-1 RAs compared to those who initiated DPP-4 inhibitors or SGLT-2 inhibitors. These findings were generally consistent with those from FDA’s clinical trial analysis and Sentinel study.
NAION cases have been reported for all currently marketed GLP-1 RA products. FDA concluded that there is a potential increased risk of rare NAION events in patients taking GLP-1 RAs. Based on these findings, FDA is requiring that application holders add information about the risk for NAION to the Warnings and Precautions section of labeling of all GLP-1 RAs.
[1] Hathaway JT, Shah MP, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW Jr, Cestari D, Mallery R, Abbasi B, Bouffard M, Chwalisz BK, Estrela T, Rizzo JF 3rd. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024 Aug 1;142(8):732-739. doi: 10.1001/jamaophthalmol.2024.2296. PMID: 38958939; PMCID: PMC11223051.
* NAION is a rare condition that can result in acute, painless, decreased vision in one eye, including permanent vision loss.
FDA Requires Safety Labeling Changes for GLP-1 RAs
FDA Drug Safety Communication – November 9, 2026
What Did FDA Find?
In July 2024, Hathaway et al. published an article titled “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.”[1] Although FDA identified several limitations of this study, the agency determined that further assessment of the potential increased risk for NAION was warranted. Therefore, FDA undertook a comprehensive evaluation of clinical trial data, animal data, and postmarketing data, including observational studies and case reports.FDA conducted a detailed review of reports of NAION in patients treated with GLP-1 RAs that were received through the FDA Adverse Event Monitoring System (AEMS), formerly the FDA Adverse Event Reporting System (FAERS). These reports were challenging to interpret because the risk factors for NAION often overlap with conditions common in patients treated with GLP-1 RAs. Therefore, FDA evaluated other data sources, described below, to further assess for a potential relationship between GLP-1 RA use and NAION.
FDA review of the available animal data did not identify a mechanism for how GLP-1 RA use could increase the potential risk of NAION.
FDA performed a meta-analysis of clinical trials across GLP-1 RA development programs because of the small number or absence of cases of NAION observed in individual trials. The primary objective of the meta-analysis was to assess the incidence of NAION events in patients treated with GLP-1 RAs compared to the incidence in patients treated with a comparator (a placebo or a non-GLP-1 RA glucose-lowering medication). There were 126 such trials for GLP-1 RAs included in the meta-analysis, including a total of 134,253 patients (78,217 GLP-1 RA users and 56,036 patients receiving a comparator) with 288,879 PY of exposure (156,947 PY for the GLP-1 RA users and 131,932 PY for the patients receiving a comparator). We identified 15 probable NAION events, 10 in patients treated with GLP-1 RAs, 5 in patients receiving placebo, and none in patients who received other non-GLP-1 RA glucose-lowering medication. Overall, the results showed a NAION incidence rate of 6.4 events per 100,000 PY in patients treated with GLP-1 RAs compared to 3.8 events per 100,000 PY in comparator-treated patients.
In addition, FDA conducted a retrospective cohort study in FDA’s Sentinel Real-World Evidence Data Enterprise (RWE-DE) Commercial Network. This study assessed the NAION incidence rate among adults with type 2 diabetes mellitus who started a GLP-1 RA or another common diabetes medication – either a sodium glucose co-transporter-2 (SGLT-2) inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor – between 2019 and 2024. The NAION incidence rates ranged from 26 to 32 events per 100,000 PY (GLP-1 RA: 30-32 events; SGLT-2 inhibitor: 31 events; DPP-4 inhibitor: 26 events). There was no statistically significant increase in the risk for NAION with GLP1-RAs compared to SGLT-2 inhibitors (hazard ratio (HR) 1.19, 95% confidence interval (CI) 0.91, 1.54). In contrast, an increased risk of NAION was observed with GLP1-RAs compared to DPP-4 inhibitors (HR: 1.43, 95% CI: 1.02, 2.01).
FDA also reviewed published observational studies evaluating the association between GLP-1 RAs and NAION. Methodologically rigorous studies consistently reported an increased risk of NAION in patients with type 2 diabetes mellitus who initiated GLP-1 RAs compared to those who initiated DPP-4 inhibitors or SGLT-2 inhibitors. These findings were generally consistent with those from FDA’s clinical trial analysis and Sentinel study.
NAION cases have been reported for all currently marketed GLP-1 RA products. FDA concluded that there is a potential increased risk of rare NAION events in patients taking GLP-1 RAs. Based on these findings, FDA is requiring that application holders add information about the risk for NAION to the Warnings and Precautions section of labeling of all GLP-1 RAs.
[1] Hathaway JT, Shah MP, Hathaway DB, Zekavat SM, Krasniqi D, Gittinger JW Jr, Cestari D, Mallery R, Abbasi B, Bouffard M, Chwalisz BK, Estrela T, Rizzo JF 3rd. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024 Aug 1;142(8):732-739. doi: 10.1001/jamaophthalmol.2024.2296. PMID: 38958939; PMCID: PMC11223051.
