Swedish study reports low vision loss risk with GLP-1RAs

1. In this cohort study, glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a higher risk of anterior ischemic optic neuropathy (AION) than sodium-glucose cotransporter-2 inhibitor (SGLT-2i) use among adults with type 2 diabetes (T2D).

2. The association was attenuated and no longer statistically significant among patients receiving metformin at baseline, suggesting that residual confounding may have influenced the findings.

Evidence Rating Level: 2 (Good)

Study Rundown: Concerns have been raised that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may increase the risk of non-arteritic anterior ischemic optic neuropathy (NAION), a rare but potentially vision-threatening condition, in patients with type 2 diabetes (T2D). However, existing studies have reported conflicting findings and are subject to several methodological limitations. This study evaluated the association between GLP-1RA use and anterior ischemic optic neuropathy (AION), which shares the same International Classification of Diseases, 10th Revision (ICD-10) diagnostic code as NAION. GLP-1RA use was associated with a higher relative risk of AION than sodium-glucose cotransporter-2 inhibitor (SGLT-2i) use, although the absolute risk remained low. Among patients receiving metformin, however, AION risk was similar between GLP-1RA and SGLT-2i users, suggesting that the overall association may be influenced by confounding. Sensitivity analyses produced similar findings, although confidence intervals were wide. The study was limited by the potential for unmeasured confounding and outcome misclassification, particularly because the ICD-10 code does not distinguish AION from NAION. Nevertheless, the findings suggest that while GLP-1RA use may be associated with a modest increase in AION risk, the attenuation of this association among metformin users raises the possibility of residual confounding. Larger studies, particularly those including patients with a history of NAION, are needed to better define this potential risk.

Click to read this study in AIM

Relevant Reading: Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy

In-Depth [retrospective cohort]: This cohort study evaluated the association between GLP-1RA use and risk of AION compared with SGLT-2i use among adults with T2D. Data were obtained from several Swedish national registries, including the Swedish National Diabetes Register, which captures more than 85% of individuals receiving diabetes medications. Eligible patients were aged 35-84 years with T2D and no prior GLP-1RA or SGLT-2i use, AION, or other conditions that could substantially affect optic nerve health. The study included 107,518 GLP-1RA initiators and 185,898 SGLT-2i initiators; among GLP-1RA users, 53% received semaglutide and 35% liraglutide. During follow-up, 62 AION events occurred among GLP-1RA users and 64 among SGLT-2i users. At 3 years, the absolute risk of AION was 0.08% with GLP-1RAs versus 0.05% with SGLT-2is (risk difference, 0.04% [95% confidence interval [CI], 0.01%-0.07%]; risk ratio, 1.78 [95% CI, 1.05-3.02]). Across the full follow-up, GLP-1RA use was associated with a higher risk of AION (weighted hazard ratio, 1.78 [95% CI, 1.12-2.85]), although absolute risks remained very low. Among patients receiving metformin at baseline, the association was attenuated and no longer statistically significant (weighted hazard ratio, 1.21 [95% CI, 0.69-2.11]). Similar findings were observed among patients using metformin without insulin and in intention-to-treat and sensitivity analyses, although confidence intervals were wide because of the small number of events. Overall, the findings suggest that GLP-1RA use may be associated with an increased risk of AION compared with SGLT-2i use, but the absolute risk is very low and the attenuation of risk among metformin users suggests that residual confounding may partly explain the association.

Image: PD

©2026 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.