JAMA Netw Open
Do GLP-1 drugs raise rare optic nerve risk vs. SGLT2 inhibitors? New VA study adds clarity
Clinical takeaway: GLP-1 receptor agonists may carry a small increased risk of NAION vs. SGLT2 inhibitors; counsel patients on rare vision changes and consider risk factors when choosing therapy.
Nonarteritic anterior ischemic optic neuropathy (NAION) is a vision-threatening condition with no effective treatment. Even a small increase in risk is clinically relevant as GLP-1 receptor agonists see widespread and expanding use.
In this JAMA Network Open research letter, investigators analyzed electronic health record data from 588,168 US veterans with type 2 diabetes initiating GLP-1 receptor agonists (n=139,546) or SGLT2 inhibitors (n=448,622) between 2017 and 2024.
Over 3 years of follow-up, NAION remained rare but occurred more often in GLP-1 RA users, with a cumulative incidence of 39.07 per 10,000 persons vs. 29.33 per 10,000 among SGLT2 inhibitor users.
This translated to an absolute difference of 9.98 additional cases per 10,000 patients and a 35% higher relative risk (cumulative incidence ratio [CIR] 1.35; 95% CI, 1.11–1.51) with GLP-1 therapy.
Findings were consistent across stricter outcome definitions, including specialist-diagnosed NAION and repeated diagnoses (CIR range, 1.34 to 1.46).
Importantly, GLP-1 RA use was not associated with increased risk of other eye conditions, such as diabetic retinopathy (CIR, 1.01), macular degeneration (1.00), retinal vascular occlusion (0.98), or optic neuritis (1.00), suggesting a degree of specificity for NAION.
“GLP-1RA use was associated with a modestly increased risk of NAION compared with SGLT2i use,” the authors wrote, noting that “the absolute risk remains low” but the finding “may warrant heightened vigilance.”
Overall, the study strengthens evidence for a small, specific increase in NAION risk with GLP-1 therapies—an effect that should be weighed against their substantial cardiometabolic benefits.
Source: Choi T, et al. (2026, April 30). JAMA Netw Open. GLP-1 Receptor Agonists or SGLT2 Inhibitors and Nonarteritic Anterior Ischemic Optic Neuropathy