Using real-world data from more than 300 000 cases, scientists have uncovered a significant link between semaglutide and reported vision problems, raising new concerns about the safety profile of this blockbuster medication.
The findings by the team from the University of Bern, Switzerland, were published in the journal BMC Medicine.
Semaglutide is widely prescribed as an anti-diabetic medicine that acts as a glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the treatment of type 2 diabetes and obesity.
A 2024 study by Hathaway et al, which investigated more than 16 000 patients over a period of six years, first raised ocular safety issues related to semaglutide. It found that the medicine can potentially increase the risk of non-arteritic anterior ischaemic optic neuropathy (NAION), a potentially vision-threatening condition.
The Hathaway study reported higher hazard ratios for NAION in patients with obesity (7.64) compared with those with type 2 diabetes (4.28).
However, the current analysis of FDA data did not directly compare risks between these groups, reports News.Medical-net.
Given the rapidly increasing use of semaglutide and other GLP-1 RAs worldwide, these observations warrant further investigation.
In the current study, the Bern University team analysed data from the US Food and Drug Administration (FDA) Adverse Event Reporting System, a post-marketing, open-access pharmacovigilance database. The main aim was to compare the medical reports of semaglutide-related vision impairment with those associated with other anti-diabetic and weight-loss medicines.
What they found
The team analysed 302 706 reports, including 17 853 mentioning obesity as an indication, 283 238 mentioning type 2 diabetes, and 1 615 mentioning both conditions.
Semaglutide’s vision impairment signal held even after adjusting for age, sex, and concurrent diabetic retinopathy, they said, suggesting the risk isn’t solely explained by underlying diabetes complications.
Semaglutide use, they wrote, was associated with a significantly higher risk of vision impairment than other GLP-1 RAs. Among 11 558 semaglutide-related reports, they identified 417 cases specifically related to visual impairment, retinopathy, or ischaemic optic neuropathy.
They observed a more pronounced risk of vision impairment when comparing semaglutide with other anti-diabetic medicines, including dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and metformin.
While vision impairment related to semaglutide use was higher when compared with other similar weight loss medications, including phentermine and orlistat, the only exception was topiramate, which exhibited higher reporting of vision impairment than semaglutide (rOR 0.30, 95% CI 0.20–0.45).
Significance
The findings reinforce the rising concern about the risk of vision impairment and semaglutide use. By analysing the FDA database, the study found significantly elevated risks of general vision impairment, retinopathy, and ischaemic optic neuropathy linked to semaglutides compared with other anti-diabetic and weight-loss medicines.
A supplementary analysis focusing specifically on retinopathy found consistent results, with semaglutide showing higher reporting odds than other drugs.
Previous clinical trials that investigated the safety and efficacy of semaglutide did not report significant vision complications except for the SUSTAIN-6 trial and a subsequent meta-analysis of 23 trials, which reported a higher risk of diabetic retinopathy complications in patients receiving semaglutide.
SUSTAIN-6 documented absolute rates of 3.0% for retinopathy complications with semaglutide versus 1.8% with placebo.
This discrepancy between the current post-marketing findings and prior clinical trial evidence highlights the significance of ongoing pharmacovigilance and real-world evidence studies in identifying rare but potentially serious adverse effects that may not be captured in pre-approval clinical trials.
Given the fact that diabetes is frequently associated with diabetic retinopathy and that this comorbidity can serve as a potential confounding factor, researchers separately analysed the semaglutide-related risk of visual impairment in patients with and without type 2 diabetes.
The findings reveal that although patients with type 2 diabetes more frequently report vision impairment, the risk of impairment relative to other anti-diabetic medications is more pronounced in patients receiving semaglutide.
These observations collectively highlight the need for further investigations and attentive post-marketing surveillance. Healthcare professionals should be aware of this potential side effect while prescribing semaglutide for patients with type 2 diabetes or obesity.
The study focused primarily on semaglutide formulations for diabetes (e.g., Ozempic), as data for the obesity-specific formulation Wegovy were limited.
Limitations
The FDA Adverse Event Reporting System database analysed in this study has some limitations. The database allows voluntary data reporting from various sources, including healthcare professionals, consumers, and manufacturers, which might induce bias.
In most cases, the dataset provides incomplete health reports of patients, which might also induce bias because of prescription preferences between classes due to relevant adverse event risk factors.
The study utilised an odds ratio-based analysis approach to determine the risk of vision impairment after semaglutide use. One limitation is that medications with substantially different adverse event profiles may generate ratios that do not entirely capture their true visual impairment risk.
Moreover, the study could not provide absolute rates of vision complications with semaglutide using FAERS data, limiting clinical interpretation. However, SUSTAIN-6 trial data previously reported higher absolute rates of retinopathy (3.0% vs. 1.8%). Future studies are required to assess the absolute clinical impact of this potential side effect.
Despite these limitations, the FDA database offers real-world data on clinically relevant adverse events associated with medication use, broadening the pharmacovigilance landscape.
The researchers said rapid weight loss (>10% body weight in six months) correlated with higher vision impairment reports, raising questions about whether metabolic shifts play a role in ocular side effects.
Study details
Increased vision impairment reports linked to semaglutide: analysis of FDA adverse event data.
Marine Massy, Stefanie Marti, Helly Hammer & Robert Hoepner.
Published in BMC Medicine on 7 April 2025
Abstract
Background
Semaglutide, a GLP-1 receptor agonist widely prescribed for type 2 diabetes and obesity, has recently raised concerns about its ocular safety. This study aimed to investigate the association between semaglutide use and vision impairment using data from the FDA Adverse Event Reporting System (FAERS).
Methods
We conducted an analysis of FAERS data, comparing reports of vision impairment associated with semaglutide to those associated with other anti-diabetic and weight loss medications. The main outcome measure was the reporting odds ratio (rOR) for vision impairment linked to semaglutide use compared to other medications.
Results
Semaglutide showed significantly higher reporting of vision impairment compared to other GLP-1 receptor agonists (rOR 1.95, 95% CI 1.75–2.17, p < 0.0001), DPP-4 inhibitors (rOR 2.46, 95% CI 2.12–2.86, p < 0.0001), SGLT2 inhibitors (rOR 3.89, 95% CI 3.35–4.51, p < 0.0001), and metformin (rOR 2.23, 95% CI 1.90–2.62, p < 0.0001). Similar findings were observed when compared to phentermine (rOR 1.57, 95% CI 1.07–2.31, p = 0.026) and orlistat (rOR 3.77, 95% CI 2.96–4.81, p < 0.0001). Topiramate was the sole exception, showing higher vision impairment reporting than semaglutide (rOR 0.30, 95% CI 0.20–0.45, p < 0.0001).
Conclusions
These findings suggest a potentially elevated risk of vision impairment with semaglutide use compared to other diabetes and weight loss medications, warranting further investigation and vigilant post-marketing surveillance. Future studies should assess the clinical impact of this potential increased risk on an absolute scale to better inform treatment decisions.
See more from MedicalBrief archives:
Vision problems flagged after GLP-1 agonists – Utah survey
Nordisk slams study linking rare blindness to semaglutide
Danish studies flag rare optic nerve damage with Ozempic