Diabetes Connect WA endocrinologist Dr GREG ONG addresses a hot topic of conversation among healthcare professionals: does the use of GLP-1 and similar agents cause sight-threatening complications?
Recently, there have been concerns that incretin-based therapies such as GLP-1 analogues (e.g. semaglutide, Ozempic) and dual GLP-1/GIP agonists (tirzepatide, Mounjaro) are associated with sight-threatening complications.
It is important for practitioners to be aware of this issue as many people living with diabetes will have heard of them via social or traditional media and will come to us with their questions.
Here is a brief overview of the issue, which may be useful when talking to patients, looking at each specific disease of concern and its association with sight-threatening complications.
Diabetic retinopathy
There is strong and consistent evidence that long-term glycaemic control will prevent or delay progression of microvascular complications over the long term.
However, an early deterioration in retinopathy, such as with soft exudates, microaneurysms and haemorrhage, can occur in the first six months after rapid correction of significant hyperglycaemia.
This phenomenon occurs irrespective of the form of treatment, including with potent incretin-based therapies (1). Therefore, it is important to arrange retinal screening at baseline and to encourage regular follow up. Treatments such as fenofibrate may also be useful in preventing progression of early retinopathy (2,3).
Non artertic ischaemic optic neuropathy (NAION)
NAION is an uncommon sight-threatening emergency arising from ischaemia of the optic nerve and pressure from nerve swelling within a small canal.
It is associated with multiple risk factors commonly seen in patients with diabetes, including hypertension, dyslipidaemia, obesity and sleep apnoea (4). The first reports of concern were from a retrospective study of patients already attending a specialist neuro-ophthalmology clinic where use of semaglutide was associated with higher hazard of NAION (5).
Several studies utilising data from health insurance databases, electronic health records databases and health registry databases have been published but have inconsistent findings (5). These studies are prone to bias and confounding due to their design, and the limited data available to researchers to balance the case and control groups.
Analysis of data from 69 randomised placebo or active comparator-controlled trials of GLP-1 agonists found that no events of NAION were reported in 64 trials.
In a meta-analysis of data from the five remaining trials, there was no increase in incidence of NAION statistically associated with GLP-1 use (6).
Other ophthalmic issues
Perhaps driven by interest in NAION, database- or registry-based studies have been published suggesting an increased incidence of non-NAION optic neuropathies (7) and uveitis (8) in patients using incretin-based therapies. However, interpretation is subject to similar concerns about confounding, bias and data quality, and there is a need for validation by higher-quality prospective studies.
Conclusion
Loss of vision has a catastrophic impact on function and quality of life, and patients are understandably concerned about recent reports. The risk of acute deterioration in retinopathy from rapid glycaemic control has a longstanding evidentiary basis but is not incretin therapy specific and should not dissuade against choosing these agents. The risks can be mitigated with appropriate screening and surveillance.
The evidence for an association between incretin therapies and NAION or other ophthalmic diseases is less robust, and there are no studies that establish causality. In most cases, the suggested higher relative hazard between incretins and other agents still translates to a low absolute risk.
One must recall the good evidence for incretin therapies for cardiovascular risk protection and weight loss and consider these against the small potential risks for threats to vision.
As always, informed consent is important for long term compliance and engagement.
Dr Greg Ong has clinical appointments at Fiona Stanley Hospital, Fremantle Hospital, and Sir Charles Gairdner Hospital where he previously served as clinical lead (Director) of Acute Internal Medicine. Greg can assist you with the management of any aspect of adult diabetes including diabetes in pregnancy.
Are you a health professional with a question about diabetes?
Diabetes WA Connect is here for you.
Our Diabetes WA Connect service supports GPs and nurse practitioners with diabetes management through phone calls and virtual case conferences with our endocrinologists Dr Gregory Ong and A/Prof Seng Khee Gan.
Call us directly on 9436 6270 or book a scheduled callback from the endocrinologist in a 30-minute time window that suits you for any diabetes-related questions.
References
- Diabetes Obes Metab. 2018 Oct 15;21(3):454–466
- Aust Fam Phys 2015;44(6): 367-370.
- NEJM Evid. 2024 Jun 21;3(8):EVIDoa2400179
- StatPearls
- Acta Ophthalmol. 2025 Sep;103(6):615-621
- Diabetes Obes Metab. 2025 Feb;27(2):1005-1009.
- JAMA Network Open 2025;8(8):e2526327
- Diabetes Obes Metab. 2025 Feb;27(2):1005-1009.
