Diabetic retinopathy is a leading cause of preventable blindness in working-age adults in the UK, arising from diabetes-related damage to retinal blood vessels. Ozempic (semaglutide), a once-weekly GLP-1 receptor agonist, effectively lowers blood glucose and reduces cardiovascular risk in type 2 diabetes. However, clinical trials have identified a potential link between rapid glycaemic improvement with semaglutide and temporary worsening of pre-existing diabetic retinopathy. Understanding this relationship, alongside appropriate monitoring and patient selection, enables healthcare professionals to maximise the benefits of Ozempic whilst safeguarding eye health. This article examines the evidence, UK guidance, and practical strategies for managing diabetic retinopathy risk in patients receiving semaglutide therapy.

What Is Diabetic Retinopathy and How Does It Develop?

Diabetic retinopathy is a microvascular complication of diabetes mellitus that affects the blood vessels of the retina—the light-sensitive tissue at the back of the eye. It represents one of the leading causes of preventable blindness in working-age adults in the UK. The condition develops when chronically elevated blood glucose levels damage the small blood vessels supplying the retina, leading to vessel leakage, blockage, and abnormal new vessel formation.

The pathophysiology involves several key mechanisms. Prolonged hyperglycaemia causes biochemical changes in retinal blood vessels, including increased vascular permeability, basement membrane thickening, and pericyte loss. These changes result in microaneurysms, haemorrhages, and exudates—the hallmarks of non-proliferative diabetic retinopathy. As the disease progresses, retinal ischaemia triggers the release of vascular endothelial growth factor (VEGF), stimulating the growth of fragile new blood vessels (neovascularisation) characteristic of proliferative diabetic retinopathy.

Risk factors for developing diabetic retinopathy include:

• Duration of diabetes (risk increases significantly after 10–15 years)

• Poor glycaemic control (elevated HbA1c)

• Hypertension

• Hyperlipidaemia

• Pregnancy

• Rapid improvement in blood glucose control

Diabetic retinopathy often progresses silently without symptoms in its early stages. Vision loss typically occurs when macular oedema develops (fluid accumulation in the central retina) or when proliferative changes lead to vitreous haemorrhage or retinal detachment. The NHS Diabetic Eye Screening Programme invites everyone aged 12 and over with diabetes; recall is typically annual, but may be every 2 years for low-risk groups according to programme policy. This enables early detection and timely intervention before irreversible vision loss occurs. Pregnant women with diabetes require more frequent retinal assessment during pregnancy and postpartum.

Ozempic (Semaglutide): Uses and Mechanism of Action

Ozempic is the brand name for semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) licensed in the UK for the treatment of type 2 diabetes mellitus. Administered as a once-weekly subcutaneous injection, semaglutide is indicated for adults with inadequately controlled type 2 diabetes as an adjunct to diet and exercise, either as monotherapy when metformin is inappropriate or in combination with other glucose-lowering medications. It is not indicated for type 1 diabetes or for the treatment of diabetic ketoacidosis.

The mechanism of action centres on mimicking the effects of endogenous GLP-1, an incretin hormone released from intestinal cells in response to food intake. Semaglutide works through several complementary pathways:

• Glucose-dependent insulin secretion: Stimulates pancreatic beta cells to release insulin only when blood glucose is elevated, reducing hypoglycaemia risk

• Glucagon suppression: Inhibits inappropriate glucagon secretion from pancreatic alpha cells, decreasing hepatic glucose output

• Gastric emptying delay: Slows the rate at which food leaves the stomach, moderating postprandial glucose excursions

• Appetite reduction: Acts on hypothalamic centres to promote satiety and reduce caloric intake

Clinical trials have demonstrated that semaglutide produces substantial reductions in HbA1c (typically 1.0–1.5% from baseline) and significant weight loss (averaging 4–6 kg). The SUSTAIN clinical trial programme also showed cardiovascular benefits, with reduced rates of major adverse cardiovascular events in high-risk patients.

The MHRA approved semaglutide for type 2 diabetes in 2018, and NICE recommends it as a treatment option within specific clinical and economic criteria, particularly for patients requiring intensification of glucose-lowering therapy or those with established cardiovascular disease. The starting dose is 0.25 mg once weekly for 4 weeks, then 0.5 mg weekly; this may be increased to 1 mg weekly and up to 2 mg weekly if needed for glycaemic control, according to tolerability.

The Link Between Ozempic and Diabetic Retinopathy Risk

The relationship between Ozempic (semaglutide) and diabetic retinopathy has generated considerable clinical interest following observations from the SUSTAIN-6 cardiovascular outcomes trial. This study identified an unexpected increase in diabetic retinopathy complications among participants receiving semaglutide compared with placebo, particularly in those with pre-existing retinopathy at baseline. The findings prompted regulatory authorities to include diabetic retinopathy as a warning and precaution in the product information, with advice to monitor patients with existing retinopathy.

It is important to understand that there is no convincing evidence suggesting semaglutide has a direct toxic effect on the retina. Rather, the proposed mechanism relates to the rapidity of glycaemic improvement. When blood glucose levels fall quickly after years of poor control, a phenomenon known as "early worsening" of diabetic retinopathy can occur. This paradoxical deterioration has been documented with various diabetes treatments, including intensive insulin therapy, and appears related to sudden changes in retinal blood flow, altered VEGF expression, and metabolic stress on already compromised retinal vessels.

In the SUSTAIN-6 trial, the increased retinopathy risk was most pronounced in participants with:

• Longer diabetes duration

• Pre-existing diabetic retinopathy

• Baseline HbA1c above 9%

• Rapid HbA1c reduction (observations suggest approximately 2% within 3–6 months, though this threshold is based on post-hoc analysis)

Subsequent analyses and real-world data have provided reassurance that the absolute risk remains relatively low, and the overall benefits of improved glycaemic control generally outweigh this potential complication. The phenomenon appears time-limited, with most cases occurring within the first year of treatment. Importantly, longer-term glycaemic control achieved with semaglutide should ultimately reduce diabetic retinopathy progression, as sustained hyperglycaemia remains the primary driver of microvascular complications.

Clinical Evidence and UK Guidance on Ozempic Use

The evidence base for semaglutide's efficacy and safety profile derives primarily from the SUSTAIN clinical trial programme, which enrolled over 8,000 participants across multiple international studies. SUSTAIN-6, the dedicated cardiovascular outcomes trial, followed 3,297 patients with type 2 diabetes at high cardiovascular risk for approximately two years. Whilst demonstrating significant cardiovascular benefits and glycaemic improvements, the trial revealed diabetic retinopathy complications in 3.0% of semaglutide-treated patients versus 1.8% receiving placebo (hazard ratio 1.76).

Further investigation revealed this risk was not evenly distributed. Post-hoc analyses showed that patients without baseline retinopathy had minimal increased risk, whilst those with pre-existing retinopathy—particularly proliferative disease or maculopathy—accounted for most cases. The European Medicines Agency (EMA) and MHRA reviewed these findings and concluded that semaglutide's benefits justify its continued use, provided appropriate patient selection and monitoring occur.

NICE guidance (NG28) on type 2 diabetes management recommends GLP-1 receptor agonists like semaglutide as treatment intensification options when specific criteria are met, including inadequate glycaemic control on dual therapy and BMI thresholds (typically ≥35 kg/m² or lower in certain ethnic groups, or if weight loss would benefit obesity-related comorbidities). Following the SUSTAIN-6 findings, the Ozempic Summary of Product Characteristics (SmPC) and specialist ophthalmology guidance emphasise the importance of:

• Assessing retinopathy status before initiating semaglutide

• Ensuring patients are up-to-date with diabetic eye screening

• Considering the rate of anticipated glycaemic improvement

• More frequent monitoring in high-risk individuals

The consensus among UK diabetes specialists is that semaglutide remains an important therapeutic option, but prescribers should exercise particular caution in patients with established retinopathy and poor baseline glycaemic control. Gradual dose titration and coordination with ophthalmology services may help mitigate risks whilst preserving the substantial metabolic and cardiovascular benefits this medication offers.

Monitoring and Managing Eye Health While Taking Ozempic

Proactive monitoring and management of eye health represents an essential component of safe semaglutide therapy, particularly for patients at elevated risk of diabetic retinopathy progression. The approach should be individualised based on baseline retinopathy status, diabetes duration, and glycaemic control.

Before starting Ozempic, healthcare professionals should:

• Review the patient's most recent diabetic eye screening results

• Ensure screening is up to date and arrange if overdue

• Refer patients with sight-threatening or referable retinopathy (e.g., pre-proliferative/proliferative retinopathy or maculopathy) for ophthalmology assessment if not already under specialist care

• Document baseline HbA1c and discuss realistic expectations for glucose reduction

• Initiate with caution and coordinate with ophthalmology if retinopathy is present, especially if severe or active

For patients without pre-existing retinopathy, participation in the NHS Diabetic Eye Screening Programme at their usual recall interval (annual or every 2 years) typically suffices. However, those with established retinopathy require enhanced surveillance. Recommended monitoring strategies include:

• Monitoring frequency individualised by severity and local protocols, with consideration of closer follow-up in the first year if pre-existing retinopathy

• Coordination between diabetes care teams and ophthalmology services

• Regular HbA1c monitoring to track the rate of glycaemic improvement

• Patient education about symptoms requiring urgent assessment

Dose titration strategy may influence retinopathy risk. Starting with the lower 0.25 mg weekly dose and gradually increasing to 0.5 mg and then 1.0 mg over several weeks allows more gradual glycaemic improvement. Some specialists suggest this might reduce the risk of early worsening, though this approach is based on expert opinion rather than definitive evidence. It requires balancing against the need for effective diabetes control.

Patients should be empowered as active participants in their eye health. This includes maintaining appointments with the diabetic eye screening service, reporting any vision changes promptly, and understanding that temporary worsening does not necessarily mean permanent damage. Optimising other cardiovascular risk factors—particularly blood pressure and lipid control—provides additional retinal protection and should form part of comprehensive diabetes management. Patients should not stop semaglutide without medical advice.

When to Seek Medical Advice About Vision Changes

Recognising and responding promptly to vision changes whilst taking Ozempic is crucial for preventing permanent visual impairment. Patients should receive clear guidance about symptoms warranting medical attention and appropriate pathways for accessing care.

Patients should contact their GP or diabetes team urgently (within 24 hours) if they experience:

• Sudden vision loss or significant vision deterioration in one or both eyes

• New floaters (dark spots or strings drifting through the visual field)

• Flashing lights or sparks in the peripheral vision

• A curtain or shadow obscuring part of the visual field

• Sudden onset of blurred vision that doesn't improve with blinking

• Distortion of straight lines or difficulty reading

These symptoms may indicate serious complications such as vitreous haemorrhage, retinal detachment, or severe macular oedema requiring immediate ophthalmological assessment. In such cases, same-day referral to an eye casualty department or emergency ophthalmology service is appropriate. If same-day assessment cannot be arranged, patients should call NHS 111 or attend A&E/eye casualty for urgent ophthalmology review. Patients should not drive if experiencing sudden visual loss or significant new visual disturbance.

Less urgent but still important symptoms include:

• Gradual blurring of vision over days to weeks

• Difficulty with colour perception

• Increased difficulty with night vision

• Problems with contrast sensitivity

These changes warrant discussion with the diabetes care team and may indicate progression of diabetic retinopathy or macular oedema requiring non-urgent ophthalmology review. Patients should not wait for their next scheduled screening appointment if experiencing these symptoms.

It is important to note that not all vision changes indicate diabetic retinopathy. Fluctuating blood glucose levels can temporarily affect the lens of the eye, causing transient blurring that resolves as glucose control stabilises. However, patients should not assume vision changes are benign—professional assessment remains essential.

Healthcare professionals should provide written information about warning symptoms and clear contact details for advice. Documentation in the patient's care plan should include their retinopathy status, monitoring schedule, and agreed action plan for vision concerns. Patients should also be advised to report any suspected side effects via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk or the Yellow Card app). This collaborative approach ensures early detection and intervention, optimising visual outcomes whilst maintaining the metabolic benefits of semaglutide therapy.

Frequently Asked Questions