New study links GLP-1 drugs like Ozempic to lower AMD risk

GLP-1 medicines such as Ozempic have reshaped modern healthcare in recent years, changing the way clinicians approach conditions including type 2 diabetes and obesity.

Although these treatments are mainly prescribed to lower blood sugar and curb appetite, researchers continue to uncover wider-reaching GLP-1 effects that seem to influence health in unexpected ways.

A new study now points to another possible knock-on effect, suggesting we still have plenty to learn about how GLP-1 receptor agonists act across the body.

GLP-1 drugs and AMD risk

Writing in Diabetes, Obesity and Metabolism, scientists report an association between GLP-1 drugs and a reduced risk of age-related macular degeneration (AMD) - a common eye condition and the leading cause of irreversible sight loss in older adults.

The research team, led by clinical pharmacology researcher Cheng-Hsien Hung at Chung Shan Medical University in Taiwan, examined patient records from more than 157,000 matched patients.

All participants were aged 60 or older, all had obesity, and none had diabetes. The dataset was divided into two groups of nearly 79,000 people each.

One group comprised patients who began GLP-1 medicines for weight management (liraglutide, semaglutide, or tirzepatide). The comparison group included those using other, non-GLP-1 medicines for weight-loss treatment.

Across several years of follow-up, AMD occurred less often among people taking GLP-1 drugs than among those using other weight-loss medicines.

In total, GLP-1 use was linked to an estimated 18 percent reduction in the risk of developing AMD during the follow-up period. That estimated reduction rose to 30 percent in cases where the AMD subtype was not specified in the records.

No link was seen for the ‘wet’ (exudative) form of AMD. For ‘dry’ AMD (also known as nonexudative AMD, and the most common form of the disease), GLP-1 use showed a trend towards lower risk, but it did not reach statistical significance.

Why GLP-1 drugs might affect the retina

Earlier studies have also suggested a protective association between GLP-1 drugs and AMD, though many of those investigations focused on people with type 2 diabetes - the condition GLP-1 medicines were originally used to treat.

In this analysis, the researchers deliberately centred on patients without type 2 diabetes, aiming to remove glycaemic and diabetic factors that could otherwise influence the results.

The reason GLP-1 drugs might help protect older adults from vision loss remains uncertain.

One proposed explanation is that GLP-1s may be neuroprotective by dampening inflammation in the retina, including suppression of an inflammasome known as NLRP3.

However, another possibility is that people with obesity who use GLP-1 treatments may lose more weight than those taking other weight-loss medicines - and that the weight reduction itself could help explain the lower risks observed.

"Weight loss per se reduces systemic inflammation and oxidative stress, which may independently reduce AMD risk," the researchers explain in their study.

"If the effect is primarily weight‐loss mediated, the therapeutic implication shifts from 'GLP‐1RAs are retinally neuroprotective' to 'greater weight loss by any means may protect against AMD', an important distinction requiring prospective mechanistic studies."

If that interpretation is correct, it aligns with research from a decade ago - before semaglutide reached the market - reporting that AMD risk rose by 2 percent for every 1 kg/m^2 increase in body mass index (BMI) among people who were overweight or living with obesity.

Study limitations and what researchers want to see next

Either way, the team emphasise that further work is needed to pin down what is actually driving the association.

The median follow-up time was just 1 year for GLP-1 users, compared with 2.5 years in the comparison group.

Put simply, these were people newly starting treatment who were observed over a relatively short period, so the apparent benefits may not necessarily last.

"Whether the observed benefit reflects direct GLP‐1RA retinal neuroprotection, greater weight‐loss magnitude or both cannot be determined from the current observational data," the study authors conclude.

"Further mechanistic research, prospective studies with longitudinal weight and ophthalmologic outcome data, individual‐level analyses accounting for unmeasured confounding and investigation of younger cohorts (e.g., ≥ 50 years) are needed to validate and characterize the clinical implications of these findings."

The findings are reported in Diabetes, Obesity and Metabolism.

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