GLP-1 drugs found to protect against diabetic retinopathy

GLP-1 receptor agonist drugs protect against diabetic retinopathy, a common complication of diabetes that can lead to sight loss, suggests new research being presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Vienna, Austria (15-19 September) and published in the journal Pharmaceutics.

GLP-1 drugs such as semaglutide are widely used to treat type 2 diabetes and obesity. They do this by mimicking the action of GLP-1, a hormone that helps the body make more insulin when needed, slows down digestion, curbs appetite, and increases feelings of fullness.

Many tissues around the body have GLP-1 receptors (proteins that respond to the hormone) and recent research has suggested the drugs also have anti-inflammatory and antioxidant effects.

For example, some studies have indicated they reduce the risk of diabetic retinopathy, the leading cause of blindness among working-age adults. More than 90% of people with type 1 diabetes and 50-60% of those with type 2 diabetes develop this condition, in which high blood sugar levels damage blood vessels in the light-sensitive tissue at the back of the eye.

Diabetic retinopathy represents a major public health challenge. Globally, it is projected that over 191 million people will be affected by it by 2030, with around 56 million experiencing vision-threatening stages of the disease. These statistics underscore the critical need for effective screening, early detection, and, crucially, more effective treatments."

Ioanna Anastasiou, Study Lead, National and Kapodistrian University of Athens

It is thought that much of the damage to the retina is done by free radicals, molecules that can damage cells and are produced in higher numbers when blood sugar is high. The theory is that GLP-1 drugs protect the retina by increasing levels of antioxidants, compounds that neutralise free radicals.

However, other studies have suggested that GLP-1 drugs increase the risk of diabetic retinopathy or exacerbate it in those who already have it. 

To provide some clarity, Dr Anastasiou and colleagues carried out a detailed study of the effect of GLP-1 drugs on retinal cells in diabetes-like conditions. 

For the lab-based study, human retinal endothelial cells were treated with a range of different concentrations of semaglutide. The cells were kept in media with high glucose levels and oxidative stress (in which there are more free radicals than antioxidants) for 24 hours.

They were then put through a series of tests. The results showed that the cells that were treated with semaglutide were up to twice as likely to still be alive than cells that were untreated. They also had larger stores of energy.

Three markers of oxidative stress in diabetic retinopathy were markedly lower in the treated cells: levels of apoptosis (a form of cell death) decreased from approximately 50% in untreated cells to about 10% in semaglutide-treated cells; the production of mitochondrial superoxide (a free radical) decreased from about 90% to about 10%; and the accumulation of harmful compounds called advanced glycation end-products also fell substantially.

Further analysis showed that genes involved in the production of antioxidants were upregulated, or more active, in the treated cells, compared with the untreated cells. This result – and the enhanced survival – indicate that semaglutide was repairing damage to the cells, says Dr Anastasiou.

Looked at as a whole, the results indicate that GLP-1 receptor agonists enhance retinal cells' defences against damage in diabetes-like conditions.

Dr Anastasiou explains: "In experiments in the lab, GLP-1-receptor agonists exerted powerful antioxidant effects which protected retinal cells against the type of damage that can occur in diabetes.

"Our study did not find that these drugs harmed the retinal cells in any way – instead, it suggests that GLP1-receptor agonists protect against diabetic retinopathy, particularly in the early stages.

"Excitingly, these drugs may be able to repair damage that has already been done and so improve sight.

"Clinical trials are now needed to confirm these protective effects in patients and explore whether GLP-1 receptor agonists can slow, or even halt, the progression of this vision-robbing condition."