Risk of NAION and Semaglutide

Pubblicato il

Monday, 8 July 2024

Argomento

Retina

Semaglutideapproved by the FDA in 2017 for the treatment of type 2 diabetes and in 2022 for the treatment of obesity, has been in the limelight on social media for some time now and - unfortunately - not only as a 'miracle' drug for losing extra kilos!

Attention for this drug has increased recently because it is taken not only by obese individuals, i.e. people with a body mass index of over 30.0 kg/m²but also a lot of overweight people, eager to lose weight and disappointed by the unsatisfactory results of both sports and various diets.

Semaglutide is a member of the GLP-1 agonistsdrugs that mimic the action of a natural hormone, the 'glucagon-like peptide-1"(referred to as GLP-1). These drugs were authorised, therefore, with a specific indication: the treatment of diabetestype 2. Their mechanism of action induces, in fact, an increase in the production of insulin, the hormone that lowers blood sugar levels. In addition, these drugs reduce the secretion of glucagon, the hormone that increases glycogenolysis, i.e. the release of carbohydrates that are stored in the liver. They thus enable blood glucose to be kept under control.

The use of these anti-diabetes drugs also for weight loss stems from the fact that, by mimicking the behaviour of the GLP-1 hormone, they have the ability to slow down gastric emptying as a result of food intake and reduce appetite by sending satiety signals to the brain. Once taken by patients, they uptake GLP-1 receptors in certain areas of the brain that regulate eating behaviour, causing the person who took them to stop eating. Thanks to their ability to stimulate insulin secretionGLP-1R agonists have been used successfully in the early stages of type 1 diabetesbut with an effect on blood glucose control that fades after several months of treatment. They are also recommended for blood glucose control in patients with type 2 diabeteseven before starting insulin therapy, because the risk of hypoglycaemic episodes is very limited, as well as the body weight reduction effect, which is often high in these patients. Since 2016, many clinical studies have shown that GLP-1R agonists can be useful in preventing major cardiovascular events, such as acute myocardial infarction or stroke, and associated mortality.

A recent cohort study of 16,827 patients revealed a potential risk of Non-Arteritic Anterior Ischaemic Optic Neuropathy (NAION) in patients who were prescribed semaglutide for diabetes or obesity compared to those who were prescribed non-glucagon-like peptide receptor agonists.

Non-arteritic anterior ischaemic optic neuropathy (NAION) is the second most frequent form of optic neuropathy and is an important cause of blindness in adulthood.

In the study cited 710 patients had a diagnosis of type 2 diabetes (median age 59 years and 52% women) and 979 (median age 47 years and 72% women) were overweight or obese. In the population with type 2 diabetes who had taken semaglutide, there were 17 cases of NAION, compared to 6 patients on non-GLP-1 RA antidiabetics. In overweight or obese patients treated with semaglutide, 20 cases of NAION occurred, compared to 3 reported in the group treated with non-GLP-1 RA. The diagnoses of NAION were made by experienced neuro-ophthalmologists.
The pathogenesis of NAION remains unclear and the incidence is reported to be 2-10 cases per 100,000 people.

It can, therefore, be concluded that there is an increased risk of NAION among individuals taking semaglutide compared to patients on other drugs for the treatment of type 2 diabetes and obesity or overweight.

As with any drug, clearly, therapeutic benefits are inseparable from adverse effects.

As for the viewpatients with diabetic retinopathy who received semaglutide had a higher risk of exacerbation of retinopathy, reported a higher rate of proliferative retinopathy progression and risk of new-onset macular oedema. There was no previous evidence from the scientific community of an increased risk of NAION in association with semaglutide, and the study does not inform on a mechanism to link semaglutide to NAION. However, despite evidence of neuroprotective properties, GLP-1 receptor expression in the human optic nerve and GLP-1 RA-induced enhancement of sympathetic nervous system activity could influence optic nerve head perfusion and potentially increase the risk of NAION.

Some limitations of the clinical study should be noted, with regard to geographical, organisational and care aspects and the uncertainty of therapeutic adherence of patients treated with semaglutide. It will therefore be necessary to conduct a larger, retrospective, multicentre study, with the analysis of all GLP-1RA drugs. It will also be necessary to overcome the limitation caused by the non-existence of an ICD-10 code for NAION and perhaps test the use of innovative AI algorithms.