What specific risk factors do you discuss with patients who are prescribed GLP-1 agonists?
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Recent research has suggested that GLP-1 agonists used to treat obesity might be associated with a stroke in the optic nerve, but association is not the same as causation.
We call a “stroke in the optic nerve” nonarteritic anterior ischemic optic neuropathy (NAION). This is a fancy way of saying lack of blood flow (ie, ischemia) of the front part (ie, anterior) of the optic nerve. The association with GLP-1 agonists could be causal or coincidental because diabetes and obesity, with associated conditions such as hypertension and high cholesterol, are risk factors for NAION. Any candidate for one of these drugs already is harboring those risk factors. Specificity of effect is one of the Bradford Hill criteria to determine if causation can be deduced, and it means that exposure should be specifically linked to the outcome and cannot be attributed to chance alone or better attributed to another cause. For this, among other reasons, the Harvard study is hypothesis generating and not hypothesis testing: While an association exists, more research is needed to establish causation.
My conversation with patients is structured around the concept that all medications have risks, benefits and side effects. Ultimately, it is up to them to make a risk-benefit and quality of life decision on whether they want to take the medicine. In my opinion, the most important lesson to learn from a study like this is that informed consent is paramount. We are used to doing informed consent for surgery and procedures but not equally good at doing informed consent before prescribing medications. An informed consent decision should be made and documented before starting any medications that could potentially blind the patient, and with GLP-1 agonists, I see different scenarios for informed consent.
Patients with preexisting ischemic optic neuropathy should be advised that there is a small but unproven risk of this agent causing NAION.
For patients without vision loss, the conversation is a little different. I tell them that there is a small risk, but the risk factors for ischemic optic neuropathy overlap with the risk factors for being obese and especially for having diabetes. Therefore, either way, whether they take or do not take the medication, there is a small risk for NAION. It is not framed as no risk vs. high risk but low risk vs. low risk.
Part of the decision-making is the risk tolerance of the individual. For monocular patients, the risk is higher, and the risk-benefit analysis is different because even though the odds ratio is probably the same, the risk for harm and the severity of that harm has to be individualized.
Andrew G. Lee, MD, Healio | OSN Neurosciences Section Editor and chairman of the department of ophthalmology at Blanton Eye Institute, Houston Methodist, can be reached at aglee@houstonmethodist.org.
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