It's difficult not to get irritated. Take a look at this: https://youtu.be/hxid7FofhMw?si=AVotindUtCUXu7FE&t=3285
That's David Sinclair. He's a Professor of Genetics at Harvard Medical School, and he's telling millions of people on the Joe Rogan podcast that GLP-1 drugs have doubled sudden blindness [1].
Now of course this sounds scary, and it makes you wonder if you need to stop your GLP-1, or warn your friends and family members to stop.
Table of Contents
- A Stroke In The Eye, And How Often It Happens
- Thirty-Seven Patients In One Boston Eye Clinic
- The Exchange On X
- Why This Irritates Me
- What The Clinical Guidelines Actually Say
- What I Actually Warn My Patients About
- References
A Stroke In The Eye, And How Often It Happens
NAION stands for non-arteritic anterior ischaemic optic neuropathy, and it happens when blood flow to the optic nerve drops.
People often call it an optic nerve stroke. It causes sudden, painless vision loss in one eye, and it's usually noticed upon waking up.
Now, if you're above 50 years of age, NAION happens in roughly 1 in 10,000 people every year [2]. So, 1 in 10,000. Remember that number.
Despite its frequency, we don't exactly know what causes it. But we do know that things like diabetes, smoking, high blood pressure and high cholesterol all increase your risk.
So in other words, these are the exact types of people who are prescribed a GLP-1 medication.
So where did the alarm start that GLP-1 medications themselves might also increase the risk of NAION?
Thirty-Seven Patients In One Boston Eye Clinic
Enter Joseph Rizzo, who like Sinclair is also at Harvard. Rizzo is a Professor of Ophthalmology, and he noticed that his NAION patients seemed to be on semaglutide — that's a GLP-1 medication — more often than what he'd expect. So his team went back through the records and they counted [3].
Among their patients with type 2 diabetes, 17 on semaglutide developed NAION, against six in the comparison group.
Among those who were overweight or obese, 20 were on semaglutide against three. So a total of just 37 NAION cases were taking semaglutide. Now bear in mind that this was out of 16,827 high-risk patients, at one ophthalmology clinic.
So the actual risk of NAION is tiny, and given the small amount of cases, we don't know from this one study whether GLP-1 medications do truly increase the risk or not.
And the authors of this paper, they point out these issues. It's a retrospective paper, and again, tiny numbers. And they finish by concluding that the design of their study did not enable query into the causal relationship between the two.
And get this — their manual review of the records for the study revealed that 40% of cases coded as ischaemic optic neuropathy were not actually NAION, but rather arteritic ischaemic optic neuropathy from giant cell arteritis, or other forms of ischaemic or non-ischaemic optic neuropathies [3].
So far then, we know that diabetes and metabolic syndrome increase the 1 in 10,000 risk of NAION — the exact patients whom GLP-1 medications are prescribed to — and we've got a very controversial paper that tentatively suggests a possible link with GLP-1s. But that's not at all what Sinclair makes it out to be.
Nothing here is a criticism of Rizzo or his work. He's done great work. It's how people like Sinclair have actually covered this paper.
The Exchange On X
Given the amount of people who use GLP-1 medications by now, if there was a huge risk of increased blindness, we would know many people who are blind. But you do not, because these studies don't apply to the general population.
This is how a data scientist on X called Crémieux was responding to David Sinclair [4]:
"I pointed this out before in a post linked in the thread that David is replying to, meaning that in addition to being daft, a liar, or both, he's also not circumspect, because his specific links were already shown to lead to absurd conclusions. David's only holds up in weak studies with small samples, poor controls, and results that imply HUGE portions of the population should've already gone blind — and they have not, so they are obviously wrong."
Sinclair then responded to that post by saying, "Are you paid to post this? Read the scientific literature" [5].
For which David Sinclair was community noted, saying: "The linked studies examine patients at one specialist clinic and do not show sudden blindness has doubled in the general population; NAION remains very rare (up to 1 in 10,000) with GLP-1 drugs."
Why This Irritates Me
Like I said at the start, I struggle not to get irritated here, because poor scientific communication like what Sinclair constantly does makes my patients' health worse at the clinic.
It creates more work for primary care physicians like me to correct these errors, and it uses up my patients' valuable time to explain to them why a Harvard professor is wrong.
Especially because Sinclair's got financial interests in spreading this garbage. He is developing a therapy that he believes will help with this issue that isn't actually an issue. So he's financially incentivised to play it up [4].
What The Clinical Guidelines Actually Say
Here's what the clinical guidelines actually say about NAION. Subsequent studies have yielded mixed results, with some suggesting an association and others finding no increased risk. Additionally, the biologic plausibility of a mechanistic link between GLP-1s and optic nerve ischaemia remains unproven, and GLP-1s appear to be neuroprotective in other settings [6].
What I Actually Warn My Patients About
So here is what I do warn my patients about regarding GLP-1 medications. I do warn them about muscle loss.
Any weight loss strategy will result in some muscle mass loss. It's not specific to GLP-1s — any type of weight loss seems to be associated with this. And there are specific things that a patient can do to minimise that muscle mass loss: things like resistance exercise, and making sure they're getting enough protein in their diet.
There was a concern about pancreatitis and thyroid cancer, but the real-world data on both of those issues have been reassuring.
And while I personally take low-dose tirzepatide, I've got no financial interest in GLP-1 medications.
References
1. https://www.youtube.com/watch?v=hxid7FofhMw
3. https://doi.org/10.1001/jamaophthalmol.2024.2296
4. https://x.com/cremieuxrecueil/status/2086197651574304954
