"Blindness linked to weight loss/diabetes drugs..."

(Joey) #1

More news about the miracle drug, semaglutide, from the folks at CNN…

“Still, doctors say it shouldn’t deter patients from using the medicines to treat diabetes or obesity.”

Can’t think of any reason, can you? :thinking:

(You've tried everything else; why not try bacon?) #2

It’s like the risk of cancer from low cholesterol levels. Much more important not to die of a heart attack; dying of cancer is okay.

EDIT: Alas, my hopes for shoddy data were not borne out. From the study, in JAMA Ophthalmology:

16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023.

Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non–GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non–GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non–GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001).

So the study is decently powered, the effect size is worth paying attention to, and the statistical significance suggests that this is a real effect. Ouch! This is still an epidemiological study, but the data have to be taken seriously. We shall have to see whether further research supports these observations.

(Joey) #3

@PaulL Thank you for the careful review.

Frankly, I didn’t bother doing a deep dive since I (reflexively) assume that any study touted on CNN suggesting dangers to a pharmaceutical product is likely based on some reasonably valid approach given: (a) unless you’re preparing a class action lawsuit, there’s little money in reaching conclusions of harm, and (b) CNN makes lots of money via drug marketing.

So I refrained from tossing this one in the Show Me The Garbage category.

Of course, that’s not really how science works. So, folks should just take drugs and carry on. :test_tube:

(Bob M) #4

A hazard ratio of 7.64 is pretty high, as are the percentage differences. Definitely something to address.

(Joey) #5

No argument here.

(Bob M) #6

I know, I can’t believe I actually thought that an epidemiological study is … (potentially) useful. Gasp! What am I doing? :wink:

(Joey) #7

Experts agree … they’ve worn you down. :face_with_monocle:

#8

My first reason would be a network that’s only trick in life is fear mongering, combined with GLP-1 being something our body makes anyway makes it pretty unlikely.

Second reason would be this

The study, published Wednesday in the medical journal JAMA Ophthalmology, cannot prove that semaglutide medications cause NAION. And the small number of patients — an average of about 100 cases were identified each year — from one specialized medical center may not apply to a broader population.

3rd reason would be it came out of Mass Eye and Ear, which has been screwing me up and being wrong about things since I’ve been a kid.

(Joey) #9

@lfod14 All fair points to give one pause. Sorry to hear that Mass Eye & Ear has missed the mark in your own life’s experience … I’ve heard of disappointments with similarly hailed institutions from both family and friends over the years.

Having said that, my going-in bias re: drug manufacturers’ products is always a baseline of skepticism.

Their mission is supposed to be coming up with good health solutions that balance risk and reward toward the health benefits side of the scale. Sometimes they even manage to do so …but quite often they don’t.

So my radar for bad pharma is always on alert.

Generally, when an “associative” study makes a pronouncement, I tend to put little stock in it. But when the association in question concerns really bad side effects - like those horrible adverse outcomes you hear rushed through at the tail of a 2-minute drug ad on TV - I am inclined to suspect there’s probably a there there.

(Bob M) #10

While GLP-1 is something the body makes, the drug is not. Every drug has many effects, and we often don’t know what those are.

#11

Fair enough, but they’re also forced to list every single thing that’s ever happened, and from what I know, they even kick that up a notch just for CYA reasons. When it comes to Semaglutide, most of us that were on the wagon before they all hit fad status basically agreed as a community that the diabetic dose progression is way too fast, the dosages ramp up almost right from the begging, and for fat loss it’s simply not needed. Run the minimal effective dose until it doesn’t work…then up it to the next one and ride that out.

That one is just my conspiracy theory, but it (could) be, because the A1C was their main goal when coming up with that… OR (my idea) because it keeps you running out of it faster! Given the majority of people are paying way too much for them, that’s just good for business. If I was paying what half the people are, I’d just be using something else.

(Joey) #12

As long as we all have our conspiracy theories to cling to, everything will be all right in the end.
Happy 4th :fireworks:

(Bob M) #13

While I’m not a fan of any epidemiological study, drugs (and a lot more) are weird. There are so many people and you don’t find out what is really happening until you get a lot of people taking a drug.

Case in point: I took berberine, which has a really good safety record. But it was by far the worst supplement I’ve ever taken. All of my energy went away. I was tired, angry, felt bad. Even yelled at my wife, which is unheard of. Yet I know people who don’t have those effect.

Another case in point is PANDAS: “pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections”. We think my daughter has this, as she has all the initial symptoms (sudden OCD, tics, depression, anxiety). It’s often caused by strep (in the title), but many kids get strep yet very few get PANDAS. I listened to one podcast where the guy thought that it was a lock and key. If you had the “right” (or the “bad”) genetics and the strep was the “right” (or the “bad”) shape, the key of strep fit into the lock of brain cells, and you got brain inflammation, which causes the OCD, tics, etc. It doesn’t happen with everyone, only certain folks.

Covid is similar. My brother (2 years younger than I am) got (the original flavor of) covid and said it was like a cold. A gentleman in our town got covid around the same time, about the same age, and spent 12 days on a ventilator and over 40 days in the hospital.

You don’t find these things until you treat thousands of people. Then, there is some group out there – whether it’s genetics, diabetes, nascent eye issues, who knows yet? – that has an issue. And this issue is particularly interesting because it’s at a very low level in the general population, but a higher level in people taking the drug.

It’s akin to statins and diabetes: only through epidemiological data with thousands of people did they ascertain there’s a link between statins and increased diabetes.

For me, I’d like to see some indication as to how the drug is causing this. For instance, I see all the time that saturated fat raises LDL, but I’ve never once seen a plausible mechanism for that. Same with red meat being associated with developing diabetes; how is that possible? Under what mechanism?

It’ll be interesting to see if they uncover anything along these lines. It’ll take a while, though, because they’d have to look at the people who get this blindness, figure out what is the same between them, then determine possible elements of causation.