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Ozempic increases risk of debilitating eye condition: studies (sdu.dk)
79 points by Erikun 11 months ago | hide | past | favorite | 101 comments


Interesting synchronicity of seeing this article. I just had an optometrist appointment this morning and my glasses prescription updated/renewed. The only medication I am on is Ozempic for weight management, ~8 months, lost ~40 lbs so far. My old prescription was -1.75 / -1.0 (about 5 years ago), and my new one is -0.5, -0.5. My optometrist said it was unusual but likely due to having blood glucose under control as it changes the blood pressure and shape of your eyes slightly.


How old are you? I'm almost 50 and in the last year my long distance vision has improved however I need stronger reading glasses and find it tricky to do closeup work. I was on mounjaro between Feb and Sep this year.


Isn't that an improvement, in your case?


Sounds like three or four to me.


It drives me nuts when these things say stuff like "doubles your risk" w/o giving the original risk. Risk doubling from 5% to 10% is not in the same universe as risk doubling from .02% to .04%, which I believe is the actual risk in this case.


It's really frustrating because both papers clearly lays out the numbers in natural frequencies:

> During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide 51 exposure associated with a higher incidence rate (0·228 vs 0·093 per 1000 person-years, p<0·001) 52 and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 53 1·54-3·12), even when multiple other factors were taken into account.

> In this cohort study conducted in Denmark and Norway, use of semaglutide was associated with an increased risk of NAION; the pooled hazard ratio was 2.81 (95% confidence interval (CI) 1.67 to 4.75) and the incidence rate difference (absolute risk increase) was +1.41 (95% CI +0.53 to +2.29) NAION events per 10,000 person-years. The finding was consistent across sensitivity and supplementary analysis.


Ah, hidden right at the end inside the "about the studies":

> Both Danish studies show that the risk of developing NAION for the individual patient receiving treatment with Ozempic is only 0.2 per thousand per year, which is fortunately significantly lower than in the American study. NAION is a relatively rare condition, and the extra risk is therefore low. The researchers estimate that for every 10,000 people treated in a year, between 1.5 and 2.5 extra cases will be seen.

Sadly it's still relative, and they still leave you the mental maths to work out the natural frequencies.


In terms of outcome, it maybe a tolerable risk, but anything that flat out doubles the risk ratio is fairly concerning; in particular, where the mechanisms are not well understood.


When the numbers were small to begin with, a doubled risk ratio could just be the result of statistical noise.

You are right in that the mechanisms may not be well-understood. This does warrant further study, as the paper concludes.


the studies obviously adjusted for variance when considering if their conclusions are significant, you're beating up a strawman


I'd happily double my risk of being hit by a meteorite for $10000.


0.02% relative risk increase implies 2 in 10,000 will end up with the condition where they would not otherwise.

Your chances of being hit by a meteorite are _at most_ 1 in 1,000,000.

My happiness would not extend across several orders of magnitude like that, but perhaps, some people just need the $10k more than I would.


All medications increases the risks of side effects, but they are prescribed because the benifits outweigh the downsides - even if little is known about their mechanism.


> but they are prescribed because the benifits outweigh the downsides

Some are. Some are simply prescribed because the patient asks for them.

> even if little is known about their mechanism.

I wouldn't take it unless my condition was immediately life threatening and there were no other medications available. There are very few classes of treatment that fall within these parameters.


> Two independent studies from the University of Southern Denmark (SDU) show that patients with type 2 diabetes who are treated with the drug Ozempic have an increased risk of developing damage to the optic nerve of the eye [NAION], which can lead to severe and permanent loss of vision.

> The condition [NAION] is often developed by patients who are at particular risk of cardiovascular disease. The risk factors are diabetes, high blood pressure and high cholesterol. Patients affected by the condition also tend to have some physical conditions in the eye, which can be the triggering factor.


Appears to be two science research papers:

Paper: https://www.sdu.dk/-/media/files/om_sdu/fakulteterne/sundhed... "Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic2 neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes."

Preprint : https://www.medrxiv.org/content/10.1101/2024.12.09.24318574v... "Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish–Norwegian cohort study"


Important to note that this side effect is still very rare and that we still use drugs with similarly serious and rare side effects.

The authors of the study do not recommend abandoning these drugs, rather we should understand and manage the risks.


Also important to note that these studies are observational and do not prove causation. While the authors attempted to correct for covariates, it is highly likely that the patients who received semaglutide were generally sicker than those who did not.

While further study is necessary and some degree of caution may be warranted, it is still entirely plausible that semaglutide has no causal influence on NAION.


The endlessly repeated truism that "these studies don't prove causation" isn't really saying anything, as the same could be said for every long term human drug study. This line of thinking was the reasoning behind ignoring the link between cancer and tobacco products for decades, because the studies establishing that link were and are observational studies, considering that a controlled experimental study on humans establishing the same would be completely unethical.


>This line of thinking was the reasoning behind ignoring the link between cancer and tobacco products for decades

I wish people would stop repeating this falsehood.

The mass consumption of tobacco only really started after 1910, with the mechanisation of cigarette manufacturing. There was a multi-decade time lag between this explosion in tobacco use and the long-term sequelae of lung cancer and cardiovascular disease. The causal link was established beyond any reasonable doubt in the late 1950s, which was really the earliest point at which we had clear data; it took only a few years for all major medical bodies to endorse this as the consensus position and start lobbying for legislative action.

"We didn't know" is a propaganda line rolled out by the tobacco industry, the asbestos industry, the fossil fuel industry and others. The lack of action wasn't due to any scientific uncertainty, but naked corruption at the highest level. There was an overwhelmingly clear scientific consensus which was privately accepted as true by these industries, but they paid off politicians to protect their profits.

We genuinely don't know if this is a real risk; NAION is a rare disease, which greatly increases the difficulty of making accurate inferences even from very large amounts of data. We can be extremely confident that the magnitude of risk is vastly smaller than the risks caused by Type 2 diabetes and obesity.


It wasn't a perfect example, which I borrowed from my recollection of The Book of Why (Pearl, 2018), but your response is besides the point that saying "these studies don't prove causation" is saying nothing. It is the most tiring over stated pointless truism, which is so often said as a response to long term observational drug studies, despite virtually none claim to be establishing causation. This phrase "correlation is not causation" is repeated ad nauseam in response to studies simply drawing correlations, mostly in order to write them off or ignore them. It has gotten to the point where I now expect at least one person to say it as a response to every single study I see posted on the internet where a comment section exists, as if there is some internet law that obligates people to state this truism if it hasn't been stated yet.


Threshold for semaglutide use seems pretty low. And the article mentioned that its 'usually' diabetes patients which I took to mean it even included users who were overweight but not diabetic.


Doesn't untreated diabetes also cause blindness in some people? definitely seems better to take it than not.


It does. High blood sugar levels are hard on every system in the body.

One thing about semaglutide is that it can lower blood sugar levels past normal, too. One of my diabetic friends had to lower her dose of Ozempic precisely for this reason. In general, it wouldn't surprise me if pathologies that involve ischemia could be exacerbated by a treatment that lowers energy supply as well.


Obesity goes hand in hand with hypertension, so this is a double-whammy for organs with particularly sensitive microstructures (like eyes but also kidneys).


Lowering blood sugar below normal levels is hardly unique to semaglutide or GLP1s in general. Most drugs targetting type 2 diabetes can do so and sometimes need to be adjusted to prevent hypoglycemic events. Insulin in particular poses a significant risk of hypoglycemic events which is why many insurances cover continuous glucose monitors for those taking insulin.


GLP1 agonists on its own, has a very low chance of cause significant hypoglycemia because it's action the blood glucose dependent. It almost exclusively happens when patient are taking another agent is taking a diabetic medication that has a proven track record of causing hypoglycemia on it's own


And obesity has passed smoking as the leading cause of preventable death in the US.


> seems better to take it than not.

If you have debilitating diabetes that has failed to respond to changes in exercise and diet. If your taking the drug as some type of "weight loss short cut" you should possibly reconsider that position.


Different damages, one is on blood vessels, the other on optic nerve. So you could even get both


This was addressed in the article:

"This is a serious but very rare side effect. Often, we only learn about this kind of thing after a new drug has been on the market for a few years, as is the case with Ozempic. It should be emphasised that it is neither more serious nor more common than the rare side effects of many other medicines that we continue to use. It is, so to speak, just a new piece of the puzzle of understanding how this drug works, explains Anton Pottegård."


The base rate is 1.5 to 2.5 cases per 10,000 people per year, according to the article.


To make that clear:

> The researchers estimate that for every 10,000 people treated in a year, between 1.5 and 2.5 _extra_ cases will be seen.

The existing rate is about 2 per 10,000 people per year:

> Both Danish studies show that the risk of developing NAION for the individual patient receiving treatment with Ozempic is only 0.2 per thousand per year, which is fortunately significantly lower than in the American study. NAION is a relatively rare condition, and the extra risk is therefore low.


Such a curiously-worded headline, to refer to Ozempic specifically – quite a recognizable & understood term at this point! – as just some "Danish diabetes medicine".

I almost expected the source to be some group with a resentment towards Denmark – maybe Greenland separatists? – but no, it's just a Danish university that doesn't want to say 'Ozempic' in the headline directly.


Maybe the university thinks that Ozempic is not a well known brand in Denmark so being vague will get more clicks. 0.4% of them get a Ozempic prescription per year vs 1.7% of Americans per year. Seems crazy when "Nearly 1 out of every 5 Danish jobs created last year was at Novo", but it's possible.

Another possibility is that they don't wanna tarnish a brand that saved the country from recession last year. No point picking fights with industry over some observational study that has no predictive power


The data seems a bit strange. The peaks better align with our good old COVID, than with the semaglutide prevalence.

So it might be reading complications from COVID, rather than semaglutide.


The medicine: semaglutide (Ozempic, Rybelsus, possibly Wegowy)


The eye condition: non-arteritic anterior ischemic optic neuropathy (NAION)


Non-arteritic → Not involving arteries [0]

Anterior → Front part

Ischemic → Low blood flow

Optic → Related to the eye

Neuropathy → Nerve damage [1]

"Non-arteritic anterior ischemic optic neuropathy (NAION) refers to loss of blood flow to the optic nerve (which is the cable that connects the eye to the brain). This condition typically causes sudden vision loss in one eye, without any pain." - https://www.brighamandwomens.org/neurology/neuro-ophthalmolo...

[0] This differentiates it from a similar condition that does involve arteries

[1] More literally, nerve sickness


Thanks, chubbyemu ;)


in patients with Type 2 diabetes


this part was both clear and unclear to me - does it exclude patients using it for weight loss or not?


They didn't study patients using semaglutide for weight loss only.

I guess a Bayesian would increase their estimated probability of such a problem also for the weight loss case, but not by as much (as diabetes predisposes people to other ailments).


What you are saying makes sense. Subjectively I feel like they could have done a better job at making this distinction clear given the explosive use for weight loss - but maybe it's just because my interest in this is outside of diabetes.


[flagged]


The cases of NAION observed post-Ozempic usage in Denmark is 150 (up from 60-75) out of 424,152 patients, for a rare ailment that already affects patients specifically with diabetes. Sorry to say those taking it as a "shortcut" in your words are even less susceptible.

As someone who's been fortunate enough to be fit and able to work out their entire life, not sure how there are people like you who shun and shame those trying to gain a semblance of control over their weight in a world where it does have a real impact whether they get serious medical attention or not. Your likely skewed thoughts on vanity be damned, bigger people are treated worse across the board and GLP-1 is a genuine salve.


Vaccines? Toothpaste? Laser eye surgery? Cataract surgery?


If I know anything about America, they're gonna work at finding a remedy for blindness instead of getting on a treadmill.

Just like they won't fix school shootings by implementing gun control but will talk for days about motives.

They always try and fix the consequence of the problem and not the problem, it's pretty funny to watch from the outside.


[flagged]


Different damages, one is on blood vessels, the other on optic nerve


> NAION is damage to the optic nerve of the eye caused by a sudden stop of blood flow to the optic nerve.

Sounds like it's related to blood flow also.

(Didn't read remainder of article)


> In Jakob Grauslund’s study, the researchers divided the patients into two groups: those who were treated with Ozempic and those who received other treatment. In the statistical analyses, age, gender, blood sugar and a wide range of other conditions were also taken into account.

They are comparing patients with diabetes in both groups


someone should do a study to determine whether diabetics develop blindness more often when on ozempic

perhaps this is that study


Yes, this is that study:

“Patients with type 2 diabetes who are treated with the drug Ozempic have an increased risk of developing damage to the optic nerve of the eye.”


I really don't like these medicines that give people who indulge themselves excessively an easy way out. Maybe these side effects are nature's price for not doing the work.


Well, let's not give you any medication for any disease you are afflicted with. It's an easy way out. Get a bacterial infection? Should have been cleaner. Get a virus? Why you expose yourself. Develop cancer? We know there are millions of lifestyle choices that push the needle towards development bit by tiny bit, why didn't you avoid all of those? All of these are nature's price for not doing the work. Why are you taking the easy way out to discuss this on the internet? Why not go talk to someone about it in person. But don't drive, or wear clothing made by others, or live in a home constructed with modern methods using modern materials.

Or... This could be a ridiculously awful take. Convenience or the "easy way out" is one of the biggest drivers of technological advancement in human history. The fact you are able to make this post at all means you have been a beneficiary of the "easy way out" in countless ways. All you're actually doing here is moralizing about fat people.


Catching a disease is not the same as willfully and knowingly overeating to the point of obesity. That is a very poor comparison.


It's actually not, because lifelong exposure to known carcinogens is actually very similar to slowly overeating and gaining weight. Do you eat grilled meat? Enjoy your PAHs and HCAs - if you ever get cancer, seeking treatment is going to be the easy way out, something you could have avoided by "putting in the work."

But you also ignored all of the other things you do every day that are the easy way out.


Sod off. Your take on overweight being ”willfully and knowingly overeating” is ignorant and naive beyond recourse.


There's nothing ignorant about it, you don't get to be obese by accident. Sorry, that's just the truth.


Basically no one chooses to be obese. It happens bit by bit over time, with small poor choice after small poor choice stacking up.

Don't worry. You'll still get to feel superior about not being fat - you can just proclaim loudly that you did it without a GLP-1. Those that think like you will give you the applause you're looking for, I'm sure. And everyone else can roll their eyes and move on with their day.

"Not liking" medication that greatly improves people's lives and greatly reduces their risk of early death just because you think it's the "easy way" and "not doing the work" makes you an asshole. Rooting for them to have significant side effects also makes you an asshole.


You are choosing to be obese by making those choices repeatedly in spite of the obvious consequences. It didn't sneak up on you out of nowhere. Calling me an asshole is beside the point, it's just a word for a person who says things that are true that people don't want to hear.


This is pretty naive, tbh. Interoception varies between people, as does availability of food, vulnerability to addiction, education, etc.

It's like telling people with depression to not feel sad. There exist chemical, hormonal, and biological drives that vary wildly between humans.


Again: If you get cancer, are you going to skip treatment because you didn't avoid every known carcinogen? Cancer is an obvious consequence of carcinogen exposure, and I would bet quite a lot of money that you are not avoiding exposure to every carcinogen you are aware of. I also doubt you're "putting in the work" to educate yourself on all of the known carcinogens, either.

And no, you're not an asshole for saying that people hold some responsibility in getting fat. You're an asshole because you're wishing further harm on them vs. them having a safe and effective treatment for it. Even if becoming obese wasn't a complex and multifaceted topic (and this is well established science, not some fat-apologist bullshit), even if people just pushed a button that said "make me fat" for some reason, we should all wish for them to have as easy, safe, and effective of a method as possible for returning to a healthy body weight.

What possible moral justification could you have for literally wishing people will have negative health outcomes because they want to use medication to assist them in their weight loss?


> Even if becoming obese wasn't a complex and multifaceted topic (and this is well established science,

That "Science" itself is fat apologist bullshit. This kind of Science is a joke, a way to legitimize the removal of personal responsibility and agency. It's activism, not Science, the same way addiction has become a mental illness or criminality an economic outcome under the guise of fake Science. The moral justification for wanting someone to "do it themselves" and have to pay for their choices is that it creates wiser, stronger people and wiser people make better societies (though it is also it's own good). What you are proposing is a society of meat bags with no agency who get bailed out of their poor choices. That makes for an obese soul.


Why do you think science has any obligation to track with your own personal morals, is concerned with agency, or has anything at all to do with "souls?" Science is about understanding the how and why of things, on a factual basis. It has no responsibility to align to your worldview.

I also notice you continue to refuse to engage on the very applicable analogy of carcinogens, cancer, and receiving treatment. I can only imagine it's because you know you would seek treatment if your life depended on it, despite the need for it being influenced by your actions.

Regardless, I hope you never need to be in a situation where you have to choose between compromising the morals you're espousing now and getting treatment, and if you ever are, I hope you realize how foolish these ideals are, and that you get the treatment you need.


I didn't say that it does have an obligation to do any of that. If anything it's the opposite, I think Science should abstain from turning moral issues into materialistic "facts" which is what they are attempting to do by turning everything that used to be a character or moral issue into a biological or physiological issue so that now every criminal, misfit and glutton is actually a victim of mental illness or addiction (and addiction is a physical, biological phenomenon) where conveniently all agency and personal responsibility is removed and no one can be blamed or impugned for anything and no one is ever at fault. I don't know what is even supposed to be left of a person when bad choices are not even choices anymore, as if only good choices are real choices and we can go around patting ourselves on the back forever. It's just so pathetic and absurd. If you need to tell yourself that being fat, dumb or lazy is not your fault, go ahead, I'm sure they'll discover a biological basis for laziness soon enough and we can all call ourselves differently motivated or whatever stupid euphemism they'll come up with and breathe a sigh of relief. At the end of the day you're just lying to yourself.


This medicine works by softening the indulgence instinct. It doesn't let you gorge all day and be thin, it makes you not want to gorge.


If you literally cannot stop yourself from being obese any other way, then Ozempic and similar may be a good choice.

But the side effects are large. You can never, ever stop taking it. We don't know what being on it for decades causes. There are anecdotes that it numbs you out emotionally.

There are no shortcuts in life. There is always a tradeoff.


1) Side effects not much more than the most tame of drugs, like aspirin. This one, if it exists, is incredibly rare.

2) You can stop taking it, obviously. Just like any medicine, the effects will wear off, but there's no rebound effect or risky side effect from coming off. You simply return to your previous state.

3) There's more positive anecdotes than negative basically wherever you look. I have a friend who took it and while he lost 20% of weight, he plateau'd - I asked him if he was going to cycle off it and his answer was an emphatic no - I asked why, he said beyond the positive weight effects it: massively curbed his weed addiction, curbed his social media addiction, improved his sleep, and because his compulsive behaviors were down he was doing better at work, reading books for the first time in years, and going to therapy which had helped his dating life. No joke, I was floored at how ridiculous the answer sounded, especially as this was a pretty bro-y friend. Yet I've heard many anecdotes like this from others, one friend stopped a 15-year pack-a-day cigarette addiction they'd had since high school.

4) Some of the other positive trade-offs: reduces addictive behavior, heals heart/bones/brain, dramatically reduces inflammation and can fix inflammatory disorders, positive early studies for Alzheimer's and Parkinson's, etc.

5) There may be no completely free lunches, but there are nearly-free lunches all the time for people with ailments. If I have debilitating GERD, there are antacids that essentially save my life with only mild side-effects. If I have bad eyesight, glasses are a miracle cure. This is all over medicine. If I'm getting surgery, 100/100 people will choose the mild side-effects of anesthetics over the pain.


The most interesting aspect of GLP-1 agonists is indeed the reduction of inflammation.

All the effects on the mind like reduction of addiction, compulsions, craving have a direct basis in neuroimmunobiology. Neuroimmunopsychiatry.

As I see it, it’s a productive and reasonably accurate view to look at things in the way that inflammation is suffering. Neuroinflammation and suffering being one and the same.

In addiction, in craving, there is neuroinflammation. In getting the fix there is a reduction of inflammation.

Neuroinflammation also makes us angry; it’s behavior-modifying from a social point of view too.


Using glp1s for addiction treatment is in active study because of anecdotes like your friends. Hopefully there are some solid results soon.


That’s not true. It’s like anything else, it’s about you.

I was on it for 18 months, it allowed me to lose weight and change my habits in a way that has persisted. I lost 90 pounds, and gained back 15, which I attribute to an injury that stopped me from running. I’m back in action now and down 5.

I cannot stress how transformative this drug was for me, at a time of my life that was particularly difficult.


Human civilization is built on the creation of shortcuts. Insulin is a shortcut for T1 diabetics to avoid death.


Civilization is built on long term sustainable practice, shortcuts in response to the lack of such practices is how civilizations burn down.

Obviously T1 diabetics need to take medication because there's not much else they can do whatever side effects that has, but the topic is obviously relevant and posted here because these drugs are currently being used/abused for weight loss. Given that sustainable, side effect free ways to lose weight exist (with many additional benefits) that is what a healthy human civilization would do, instead of opting for drugs with utterly unknown side effects, potentially really bad ones, like in this case.


> Given that sustainable, side effect free ways to lose weight exist (with many additional benefits)

Just because it exists doesn't mean it's statistically applicable to a population of people. I've yet to see real evidence that on a population scale, sustainable and side effect free ways to lose weight exists at a statistically significant level. If you're 100+ lbs overweight and you lose it all without any medical intervention for over 5 yrs you're basically a statistical freak.


See France

https://bigthink.com/strange-maps/global-obesity-rates/

It’s a policy intervention from the mid 2000s onwards and I kinda doubt the policy is “mandatory Ozempic injections”.


This is not a study. Furthermore, this isn't even a report on losing weight!


Not to mention that the human body is completely opposed to losing weight, and will do anything it can to convince you that what you really need to do is to gain it back.


This was something that astounded me about my weight. It is static. Has been static since I gained it all (when my thyroid quit working at 18 - over 4 months I gained 100 pounds). Since that date more than half my life ago, I have been the exact same 220lb +/- 5lb depending on time of day. Through caloric deficits, through hiking and jogging (run many 5ks, and just recently hiked 125mi through the mountains). I'm fit, I eat well, but I'm BMI of 34, and my weight never fluctuates.

My wife has wanted me to get on ozempic, but I'm actually scare of side effects, and the cost is atrocious in the US.


> I've yet to see real evidence that on a population scale,

I mean visit Japan if you want to see a large nation manage its populations weight, but the entire reasoning is completely backwards. Statistics doesn't have a will of its own or causal powers, it's a description of aggregate behavior. Change the behavior and you get some new statistics. 100 years ago you didn't have a single statistic showing that obesity was an issue. What evidence do you need that making people move more and eat less will make them lose weight, there's no law of nature operating against you.

The obvious reason to even think like this is indicative of the problem, that in a lot of places we're so unused to simply enforcing sane cultural norms and incentivizing healthy behaviors and discourage crappy ones that people think it breaks some kind of ironclad law.


> What evidence do you need that making people move more and eat less will make them lose weight, there's no law of nature operating against you.

IDK, any evidence? We've been telling people to move more and eat less for literally decades and it doesn't work to make them lose weight on a broad population level.


Perhaps a better phrasing would be, "There is no free lunch." If you prefer to take Ozempic rather than monitoring caloric intake and exercising, then there are consequences. But if the consequences are worth it, is up to the individual.


Someone reading this might assume its zero sum to you - as if people on Ozempic have not already been exercising and monitoring caloric intake without the associated weight loss/health results they desire - and have only chosen it because they don't want to try something else.

I'm sure you aren't trying to come across as fat shaming, but the reality is of course not zero sum. Diet and exercise doesn't magically work for the entire population.

Diet and exercise definitely worked for me but im not willing to be a sample size of 1 in the face of so many others with legitimate stories.


Diet alone is 100% guaranteed to cause you to lose weight. It really is as easy as counting calories. It is a scientific fact. It is physically impossible to gain, or maintain weight, if you cut caloric intake sufficiently.


Yes, and abstaining from alcohol is guaranteed to stop alcoholism! It is a scientific fact. It is physically impossible to be an alcoholic if you cut alcohol intake sufficiently.

It's so simple, really.

(See the problem here?)


I see what you're claiming is the problem.


No one here is stating that physics stops working for fat people. Obviously, your body needs an energy source to function and when you deprive it of that energy source it will go to your energy reserves. There might be some woefully ignorant people that claim otherwise elsewhere, but that's not the position of the person you are referring to.

But you're saying "it is as easy as doing activity x" without concern for the difficulty of that activity. There are a wide variety of reasons some people might get fat, but once you are fat, it is far more difficult to get not-fat than it was to get there in the first place. There are a wide variety of feedback loops within the body, including epigenetic ones, that make it much harder to lose weight and keep it off.

Once upon a time, it was trivial for me to not eat garbage food, or too much of any sort of food. I had more trouble trying to eat enough to be in a large enough caloric surplus to get enough protein in and stay in a large enough caloric surplus to build muscle. I never had "food noise" or anything of that nature. Then life happened, my circumstances changed, and I had less time to worry about food. I spent more time going out with co-workers and friends eating and drinking. Other nights, I was too busy to cook, and ordered in more. My weight went up, and before I really realized it, I had put on significant weight. And I realized that something I had found trivial before, something that had taken zero willpower, that I had never struggled with... was something that was incredibly mentally taxing.

Could I count calories and lose weight? Of course. Could I add exercise back in to my routine? Yep. But it was difficult in a way that I never had understood back when I was fit, in a way that I never would have believed could happen to me. And as soon as I got busy again, or had other things occur in my life that took priority, the mental effort to keep "just counting calories" and push down my food cravings and hunger no longer seemed worth it.

I could exert a huge portion of my willpower on this, struggle with it, remove my capacity to spend more time having care and empathy for others, forcefully deprioritize other things in life... or I could use a GLP-1.

I know which path made sense for me, and it's been a hugely beneficial thing in my life.


Eating is 100% guaranteed to cure starvation.

Not drinking is 100% guaranteed to cure alcoholism.

Buying a house is 100% guaranteed to solve homelessness.

It's really that easy.


Agreed. And if you want to stop smoking or gambling it really is as easy as not doing it.

Except reality is it's hard. Addiction is a real issue, people have underlying compulsions and habits as difficult to break as with physical pressure. For some people monitoring caloric intake isn't the option it is for others.


You are not wrong. Starving yourself works, obviously. What doesn't work is maintaining people in a state of starvation. It becomes extremely hard if there are other tasks stealing focus (for example, work), or if you have a high basal metabolic rate, or if you have diabetes, etc.


This is an intellectually dishonest statement.


I am the guy with an appointment with Ozempic prescribing doctor. I will seriously think about it twice. “Normal” starving does not have any very rare and very bad consequences. It’s just very very difficult.


It's true, it isn't a free lunch. You, or your insurer, has to pay for it. It needs to be injected. It won't work as well if you insist on eating a pint of ice cream three times a day. And so on.


>It won't work as well if you insist on eating a pint of ice cream three times a day.

Yeah, good luck with that.

GLP-1 agonists reduce your desire for, and for many people, your ability to consume things like “a pint of ice cream three times a day.” That’s kinda the point.


The sarcasm in my reply did not come across it would seem.

"No free lunch" does not in any sense imply that there are no positive-sum decisions to be made.


Whoosh. I’m slow.


Insulin is not a "shortcut." It's a genuine product of the human body. Some people just don't produce enough in response to other metabolic changes.


Clinical trials started in 2008. Thats decades for something major to appear. There are minor things, but people can simply stop taking it. Given the weight lost causes years of healthy lifespan to be gained, it would take a monumental problem that would have been seen by now to make it not worth it for a lot of people who can't lose weight on their own.


> You can never, ever stop taking it.

You can't stop taking it without gaining the weight back (unless the lifestyle change sticks), but everybody stops taking it in the medium term. The side effects are horrible and stack up over time.

We'll start seeing the miserable condition of very long-term users (or maybe, hopefully, their bodies will reach an equilibrium!), and we will be able to use the sacrifice of their health in order to understand how better to counteract the long-term side effects, or to get hints on how to design the next class of miracle weight loss drugs.

I'm never going to take them. There are better ways to lose weight, with no side effects, and they slowly and stably got me from a 28 BMI to a 22 BMI. I will push the people I love towards those rather than to a set of powerful, expensive drugs with wild side effects that somebody invented a week ago. But I am not hostile to the concept in any way.

> There are no shortcuts in life. There is always a tradeoff.

There are an enormous number of shortcuts in life. This is just the Law of Averages as Protestant superstition stated as a pithy self-help maxim. Taking shortcuts rather than going the long way is almost the definition of intelligence. If you see a bunch of points laid out in a rectangle, you can count them one by one, or you can count the ones on the sides and multiply. There's no tradeoff.


> You can't stop taking it without gaining the weight back (unless the lifestyle change sticks), but everybody stops taking it in the medium term. The side effects are horrible and stack up over time.

Some people experience significant side effects. Many people do not. Tirzepatide seems to induce even fewer side effects in general than semaglutide.

> We'll start seeing the miserable condition of very long-term users (or maybe, hopefully, their bodies will reach an equilibrium!), and we will be able to use the sacrifice of their health in order to understand how better to counteract the long-term side effects, or to get hints on how to design the next class of miracle weight loss drugs.

I'm active on several GLP-1 related forums. On those, people near-universally report side effects lessening over time, from those that have significant side effects to begin with.

The next generation of drugs is arriving now. Eli Lilly is finishing up their initial phase 3 trials for retatrutide at EOY, and in a matter of months I've seen it reduce my ALT levels from edging towards an indication of NAFLD to right in the middle of optimal. Preliminary results from the trials in general seem very positive, so I imagine FDA approval will come later '25/early '26, though the glucagon receptor activity does seem to increase resting heart rate in many people (including myself, though tirzepatide did as well, to a lesser degree.)

> I'm never going to take them. There are better ways to lose weight, with no side effects, and they slowly and stably got me from a 28 BMI to a 22 BMI. I will push the people I love towards those rather than to a set of powerful, expensive drugs with wild side effects

I would agree if you have success in losing weight with other methods, there's not a strong reason to go on the GLP-1s. We do have some evidence that they have other positive health benefits even without the weight loss, but there are some side effects, yes, and we of course do not strongly know what happens if you take these for decades on end. On the other hand, we know that improving diet and increasing exercise are basically all net positives, outside the minimal injury risk that comes with exercise.

I do think you are overstating the side effects, though. There seems to be some small risk of sight issues, though I would like more data here - we know that diabetes is significant risk factor for eye disease, and I'm curious how well these results will be replicated in general, and how well they translate to non-diabetics taking them purely for weight loss. We've also seen thyroid cancer in rodent studies, and while so far no human studies have found an increase, I wouldn't be surprised if there is some risk increase for humans.

> somebody invented a week ago.

We're actually about two decades in on the GLP-1 class of drugs being in-use by humans, but obviously semaglutide and tirzepatide have really ratcheted up adoption.


Can you point to some forums? I'm considering a GLP-1 agonist because I have an impaired ability to feel fullness, and as a consequence I eat all the time (mostly healthy stuff, plants). Want to hear more about others experiences and maybe make some connections with people who aren't going to moralize over "you are wired differently and are therefore a bad person"


Sure. glp1forum.com




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