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I'm not very familiar with the approval process for new drugs, but as far as I know it involves some initial step where the safety is assessed, and then the effectiveness. But I don't think either of those are actually long term processes (like, longer than 5 years).

So it scares me a bit when something like Ozepmic pops up and tons of people jump on it, without knowing the long term effects that might appear. I read the other day there's an entire subreddit devoted to Ozempic side effects, and those are only short term ones (maybe those being discussed there were already discovered during the trials, I don't know to be honest).

Are my fears unfounded and just the result of my lack of knowledge around the approval process and/or the inner workings of drugs?



Semaglutide has been on the market since 2017 and clinical trials commenced in 2008. So we have a fair amount of data on longer-term users. It wasn't being used for general obesity until recently.


But has it had long-term studies as a weight-loss drug instead of a diabetes treatment? The results might be different.


it might be, but the question is if there's some long term bad effect, like it causes brain bleeds if you take it for 20 years or something. I don't think patients taking it for weight-loss instead of diabetes changes the underlying biological processes that happens as a result of taking the medication, so long term studies based on diabetes patients is useful information for non-diabetes patients.


My doctor has been prescribing it for obesity for about five years.


Doesn’t work for everyone. I have relatives on it. Still big. The best improvement they made was giving up alcohol.


Giving up alcohol is huge though


Yeah, I just meant that they've done both, Ozempic and Alcohol, it was a noticable change after giving up the alcohol, awesome weight loss, the Ozempic hasn't changed a lot.


the belief is that the ozempic is what's allows the giving up of alcohol


There's always tradeoffs. Ozempic probably has some long term side effects, but are they worse than obesity? Probably not. (And an intervention based on ozempic is far more likely to cause lasting change than one based on a prescribed behavioral program.)


> (And an intervention based on ozempic is far more likely to cause lasting change than one based on a prescribed behavioral program.)

I was under the impression that for lasting change the behavioral program was pretty much required anyway, unless the patient wants to take Ozempic for the rest of their life. It helps someone go from obese to the point where they can exercise to maintain their health but they still have to eat healthy and exercise afterwards.


Yes: for most obese people, to become not obese and stay so for the rest of their life, lifelong Ozempic is the only thing that works at scale. Behavioural interventions more or less don't work (on an individual level they occasionally do, but on a population level they don't).


GLP-1 agonists have been around for a while. They're just gaining popularity lately, it seems. The first one was approved in the US in 2005 (exenatide).


Hey don't worry, your fears are mostly unfounded -- GLP1 Receptor Agonists have been an effective treatment method for type 2 diabetes for a very long time. They're well studied, researched and trialed, at this point, and many side effects are known.

I'm a bit biased of course (I do a lot of trying to keep up with the research and effects of GLP1 drugs), but I honestly don't think the weight loss scene has seen something so effective and safe for a very long time.


Isn't the worry that Ozempic is only "effective and save" as far as all the other weight loss drugs being utter predatory bullshit ?

Last time I looked into it the "loss" is only happening while taking the medication and you get back to normal once you stop, regardless of how long you’ve been taking it. So if stabilizing at a thinner state is your goal, the drug would be mostly useless or you should be ready to take the rest of your life.

Going only a tad too far, it feels like recomming meth for its energizing and diet effects, that's not something we want at wide scale.


The medication suppresses appetite, so one wouldn't expect it to continue working when it isn't being taken. It's a treatment, after all, not a cure.

What it can do is help one "bootstrap" into healthy habits. Someone who is sufficiently overweight might suffer injuries from exercising, which makes it difficult to lose that weight. Someone who's drank a soda every morning for decades might break the habit if they stop for long enough.


Why quotation marks around loss?

Why does it feel like recommending meth? Are they similar in addiction and harmful effects?


Because the loss is very limited, and most people regain after stopping medication. As discussed in the other thread, within about a year or so there's already a two thirds rebound, and patients don't see as much health improvement as through exercice for instance.


And my cholesterol goes back up when I stop taking statins. I don’t get this very common argument.


I mean come up with a pill that changes your eating habits and doesn't just repress them. Don't think anyone's got close to that yet.

In the meantime overweight people are going to take what they can get.


> I mean come up with a pill that changes your eating habits and doesn't just repress them. Don't think anyone's got close to that yet.

So GLP1 gene therapy (if it ever gets here) might be the most reasonable way to achieve this, and might be the safest we've ever seen so far outside of maybe brain control.

> In the meantime overweight people are going to take what they can get.

100%. And AFAIK GLP1s are some of the safest we've seen so far, and much more effective than "eat less and move more" (as true as that may be).


Tobacco did that (imagine going for nicotine patches instead of smoking), meth did that, a lot of things do that. It all comes down to the side effects and whether it's worth having the drug around.

Up until now we say "no, fuck it" after a few decades of having the thing widely available. My point is wether we should shortcut the cycle and so no _before_ doing the society wide trial and having to fight for decades to have it stop.

> In the meantime overweight people are going to take what they can

Most don't take anything right now


Tobacco and meth happen to be some of the most highly addictive drugs that exist, that also have the side effect of weight loss.

I don't think I've seen anybody tweaking out for a fix of ozempic, though please feel free to inform me if addiction is an actual side effect that I've not heard of.


Withdrawal for tobacco is basically mild discomfort. It can't be in the same class as drugs that cause seizures, profuse sweating, and death upon immediate cessation.


Depends what you mean by mild. For me, going cold turkey from nicotine was migraines, severe anxiety, irritability, and fatigue. Not life threatening, but I was unable to function. That said, tapering off with a controlled time-release dosage (patches) was sufficient to reduce it to actual mild discomfort for me.


Ozempic has started to be in wider use very recently, and we know it has a side effects of restraining dopamine release.

My point is we still know very little about long term effects, and in particular about what happens when the brain's reward centers are affected at scale (for a diversity of people) + for years.

Yet we're already going down the path of the "miracle drug" [0] and that freaks me out.

[0] https://www.amazon.com/Miracle-Drug-Crystal-Meth-ebook/dp/B0...


> Isn't the worry that Ozempic is only "effective and save" as far as all the other weight loss drugs being utter predatory bullshit ?

Yes, but note that there are other more legitimate alternatives like gastric bypass, etc!

> Last time I looked into it the "loss" is only happening while taking the medication and you get back to normal once you stop, regardless of how long you’ve been taking it. So if stabilizing at a thinner state is your goal, the drug would be mostly useless or you should be ready to take the rest of your life.

This is untrue -- most people do not bounce all the way back to their original weight once they stop, and simply having the space from what seems to anecdotally be quite annoying symptoms ("food noise") might be well worth it.

https://glp1.guide/content/do-people-regain-all-the-weight-l...

> Going only a tad too far, it feels like recomming meth for its energizing and diet effects, that's not something we want at wide scale.

It's absolutely not this -- there are studies and trials on how GLP1 RAs work, their effects, and at this point they are a go-to effective treatment for type 2 diabetes, and the FDA has just approved them for heart disease.

The way they work is not completely known (for example the mental effects seem to be underweighted), but the mechanism of action is completely different a drug like meth.


> This is untrue -- most people do not bounce all the way back to their original weight once they stop, and simply having the space from what seems to anecdotally be quite annoying symptoms ("food noise") might be well worth it.

5% weight loss at the end of the day, and no cardio metabolic improvement [0]. So basically the net change was super small and cosmetic. I understand this could still be useful for very specific cases, but it's more of a niche that we're willing to admit.

> the mechanism of action is completely different

I hear you, I and I think we'll see more and more diverse drugs with different mechanisms. I'm just not sure we should be saying "this time it's different" every single time when we could take more measured approach before pushing it to the masses. Right now we're already in the YOLO phase waiting to see how it will pan out now that everyone and their dog want the miracle weight loss drug.

[0] https://pubmed.ncbi.nlm.nih.gov/35441470/


> 5% weight loss at the end of the day, and no cardio metabolic improvement [0]. So basically the net change was super small and cosmetic. I understand this could still be useful for very specific cases, but it's more of a niche that we're willing to admit.

Hey 5% weight loss is pretty good! And remember, there maybe a period of time where the process repeats after getting off (no research to support this yet).

Also, I think you're under-estimating the psychological benefits. The lessened/blunted impulses to eat/do other addictive things might prove to be way more valuable in the time frame than simply the weight loss.

Also, note that the 5% is basically the worst case -- it's possible for more motivated people to keep more than that off, especially if they change their lifestyles appropriately, and importantly the drugs help people get in a headspace to do that.

> I hear you, I and I think we'll see more and more diverse drugs with different mechanisms. I'm just not sure we should be saying "this time it's different" every single time when we could take more measured approach before pushing it to the masses. Right now we're already in the YOLO phase waiting to see how it will pan out now that everyone and their dog want the miracle weight loss drug.

Yeah but I'd say this time it is different -- we've literally never had any weight loss drug that was this effective with so few side effects, and is well studied and essentially has an arms race between the largest pharma companies in the world to produce.

I agree with you though -- it's not a miracle drug, but it's the closest we've seen so far, so that's worth celebrating.

Personally I don't think anyone has to push this drug -- the masses are demanding it -- it's just that only rich people/lucky people with good health plans can afford it so far.


Seems like a valid ethical consideration, no doubt. But remember some people are suffering very serious harms already. A new drug might have side effects, but are they worse than the physical and social harms of being addicted to alcohol?

The ethical considerations are more difficult when it comes to someone who simply wants a little help. Consider the common case of someone mostly happy and successful, but is a little overweight and has been struggling off and on for decades to lose 20 pounds; almost all of us have been there, or will be. Do you give those people the drug? Do you allow them to choose for themselves, or should big organizations decide for us?


No, not at all. While I think we have a pretty fantastic drug approval process (that got a frustratingly bad rap for all the wrong reasons during covid), long term consequences will remain to be seen.

It's just that these considerations run up against a very solid understanding of how much death is caused by being overweight and having high blood pressure.

Right now, Ozempic does not have to be very good, to be most likely a lot better than the alternative.


The status quo (obesity) is extremely dangerous, so whatever potential danger you're thinking may exist would have to exceed that.


Unless that's a false dichotomy. Obesity can be treated in less harmful ways. Companies can be regulated into only including a safe amount of sugar in drinks and foods that arent considered sweets


But when are those changes going to happen? Ozempic is available today.


> extremely dangerous

I wish I could just quip a "citation needed", but we're at a point where the visceral hate for fat includes researchers spitting out feel good papers going with the flow, as funding is basically guaranteed.

We don't have satanists, so this has become our day's moral panic IMHO:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885862/


Are you suggesting obesity is not harmful?


Obesity is correlated to potentially harmful issues. That's a difference that matters when people reverse the goals and the means, reducing obesity often doesn't equate to solving the related issues.


> So it scares me a bit when something like Ozepmic pops up and tons of people jump on it, without knowing the long term effects that might appear.

It isn't that different from what happened with vapes and e-cigs, and they were even worse (nicotine-based, explicitly harmful).


I’m not sure I understand your point. Vapes and e-cigs are less dangerous to your health than regular tobacco cigarettes.


> So it scares me a bit when something like Ozepmic pops up and tons of people jump on it, without knowing the long term effects that might appear.

Test in production. YOLO!


Considering it's not ethical (or legal) to spin up a test human what else are you going to do?


Yes. I am very worried about the long term effects of this. While I have no need for this drug, I worries me for the broad population. There are problems known already (cancer).

I understand that it is a trade off if you are obese. A buddy of mine died with 43 bc a combination of obesity and COVID. Yes, it might be justified for high risk patients but currently it looks like it will become a life style drug like Viagra. And a drug that digs so deep into your metabolism and take it for life? Call me a sceptic.




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