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Ozempic will disrupt big tobacco, candy companies, and alcohol brands (curingaddiction.substack.com)
147 points by robertn702 on April 28, 2024 | hide | past | favorite | 197 comments



Ozempic costs $1000/month (in the US) but $5/month to manufacture [0]. I think if this drug and others are to have a significant anti-consumption effect on other companies it needs to be vastly more accessible, which first requires more accessible healthcare in the US, which is unlikely to happen.

Also it's an injection, which raises the barrier. If drugs like these become orally administered and over-the-counter, then yeah, I'd be more confident that it could have a positive effect. But currently, it looks like a drug that few can access/afford in the US.

[0] https://www.sanders.senate.gov/press-releases/news-sanders-s...


You can buy pharmacy compounded semaglutide through online portals, e.g. Ro

It's $450/month out of pocket (no insurance coverage)

Therefor, there will actually be price competition and we should see pretty cheap prices in the coming years.

I'm not sure exactly why pharmacies are free to compound it independently. I guess whatever patents exist on Ozempic/Wegovy etc aren't sufficient to squash competition.

The $1000/month for Ozempic is purely a name brand markup. I'd guess we'll see prices closer to $100/month for the compounded variants within a few years


There are dangers/risks to buying pharmacy compounded semaglutide -- not really a great thing to recommend widely. It's hard to depend on whatever pharmacy people might be able to find locally or through some hopefully trustworthy portal.

That said, with China and more notably India entering the GLP1 RA race, there will be much cheaper options very soon, hopefully!



Can you articulate those dangers? Compounding is a well developed means of sourcing drugs and GLP has been around for decades. What specifically should people be mindful of?


Well quality of the compounder/pharmacy is the real issue here -- of course it's not that the process itself is flawed, more that it's basically impossible for a layman consumer to inspect/assess quality/safety.


How does the layman consumer inspect/assess the quality/safety of other drugs or really any other substance that they ingest?


That's a fair question - they obviously can't inspect pharmaceutical factories. That said, the FDA has much more power to regulate drug manufacturers than pharmacists and most drugs are manufactured in a few locations that are much easier to inspect. They only have to make sure one or two locations are set up correctly and a significant chunk of the application for clinical trials is quality control procedures.


There are shady online compounding pharmacies based in other countries and you don’t know what you’re getting, as with any prescription drug. I’m guessing that was he meant.

But from a reputable one regulated by an industrialized nation, it would not be fitting to call them dangerous.


I have bought generics from India but can we really say GLP1 generics in India are better than compounded GLP1 in the US? It seems inconsistent to recommend one over the other.


Well I'm more looking for GLP1 generics developed whole-cloth in India.

India is quite good at pharmaceuticals -- their generics basically serve the rest of the world that are priced out of US-made products IIRC.

Ex. their generic version of Paxlovid:

https://www.reuters.com/business/healthcare-pharmaceuticals/...

Basically, with the expiring patents coming up on a bunch of these drugs:

https://www.biospace.com/article/9-drugs-losing-patents-or-e...

We're going to be in interesting waters soon.


> Therefor, there will actually be price competition and we should see pretty cheap prices in the coming years.

Considering how man times pharmaceutical companies have been lightly taken to task for doing the exact opposite, this seems extremely optimistic.


Currently they cannot manufacture enough to cover demand at $1000/ month. Why would the price come down before they can supply current demand?


> Why would the price come down before they can supply current demand?

Because in exchange they could unlock a bulk order from e.g. the U.S. government. That in turn could unlock economies of scale that let them price competitors out of the market.


They are literally buying up as many factories as they are allowed to do. Money is not the issue - getting access to production lines is.


> Money is not the issue - getting access to production lines is

You don’t think having the heft of the U.S. government behind one of those parties will help with that access?


What I'm trying to say is that the supply is constrained, not the demand. And the supply of factories themselves are constrained as well. So they need to build more factories, which they are doing at an impressive pace. And for building factories it's similarly not the land or the money or the red tape that's the issue. It's the time to build a factory that's the limiting factor.


I interviewed for a contractor involved in building factories for Novo Nordisk. The timelines sounded insanely ambitious.


Do you see the US government wanting to disrupt these industries, many of which are political donors?


> Do you see the US government wanting to disrupt these industries, many of which are political donors?

When the one being disrupted is a European pharma? Yes.


The article is about disrupting big tobacco, candy companies, etc. being disrupted by a European pharma. Why would the US gov’t make a massive order to bring down costs to disrupt homegrown companies?


> Why would the US gov’t make a massive order to bring down costs to disrupt homegrown companies?

Have you been around our lawmaking institutions, or lawmakers? The idea that we'd sandbag something like Ozempic, which by the way is being negotiated for mass deployment through Medicare [1], to save the likes of Frito-Lay is nuts. Even if we reduce American politics to the lobbyist-conspiracy model, which isn't terribly predictive but whatever, you're pitting big pharma against chips and fast food.

[1] https://qz.com/wegovy-ozempic-weight-loss-drugs-medicare-rul...


Isn't the US Gov'mnt required to buy prescription drugs at market value? One of the Medicare Prescription Drug Expansions from the GW Bush era.

They're not buying generics, and even at a 20% discount will get hosed compared to the $7 generics


Don't they have a patent which makes competition non-existent for the near future?


There are numerous compounding pharmacies selling generic ozempic (Semaglutide)

There is competition, I see ads on Facebook and Instagram for it all the time, there are clinics all over where I live advertising Semaglutide treatment for weight loss.


Additionally, "Ozempic" (semaglutide) has become the blanket word to describe an entire class of drugs (GLP-1 Agonists) that all kind of do the same thing. Some of which have already been proven in clinical trials to be even more effective than Ozempic (ex. Tirzepatide)

It's like when COVID hit and somehow "Zoom" became the shorthand for online video meetings even though there were (and still are) a ton of options for that functionality on the market.


There are multiple formulations, e.g. Ozempic vs Wegovy.


Both Ozempic and Wegovy are manufactured by Novo Nordisk. That’s not competition. It is market segmentation as they are marketed for different uses.


Oh, didn’t know that. Doesn’t Eli Lilly have a competitor?


They do. It's called Mounjaro.


Ozempic is for diabetics, wegovy is for weight loss


The govt has already subsidized production through investing in research they've leveraged.


I mean sort of, maybe. It's a danish company, that's already the largest contributor to research, also from a grant perspective. The Novo Nordisk Foundation is supplying research grants at like 5 times of the size of the danish government. And that's without taking into account the grants and research done by Novo Nordisk, the company itself.


> price competitors out of the market

Are there competitors or are they under patent protection?


Are you suggesting they shouldn’t manufacture more?


No, they certainly should, and according to them they are trying to. There is currently an unknown level of demand at the current price point, all we know is that it is probably far more than current supply. There's every reason to believe that they will increase production as fast as possible and still only meet demand over a year from now.

Once demand is met, there starts to be an argument for lowering the price and growing the market. Getting the price down to half the current price is when we start to see health benefits that outweigh the cost of treatment and an obvious win for insurance companies to start covering it for everyone.

But until there is supply, lowering cost just means more people fighting over the same supply, not more people getting access.


There’s a pill form called Rybelsus that works similarly, but has some gotchas. Namely you need to take with water when you wake up and eat nothing for 30m.

From a lifetime value perspective, I think it’s priced cheap. This drug is a miracle drug and is going to eliminate a lot of suffering and healthcare costs.


That sounds pretty great! I adopted intermittent fasting this year, so I skip breakfast anyway.


In worst case, Ozempic patents expire in 2031, which is not that far.


The worst case is worse than that: in addition to composition of matter patents there are dosage patents that can be invoked.

https://www.fiercepharma.com/pharma/novo-nordisk-patent-sema...


I am not familiar with pharma patents. Are you saying, for example, a 300ml dose could have a patent with different expiry than a 400ml dose?

I could see patenting mechanism of delivery, like injections versus oral, but not the example above.


Pharma is notorious for changing the formulation just enough to acquire a new patent to restart the clock. I wouldn't be surprised if the dosage was a factor in the process.


That doesn’t mean the existing drug can’t be sold as a generic.


Sometimes it means exactly that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4968089/

Of course you could still sell the same drug if you get it approved with a different dosage but that is a long and costly process.


That still presupposes a new patent with new dosage.

In this case, is there a dosage patent on ozempic’s current dosage? If manufacturers tweak ozempic’s current dose and get a patent, what’s to stop the existing dosage from being made by generics?


I really don't think you're being skeptical enough.

https://www.nbcnews.com/health/health-news/gaming-us-patent-...


Money to be made. Competitors will enter the market. Oral options will be come eventually. Prices will drop. Don’t distort the natural market with price controls. You’ll get less product options and higher costs. With all the obesity, this is going to be a gravy train.


> Prices will drop

This seems incredibly optimistic considering all of pharmaceutical history in the united states.


Rybelsus is an oral version of semaglutide which has good efficacy.


Plenty of ongoing research into orally active analogs and cheaper variants. Give it a year or two.


Rybelsus is available in tablets and costs €130 in Spain.


$947 in the US, LOL.


> As Chairman of the Senate Committee on Health, Education, Labor, and Pensions (HELP), I am calling on Novo Nordisk to lower the list price of Ozempic – and the related drug Wegovy – in America to no more than what they charge for this drug in Canada.

I'm not aware of how legislation works in US but I feel like a senator should have more power than just "calling on" a company?


If obesity is an “epidemic”, and the US just forced TikTok to sell based on national security concerns, what’s stopping Uncle Sam commandeering Novo to either sell off its Ozempic ownership as a subsidiary to force a lower general sales price, or forcing to nullify its patents?

I’m speaking legally rather than economically. If the US Gov did this, big pharma would stop investing in research (even though I wouldn’t be surprised if USG pays for the private research in the first place) and cause worldwide slowdown in new medicines all in the name of profits


>and the US just forced TikTok to sell based on national security concerns

First, worth noting that this is very much TBD. There are grave 1st Amendment concerns with the government's efforts there and it is very much an open question for now whether the effort will actually hold up in court. That said:

>what’s stopping Uncle Sam commandeering Novo to either sell off its Ozempic ownership as a subsidiary to force a lower general sales price, or forcing to nullify its patents? I’m speaking legally rather than economically.

So as a practical matter, and as with TikTok, Novo Nordisk is not a domestic company it's a foreign one. But unlike TikTok where China is a geopolitical opponent, Novo is Danish and thus part of a close ally. Second the people pushing the TikTok thing are fine with TikTok going away entirely in the US, that's the stick. The US has zero power jurisdiction over China just as the reverse is true, but can police its own market and thus say "comply or lose access to our market". Same as how the EU is pushing stuff like the DMA. Since the US market is valuable that's a sizable stick, but TikTok very likely even if they lose will tell the USG to pound sand and just leave, but Congress/WH wouldn't mind that.

But here the whole point is that people desperately want this product. So if Novo said "no, and we're ceasing all sales in the US" they'd take a major financial hit sure, but there'd also be massive blow back in domestic and international politics. It would definitely be questioned on various US/EU trade agreements which would have messy legal implications, and invite tit-for-tat. Nationalizing foreign IP would implicate a bunch of treaties and US itself pushed hard and benefits from.

But putting all that aside and pretending it was all domestic (or going specifically after domestic components), there is still the Takings Clause of the 5th Amendment. The government could legally seize it using eminent ___domain powers, though it'd no doubt face as good a legal fight as the highest paid law firms could put on. But I don't think there's any doubt this would be a clear case of public use and courts have approved vastly more dubious and worse takings.

However, there's no dispute government would then have to pay the entire fair market value for it, whatever anyone else would have to pay to buy the whole shebang right now. Novo as traded on the NYSE has a market cap of over $430 billion, and a sizable chunk of that is from this product which has sold well enough to measurably boost the entire Danish economy. The stock has nearly tripled in just the last year and half or so. Even if the US part of that one component was "only" 25%, $100b is not nothing, not even for the USG. And FMV might well be double or more.

There would be other legal avenues to explore but that's a big one, and in turn it's not actually clear it'd save the US any money which is kind of the point, eminent ___domain isn't supposed to be used that way but for some critical greater good. You can gain control but you have to pay for it.


Eh, calling on a company to do a thing is some mix between public fact finding and threat here.

It allows the public to comment and maybe the senator will like the public support they are getting. Alternatively a pharma lobbyist will show up and toss them a few hundred thousand in campaign contribution promises. And they'll weight the relative value of those things. Depending on how that goes they (or another senator seeing this play out) will actually make an issue of it and it will start the more formal processes.


He is asking them, using the official power of his office, to do the right thing so legislation doesn't need to be drafted. Either they choose to do the right thing today and not be subject to regulations, or they can get punished with regulations at some point in the future.

If you think things happen differently in Canada, you don't understand how the sausage is made.


He would if he had broader congressional support, but opposing forces are strong (lobbies, pro-market ideology, etc)


They do, they can propose and vote on legislation. And some budgetary and people nominating powers.


1000 a month per patients will handily fund an awful lot of high priced lobbyists. Such congressional proclamations are arguably just a clarion call to K Street


that seems unconstitutional and also terrible precedent to set. why do any research if you can just piggyback on others?


Ozempic is the injectable version of semaglutide. Rybelsus is the orally administered form. It has been available for several years but isn’t as effective as the injection.

Eli Lilly who makes the Ozempic rival Mounjaro is in late stages of clinical trials for their oral GLP-1 medication.


Zepbound is $550/mo with the manufacturer coupon without insurance.


The fact that its $1000/month only increases its anti-consumption effects because people will have that much less each month to spend on alcholol/candy/cigarettes....


This reasoning is valid if the first pill costs $10B


I’m reminded of the bit in 1984 where they’re trying to remove the pleasure from orgasms. I don’t entirely disagree that this would be good to make accessible but removing the joy from eating is so bleak


It doesn't remove the joy, just the need. The first thing I noticed after starting is I wasn't hungry all the time. That constant sense of hunger made me eat when I didn't need to. Now I can eat a nice meal, but much of the time I don't feel a need to eat, so I don't.

Edit just to add that in 10 months I've lost 40lbs and halved my insulin usage. That insulin is the pricy synthetic stuff (Tresiba and Novolog), so the cost of the mounjaro is probably close to paid for by that decrease.


Is that really true? Everyone I’ve talked to has suggested they don’t really enjoy high reward food anymore and so they end up eating healthier. In part because nutritious food tastes comparatively better.


You get the same effect when you go zero carbs


Ozempic doesn’t remove the joy from eating. It just makes you eat much less. If anything it leads to eating less of really amazing food.

Think enjoying tasting menus instead of double baconators.


only while administered. this is a feature, not a bug

some people need the kick start to experience the effects of a healthy living


People will pay for it even if it was a sharp-ended, spiked suppository made out of powdered Carolina Reaper. Because they believe it makes you look "good".


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.


Re: "mounting concern" about the profits of processed food & tobacco companies, here you are also the 2018 classic of the genre:

> Goldman Sachs asks in biotech research report: ‘Is curing patients a sustainable business model?’

https://www.cnbc.com/2018/04/11/goldman-asks-is-curing-patie...


The actual report (not linked to by CNBC of course) says

The potential to deliver “one shot cures” is one of the most attractive aspects of gene therapy, genetically-engineered cell therapy and gene editing. However, such treatments offer a very different outlook with regard to recurring revenue versus chronic therapies, particularly in certain diseases where it is possible to cure a large proportion of the prevalent patient pool (or at least prevent an additional dose from being required for an extended period). While this proposition carries tremendous value for patients and society, it could represent a challenge for genome medicine developers looking for sustained cash flow. GILD is a case in point, where the success of its hepatitis C franchise has gradually exhausted the available pool of treatable patients. We highlight several potential solutions for these genome medicine companies to sustain an attractive profile. Solution 1: Address large markets: Hemophilia is a $9-10bn WW market (hemophilia A, B), growing at ~6-7% annually. We estimate that the hemophilia A market currently represents ~$6.5bn, while hemophilia B is ~$1.2bn. Solution 2: Address disorders with high incidence: Spinal muscular atrophy (SMA) affects the cells (neurons) in the spinal cord, impacting the ability to walk, eat, or breathe. It is the leading genetic cause of death in infants. SMA affects ~1 in 11k babies, and 1 in 50 individuals in the US is a genetic carrier. Cancer is also a sustainable market given the patient population is almost entirely incident driven. Solution 3: Constant innovation and portfolio expansion: There are hundreds of inherited retinal diseases (genetics forms of blindness). Once a gene therapy is approved for a genetic eye disease, the validated platform could be used to quickly develop many more eye-based gene therapies. Pace of innovation will also play a role as future programs can offset the declining revenue trajectory of prior assets.


this seems like a valid recommendation

or innovators dilemma upsets or forces the incumbents. the transformer (attention is all you need) model paper did release in 2017 and Google did nothing about it until OpenAI forced their hand

awaiting this happening to pharma as well as new technology reduces the barrier to entry for innovators


That's the same thing said with more words.


No, it’s saying there is a limited part of the drug market where curing may not be as profitable as maintenance. So they’re trying to find alternate ways of financing that development. For most of pharma, curing is a payday.


> there is a limited part of the drug market where curing may not be as profitable as maintenance

That's the same as asking,

> "Is curing patients a sustainable business model?"

The offense in question is letting profits effect a decision to develop a treatment over a cure. You're literally spelling out the bad thing.


I think it is good and honest for companies to acknowledge that the current incentives work against trying to achieve [SOME_GOOD_RESULT], as in that case the first step towards getting that thing done would be figuring out how can we change the money flow so that there would actually be motivation for companies to direct their R&D efforts towards that.

If the society says to manufacturer "if you do this, you'll get less money from us" that is effectively the society saying "please don't do this". People and governments vote with their wallets about what they want, and if they're "voting wrong" or ineffectively, then they need to change what they pay for, instead of being surprised that they don't get what they disincentivize.


It has always been what I have observed (used to be a buy side analyst covering pharma among other things in a previous career) but good to see a big bank say so openly.

My favourite example is ulcer drugs. Big pharma has found many drugs to control it, lifelong, but a critical cure for many cases was found by doctors with limited funding https://duckduckgo.com/l/?uddg=https%3A%2F%2Fwww.nobelprize....


what is wrong with some people?

Way for Goldman Sachs to say the quiet part out loud. Not curing people so you can sell them something that merely deals with the problem's effects. This shouldn't even be up for discussion.

Seems like one company is selling the cure to a problem another company (companies) caused. Not to be all "capitalism bad" but I thought promise of the Invisible Hand of the Market was that it was supposed to make life better by directly solving everyone's problems. Instead, it seems to be creating more and (as Goldman Sachs admitted) not even trying solving those.


Can't wait for 2034 Goldman Sachs report: "Can we sell cocaine to toddlers?", "Can we re-lead the water? People are too smart anyway"



If these drugs turn out to be significantly more effective for a wide range of addictions than past approaches, that would indeed be a major societal shift.

I wouldn't try any of them right now, but if my insurance covered one for treating alcoholism at some point I'd give it a shot. If it actually worked it would likely significantly improve not only my life experience, but also my productivity and thereby the lives of others I have an impact on. It's a nice thought.


Have you considered naltrexone?


I appreciate the thoughtful suggestion. I have not actually tried it, but I've read many accounts from other alcoholics trying to quit who have done so (among a couple dozen other approaches), and came to the conclusion that it's not for me right now. If I did give it a chance I would probably have to go with an implant, which I would only do under extreme circumstances.

What it boils down to is that on some level, I often feel death would be preferable to not being able to experience the 'reward' my brain has been long conditioned to expect from my next drink. If there was a lasting way to shift that to something healthier it would be miraculous. Simply taking it away would just drive me to despair. Having attempted suicide in the past, I do everything I can to avoid that situation again, and unfortunately drinking became a big part of this effort.


In a Youtube video {Leveraging Dopamine, 2023}, neuroscientist Andrew Huberman defines addiction as "a progressive narrowing of the things that bring us pleasure".

I worry that framing the goal as, "a lasting way to shift that to something healthier", will prime you to switch from one addiction to another. I would prefer for you to frame it as diversifying the sources of pleasure in your life and becoming able to take pleasure (and consequent to take interest) in practical things that you currently experience as tedious obstacles that must be endured so that you can get your next drink.


People like Scott Galloway have been saying this for a while, and he's completely right. The research isn't all there quite yet for stopping addiction, but the research definitely points to GLP1's effectiveness at reducing food cravings, appetite (and anecdotally "food noise") for people taking it.

If you're looking for a quick primer on what the term "GLP1 Agonist" even means: https://glp1.guide/content/what-are-glp1-agonists/

This will absolutely have a huge effect on companies that sell ingestable... "luxuries"/addictive substances -- the only thing holding back the deluge of change is the accessibility/pricing of the drugs.

It also seems like the next phase of this is gene therapy:

https://glp1.guide/content/a-glimpse-of-the-future-glp1-gene...


I like that four out of the six posts on the Curing Addiction substack blog are about ozempic


hi! this is my substack post and new policy org. thanks to whoever posted this. hope you will subscribe!

we are looking for folks with MDs and PhDs or other experience in the field or in EA type writing to join the project. the thesis is that the addiction crisis is solvable if we put sufficient resources into new medication development, including GLP-1 for addiction and powerful non opiate painkillers like the Vertex drug that will be approved early next year.

addiction is the number 1 cause of DALYs in the united states if you include opiates, stimulants, alcohol, and cigarettes.

the right policies can get new treatments to people rapidly without massive public costs and without disrupting incentives. but we're currently on track for at least another decade of massive damage if we don't change things. join the effort!


These effects started being priced in last year. Citrini on Twitter called a lot of this out in advance and made a bunch of money on long/short plays. Might be some room left to run, but be careful shorting potato chip companies and fast food because you think you found a secret.


When I took Ozempic I had these side effects:

* Low libido and erectile dysfunction * Constipation, diarrhea, and extreme bloating (burping all night long) * Often difficulty sleeping. Waking up a lot. Very restless.

We need a drug that doesn't slow digestion but decreases hunger and increases satiety.


> We need a drug that doesn't slow digestion but decreases hunger and increases satiety.

This is exactly what it does for me. The only side effect I have is a little bit of occasional acid reflux.


These are some interesting side effects -- I'm not sure I've seen low libido very commonly -- have you noticed any other reports/disclosures of that sort of side effect?

Note that GLP1 RAs do decrease hunger, and their effects are very much also psychological. It's not simply a digestion slowing pharmacological effect.


> have you noticed any other reports/disclosures of that sort of side effect?

There are a few articles in the news. Nothing substantial yet.


Many years ago as a teen I worked seasonally at a big blue/yellow electronics store that sells TVs, computers, appliances....and candy at the register. Curious, I asked my manager about it.

"Oh yeah, someone comes in here to buy a $10 HDMI cable, and impulse buys a $2 candy bar at checkout. Instant 20% more sales. Gas stations, pharmacies, they all do it."


It ought to be illegal. Ideally I could choose to shop somewhere that didn’t do that, but like your boss said, they all do it. It makes shopping with small children hellish.


the UK is supposed to have made it illegal to have unhealthy stuff etc. near checkouts and illegal to include them in certain promos (e.g. buy-one-get-one-free) - I thought it had passed into law years ago, but when I had a quick look it isn't even due to take effected until 2025 and until then everyone is ignoring it anyway.


Imagine if you could sell cigarettes by the stick at the register. $1 for a cigarette.


And casinos apparently.


Take-for-life drugs with random paralysis as side effects that cost $12k per year might not be affordable by governments when half of society is obese.


We could also clamp down on addictive shit like Doritos and Oreos like we did with tobacco. Unbelievable that people will need to take a drug to escape the treachery of junk food companies everywhere you turn.


To achieve similar controls over sugar (and specifically fructose) as those put in place by eg the Cigarette Labeling and Advertising Act[0] (which mandated Surgeon General's warnings on cigarette packaging), the Public Health Cigarette Smoking Act of 1970[1], and the Family Smoking Prevention and Tobacco Control Act of 2009[2], we might need to first see lawsuits similar to those against tobacco companies. Litigation played a major role in shifting public opinion and policy, eg the 1998 Tobacco Master Settlement Agreement[3].

0. https://en.wikipedia.org/wiki/Cigarette_Labeling_and_Adverti...

1. https://en.wikipedia.org/wiki/Public_Health_Cigarette_Smokin...

2. https://en.wikipedia.org/wiki/Family_Smoking_Prevention_and_...

3. https://en.wikipedia.org/wiki/Tobacco_Master_Settlement_Agre...


Increasing and sustaining corn syrup consumption has been a key republican party strategy to win over rural farmers and agribusiness since the 70s. I just don't see them changing.


> A policy of cost-restriction and access guarantees would bring massive public health benefits.

Ah yes price controls, the best way to keep something inaccessible to everyone except those with personal connections.


For many (most?) drugs, the actual cost to produce the drug is usually far less than the selling price as it is an enforced monopoly. Given that monopoly, price restrictions don't actually restrict supply as the single supplier will still try to sell as much as they can to make as much as they can.


It probably wouldn’t have much of an impact on the sales or marketing of this product, but it’d definitely have significant impacts on drug manufacturers’ future plans (by reducing expected ROI & discouraging the development of ‘marginal drugs’).


Would it? Drug manufacturers don't really do as much 'R&D' as we assume, they buy biotech companies that have already discovered drugs. Also, why would a company stop wanting to make money? 'We are only going to make $5billion instead of $15 billion, let's not bother with that one.'


> 'We are only going to make $5billion instead of $15 billion, let's not bother with that one.'

Well, yes. If there's a 10% chance of success, these differences matter. Decision making happens at the margin.


How would they know how much one drug would make vs the other while in the research phase?


Private capital doesn't get allocated based on omniscience of future outcomes. It's about approximations of risk to reward in an environment of uncertainty. If you add risk or reduce reward of biotech, you get less private capital in biotech. Investors will allocate in other sectors with better risk to reward.


[flagged]


What is the moral issue? How is it evil?


Everyone already knows that diet and exercise are "the" solution to obesity, and yet it keeps getting worse.


If diet and exercise as an intervention were subjected to approval as a medical treatment they would never be approved. As a medical intervention they are rarely effective and when they are the effects are almost always temporary and relapse is worse than the original state. It’s about as effective as teaching abstinence to treat alcoholism or opioid addiction - but abstinence isn’t an option for food addiction.


Microplastics? Pesticides? Antibiotics in the feed?


The original proposed mechanism was probably wrong, these drugs probably make you change your diet. Or at least eat less, obviously you have to be concerned with nutrition.


[flagged]


Alcohol is a central nervous system depressant, so it can slow down vital functions leading to loss of consciousness and respiratory depression.

Nicotine is highly addictive and can lead to immediate withdrawal symptoms if usage is abruptly stopped. Short-term side effects include nausea, dizziness, and headaches. Smoking tobacco can also cause respiratory irritation. Long-term use can lead to serious health issues, including various forms of cancer and cardiovascular diseases.

Sugar can contribute to metabolic issues such as insulin resistance, which has immediate effects on metabolism and can lead to long-term health problems like type 2 diabetes.

All three substances—tobacco, sugar, and alcohol—have well-documented immediate effects on the body that can range from desirable (e.g., feeling relaxed or euphoric) to harmful (e.g., intoxication, poisoning, or overdose).

But let's focus on sugar for a minute. Research suggests that sugar intake alters composition and function of gut bacteria, which can have a whole host of knock-on effects. Fructose, additionally, drives inflammatory responses throughout the body which stresses all your organ systems. Chronic inflammation promotes heart disease, diabetes, arthritis... you name it. Sugar has links to changes in brain function, increasing risk of depression (this might be due to inflammation[0]) and may contribute to a greater likelihood of developing neurodegenerative diseases like Alzheimer's.

Sugar also raises triglyceride levels, and low-density lipoprotein (LDL) cholesterol profiles. Dietary sugars lead to higher de novo lipogenesis (DNL), increasing risk of cardiovascular disease. An increase in DNL can lead to an overproduction of triglyceride-rich very low-density lipoprotein (VLDL) particles, which are eventually converted into LDL particles in a process known as "adipose tissue remodeling". The phrase "adipose tissue" should strike fear into your heart, as this is the unsexy "fat" tissue that can lead to stigma and discrimination, negative judgments from others, joint stress, musculoskeletal disorders, and increased risk of injury.

So there's a mountain of evidence that you're wrong about Tobacco, sugar and alcohol.


Buddy, I have some bad news about tobacco and alcohol...


I had the thought there are gonna be some people on these drugs who will still find a way to have bad diets that keeps them fat and unhealthy. Since they have less appetite instead of a sandwich and a milkshake they will skip to the milkshake only.


When I was on Ozempic, I just didn't want the milkshake. It rewires all reward centers.


If they invent something like this but for procrastination, they'd get a Nobel prize.


It is called dexamphetamine. Or more more commonly these days, lysdexamphetamine.


Adderall is used pretty effectively for this.


Adderall and Vyvanse?


Anecdotally, those don't cure procrastination. They mostly cure issues with consistency and throughput once the task has begun. Starting the task is still the same hill to climb as it was before.


Oh God, imagine the self-, peer, and top-down pressure to take that, both for students and working adults.


No need to imagine, there's a reason Adderall, Vyvanse, and just about any amphetamine are banned in Japan.


You cant take these drugs forever afaik. Do they have permanent effects? It's just absurd to me the world has come to the point that we need these drugs in the first place but it makes total sense when you look at America for example. Awash in hyperpalatable processed "food" and corrupt food guidelines, a medical industry that "manages" chronic metabolic preventable disease but never cures it when probably 99% of cases could be reversed naturally. Big pharma and big food play their roles. Just insanity.


> absurd to me the world has come to the point that we need these drugs in the first place

GLP-1 looks increasingly like a miracle drug. We see problems of addiction and obesity skyrocketing across the developing world. It’s not cost free, but it’s a hell of a lot better than the majority of America, China and India becoming potatoes.

When vitamins were discovered, there was similar moralising about there being no free lunch. With the benefit of hindsight those concerns were misfounded. Perhaps Ozempic has terrible side effects that haven’t been noticed since 2005. Given that timeline, however, we can confidently say someone obese taking the drug is better off with it.

> never cures it

I have friends who took it, lost weight and then stopped. The rebound was real but nowhere close to what they lost. (The lifestyle changes also mostly stuck.) For all practical purposes, their fatness was cured.

> when probably 99% of cases could be reversed naturally

Scientifically unfounded.


Here's some more reading about reversing type 2 diabetes naturally. The current paradigm that one requires chronic disease management for the rest of their life is entirely false.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400171/#:~:tex.... "Although treating type 2 diabetes complications is of utmost importance to protect organ damage, it is now increasingly recognized that even the more ambitious goal of diabetes remission may be possible [6]. Thus, while there is little doubt that healthy lifestyle habits are the cornerstone of prevention of type 2 diabetes, they could also be used as an effective treatment to even potentially reverse type 2 diabetes. In this regard, the interesting narrative review published by Hallberg SJ and colleagues [7] has summarized the evidence that type 2 diabetes reversal is possible with the use of three different approaches: bariatric surgery, low-calorie diets and carbohydrate restriction."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716578/ "Unlocking the Potential of Type 2 Diabetes Mellitus Remission"


Reversing type 2 diabetes naturally is not scientifically unfounded at all. Look online in the right places and there is tons of people that have been able to stop taking all their insulin and metformin etc by fasting, compressing feeding windows, cutting out all carbs.

Even the ADA had to finally acknowledge this is possible in a statement back in 2021: https://diabetes.org/newsroom/international-experts-outline-...

It's not such a crazy idea really - You consume so many carbohydrates that you overproduce insulin and become insensitive to it in a vicious cycle. The more you fast, stay in a ketogenic metabolic status, reduce carbs and/or go zero carb, compress your feeding windows the more insulin sensitive you become.

There is no such thing as an essential carbohydrate. Your body can maintain your glucose needs by converting proteins into glucose. Fat and proteins are essential. Glucose is not it can be produce by liver.


> Reversing type 2 diabetes naturally is not scientifically unfounded at al

It’s absolutely possible. It’s unfounded that it even medically works for 99% of people, and that is while ignoring the obvious compliance problem.

> stay in a ketogenic metabolic status

Want to point out the naturalistic fallacy in assuming putting your body into an extreme condition for the long term is less harmful than a drug. (I say this as someone who intermittently fasts.)


It is absurd to you because you don't constantly crave food. It is easy for someone to say 'just don't eat so much' when they don't want to, but it is hard to not do something when you want it constantly and have access to it. Next time you are really thirsty, just don't drink anything -- then imagine something like that all the time.

> when probably 99% of cases could be reversed naturally.

What does that even mean? We aren't 'naturally' exposed to such calorie dense foods all the time and aren't 'naturally' supposed to be able to get any food with so little effort. What is natural about processed foods?


On the contrary, most weight loss doctors consider these drugs to be like statins. You take them for the rest of your life. The number of people who maintain healthy habits after stopping them is shockingly low.


> number of people who maintain healthy habits after stopping them is shockingly low

Source?



>It's just absurd to me the world has come to the point that we need these drugs

I agree. People did not need these drugs in the past but instead of fixing the social and economic structures which caused the obesity epidemic we tell people to take drugs to manage.

Oh, and take Adderall so you can focus. Again, nobody needed this in the past.

And Xanax to manage the anxiety people did not use to have either.

Feel unhappy and alone? They will make a pill for that too.

"Brave New World" turned out to be even more prophetic than "1984".


May I ask about your experience since leaving Ozempic compared to before you started taking it?

I'm not considering taking Ozempic nor am I aware of anyone who has, so I'm curious.


I haven't taken it, but my wife has and since she's been off, while she is eating more, it mainly appears to be maintenance as she's not really losing nor gaining weight anymore. Food just doesn't seem to be as big of a deal. We can enjoy a nice steak going out it's not as much as a draw.


But it still doesn't sound like a sustainable lifetime solution.

I think it makes great sense if you're badly out of shape, you fix it, and then you can maintain a healthy weight. But going on ozempic every few years sounds really bad.


"Sounds really bad" is orthogonal to "is really bad".

There's a heuristic that goes, "Shortcuts will catch up to people eventually," but I'm ok with letting the evidence bear that out.


Yeah that's the kind of folk wisdom that causes people with psychiatric conditions to stop taking their medications. It's very ignorant and harmful.


I don't think that's a fair analogy. Psychiatric medications don't have a non-pharmacological alternative in many cases. You can't just consciously do something and not be depressed or schizophrenic any more.

However, putting food in your mouth is a completely conscious decision. If people have problems with controlling that then I think that's what should be treated, instead of medicating your body to react to food differently. I think a future where we turn to drugs on an ongoing basis to compensate our unhealthy lifestyles is pretty dystopic.

Again, if someone is obese and struggles to lose weight I think Ozempic sounds like a great way to get on the road to health. I just don't think you should take it for the rest of your life instead of changing your lifestyle.


What you call dystopia, I call paradise. Evolution didn't give us bodies that are adapted to life in modern technological society. The better technology gets, the more unnatural the world gets for our bodies. People who are unfit to live won't die, because technology breaks the evolutionary process. Since we know that technology is better, the only way we can keep having it and thrive is by using more technology to hack our bodies so they're adapted for existence in the modern world.


I don't see it that way. Obesity is caused by deteriorating diets and lack of exercise. I don't think the solution is to keep the poor diet and lack of movement and treat only the resulting obesity. That's WALL-E, not paradise.

Many things get better with time and progress but I don't think our current lifestyles are some kind of evolutionary peak.


What do you think the ultimate causes of poor diet and lack of movement are?

All other things considered, how important is it that proximate or ultimate causes of obesity are addressed?


> What do you think the ultimate causes of poor diet and lack of movement are?

Cheap and plentiful high-calorie food and you're not forced to move if you've got a desk job. That might be modern but that doesn't mean it's better.


Is there any way to validate the claim in a way that excludes type one error?


> doesn’t sound like a sustainable lifetime solution

Would you same the same thing about insulin or statins or even caffeine? Why couldn’t something like Ozempic be something you take long term?


Because it has many bad side effects and it's only treating the symptom, when the real problem is eating too much? Should we keep medicating people for damage that they're continuing to do to themselves willingly?

With regards to caffeine, as a doctor would you prescribe lifetime energy drinks to people who intentionally don't sleep enough?

Insulin is totally different because if you're diabetic and you don't take it, you die. There's no cure for diabetes, so there's no other option but to take it for the rest of your life.

But if you've lost weight (either with ozempic or not), it's possible to not be obese again, you're totally in control of what you put in your mouth. It feels really weird to me to keep medicating people forever when there are well understood ways to manage your weight.

I think it's probably a great solution to help people who have lost control of their weight and need to get back on track. But using it to compensate for an unhealthy lifestyle going forward just seems like bad health policy.


The way it is done, people take them for the rest of their lives. It is not something you are supposed to get only for a while, it is not a cure in that sense. It’s still miles better than the alternative, which is staying obese.


For me, it's just less hunger and being full faster. I still want the milkshake, just a smaller one and less often.


It’s not about either or but portion control and limiting caloric intake. Also with alcohol it’s reduced consumption.


In March 2023, Novo Nordisk was suspended from the ABPI for a period of two years, for engaging in misleading marketing practices that amounted to "bribing health professionals with inducement to prescribe".[59] This is only the eighth time in the last 40 years that ABPI sanctioned a member organization.

https://en.m.wikipedia.org/wiki/Novo_Nordisk


"It’s pretty amazing that a reporter can write with a straight face that people eating less Doritos and Oreos is a ‘mounting concern’!"

This is a really bad-faith interpretation of what the reporter said. The "mounting concern" is linked to a CNBC video. It's obvious in context that it's the investors in processed food companies who are concerned, not the reporter herself.




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