Of all things my taxes go to, I would love it the United States Government would buy the patent for this drug and make it freely available to anybody who wants it.
The number of things it apparently just cures is staggering.
I have been on compounded GLP-1 for a month, prior to this I was a highly functional alcoholic, basically starting drinking after work every night and going until I passed out. I've drunk well over 50 beers (probably more) a week for the last 20 years. I have not had a drink since going on it.
I have been reading obsessively about this drug since going on it. I have been fortunate enough not to suffer side effects on it, save for one -- frustration with the cynicism around it. A cynicism I shared prior to experiencing its effects.
I am convinced that, barring any life threatening long term side effects, this is the most important drug of our lifetime (from a first world perspective) or until a silver bullet cancer drug is found. The potential to be the tide that lifts so many boats and alleviates so much physical and emotional pain and suffering on a population level is almost overwhelming to think about.
> barring any life threatening long term side effects
There's the rub. We have not been prescribing semaglutide very long, and I won't trust it until we've had enough time to suss out long term side effects.
My father was on a long-term maintenance dose of immunosuppressant (I think prednisolone, but I could be misremembering) following his kidney transplant. When it was first prescribed to him, the long term side effects were either not known at all or not widely known. By the time these side effects were more widely known, it was too late, as he was already losing his vision (cataracts) and mobility (cartilage was being destroyed). He spent his last few years in pain.
I am very cautious about the potential for damaging long-term side effects.
> There's the rub. We have not been prescribing semaglutide very long, and I won't trust it until we've had enough time to suss out long term side effects.
We've been prescribing GLP-1s for almost 20 years now. Not to say they all should behave identically, but from a Bayesian inference perspective these things really do appear to be quite safe.
Risk factors for NAION are basically all the things that you go on these drugs to treat - type 2 diabetes, sleep apnea, cardiovascular disease, blood pressure, etc. One observational study that shows some correlation isn't enough for me to be particularly concerned about it.
> As of March 31, only 4 cases of gastroparesis were recorded for semaglutide—the active ingredient in Ozempic and Wegovy—in the FDA Adverse Event Reporting System (FAERS), a surveillance database updated by healthcare professionals, consumers, and manufacturers. For tirzepatide—the active ingredient in Mounjaro and Zepbound—there is just one case logged.
I don't have more recent numbers, but these seem pretty low.
I don't think anyone is saying that there is no chance of significant side effects in people, but when measured against the risks of being obese, they'd have to be very bad and impact a significant number of people taking the drug.
Gastroparesis is a serious, life-threatening side effect.
It occurs in a small number of patients, sure, but maybe that just means I am more risk averse than you. My calculus is simple. I don't need wegovy. I can lose (and am losing) weight without it. Sure, it would be easier with wegovy, but it is not necessary. I am not going to take an unnecessary drug that has a nonzero chance of killing me.
Excellent! A huge chunk of people try and fail to do this for a wide variety of reasons.
If you can lose weight without the help of a GLP-1 drug, then yeah, that is likely the safest option. But most people aren't choosing between using a GLP-1 drug to lose weight or losing weight without it - they're choosing between staying fat and using the GLP-1.
We need to keep in mind that this drug address pretty much all of the biggest killers in the West. Not just one, but almost all of them. You name it - heart disease, obesity, alcoholism, smoking.
These things we already know are dangerous, and we also already know they're the most prevalent. We're not treating mesothelioma here.
> I am very cautious about the potential for damaging long-term side effects.
This is fair. But I'll ask you this: how long would it take for you to trust it? Assuming there are no side effects beyond what we know now, which are:
* gastroparesis is a small number of patients
* elevated thyroid cancer risk in mice
* nausea and general uncomfortableness when taking it (some percentage, not all)
* muscle and bone loss which seems to be roughly on par with any rapid weight loss approach
* a small percentage of people develop malaise, anhedonia and suicidal ideation
* a propensity to gain some percentage of weight back and/or relapse in addictive behavior when going off the drug
These are the side effects we know about with over a decade of prescribing GLP-1 agonists. Assuming these continue to be the primary side effects, how long would you wait until you are comfortable in trusting they are the only ones?
Agreed. The constant cynicism about everything, framed by some stupid moral hazard nonsense, is exhausting.
It reminds me of the British reaction to the famine in Ireland - the good ministers were concerned about the moral health of the Irish. If they were provided with charity food, it would be a terrible tragedy if they became dependent. Just let them starve to death, with a clean soul.
I do not have ADHD. I am not sure exactly why I drink so much -- there are a number of alcoholics on both sides of my family, but I also spent many years drinking in bars in a big city, living a very social life. During COVID I became much more of a solitary drinker and over the last five or so years I have drank out of a sense of malaise. Every morning became the day I was going to take a break and every night there was an excuse to start drinking again.
The strange thing about GLP-1s effect on my desire to drink is how it manifests: I just don't care about drinking. I actually _could_ drink and be fine I think, I haven't tested it. I don't go through life with the burden of the knowledge of my own addiction. I don't have to be vigilant about triggers and self-assess my actions. I just don't drink.
I noticed that I did not want to drink the day after my first shot. It was that fast. If anything the closest I came to drinking came from routine, not desire. That is to say, what is an afternoon watching football if not with a beer in hand? But I was able to move past that.
One thing I should make clear, no matter how heavy a drinker I have been at times in my life, including with liquor, I have never had a physical addiction. A person deep in the throws of physical addiction will need to approach this carefully.
I did not, but like I said above I've never had physical addiction such that it caused serious withdrawal symptoms (night sweats, seizures, etc have never been an issue for me), so I'm lucky in that respect. Mostly just tremors or what not when I'm on a string of binge drinking nights. I'm a big guy so I don't know if that's why, or just that I am lucky. In the last decade or so I primarily drink beer, mostly because I'm a very fast drinker and I will drink everything under the roof when I get a full head of steam, so I defensively avoid keeping liquor around.
My sleep has been pretty hosed up since I started but it wasn't like it was great before. I am also probably suffering from sleep apnea and I'm hoping to address that soon as I probably have another 4-6 months at the current weight loss rate before I am at a normal BMI.
Novo Nordisk's market cap is $500 B, mostly on the basis of GLP-1 drug profits, and the US' entire discretionary budget is $1,700 B. Even if Denmark would allow the sale, and even if somehow the US did not need to pay a premium to shareholders (typical in acquisitions), that would still be a very substantial expenditure.
The EU loves to ransom US tech companies for budget money. It's very clear that this is an opportunity for the US to similarly damage a big EU company by threatening its patents in the US, or otherwise hitting Novo for tens of billions of dollars in ransom money. The US market is by a huge margin the most important drug market in the world, and especially for Novo.
Find an abusive excuse to invalidate their patents if all else fails. Let Europe learn a valuable lesson in trade wars.
At this point in time, you are in no position to be teaching any lessons to the rest of the world, other than cautionary tales of wasted potential and the self-inflicted wounds of a belligerent populace.
Voting majority is also controlled by the Novo Nordisk Foundation. It's already the wealthiest foundation on the planet so they're unlikely to give up their flagship enterprise.
We already know the side-effects of the alternative because Western society as a whole has been living them.
It's bad. The obesity epidemic causes pretty much everything bad. This drug doesn't just solve one thing, it solves hundreds or thousands of things all at once.
This is the question and for people that are older the scales steadily tip towards just taking the damn drug because in 20 years they're likely to be dead anyways.
Seems like you need to increase the usage of it as your body starts adapting to it and the weight loss plateaus. IMO, I think the hype around this drug is a bit much and I expect a significant number of users won't be able to meet or maintain their weight loss goals with it.
I do think the dosing schedule should receive more personalization per-person. The schedule for tirzepatide is 2.5mg a week for the first month, then 5mg, then 7.5, etc.
For me, a month in on 2.5, I was still struggling to force myself to eat enough. Zero need to move up. Some people don't feel anything at all until they're on 7.5mg, though.
There's also a lot of people seeing better success with smaller doses more frequently, too. Instead of moving up to 5mg, I'm doing 2mg every 3-4 days. Loss is still steady and I'm not seeing any indication I'll need to bump up any time soon.
I’ll make my usual response: we know that being obese is basically the worst possible thing you can do to yourself, and the longer you are, the worse it is. The side effects are going to be pretty awful just to negate that, much less all the other things they seem to be good for.
>> being obese is basically the worst possible thing you can do to yourself
Lol. I can think of dozens of worse things. Drinking. Cocaine addiction. Meth. Winding up in prison for some reason. Riding a motorcycle without a proper helmet. Getting into a plane flown by Harrison Ford. Even simple unprotected sex can lead to massive medical problems. Ever looked up the average life expectancy of professional athletes, especially the NFL? It isn't great.
Being obese is probably worse for you. NAFLD has long eclipsed alcohol related liver issues.
> Even simple unprotected sex can lead to massive medical problems
Even treated HIV is probably less of a risk to your long term health than obesity, but I'm not a doctor.
> Cocaine addiction. Meth
OK, yes, there are illegal drugs that are going to be worse for you than being fat.
I'll rephrase:
Being obese is basically the worst possible thing you can do to yourself that affects a huge portion of the population of the western world.
Very very few people are riding motorcycles without a helmet, even fewer are getting into planes flown by harrison ford, only a tiny tiny tiny fraction of the population even has the option of being a professional athlete.
I like how the implicit sorting at the end here suggests Harrison Ford is ferrying around more people than there are professional athletes. Busy fella!
Okay, GLP-1 don't solve these but these aren't medical issues. This is just danger
> Even simple unprotected sex can lead to massive medical problems
Mmm... not really. People overblow this. Pretty much all STIs are completely harmless to your health if treated. One shot of penicillin and you're good to go. Your average flu is probably much worse than syphilis or chlamydia. HIV is the "biggest" risk, but HIV doesn't even impact your lifespan anymore.
Actually I recently listened to a fascinating hour long interview with Lotte Bjerre Knudsen (ACQ2 podcast) from which I learned that the original research started in the early 90s. I'm not an authority but I'm pretty well aware of the history. However, I'm still waiting for the other shoe to drop if you don't mind.
And I don't care about votes up or down. But I appreciate your theory on how they're playing out!
Is there a law of nature that says a chemical compound has to have a side effects of medical concern for a significant portion of people that ingest it?
One of the most commonly consumed drugs on the planet seems to indicate there is no such thing - caffeine in reasonable quantities is tolerated by the overwhelming majority of human beings and research indicates that even outside of the stimulant effects that humans use it for, it is beneficial. We have significant evidence that caffeine in the 100-400mg per day range decreases risk of heart disease and stroke, and smaller but still compelling evidence that it is protective against diabetes.
Irregular use does seem to cause a small increase in heart rate and blood pressure, but this fades in the overwhelming majority of users as they make the usage more regular.
Too much can cause adverse outcomes, such as anxiety, and in some people timing might be important for maintaining sleep quality, but the vast majority of us would see positive impact from consuming a cup or two of coffee in the morning with little to no concern around side effects.
Absolutely, I'm sure there's all kinds of drugs that are totally safe. And I have no reason to think that this one isn't. But it does seem to follow a classic pattern - people get unhealthy because modern life and technology have removed them, in a period of decades, from the environment, incentives, and activities that have shaped their bodies for millennia. And rather than looking at the simpler solutions - in this case just being more active and eating better - some new technological solution is created to fix the problem that the earlier technologies accidentally created. Then the cycle continues and other non-intended consequences ensue. So that's all I'm saying - it's interesting to watch humanity progress. Hope it works out for everyone and it's a smashing success!
> And rather than looking at the simpler solutions - in this case just being more active and eating better
I think this is the part where the argument falls apart, though. My relationship with food is vastly different now than it was when I was a teenager or in the front half of my 20s. It was easy for me to eat a healthy amount of food and exercise. I never struggled with it. It didn't take any particular amount of willpower to avoid overeating. I even was able to fairly easily bulk and cut because I was focused fairly heavily on lifting weights - the bulking was harder for me than the cutting!
But as I got busier with other aspects of my life, it became easier and easier to just grab some fast food, or swap over to eating almost entirely uber eats during the pandemic. Before I realized it, it was suddenly very hard to eat less. It was still possible - I would lose weight, manage my eating, exercise, etc. - but something would always happen that caused me to lose track and backslide. A huge project at work, a bad breakup, tearing my meniscus while lifting. But all of these attempts took significant effort and willpower from me, something that I had never struggled with before. It wasn't my metabolism slowing down - I was always hungry in a way that I had never faced when I was a slimmer person, and fighting it caused significant impact to my mood, ability to focus, stress levels, etc. Tirzepatide has put my relationship with food and hunger back to being much closer to how it was when I was younger.
There are tons of feedback loops that are well documented that makes it more and more difficult to lose weight once you've put it on and kept it on for a while. It's certainly true that there's no magical situation where people can eat fewer calories than they use and not lose weight, but for a huge amount of people, these GLP-1 medications are a far simpler solution.
> Hope it works out for everyone and it's a smashing success!
You're getting downvoted here but I think there is precedent behind your statement. History is littered with weight loss drugs that had to be pulled because the shoe eventually dropped. Usually that was addiction or death which, admittedly, neither have been shown in the GLP-1's but, given the history of weight loss drugs, it's not unreasonable in my opinion to be cautious.
I'm not a chemist, biologist, or pharmacologist, but wouldn't it be more reasonable to be cautious based on how analogous the method of action is to other drugs, rather than the effect? GLP-1s don't work in the same manner that phen/fen did, for example.
DNP is an extremely effective drug for weight loss, but no one who knows anything about how it works would think that it would be reasonable to compare it to the GLP-1s, and anyone who knows how it works would also plainly see the dangers around its use.
GLP-1 type drugs have been on the market for decades now as well, and while they are not perfectly safe, we've got a good amount of data around the short to medium term side effects.
First-gen GLP-1 goes off patent in 2031 (e.g. semaglutide). Seems far off, but is frighteningly close for Novo. Tirzepatide gets genericized in 2039 and has better efficacy, which is why Lilly is in such a strong position right now.
There is an enormous amount of biotech work to develop next-gen versions that have better half-lives, lower adverse events, and most importantly, have long patent lives. But it seems base GLP-1 are good enough that we should see massive societal change starting next decade.
Lilly is probably in an even stronger position if retatrutide continues to look as good as it has in the current trials. Better weight loss than tirzepatide, and recent results have shown it has excellent results on reducing fat deposits in the liver... and NAFLD is the leading cause of severe liver disease in the world.
It'll never happen, as long as American culture views body weight as a moral failing. We can't make it easy for people to fix the things we want them to fix, after all.
It is such a fucking no-brainer. The costs of obesity, both monetary and in terms of human suffering, are staggering. Absolutely fucking staggering. We should be making this as available as humanly possible, NOW.
Yeah, what could go wrong with screwing with the neurochemical reward system of the entire population. Surely that will have no unintended side effects. It's literally a free lunch!
what could go wrong with screwing with the neurochemical reward system of the entire population
We already know what can go wrong.
We already did that decades and decades ago. Sugar, for example. Aside from so many foods being laced with it, you can now simply walk into a store and buy a kilogram of sugar and eat it. So many other examples. That ship sailed a long long time ago. All we can do now is nudge the dial the other way.
He's saying we already have completely fucked our reward system.
That's why 75%+ of American are literally eating themselves to death. And they can't stop. And no, "discipline" isn't a solution.
If anything, I'd say Ozempic brings our reward systems to be more in line with modern reality. Monkey brain doesn't work when you have the unhealthiest food available constantly at your finger tips.
Regardless of your stance on anything, it should be obvious we have a HUGE problem. I'm sorry, but a "do nothing and hope it works" approach is now off the table. We need real, tangible solutions. Not moral grandstanding.
Hmm not quite. The bigger issue at hand is the large group of metabolic disorders linked to our unhealthy eating habits Alzheimer’s is now often referred to as Type 3 diabetes.
This drug in a nutshell partially paralyzes the stomach and upper intestine causing food to move through slowly. This has the effect of reducing food cravings as you literally stay full longer.
However slowing down the stomach muscles has many risks and many side effects.
Yes this drug is great for people who have struggled with weight loss and may not realistically be in a position to work on diet and exercise.
However this drug is not a substitute for the larger issue at hand. Many (possibly most) Americans are not living healthy lives in terms of mind, body (maybe spirit).
Improving physical activity leveled.. learning to eat less and to eat healthy should be a national priority. If anything the US government lack of addressing the elephant in the room and the underlying cause of many of these metabolic orders should outrage all Americans.
It doesn't appear that this is the issue. You can't explain a recent trend (obesity) using something that hasn't changed recently. And exercise is not very effective for weight loss compared to diet (it's something like 20%/80%).
The number of things it apparently just cures is staggering.