For the group, because I can never keep the terms straight:
Semaglutide is one specific drug within the class of GLP-1 agonists. Other examples include Liraglutide (Victoza, Saxenda), Dulaglutide (Trulicity), and Tirzepatide (Mounjaro, though this is technically a dual GIP/GLP-1 agonist).
Semaglutide is available under several brand names for different uses: Ozempic (type 2 diabetes), Wegovy (weight management), and Rybelsus (oral form for type 2 diabetes).
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.
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.
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.
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.
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.
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.
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.
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.
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%).
* Blood sugar levels (or whatever this is a proxy for)
* Weight
* The changes the GLP-1 Agonists make to the body itself.
While it is simple to say if you reduce the weight, you reduce the blood sugar levels, and so the GLP-1 is unnecessary, you can look at many accounts of using Ozempic where it talks about reducing the "food noise."
That is, Ozempic makes it easier to eat the right things. I'm a "normal weight" through grit, but I don't think my life is better through said grit - in fact, I'd say it's significantly worse. In my earlier life, I was naturally thin, and I can say that my weight increase wasn't a significant change to my diet, nor was my weight loss: I just had to be hungry and irritable more.
So, fundamentally, the cause and effect doesn't matter, because the drug makes it easier to be a more healthy weight and to control the blood sugar.
I keep making the comparison to nicotine gum/patches, but for food. I'm hoping that such a simple analogy might help some people move past their innate biases, but not much traction so far.
In western societies with high levels of obesity, health is a signal of wealth and prestige. There's no "innate bias" here, just alarm over the debasement of the value of being thin and healthy. It's a cruel posturing, nothing more.
> nor was my weight loss: I just had to be hungry and irritable more
Yes! I keep trying to explain to folks that this is the benefit of these drugs, they let you keep a healthy relationship with food, maintain "intuitive eating" where you aren't constantly fighting and discarding your hunger signals, and aren't (as) miserable doing it.
I did it the hard way, I wouldn't wish it on anyone.
Another interesting point from the study (full paper linked in a other comment) was the comparison of semaglutide to other GLP-1 agonists taken by patients, with the impact being significantly higher vs. those.
Obviously we need some more double blind studies dedicated to this class of drugs and Alzheimer's, but this informs the direction researchers and drug companies will likely map out.
It might help knowing that Ozempic will not make you skinny. IIRC it increases the effects of a healthy lifestyle change by 15%, effect which is lost if you leave it. The life style change (activity and nutrition) alone is more important, cheaper, and as permanent as you want it to be.
> It might help knowing that Ozempic will not make you skinny.
Plenty of people find their appetite capped at a level where the caloric intake will make them skinny. If they don't eat right and exercise, though, it won't necessarily bring them to great health. Like all caloric restriction, you will lose muscle mass if you don't ingest enough protein and perform resistance training, so you could still end up with a suboptimal lean body mass:fat ratio.
>IIRC it increases the effects of a healthy lifestyle change by 15%,
I'm not sure what this means. In the clinical trials for weight loss, semaglutide patients lost 10-15% of their body weight over the trial period, which might be what you mean? The trials don't indicate that this is the maximum, however - people have seen sustained weight loss for periods longer than the trials. Nor did it require people follow a specific diet or exercise plan. Plenty of people lose weight just eating less of what they were already eating - though this is generally not the best way to approach it.
>effect which is lost if you leave it.
Some number of people regain some or all of the weight they lost when going off the medication, but not all. However, the current indication is that people should be allowed to remain on the drug to maintain (generally at a lower dose) indefinitely if they need to. If the safety profile changes, this recommendation might also change.
>The life style change (activity and nutrition) alone is more important, cheaper, and as permanent as you want it to be.
Agreed. I'm someone who was quite fit when younger and let a variety of factors cause nutrition and exercise to fall farther and farther back on my priority list, and so far, tirzepatide has made it much easier for me to prioritize these things and enjoy them. I'm fairly confident once I have spent some time back at a healthier weight and developed long term habits around these things I'll be able to go off of it.
And how do you isolate being skinny because you are regularly active and eat well vs. being skinny because you are sedentary and eat garbage but then chase it down with a drug?
I think it's worth looking at the people taking it. While there is definitely nutritional education that needs to happen in behavior intervention, the key benefit to Ozempic is that people talk about it "turning down the food noise."
Those choices become easier when you have assistance.
This would be amazing if true, but the lack of randomization makes me nervous. What if, like, patients who are about to get Alzheimer's are less aggressive about asking their doctor for semaglutide (which has been in shortage for a while), and that explains the trial results?
Alzheimer (the regular one, not the early onset) is a progressive condition usually not detected early. Moreover, keep in mind it is possible we understand less about Alzheimer than we thought, from the very start
> nationwide database of electronic health records (EHRs) of 116 million US patients.
If you are expert in this space: Is such a dataset available publicly? If so, are there examples of other studies that have used this? Where does one go to read more about the mechanism of this study? Thanks!
I really really really wish my records were kept tight, offline, air gapped, or otherwise not stored on a cloud system with Trust Me Bro™ HIPAA-compliant security.
(The Trust Me Bro™ security aspect is the "It's secure because people will go to jail" and "We so totes won't use this easily subpoenaed data against you" security, when it would be best if the data stayed on a RAID in my doctor's office and an offsite VPN-linked backup instead. This goes 20x for psychs.)
According to this article, it's been (sorta) reproduced once, which is better than most studies. About 40-60% of scientific studies are not reproducible.
Given that, I'd want to see more reproductions.
Also, I'm very annoyed by our American culture which tries to fix problems with drugs, rather than preventing them from happening in the first place with good diet, exercise, sleep and stress management.
I think the food manufacturers are culpable here, and "manufacturer" is really the best word to use. They're more like chemists cobbling together edible compounds than farmers growing things that provide nutrition.
Absolutely. And every time I come on HN to point out processed foods are bad, I always get the feigned confusion "But are cooked carrots a processed food"
> good diet, exercise, sleep and stress management
The problem is these are individual solutions. We have a societal-wide problem. These solutions are therefore useless. You can't solve societal problems with individual solutions.
For example, I can't say "people shouldn't steal because it's immoral". It's true, and for me or you that might be enough to keep us from stealing. This is an individual solution.
The societal solution is how do you demotivate people from stealing? Now we're not talking about morals. We're talking about economics, poverty, crime prevention, the criminal-industrial complex, etc.
If you're waiting around for the day that American "culture" magically reverses itself and everyone wants to be healthy by their own accord, it will never come.
If you want an example of changing "culture", look at smoking. Hint: it has nothing to do with "being healthier". The changes we made were not about that.
Culture definitely changes, or else there would be no different cultures.
I like bottom-up way to approach it, rather than only top-down via policy.
Be healthy yourself and hopefully that bleeds out to your family and friends. If enough people do it, you have a different culture. Certainly possible given all the cultures that do prioritize these things.
I agree with your sentiment, but frankly human nature just doesn’t work that way. We don’t have self control. We weren’t evolved for a world of abundance. This is no one’s fault, and it’s everywhere, china is getting fatter than most countries now.
Realistically, ozempic is a miracle and it seems to be a solution to numerous issues of our world.
It would be nice if it wasn’t so, but apart from the 10% of people who can control themselves (which also causes psychological issues btw), most people just can’t.
I reject your assumption that "This is no one’s fault, and it’s everywhere, china is getting fatter than most countries now."
It's the food industrial complex's fault, along with many others (politicians, individuals without self control, etc)
I lived in rural Colombia for 4 years. People had access to the junk food, but it wasn't consumed very much because the veggies and meat are all produced locally and super tasty and cheap. And the local dishes were extremely meat and veggie based.
Oh, and most people know how to cook there.
It's not a fact of human nature to be unhealthy. It's a fact of modern culture.
Obesity is on the rise in a huge percentage of developed nations, and not just western ones. Even South Korea has seen a huge spike over the past decade - the amount of obese men /doubled/ between 2009 and 2019. It went up 3x in China between 1993 and 2015, and is on track to be over 20% by the end of the decade. Japan is increasing at a much slower rate, but it's still going up. 25% of people in India are overweight, with that number and morbid obesity numbers also increasing.
Basically every country sees obesity rise as the people gain access to the modern diet.
I don't care obesity is rising here and there, the fact that it is culturally induced remains, as it remains that a change lifestyle is the largest defense against obesity. Enjoy the magic pill for the rest of your life.
I'm fairly confident in my ability to get back in the same routine I had in my 20s and take myself off of it, but if staying on it is what it takes for me to remain fit and eating well, then sure. I don't mind giving myself an injection twice a week in exchange for good health.
If not needing it makes you feel superior, I'm glad you've found a source of self validation.
Where? In Japan, obesity among men has increased by 1.5x over the past several decades. It remains quite low, but the rate is still increasing year over year (slower with women). Vietnam, a country with one of the lowest obesity rates in the world is seeing an increase - the overweight and obesity rate has basically tripled since the early 2000s.
Alright - so whole community intervention, including literal celebrity chefs appearing and building out menus, can improve the situation.
Yes, if we remove all of the modern, processed, high calorie, energy dense, sugar heavy foods out of a place we can improve the obesity rate.
I hope you understand why individuals are going to take things into their own hands vs. waiting for massive societal change. I thought you were referring to whole cultures or countries making significant change here, not small communities.
TL;DR from the article:
The study found that patients prescribed semaglutide had a significantly lower risk for Alzheimer’s disease than those who had taken one of the seven other diabetes drugs. The results were consistent across gender, age and weight.
The biggest difference was seen when comparing patients who took semaglutide to those who took insulin: Semaglutide patients had a 70% lower risk of Alzheimer’s, the study found.
With the constant stream of positive news around GLP-1s, and ever-growing list of things they treat, we may all wind up on some dose with only the dose varying depending on what illness they're targeting.
> With the constant stream of positive news around GLP-1s, and ever-growing list of things they treat, we may all wind up on some dose with only the dose varying depending on what illness they're targeting.
So far, I haven't seen much evidence that GLP-1s have a positive effect on people who aren't overweight. And while I'll be the first to admit that the proportion of people who could benefit from these drugs is quite large, it's pretty far from everyone.
> So far, I haven't seen much evidence that GLP-1s have a positive effect on people who aren't overweight.
It is licensed, tested, and sold as a Type-2 Diabetes medication. Are you claiming it is ineffective for that purpose? Or if you're under the impression that no healthy weight T2 Diabetics exist, I have some news for you...
It is also being studied for: opioid addiction, alcoholism, Alzheimer's/Parkinson’s, Cardiovascular Disease, NASH, and PCOS.
"So far, I haven't seen evidence" may be more related to what you have read than what is available for you to read.
Don't dismiss the most important question -- does semaglutide really have any effects outside its current intended use for diabetes and weight loss?
In other words, would a thin, metabolically healthy person benefit from taking semaglutide?
So far, all of the wonderful benefits from taking the drug seem to be explainable by reduced caloric intake / weight loss / better glucose control in overweight and/or diabetic people.
> In other words, would a thin, metabolically healthy person benefit from taking semaglutide?
That's what this thread is about; and multiple other studies looking at different diseases/illnesses/addictions. Time will tell. It is currently approved for T2 Diabetes and Obesity.
There's also the intriguing possibility that many other diseases and even addictions have a heretofore-unknown metabolic component. The idea of some addictions -- even to things like heroin or gambling -- being partially metabolic does not seem far-fetched to me.
GLP-1 have already been on the mass market longer than Fen-Phen (7-years for Fen-Phen Vs. 15+ years, even just Semaglutide has been available longer than Fen-Phen now, and Semaglutide is a third-gen GLP-1).
Honestly, this retort can be made about any/all new drugs entering the market. If you had a legitimate retort/critique I'm sure you would have presented it, but this is all we get.
This is what happens when you start out with "[thing] is bad" then work backwards to figure out a reason.
Ultimately the main reason it's bad right now is it's expensive. Far beyond the amount needed to recoup research investment and far far far far far far far far far beyond what it takes to synthesize.
Low-end cost of $1000 a month is a lot. That's an expensive car lease, or half a cheap mortgage.
Suddenly USGov issues emergency production licenses and orders domestically to drop that down to effectively $0.10/kilodose on the market.
Suddenly when Denmark (or whoever) whines, USGov sends a cumulative NATO military defense bill, tells them they are the reserve currency, they have bigger nukes, and tough shit next time don't pork barrel the American people.
Lots of options for Americans; question is, can we be unprincipled enough to take the steps neccessary? :^)
I fully agree. Least of all because it is sold at between $60-200 abroad full-priced. Those countries just have price controls; the pharmacies are still making 80%+ profit margins in those places.
Ultimately, a lot of people will literally die because of this greed. That isn't hyperbole.
I mean it's literally as if people don't understand how drugs work, or what drugs actually do to human bodies.
It is as if those who do not remember the past are repeating it, already.
So many shills are singing the praises of this wonder drug.
In India we're all the rave
Discovered that it's great as aftershave, oh-ho
Dropped in the sea just off Japan
Swapped twenty bottles for an aqua-walkman, oh
Immunity from ridicule
Improves your brains if you're a fool, oh-ho
And I read in the Middle East
Traded some for a hostage release
Now if you're bald it'll give you hair
If you've got straight trousers it'll give you flares
Feeling up you'll get depressed
Out of style here's a brand new dress, oh
It was really vile weather
When we got tarred and feathered
You could hear the six-guns sound
As they chased us out of town
How long has Ozempic been around? I've never heard of it until very recently (maybe the last month or two) and suddenly I'm seeing it all the time. Maybe this is an instance of Baader-Meinhof phenomenon, but it doesn't feel like it.
Ozempic has been around about 10 years used mostly for diabetes, but it's use for weight loss management has exploded with the release similar drugs using the same core principles such as Wegovy and Mounjaro. There's also definitely a compounding effect of it being successful for people and them telling their friends.
I just listened to an in-depth analysis of this last night. All of these great effects can be explained by reduced caloric intake / weight loss / better glucose control. In other words - it just means it works as intended.
So while it's an amazing drug / new class of drugs, it probably will not lower risk of Alzheimer's in metabolically healthy people.
If it independently helps lower the risk of Alzheimer's even in people that are not diabetic and are of healthy body weight, then it might be worthwhile for those people to take.
If it's purely around the weight loss, etc., then it won't.
I don't think the comment was meant to minimize the impact of losing weight on health.
You might think that these two (get skinny and lower Alzheimer's risk) are the only two benefits, but don't forget that this drug is also pretty much the end of the road for the "More People Should Be Fat!/HAES movement".
Agreed. I'm down for being empathetic to fat people - as a fat person! - but I have never understood the movement to just deny reality and act like it's acceptable to be fat from a health perspective. Obviously fat people should still have access to healthcare, but putting our heads in the sand and pretending that it isn't a situation that has huge impact on our quality of life and lifespan has always struck me as absurd.
Because other interventions have the consequence of actually working.
If we compare the efficacy of "telling people to lose weight" vs taking ozempic, there is a stark contrast. Pooled results show that education and counselling[sic] did not significantly reduce weight (SMD –0.73, 95% CI –1.89 to 0.42, n = 3 studies; I 2 = 98%)[1]. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo[2].
Telling people to just lose weight is not an evidence-backed intervention to affect weight loss. Continuing to practice it is equivalent to practicing folk medicine or alternative medicine. Despite us wanting it to work, it does not. Like all interventions, pharmaceutical interventions have the possibility of side effects, and it's up to the patient and doctor to weight risk vs reward. There is variation in both for each case, but we have to keep in mind that the mere existence of side effects is not typically a reason for categorically deciding against using a drug.
My bad guys, didn’t mean to be negative in my original post.
Definitely lacking in compassion. Whether it be obesity or anorexia, these are almost always symptoms of something deeper underlying. I shouldn’t be so flippant.
I think I still have to stand by my belief that semaglutide won’t truly solve people’s relationship with food though. That requires going deeper than the temporary solution drugs might provide.
> I think I still have to stand by my belief that semaglutide won’t truly solve people’s relationship with food though.
That sounds fair. I see a lot of over/under weight results as a symptom of a maladaptive coping mechanism for some other issue. Sometimes the issue is simply not having meaning in one's life, but it really can be anything from depression, to anxiety, to lack of friends because of social phobias or low self-esteem.
Looking at this this way helped me find more compassion and less contempt. I hope it helps you too
Do you think obese people have never tried just eating less? That doctors never tell them to do this and they never give it an attempt?
Yes, it is possible for every obese person on this planet to eat less and stop being fat. 100%.
But for some people, this is actually really difficult to do! And the more fat you put on, the more feedback loops there are in your body that push you towards eating more. Insulin and ghrelin response are big ones, but it wrecks your sex hormones, too - you're almost certain to see massive testosterone drops in men, which further stimulates your body to deposit more fat and build less muscle.
Being told to lose weight by diet and exercise is probably the most prescribed treatment on the planet, and one with one of the absolute lowest success rates.
So easy to invent imaginary diseases to cover for decadent lack of willpower and portray a decent life hygiene as something as heroic as firewalking or quitting crack.
My mom is obese because she developed an autoimmune disorder while she was pregnant with me that attacks her thyroid. She has extremely abnormal thyroid cells that have to be biopsied twice a year and she has to take daily thyroid medication or she will die. She is about to start on Ozempic as well because the thyroid medication is not enough.
To manage her disease, she eats much less and much healthier (e.g., steamed kale for dinner every night) than everyone else in my family, and yet she is the obese one amongst us.
Please stop acting like life-saving drugs are evil and everything can be managed through willpower alone. My mom would be dead without modern medical science, and I would have died in the womb with her.
Are your seriously implying that your special case is statistically significant or that people like me are against the use of medicine for these? Your blog post completely misses the point: I didn't write imaginary just for kicks.
Statistically, people that manage to quit most chemical addictions have lower recidivism rates than people who lose weight through dieting.
So, possibly it is?
I for one have far less trouble keeping any of my drug and alcohol use to reasonable levels than I do avoiding overeating. I can quit drinking or smoking pot for months or years on end without even much thinking about it, but my attempts to lose weight without tirzepatide tended to be huge struggles that I would crash and burn on after 6 or so months.
The entire point of the ADHD diagnosis, in fact, is about the inability or reduced ability to "just focus more", and the medicine's purpose is to alleviate that imbalance
“Why” is a weird question. We don’t know why. We do know that people don’t just eat less. Haven’t in decades. No plan that relies on changing that is practical.
> Why not just lose weight by eating less? I know that sounds like a dumb question.
Because it requires willpower and discipline, this just a pill/injection doing all the heavy work for you. Hence the success in USA. There are countries where this drug is semi unknown.
And it's becoming more and more known because obesity is a growing problem for nearly the entirety of the developed world.
If you're so convinced that obesity is a moral failing, then just put 'no fatties and no fake skinny glp-1 users' in your tinder profile, and all of the rest of us can move on with our days.
I don't know where you live, but the places where obesity isn't on the rise are heavily outnumbered by the places where it is. It's a global problem.
Easy and cheap access to calorie dense food and food heavy in sugars seems to nearly universally be something that significant portions of the population have difficulty resisting overindulging in, regardless of culture.
For the group, because I can never keep the terms straight:
Semaglutide is one specific drug within the class of GLP-1 agonists. Other examples include Liraglutide (Victoza, Saxenda), Dulaglutide (Trulicity), and Tirzepatide (Mounjaro, though this is technically a dual GIP/GLP-1 agonist).
Semaglutide is available under several brand names for different uses: Ozempic (type 2 diabetes), Wegovy (weight management), and Rybelsus (oral form for type 2 diabetes).
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.
https://www.drugwatch.com/legal/ozempic-lawsuit/
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.
Wow, someone experienced an adverse effect from a drug and are suing?
This adds literally zero information.
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.
>I can lose (and am losing) weight without it
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've been prescribing GLP-1s [for diabetes] for almost 20 years now
The dosage though for losing weight is 3 or 4 times the dosage for diabetes.
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?
We've been prescribing semaglutide since 2017 and the predecessor since 2010.
Exenatide, a GLP-1, was approved in 2005.
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.
Calling it: It’s because it’s antiinflammatory. (It is antiinflammatory. Calling it: That’s the reason.)
2.5mg?
Still titrating up, will be there in a month.
Can you describe what happened that you don't want to drink?
Edit: oh, I see you describe it elsewhere in the thread. Thank you for sharing.
do you have adhd, and do you think your drinking is at all related to adhd/lack of executive function? just curious, not implying.
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.
how long did you keep drinking after starting? thanks for response
No prob.
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.
If you are interested in this topic, I highly recommend reading this newsletter: https://recursiveadaptation.com/
There is a lot of great writing on this subject and some real world testimonies in there. Also happy to answer any more questions here.
Did you have any withdrawal symptoms after stopping alcohol so suddenly?
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 correct unit of measurement here is Iraq wars.
Purchasing NN Would cost roughly 0.2 Iraq wars.
That is a sensible unit.
This ignores the fact that the patents expire in 5-7 years, GLP1 is (relatively) trivial to produce and will be a $100 generic by 2032.
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.
That's not the way to go about it at all.
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.
Not to be that guy but obesity is arguably kind-of a national security emergency thing...
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.
Gonna be fun discovering what side effects it causes in 20 years tho.
- Significantly increased mortality risk
- Higher rates of cardiovascular disease
- Type 2 diabetes
- Sleep apnea and breathing problems
- Osteoarthritis due to excess pressure on joints
- Multiple types of cancers (colon, breast, endometrial)
- Depression and anxiety from social stigma
- Reduced mobility and quality of life
- Higher medical costs (~$1,429 more annually per person)[1]
- Decreased workplace productivity
- Shorter life expectancy (can reduce by 5-10 years)
Oh no wait, sorry, those are the effects of obesity.
[1] https://pubmed.ncbi.nlm.nih.gov/19635784/
Right, this is what people aren't understanding.
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.
The real question is whether these side-effects are going to be worse than 20 years of not taking it.
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.
You might be right, but it has been in testing/development for 20 years now.
Take a look at exenatide, a GLP-1 that was FDA-approved in 2005.
https://www.perplexity.ai/search/does-exenatide-lower-or-ext...
It will likely save so many lives, it may still make sense to take it with those risks.
Liraglutide, the predecessor to semaglutide, has been on the market for 15 years :)
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.
it'd have to be pretty bad to outpace mortality for being obese
Exactly. I see all these breathless claims of new uses and how wonderful this drug is and wonder when the other shoe is going to drop.
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.
> drinking
GLP-1 solves this too
> Cocaine addiction
GLP-1 solves this
> Meth
GLP-1 solves this
> Prison ... no helmet
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.
> Drinking
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.
> Drinking. Cocaine addiction. Meth.
Ozempic treats all of those too.
You're getting downvoted because you didn't even care to do a simple Google search as to when the first GLP-1 was released. 2005. Almost 20 years.
We have the data.
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!
Me too!
> just being more active and eating better
You're grossly underestimating the problem.
40+% of the population are obese.
This isn't just a few pounds to lose. This is 60, 70, 100lbs.
The task is to lose the weight forever.
For which long term weight loss success numbers are abysmal.
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.
GLP-1s are completely different from all those drugs. There's no reason to use them as evidence for it.
They don't have to buy the patent, they can issue a compulsory licence for it https://en.wikipedia.org/wiki/Compulsory_license#United_Stat...
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.
God save us if a non US company is successful, or -gasp- profitable.
One could assume that the US purchasing the patent would be very profitable for the company selling it.
whoa that is a crazy, powerful idea. my favorite kind.
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.
Because you can buy sugar from the store, having the US subsidize ozempic for for the entire population makes logical sense. Got it.
That's not even close to what he said.
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.
Perhaps you could take your childishness elsewhere. It does grow tiring.
You are not the arbiter of what is "childish".
This style of condescension does grow tiring.
oh, so i guess you live outside and hunt animals for food? how's your all-natural neurochemical reward system?
If I'm not completely natural, then the entire population should have access to subsidized ozempic. Got it.
ie subsidized ozempic means everyone will use it?
You aren't making compelling points by pretending the OPs are stating things they are not.
so you used the same logic that i made fun of in your post to make fun of the logic in your post... to say that my post was silly?
>> The number of things it apparently just cures is staggering.
It cures behavior, not directly disease. I see red flags. Firefly did a movie about a drug that interfered with people's motivations to do things.
What evidence would it take to change your no-free lunch heuristic?
Are you seriously suggesting that Ozempic might lead to the Reavers from Firefly?
I don't remember seeing any overweight or obese people on Miranda.
Thank you
Nothing is being healed, we are just helping people cope with excess
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.
Just my two cents
> is now often referred to as Type 3 diabetes.
No it isn't. Stop trying to make fetch happen.
> Improving physical activity leveled
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%).
How do you isolate this from the therapeutic benefits of simply losing weight and being skinny?
There are multiple confounding factors:
* Blood sugar levels (or whatever this is a proxy for)
* Weight
* The changes the GLP-1 Agonists make to the body itself.
While it is simple to say if you reduce the weight, you reduce the blood sugar levels, and so the GLP-1 is unnecessary, you can look at many accounts of using Ozempic where it talks about reducing the "food noise."
That is, Ozempic makes it easier to eat the right things. I'm a "normal weight" through grit, but I don't think my life is better through said grit - in fact, I'd say it's significantly worse. In my earlier life, I was naturally thin, and I can say that my weight increase wasn't a significant change to my diet, nor was my weight loss: I just had to be hungry and irritable more.
So, fundamentally, the cause and effect doesn't matter, because the drug makes it easier to be a more healthy weight and to control the blood sugar.
I keep making the comparison to nicotine gum/patches, but for food. I'm hoping that such a simple analogy might help some people move past their innate biases, but not much traction so far.
In western societies with high levels of obesity, health is a signal of wealth and prestige. There's no "innate bias" here, just alarm over the debasement of the value of being thin and healthy. It's a cruel posturing, nothing more.
> nor was my weight loss: I just had to be hungry and irritable more
Yes! I keep trying to explain to folks that this is the benefit of these drugs, they let you keep a healthy relationship with food, maintain "intuitive eating" where you aren't constantly fighting and discarding your hunger signals, and aren't (as) miserable doing it.
I did it the hard way, I wouldn't wish it on anyone.
Another interesting point from the study (full paper linked in a other comment) was the comparison of semaglutide to other GLP-1 agonists taken by patients, with the impact being significantly higher vs. those.
Obviously we need some more double blind studies dedicated to this class of drugs and Alzheimer's, but this informs the direction researchers and drug companies will likely map out.
Omg, you figured it out! Shit.
All we need to do is just tell a few million people to lose weight.
I think you misunderstood what they were asking.
If it’s the drug and not the weight loss that lowers Alzheimers risk, then even people who are not overweight might benefit from the drug.
"That was Easy!"™
It might help knowing that Ozempic will not make you skinny. IIRC it increases the effects of a healthy lifestyle change by 15%, effect which is lost if you leave it. The life style change (activity and nutrition) alone is more important, cheaper, and as permanent as you want it to be.
Losing weight is still a hard endeavor.
> It might help knowing that Ozempic will not make you skinny.
Plenty of people find their appetite capped at a level where the caloric intake will make them skinny. If they don't eat right and exercise, though, it won't necessarily bring them to great health. Like all caloric restriction, you will lose muscle mass if you don't ingest enough protein and perform resistance training, so you could still end up with a suboptimal lean body mass:fat ratio.
>IIRC it increases the effects of a healthy lifestyle change by 15%,
I'm not sure what this means. In the clinical trials for weight loss, semaglutide patients lost 10-15% of their body weight over the trial period, which might be what you mean? The trials don't indicate that this is the maximum, however - people have seen sustained weight loss for periods longer than the trials. Nor did it require people follow a specific diet or exercise plan. Plenty of people lose weight just eating less of what they were already eating - though this is generally not the best way to approach it.
>effect which is lost if you leave it.
Some number of people regain some or all of the weight they lost when going off the medication, but not all. However, the current indication is that people should be allowed to remain on the drug to maintain (generally at a lower dose) indefinitely if they need to. If the safety profile changes, this recommendation might also change.
>The life style change (activity and nutrition) alone is more important, cheaper, and as permanent as you want it to be.
Agreed. I'm someone who was quite fit when younger and let a variety of factors cause nutrition and exercise to fall farther and farther back on my priority list, and so far, tirzepatide has made it much easier for me to prioritize these things and enjoy them. I'm fairly confident once I have spent some time back at a healthier weight and developed long term habits around these things I'll be able to go off of it.
And how do you isolate being skinny because you are regularly active and eat well vs. being skinny because you are sedentary and eat garbage but then chase it down with a drug?
I think it's worth looking at the people taking it. While there is definitely nutritional education that needs to happen in behavior intervention, the key benefit to Ozempic is that people talk about it "turning down the food noise."
Those choices become easier when you have assistance.
This would be amazing if true, but the lack of randomization makes me nervous. What if, like, patients who are about to get Alzheimer's are less aggressive about asking their doctor for semaglutide (which has been in shortage for a while), and that explains the trial results?
Alzheimer (the regular one, not the early onset) is a progressive condition usually not detected early. Moreover, keep in mind it is possible we understand less about Alzheimer than we thought, from the very start
https://www.nbcnews.com/science/science-news/alzheimers-theo...
This publication is bogus. It is too soon to know if there is any benefit at all from Semaglutide.
> nationwide database of electronic health records (EHRs) of 116 million US patients.
If you are expert in this space: Is such a dataset available publicly? If so, are there examples of other studies that have used this? Where does one go to read more about the mechanism of this study? Thanks!
Likely this is some aggregator in the Healthcare space that uses tools that effectively fingerprint patients in each EHR.
This deduplicates patients and lets them find specific details like which medications they are on without knowing any PII.
It's very common for researchers within health systems to want to collaborate and combine populations to perform retroactive data analysis.
There is no public dataset of EHRs of this size.
I really really really wish my records were kept tight, offline, air gapped, or otherwise not stored on a cloud system with Trust Me Bro™ HIPAA-compliant security.
(The Trust Me Bro™ security aspect is the "It's secure because people will go to jail" and "We so totes won't use this easily subpoenaed data against you" security, when it would be best if the data stayed on a RAID in my doctor's office and an offsite VPN-linked backup instead. This goes 20x for psychs.)
Almost all health datasets are not public
According to this article, it's been (sorta) reproduced once, which is better than most studies. About 40-60% of scientific studies are not reproducible.
Given that, I'd want to see more reproductions.
Also, I'm very annoyed by our American culture which tries to fix problems with drugs, rather than preventing them from happening in the first place with good diet, exercise, sleep and stress management.
I think the food manufacturers are culpable here, and "manufacturer" is really the best word to use. They're more like chemists cobbling together edible compounds than farmers growing things that provide nutrition.
Absolutely. And every time I come on HN to point out processed foods are bad, I always get the feigned confusion "But are cooked carrots a processed food"
A drug that reduces appetite is kinda tackling good diet, at least.
Keyword is "kinda"
> good diet, exercise, sleep and stress management
The problem is these are individual solutions. We have a societal-wide problem. These solutions are therefore useless. You can't solve societal problems with individual solutions.
For example, I can't say "people shouldn't steal because it's immoral". It's true, and for me or you that might be enough to keep us from stealing. This is an individual solution.
The societal solution is how do you demotivate people from stealing? Now we're not talking about morals. We're talking about economics, poverty, crime prevention, the criminal-industrial complex, etc.
If you're waiting around for the day that American "culture" magically reverses itself and everyone wants to be healthy by their own accord, it will never come.
If you want an example of changing "culture", look at smoking. Hint: it has nothing to do with "being healthier". The changes we made were not about that.
Culture definitely changes, or else there would be no different cultures.
I like bottom-up way to approach it, rather than only top-down via policy.
Be healthy yourself and hopefully that bleeds out to your family and friends. If enough people do it, you have a different culture. Certainly possible given all the cultures that do prioritize these things.
These aren't preventative drugs, they are to treat people who are already fat.
Looks like this is not exactly true given they reduce cravings.
Where did I say it was a preventative drug?
I agree with your sentiment, but frankly human nature just doesn’t work that way. We don’t have self control. We weren’t evolved for a world of abundance. This is no one’s fault, and it’s everywhere, china is getting fatter than most countries now.
Realistically, ozempic is a miracle and it seems to be a solution to numerous issues of our world.
It would be nice if it wasn’t so, but apart from the 10% of people who can control themselves (which also causes psychological issues btw), most people just can’t.
I reject your assumption that "This is no one’s fault, and it’s everywhere, china is getting fatter than most countries now."
It's the food industrial complex's fault, along with many others (politicians, individuals without self control, etc)
I lived in rural Colombia for 4 years. People had access to the junk food, but it wasn't consumed very much because the veggies and meat are all produced locally and super tasty and cheap. And the local dishes were extremely meat and veggie based.
Oh, and most people know how to cook there.
It's not a fact of human nature to be unhealthy. It's a fact of modern culture.
Lol, no. There are countries in which obesity is nonexistent.
Obesity is on the rise in a huge percentage of developed nations, and not just western ones. Even South Korea has seen a huge spike over the past decade - the amount of obese men /doubled/ between 2009 and 2019. It went up 3x in China between 1993 and 2015, and is on track to be over 20% by the end of the decade. Japan is increasing at a much slower rate, but it's still going up. 25% of people in India are overweight, with that number and morbid obesity numbers also increasing.
Basically every country sees obesity rise as the people gain access to the modern diet.
I don't care obesity is rising here and there, the fact that it is culturally induced remains, as it remains that a change lifestyle is the largest defense against obesity. Enjoy the magic pill for the rest of your life.
I'm fairly confident in my ability to get back in the same routine I had in my 20s and take myself off of it, but if staying on it is what it takes for me to remain fit and eating well, then sure. I don't mind giving myself an injection twice a week in exchange for good health.
If not needing it makes you feel superior, I'm glad you've found a source of self validation.
Imagine your reaction if smokers were to make the same point and voila, this is how ridiculous it sounds.
There are places in the world you could point to that are not obese and in fact has decreased. So it's certainly possible to emulate that.
Where? In Japan, obesity among men has increased by 1.5x over the past several decades. It remains quite low, but the rate is still increasing year over year (slower with women). Vietnam, a country with one of the lowest obesity rates in the world is seeing an increase - the overweight and obesity rate has basically tripled since the early 2000s.
Huntington, West Virginia: https://www.advisory.com/daily-briefing/2020/01/27/fattest-c...
The solution involved exercise and diet, surprise surprise. It's not magic or some law of nature that people will only get more fat and unhealthy.
If we think that way, then it will surely happen though.
Alright - so whole community intervention, including literal celebrity chefs appearing and building out menus, can improve the situation.
Yes, if we remove all of the modern, processed, high calorie, energy dense, sugar heavy foods out of a place we can improve the obesity rate.
I hope you understand why individuals are going to take things into their own hands vs. waiting for massive societal change. I thought you were referring to whole cultures or countries making significant change here, not small communities.
Typically, because less food is available in day-to-day life.
If I sold cigs on every street corner in a "skinny" country like Japan, how confident are you that I wouldn't create a smoking culture?
This is not a matter of motivation or discipline. Such thinking is short-sighted.
> If I sold cigs on every street corner in a "skinny" country like Japan, how confident are you that I wouldn't create a smoking culture?
Considering Japan has long been one of the highest per capita consumers of tobacco, apparently it's quite likely ;)
It makes your poop sit in your tummy and rot
This isn't true
TL;DR from the article: The study found that patients prescribed semaglutide had a significantly lower risk for Alzheimer’s disease than those who had taken one of the seven other diabetes drugs. The results were consistent across gender, age and weight.
The biggest difference was seen when comparing patients who took semaglutide to those who took insulin: Semaglutide patients had a 70% lower risk of Alzheimer’s, the study found.
Full link to the study itself: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz...
With the constant stream of positive news around GLP-1s, and ever-growing list of things they treat, we may all wind up on some dose with only the dose varying depending on what illness they're targeting.
> With the constant stream of positive news around GLP-1s, and ever-growing list of things they treat, we may all wind up on some dose with only the dose varying depending on what illness they're targeting.
So far, I haven't seen much evidence that GLP-1s have a positive effect on people who aren't overweight. And while I'll be the first to admit that the proportion of people who could benefit from these drugs is quite large, it's pretty far from everyone.
> So far, I haven't seen much evidence that GLP-1s have a positive effect on people who aren't overweight.
It is licensed, tested, and sold as a Type-2 Diabetes medication. Are you claiming it is ineffective for that purpose? Or if you're under the impression that no healthy weight T2 Diabetics exist, I have some news for you...
It is also being studied for: opioid addiction, alcoholism, Alzheimer's/Parkinson’s, Cardiovascular Disease, NASH, and PCOS.
"So far, I haven't seen evidence" may be more related to what you have read than what is available for you to read.
Don't dismiss the most important question -- does semaglutide really have any effects outside its current intended use for diabetes and weight loss?
In other words, would a thin, metabolically healthy person benefit from taking semaglutide?
So far, all of the wonderful benefits from taking the drug seem to be explainable by reduced caloric intake / weight loss / better glucose control in overweight and/or diabetic people.
> In other words, would a thin, metabolically healthy person benefit from taking semaglutide?
That's what this thread is about; and multiple other studies looking at different diseases/illnesses/addictions. Time will tell. It is currently approved for T2 Diabetes and Obesity.
There's also the intriguing possibility that many other diseases and even addictions have a heretofore-unknown metabolic component. The idea of some addictions -- even to things like heroin or gambling -- being partially metabolic does not seem far-fetched to me.
Why would taking a drug you don't need for the rest of your days be a good thing?
what's the alternative?
Struggling with food, being extremely overweight the rest of your life, and not being able to play with your kids because of it?
Don't stuff your face with a 2500kcal Oreo and ice cream shake?
My PCP agrees that the great results I'm getting on Fen-Phen mean I won't need to switch!
GLP-1 have already been on the mass market longer than Fen-Phen (7-years for Fen-Phen Vs. 15+ years, even just Semaglutide has been available longer than Fen-Phen now, and Semaglutide is a third-gen GLP-1).
Honestly, this retort can be made about any/all new drugs entering the market. If you had a legitimate retort/critique I'm sure you would have presented it, but this is all we get.
This is what happens when you start out with "[thing] is bad" then work backwards to figure out a reason.
Ultimately the main reason it's bad right now is it's expensive. Far beyond the amount needed to recoup research investment and far far far far far far far far far beyond what it takes to synthesize.
Low-end cost of $1000 a month is a lot. That's an expensive car lease, or half a cheap mortgage.
These things are priced against their alternatives, and so are almost definitionally less expensive than the status quo ante.
Suddenly it's a national security issue.
Suddenly USGov issues emergency production licenses and orders domestically to drop that down to effectively $0.10/kilodose on the market.
Suddenly when Denmark (or whoever) whines, USGov sends a cumulative NATO military defense bill, tells them they are the reserve currency, they have bigger nukes, and tough shit next time don't pork barrel the American people.
Lots of options for Americans; question is, can we be unprincipled enough to take the steps neccessary? :^)
I fully agree. Least of all because it is sold at between $60-200 abroad full-priced. Those countries just have price controls; the pharmacies are still making 80%+ profit margins in those places.
Ultimately, a lot of people will literally die because of this greed. That isn't hyperbole.
I mean it's literally as if people don't understand how drugs work, or what drugs actually do to human bodies.
It is as if those who do not remember the past are repeating it, already.
So many shills are singing the praises of this wonder drug.
Hasn't there been speculation/study along the lines of Alzheimer's being a form of diabetes?
Yes. For example: "Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal" https://www.sciencedirect.com/science/article/pii/S092544391...
https://www.sciencedirect.com/science/article/pii/S258953702...
How long has Ozempic been around? I've never heard of it until very recently (maybe the last month or two) and suddenly I'm seeing it all the time. Maybe this is an instance of Baader-Meinhof phenomenon, but it doesn't feel like it.
Ozempic has been around about 10 years used mostly for diabetes, but it's use for weight loss management has exploded with the release similar drugs using the same core principles such as Wegovy and Mounjaro. There's also definitely a compounding effect of it being successful for people and them telling their friends.
Trials started in 2008 AFAICT: https://en.wikipedia.org/wiki/Semaglutide#History
Finally, pharma is paying for studies showing the advantages of not being obese.
Is it the ozempic or just the healthier weight / lower calorie intake?
I just listened to an in-depth analysis of this last night. All of these great effects can be explained by reduced caloric intake / weight loss / better glucose control. In other words - it just means it works as intended.
So while it's an amazing drug / new class of drugs, it probably will not lower risk of Alzheimer's in metabolically healthy people.
"Just"?
If it independently helps lower the risk of Alzheimer's even in people that are not diabetic and are of healthy body weight, then it might be worthwhile for those people to take.
If it's purely around the weight loss, etc., then it won't.
I don't think the comment was meant to minimize the impact of losing weight on health.
Get skinny and keep my brain? No thanks. At some point this roller coaster ride needs to end.
You might think that these two (get skinny and lower Alzheimer's risk) are the only two benefits, but don't forget that this drug is also pretty much the end of the road for the "More People Should Be Fat!/HAES movement".
https://en.wikipedia.org/wiki/Health_at_Every_Size
And good riddance I say!
Agreed. I'm down for being empathetic to fat people - as a fat person! - but I have never understood the movement to just deny reality and act like it's acceptable to be fat from a health perspective. Obviously fat people should still have access to healthcare, but putting our heads in the sand and pretending that it isn't a situation that has huge impact on our quality of life and lifespan has always struck me as absurd.
Man that "movement" is such a scam that's used to promote unhealthy eating habits.
[dead]
Oh Oh Oh Ozem...I forgot the rest
Why not just lose weight by eating less? I know that sounds like a dumb question.
But genuinely, aren’t you just paying money to… not spend the money on food instead?
Because other interventions have the consequence of actually working.
If we compare the efficacy of "telling people to lose weight" vs taking ozempic, there is a stark contrast. Pooled results show that education and counselling[sic] did not significantly reduce weight (SMD –0.73, 95% CI –1.89 to 0.42, n = 3 studies; I 2 = 98%)[1]. The mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo[2].
Telling people to just lose weight is not an evidence-backed intervention to affect weight loss. Continuing to practice it is equivalent to practicing folk medicine or alternative medicine. Despite us wanting it to work, it does not. Like all interventions, pharmaceutical interventions have the possibility of side effects, and it's up to the patient and doctor to weight risk vs reward. There is variation in both for each case, but we have to keep in mind that the mere existence of side effects is not typically a reason for categorically deciding against using a drug.
1. https://pmc.ncbi.nlm.nih.gov/articles/PMC7154644/
2. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
My bad guys, didn’t mean to be negative in my original post.
Definitely lacking in compassion. Whether it be obesity or anorexia, these are almost always symptoms of something deeper underlying. I shouldn’t be so flippant.
I think I still have to stand by my belief that semaglutide won’t truly solve people’s relationship with food though. That requires going deeper than the temporary solution drugs might provide.
> I think I still have to stand by my belief that semaglutide won’t truly solve people’s relationship with food though.
That sounds fair. I see a lot of over/under weight results as a symptom of a maladaptive coping mechanism for some other issue. Sometimes the issue is simply not having meaning in one's life, but it really can be anything from depression, to anxiety, to lack of friends because of social phobias or low self-esteem.
Looking at this this way helped me find more compassion and less contempt. I hope it helps you too
Do you think obese people have never tried just eating less? That doctors never tell them to do this and they never give it an attempt?
Yes, it is possible for every obese person on this planet to eat less and stop being fat. 100%.
But for some people, this is actually really difficult to do! And the more fat you put on, the more feedback loops there are in your body that push you towards eating more. Insulin and ghrelin response are big ones, but it wrecks your sex hormones, too - you're almost certain to see massive testosterone drops in men, which further stimulates your body to deposit more fat and build less muscle.
Being told to lose weight by diet and exercise is probably the most prescribed treatment on the planet, and one with one of the absolute lowest success rates.
This is like asking why ADHD patients don’t just get over it by focusing more.
Nope it's more trying to justify smokers really.
So easy to invent imaginary diseases to cover for decadent lack of willpower and portray a decent life hygiene as something as heroic as firewalking or quitting crack.
My mom is obese because she developed an autoimmune disorder while she was pregnant with me that attacks her thyroid. She has extremely abnormal thyroid cells that have to be biopsied twice a year and she has to take daily thyroid medication or she will die. She is about to start on Ozempic as well because the thyroid medication is not enough.
To manage her disease, she eats much less and much healthier (e.g., steamed kale for dinner every night) than everyone else in my family, and yet she is the obese one amongst us.
Please stop acting like life-saving drugs are evil and everything can be managed through willpower alone. My mom would be dead without modern medical science, and I would have died in the womb with her.
Are your seriously implying that your special case is statistically significant or that people like me are against the use of medicine for these? Your blog post completely misses the point: I didn't write imaginary just for kicks.
> or quitting crack.
Statistically, people that manage to quit most chemical addictions have lower recidivism rates than people who lose weight through dieting.
So, possibly it is?
I for one have far less trouble keeping any of my drug and alcohol use to reasonable levels than I do avoiding overeating. I can quit drinking or smoking pot for months or years on end without even much thinking about it, but my attempts to lose weight without tirzepatide tended to be huge struggles that I would crash and burn on after 6 or so months.
I would state it in a kinder way maybe, but at the end of the day that's basically what you have to do? ¯\_(ツ)_/¯
The entire point of the ADHD diagnosis, in fact, is about the inability or reduced ability to "just focus more", and the medicine's purpose is to alleviate that imbalance
“Why” is a weird question. We don’t know why. We do know that people don’t just eat less. Haven’t in decades. No plan that relies on changing that is practical.
The problem is the damage to the body's metabolism and hormonal balance. The drugs help fix that damage.
> Why not just lose weight by eating less? I know that sounds like a dumb question.
Because it requires willpower and discipline, this just a pill/injection doing all the heavy work for you. Hence the success in USA. There are countries where this drug is semi unknown.
And it's becoming more and more known because obesity is a growing problem for nearly the entirety of the developed world.
If you're so convinced that obesity is a moral failing, then just put 'no fatties and no fake skinny glp-1 users' in your tinder profile, and all of the rest of us can move on with our days.
Speaking of obese - not overweight - I think I can name two people I actually met in person. Maybe one more if I really think about it? Don't know.
Maybe it is but just in a certain part of the world.
I don't know where you live, but the places where obesity isn't on the rise are heavily outnumbered by the places where it is. It's a global problem.
Easy and cheap access to calorie dense food and food heavy in sugars seems to nearly universally be something that significant portions of the population have difficulty resisting overindulging in, regardless of culture.