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Drug for treating obesity cuts body weight by 20 percent (sciencedaily.com)
86 points by LinuxBender 8 months ago | hide | past | favorite | 127 comments



One third (35%) of people who took a new drug for treating obesity lost more than one-fifth (greater than or equal to 20%) of their total body weight, according to a major global study involving UCL researchers.

The drug, semaglutide, works by hijacking the body's own appetite regulating system in the brain leading to reduced hunger and calorie intake.

Three quarters (75%) of people who received semaglutide 2.4mg lost more than 10% of their body weight and more than one-third lost more than 20%. No other drug has come close to producing this level of weight loss -- this really is a gamechanger.

The drug possesses a compound structurally similar to (and mimics) the human glucagon-like peptide-1 (GLP-1) hormone, which is released into the blood from the gut after meals.


I think it is important to note that a 10% drop (if mostly fat) can bring significant quality of life improvements for people who are experiencing issues related to obesity.

Imagine you walk around with a 30 lbs bag of flour on your back all the time. Then, all of a sudden, you are able to put that bag down.

The faster you lose weight (this is all anecdotal) the more it is like putting that bag down all at once.

Now, can they keep the weight of after losing it? Because I can gain those 30 lbs back very, very quickly.


I was overweight when the pandemic started (24% bf). I lost 10% of my body weight in a few months. It’s insane how much your athletic ability jumps just from that. I used to work out intensely before and would make marginal improvements in stamina/speed/etc.


In my experience it is losing the initial weight that is the easy part and keeping it off long term that's hard. However the mechanism the drug uses sounds promising that regard (assuming your body doesn't adapt to it), although it would mean adding another lifetime drug to my list.


Yeah, I have sleep apnea and GERD, likely related to obesity (I drank beer and coffee constantly for my entire adult life too though; coffee so I could work, beer after to relax)... but I'm wondering how much is related to obesity.

I can feel the fat pushing and creating pressure points, which contributes to both conditions. The crazy thing, is I'm not like super fat or anything. 6'2" 245lbs was my max, and I'm at 235lbs now... I felt perfectly fine at 225 when I worked out. Seems like such a small difference, but I've gotten virtually no exercise with covid, so it's not a fair comparison.

That's enough for obesity, but the crazy thing is it's not considered fat at all in the USA, if you're a guy. You just "aren't in your early 20s anymore", or have a "dad bod", or you're a loveable jolly rascal that loves life (eg. Chris Pratt in P&R). We act like it's practically inevitable and not a horrific medical condition that's causing me to be eaten from the inside out by my own acid.

I know some of this is just luck, but I wonder what truly fat people have to deal with. I couldn't imagine my reflux being better if I was say 275-300+.


Parts 6 and 7 of this Youtube series on the risks of obesity are on sleep apnea and GERD: https://www.youtube.com/watch?v=MGnVgbUHtKI&list=PLyqKj7LwU2...


If the drug can be administered long term, perhaps there is hope they will keep the weight off.


If it is the same as the glucagon hormone mentioned by the grandparent comment, it SHOULD be 'natural' and have no side effects.

But just look at reproductive hormone treatments (the pill) to see how things like this can go wrong (serious mental side effects; my sister struggled with seasonal depression for half her life, turns out it was just the pill. My girlfriend developed suicidal ideation from the Mirena coil. They stopped a research in male anticonception medication because of the mood swings).


The drug doesn't actually "burn" fat, as the previous headline suggested, but reduces appetite.

All known drugs that actually trick the body into burning more fat are kind of dangerous, some are lethally dangerous from a single overdose. And they would reduce the appetite, oppositely some cause monstrous appetite.

I'm 80-85kg 173cm man. Months of strenuous exercise doesn't barely make me reach 78-79. Though they do make me feel much better, and energetic.

A therapy needs to do both, somehow make the body consume more energy from fat specifically, and not cause excess appetite. This can be one leg of that.


> somehow make the body consume more energy from fat specifically

Any way to achieve a calorie deficit will accomplish this. There doesn't have to be a second drug to make your body use fat as energy once you've already given it no other choice.


Hearing about a drug that hijacks the body's appetite makes me feel like we're in the prologue to a zombie movie.


Plenty of drugs do things that sound scarier to me--a layperson. SSRIs change the way you think and feel. Pain killers hijack your nervous system so you don't feel pain.


Are zombies such a big problem , given modern weapons and armies/police ?


Have you read World War Z? It covers that very question in great detail.

One problem it highlights is that modern armies and military tactics are incredibly inefficient. The amount of fuel, munitions and calories they use for every kill is staggering. Also much of modern military tactics are based around putting on a massive show of force up front and hoping the enemy surrenders or retreats. That is not a problem if you only have to kill a few thousand people who's spirit to fight can be broken, and you're backed up by a fully functional logistics network. Remove the logistics network and face off against an 'army' of hunderds of thousands of enemies that will never retreat then those tactics will quickly see your fuel and munition stores depleted.

Towards the end of the book the Army has reinvented the infantry square and equipped all their soldiers with bolt action rifles to stop them wasting ammo.


World war Z is cool, but it's a fantazy. For example it pretends that tanks can't drive through a zombie horde because the tracks would come off. Thats conoletely absurd - tanks can drive through trees, let alone people, tank crews call infantry 'crunchies'.

If you want to see how a zombie horde would fare on a battlefield, look at how infantry and cavalary charges did against ww1 machineguns. It would be like that, but 10x worse.

Besides, there is the whole issue of zombies rotting and concervation of energy - after a few months they should turn to rotten goo, or motionless husks.


In WWZ, the battle of Yonkers highlighted some of the issues with traditional military techniques. The zombies had superior numbers (millions!) and required a headshot to take down. The shock and awe doctrine of the military worked on the first ten thousand zombies or so, but they keep coming.

Machine guns lack the accuracy to stop a zombie completely, and have a limited capacity relative to millions of attackers. Tanks would be able to run over zombies, but eventually would be swamped or simply run out of fuel. All the strategies relied on fighting an enemy with human emotions and a survival instinct, the two things zombies lack.


It would be like that, but 10x worse.

Oh absolutely and I think the book agrees. I recall them describing battles where the piles of dead zombies where so high the soldiers couldn't see the next wave approaching. The hard part was never killing zombies but making sure you killed all the zombies before you ran out of fuel and bullets.


Based on what I saw in the movie, didn't read the book the rate of infection is unrealistic, at least the time it takes from initial exposure to full on aggressive zombie mode was a few seconds. Realistically this would take much longer than that which means we won't end up with hordes of zombies instantly.


Your main problem in the long run is, that zombies are infectious. Imagine that in every water hole and in every dark place could be a zombie sleeping... The virus could mutate and infect animals or insects.


Armies and police are fallible even when facing a known threat. There's a trial going on in the American senate right now about that...


The global virus pandemic that is responsible for a total lockdown and a multitude of deaths and spread immediately via global transportation system wasn't enough for you?


Worse, it's mutating! It's just like most zombie movie plots.

None of those predicted the hoarding of toilet paper though.


Maybe we're just hedging our bets for multiple zombie movies?


There is a small study on another drug called Bupropion that says that Bupropion leads to a 5% in weight loss in the first 8 weeks when compared to placebo.

https://pubmed.ncbi.nlm.nih.gov/11557835/

Bupropion is also used as an antidepressant and antismoking drug.

I am taking Bupropion to treat my depression and it helps me - at least I think it does. I also think it helped me to loose a little bit of weight.

I have observed myself and with Bupropion I simply want to do stuff, go out for a walk, meet friends etc. Instead of being in bed all day. I think this is how it helps me do both: improve my depression and lose weight at the same time.

I might be totally wrong though since I have no idea regarding the actual mechanics of Bupropion and I may simply experience the "placebo-effect".


Bupropion's brand name is Wellbutrin for anyone wondering.


Bupropion gave me a psychotic episode, and to be clear I have never had anything like that happen before or since, which made it even scarier. The straight razors I had in my house were calling out to me, so I threw them behind the refrigerator so they couldn't get me. Then I had to call my mom and cry in a ball for three days before I started feeling better. It was absolutely terrifying.


Yeah Bupropion is also used a little for ADHD. It has those effects a little. Hell, there are people abusing it for those effects.

And ADHD meds were used previously for loosing weight. I think it will be the same with Bupropion.


Yeah a known side effect of some (most?) ADHD medication is loss of appetite.


I mean, Adderall is speed. Mother's Little Helper, what made for punk music, etc. Not a drug associated with weight gain.


The cash price for this drug in the US is insane: https://www.goodrx.com/ozempic?dosage=2-pens-of-1mg&form=car...

I can only imagine the fight people will have with their insurance. One of the many reasons we can't have nice things.


Reading the wikipedia page on semaglutide, I was a little confused why one wouldn't just use the peptide it's an analogue of, glucagon-like peptide-1 (GLP-1). It states the only "differences are two amino acid substitutions at positions 8 and 34, where alanine and lysine are replaced by 2-aminoisobutyric acid and arginine respectively."

The article explains that the substitutions increase the half-life of the substance in the body, so I understand that as an advantage of the drug over the naturally occuring peptide. This would be important with an injection. But the skeptic in me wonders if, the drug now is available in an oral form, if the real reason for pushing the drug over GLP-1 is because the drug can be patented and GLP-1 cannot.


So the motivation was money. I am Jack's complete lack of surprise.


Wow, for that amount of money I could just hire someone full time to slap food out of my hand.


Emphasis "in the US".

Here are Swiss prices (German/French only): https://compendium.ch/search?q=Semaglutid

While injections are still quite expensive (~$130 per 3mg), pills are available for as little as $4 per 14mg dose (and judging from the dosage information, those pills are splittable).

I don't know the reasoning behind studying the effects of injections vs oral admission.


From the article:

>The international trial was funded by the pharmaceutical company Novo Nordisk.

From the Ozempic website:

> Cornerstones4Care®, NovoFine®, and Ozempic® are registered trademarks of Novo Nordisk A/S.

Follow the money.


Thats 2mg, the study was made with 2.4mg so that's at least that price weekly...


What does this actually say? The site is blocked to those of us outside of the US, probably because the website owners can't be bothered to comply with GDPR?


Short version: lowest price for a carton (2 pens) is >$800. I would guess that each pen is a single dose.


Not even... 2.4mg a week in the study, each pen is 1mg


My mother uses this drug by perscription. 1mg pen is for four weekly 0,25 mg doses (1 month).2 mg pen is again for four weekly 0.5mg doses.

Realy good results and only one aplication per week, which is great.

We are from Slovenia. Drug is free of charge with normal insurance.


Why would they? They should just go ahead and skip the cookies banners.

The EU cannot do anything against that, so why bother.

Blocking the site is something I do not understand


$950 and $900 with coupon.

It looks like for two doses.


Let me preface this with that I am aware that hunger and fullness are very much genetically determined and that that dictates to a large degree how fat you'll be.

But there's this thing that when people get some sort of diagnosis they'll act like it's something you have absolutely influence on and the only way is to have some sort of external intervention or declare "that's just the way I am". You just have to look at how many patients gain back large amounts of weight after getting their stomachs stapled.

Exercise has a positive correlation with controlling hunger, eating differently can also greatly increase fullness and reduce hunger, cutting alcohol from the diet does absolute wonders. Maybe it won't get you to a 'beach lean' physique, but it will for sure make you more healthy.

If this drug is truly effective it will only save the patient from the direct effects of obesity, not the effects of sustaining a poor diet, a lack of exercise, or overconsumption of alcohol.


> hunger and fullness are very much genetically determined and that that dictates to a large degree how fat you'll be

Do you have any good source on that?


I don't have a true scientific source on hand, but the BBC Horizon episode "The Restaurant that Burns Off Calories" goes in a little on how genetics influence eating behaviour amongst other things.

https://www.bbc.co.uk/programmes/m000hjnr


I don't think you should be posing a challange to folks to prove well-known facts that are a single single google search away.


It is far from a well-known fact. IT is clearly disproved by looking at weight across countries and throughout time. The average American male weight has gone from 165 in 1960 to 200lbs in 2020. Obesity has gone from 15% to 45% in the same period.

Genetics have not rapidly changed in this time period.

https://images.app.goo.gl/YKogsucsMD1DUMKf6


I think you are missing the point, or have not read the relevant research. No-one is claiming revent changes are due to genetics.

The claim is: in a given group of a thousand people, eating the same food and having the same execesise, some will be obese and some will not due to genetics. That distribution is very wide, and well studied.

Thus, when you encounter a random obese person in the wild you cant conclude this is just because they eat bigmacs all day

Lastly, I do dislike comments that pick a random statement from OP and ask "where is the proof" and do not actually engage with the crux of the message. They just sidetrack discourse.


>The claim is: in a given group of a thousand people, eating the same food and having the same execesise, some will be obese and some will not due to genetics. That distribution is very wide, and well studied.

This was not the same claim. Yes, it is well understood that individuals are different. some people have a harder time and some have an easier time, for sure. This does not negate that personal choice plays a much greater role than genetics.

OP >> hunger and fullness are very much genetically determined and that that dictates to a large degree how fat you'll be

Genentech influences are only significant if you intentionally exclude dietary choice providing the "same food and exercise" to each person.

>Thus, when you encounter a random obese person in the wild you cant conclude this is just because they eat bigmacs all day

Im not sure when or why I would need to make conclusions about a specific random obese person in the wild. I'm fine with the understanding that 90+% of obesity is personal diet. This is sufficient for talking in generalities about obesity in society. If for some weird reason, I need to do a root cause assessment on a random individual's obesity, yes, this is not sufficient.

If I encounter another random obese person in the wild, I have no reason to care if the reason IS their bigmac consumption. It is their life and their choice. Lots of people value food consumption over their weight.

Lastly, I totally agree that the genetics was a footnote to the original point, but think there is value in correcting incorrect facts. If someone else wants to engage with the crux of the message, they are still free to do so. What I don't like is when people erroneously claiming that science backs up their position when it doesn't.


If a genetic factor leads to increased sensitivity to hunger or feeling hungry more often / being less satiated by food, then isn't that a genetic factor that is likely to directly influence a person's choices vis-à-vis food intake? Note I don't know whether that is the case.


Even if I did pose a challenge (I wasn't, I was just curious) it would totally be ok.


As of now, the majority of dieting attempts (over 90%) fail in the long term. People loose weight and then slowly gain it back - changing their metabolism in the process.

People can loose weight, but pretty often do it in an unhealthy way that is not sustainable. Keeping that weight in sustainable way is what issue is. We dont have intervention that would actually worked long term for that.


I'm not talking about "a diet" but diet, as in what one eats throughout the day, week, year. What is needed is not a diet, but an absolute change in lifestyle. It will not simply change the way your plate looks and how much is on it, but how your life looks.

This is a big commitment and people have a tendency to quit when one single thing fails. The key is not willpower, it is persistence. It took me years to get to a point where I felt in control of my weight. It wasn't easy and I did many stupid things but I just kept on going on.

A big part of it is not seeing a lack of progress in scale weight or body composition as a personal failure but as valuable feedback or just an "oopsie".


I know a few middle-aged overwieght people who have a healthy diet (100% home cooking) and spend 4 - 6 hours a week in the gym.

When you get older, you body is not as good at regulating itself. Think sumo wrestler - they can beat your ass and survive in a tundra, but they don't look like a model. If they could wave a magic wand and loose 10 kg, they would.


Here is a drug free way to fight 99% of the obesity out there. If you drink soda, stop. If you eat fast food, stop. If you're eating processed food, stop. If you snack, stop. These alone will have an incredible affect on your weight and health. If this all seems to difficult, start off with just one, like cutting out sugary drinks (pop, juice) and don't substitute with artificial sweeteners. You are being attacked by big food. They are killing you. You will notice results in weight loss and health by making small changes to your eating habits.


I personally find it much easier to change how much I eat than what I eat. So I started with that and only changed what I ate after I already lost some weight.


Yes, install a tracker app, track what you eat to get baseline. Increase / decrease average weekly consumption based on your long term goal. Wait until the results set it.


There is a very interesting case of a man who spent more than one year without eating solid food: https://en.wikipedia.org/wiki/Angus_Barbieri%27s_fast

He lost 125kg.


Fasting, both intermittent (< 24 hr) and extended, are increasingly being recognized as powerful tools to lose weight and cure/prevent diet-related conditions like diabetes and metabolic disorder, thanks to the work of people like Drs. Peter Attia and Jason Fung.

In my experience IF is an easy way to cut out excess calories, and EF gives me amazing energy and mental clarity, while helping me have a healthier relationship with food.

My simplistic view on fasting is that my body stored all that excess energy as fat for the purpose of being used when food is not so readily available, a situation that may have been common in the not-too-distant past but just doesn't happen for me or most Americans today; therefore it's incumbent on me to restrict food occasionally and let the body use these stores, while performing other maintenance that is limited when digestion is occurring (notably autophagy).

Note: when I refer to fasting I mean water-only (also non-caloric drinks like tea and coffee), with electrolyte supplementation for extended fasts.


I'm not an anthropologist of biologist, but I think modern life is basically incompatible with how humans evolved. I mean, we are hunters. If we do not spend the the energy to hunt what we eat, it seems clear that we get obese.

Our natural instincts tell us to eat as much as we can whenever food is available. This is because we evolved without any guarantee of frequent meals. Post food-scarcity society seems basically against our natural instincts.


> If we do not spend the the energy to hunt what we eat, it seems clear that we get obese. > Our natural instincts tell us to eat as much as we can whenever food is available.

Compounding the problem, we've identified what activates these instincts (fat and sugar), and hyper-optimized food to target the reward centers and cause people to eat _even more_ food that they don't need. Then we use what we've learned about psychology to trigger people's desire for food even when they're not eating.

Then we invent expensive drugs (see TFA) to help people lose the weight (and throw commercials at them for _those_)...


Obesity rates started soaring only in the later 20th century. I'm suspicious of explanations for recent and rapid upward obesity trends that cite our evolutionary history from before the Neolithic Revolution. Human genetics did not undergo a massive shift in the last couple of generations. We did not just recently transition away from nomadic hunting lifestyles either.

No single factor seems to line up with increasing obesity rates well enough to be blamed as The Cause. I think it may be a combination of small nudges that form strongly obesity-promoting environments.


Marketing for unhealthy foods is a 20th century thing. And marketing something as healthy when it's actually not (fat free craze of yesteryear). To me it seems this is one of the major problems. Lack of education on healthy eating, damaging advertising, and a lack of regulation around food labeling.


It is interesting, but the major turn off is that since it is primarily a diabetic drug, it messes with your blood sugar. From get go, you will want to control your sugar and/or follow strict diet.

Granted, those turn offs are for people without diabetes. People with it already have to follow that routine in their life.

All that said, it is better to have more tools than less given US population increased obesity rates.


If your weight is that serious of a concern, diabetes will be the next step anyways.


The impact on blood sugar is to reduce it, or so. That's not a bad thing. Diabetics that inject insulin (and/or take some other drugs) have to watch for low blood sugar, but it is high blood sugar that does most of the long term damage associated with diabetes.

Someone that frequently has low blood sugar should probably adjust their diet, but that's anyway going to be part of a weight loss regimen.


Thankfully, drugs should be a means of last resort; most people should be able to make do with some lifestyle changes / tweaks.


I've lost 30lbs on combination therapy of oral semaglutide (Rybelsus) and low dose naltrexone. There's some side-effects but nothing earth shattering. If I'm not mistaken the drug carries a thyroid cancer risk warning which hopefully applies only to the rodent testing group where it appeared.


I started taking some probiotics, two different kinds each day for more than one month. In particular I had one containing among others saccaromyces boulardii and one containing lactobacillus reuteri

I lost around 5% of my body weight by not being so hungry any more. I think this is due to a reduction of my suspect candidosa which was making me always crave for sugar.

As a plus I am also less humoral, and don't have mental fog any more.

I think of the human microbioma like a patch to human biology system, while DNA is the blueprint.

That said please bear in mind that I am no doctor, I have no medical or biological education... so take it for what it is, a very personal experience with also no statistical value


Gut microflora convert fiber to capric acid, which is a great source of steady nutrition without insulin for many hours after ingestion.


> In those taking semaglutide, the average weight loss was 15.3kg (nearly three stone), with a reduction in BMI of -5.54. The placebo group observed an average weight loss of 2.6kg (0.4 stone) with a reduction in BMI of -0.92.

This seems like an incredible difference. And 94% of participants made it through the whole study. What are the downsides here, or what am I missing? It’s an already approved medication that’s normally used in smaller doses, so only the safety in larger doses needs to be validated?


All of the known side effects for drugs can be found in the prescribing information

https://www.novo-pi.com/ozempic.pdf

Potential side effects include thyroid cancer, kidney problems, blindness, allergic reactions, low blood sugar, and pancreatitis


According to another comment, thyroid cancer risk


My only concern with this is the quality of food people are eating. There was a self-study performed by a research professor awhile back where he consumed nothing but Twinkie's for several months but stayed under has caloric needs, and unsurprisingly, he lost weight. However, consuming that amount of refined sugar and fat will undoubtedly lead to long term health problems.

I'm not saying it's all bad :) but patients on this medicine need to make diet [and to a lesser extent exercise] changes as well. I'm sure this is already considered.


I’m worried about the result that mass adopted drugs like these would have on society.

I’d wager that it would lead to a massive increase in consumption instead of allowing people to get healthy and then stay that way.


This drug reduces appetite which would mean less consumption overall (since overweight people are eating less). If it was a drug that magically got rid of fat, it'd be a different story


I really like the taste of good food. I would hate to lose my interest.

I'd rather try to eat less really good food, than have 'enough' of something I quit caring about?


If I had the choice of losing my sense of taste for the rest of my life in exchange for being phycially-fit, I would do it in a heart beat.

There is so much more to life than tasting food, and a lot more exciting things in life become more accessible when you're physically-fit.

I'm relatively young, and not that overweight, but the last 40 pounds or so are going to be the hardest, and the most fulfilling to lose.


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Obesity is vastly more complex than people “just” making bad choices. Tell someone who is addicted to cigarettes to quit smoking while everyone around them smokes all day and there are cigarettes cheaply or freely available everywhere.

Oh, and modify the scenario slightly: you have to smoke a little to live. And while smoking is making one person sick with cancer, other people have different genes and can smoke as much as they want with no side effects.

That is what it’s like trying to “just make good food choices” today, especially if you are genetically insulin resistant, in which case you not only need to eat “good food,” you need to eat less of it than other people or you’ll still gain weight. Oh and don’t get me started on stress and cortisol.

“Just eat healthy,” is the ignorant remark of someone blessed with good genetics.


> Obesity is vastly more complex than people “just” making bad choices. Tell someone who is addicted to cigarettes to quit smoking while everyone around them smokes all day and there are cigarettes cheaply or freely available everywhere.

> Oh, and modify the scenario slightly: you have to smoke a little to live. And while smoking is making one person sick with cancer, other people have different genes and can smoke as much as they want with no side effects.

> That is what it’s like trying to “just make good food choices” today, especially if you are genetically insulin resistant, in which case you not only need to eat “good food,” you need to eat less of it than other people or you’ll still gain weight. Oh and don’t get me started on stress and cortisol.

> “Just eat healthy,” is the ignorant remark of someone blessed with good genetics.

Yeah it's like the mentally healthy telling the depressed to cheer up. It's not that simple.


Do you really think people are choosing to be extremely obese?


Unless they're being force-fed, then yes, they are choosing it. It can be hard to lose weight, especially if raised with poor dietary habits, but it's not like people can't lose weight unless a magic diet pill is invented for them.


Sure, it's obviously possible. Just like it's possible to quit smoking without assistance, or quit heroin cold-turkey. So you're arguing that because it's possible, we shouldn't try to make it easier?


Do you think cigarette smokers are choosing to have tar in their lungs? Its the same argument - albeit there is a lack of common knowledge about what harms food can do to your body. Thats why we should promote eating healthy instead of taking drugs


We use medication to deal with a desire to smoke. There are tons of drugs for managing this.


Except change your metaphor such that you have to smoke a little bit to live.


You're right, that's a good point. Its harder to make these decisions every day, but I still know that education of nutrition and diet can give people the power to make the better choices when it comes to food; rather than giving them a pill.


They don't want the consequences of overeating. But yes, I do believe they choose to eat the amounts they do.


Here’s an interesting fact: if you’re insulin resistant (more than half the population is), then you could have a “healthy” meal like a bowl of oatmeal for breakfast, and the body’s poor insulin response actually forces all the carbs you just ate into your fat cells while denying your body fuel, thus making you hungrier. To overcome this you have to eat enough carb to still have fuel available even after your fat metabolism is satisfied. So the heavier you are the more you have to eat before you have fuel available to your body.

It’s very, very difficult to overcome genetics.


In those cases, is there medication or treatment available to help deal with the insulin response? I know hyper / hypothyroidism is a thing as well (although research has shown -thyroidism may not influence weight significantly: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711558/)


How much did human genetics change in the last 100 years? I'm very much convinced that genetics plays a role, but surely it cannot be the cause of the obesity epidemic?


I think what changed significantly in the last 100 years is the abundance and composition of our diet. In particular the quantity of sugar added to everything, and the abundance of simple starches in our diets (in particular in the US where the "food pyramid" suggests that grain is the main thing people should be eating).


"good food" is a weasel word; What do you mean? Low calorie food? Also a very broad and unspecific term.

It's not as easy as "this food is good" or "that food is bad", you need to educate yourself first; calories in and out, then macronutrients, then micronutrients, in that order.

All the diets, diet trends, and things labeled "good" and "bad" food are handwavey things, and research has shown that the common factor they all have is calorie intake reduction.


"If people could just choose X" has been a losing strategy on everything from drug addiction to climate change to boycotts of products with child labour.


If people could just choose to give me a ton of money, I'd fix all their problems.


Appetite is not a choice though and it's not easy to just ignore and do the right thing. It's not a thing you can change just like that.


While it's not a choice, there are things that influence appetite; for example, going for high calorie but poorly filling food and drink (e.g. soda), or the (I'm handwaving here) "moreish" foods.


It isn't. But change like that is exactly what you need to do. If it's good or bad to change it via a drug instead of mental discipline is another question.

But you could change your food and eat tons of it. I am a pretty slim person and i eat a lot compared to my friends. I also don't do much sport and as a developer is sit a huge part of the day. So for me it comes down to WHAT i eat and it's serving me pretty well. You don't need to fight your appetite, you can serve it and still loose weight.


> You don't need to fight your appetite, you can serve it and still loose weight.

I've lost over 150lbs and kept most of it off for the better part of a decade, so I will tell you from experience that you are full of shit.


In my experience, bodyweight functions like a closed loop control system that uses hunger signals to address the error signal. The error signal is basically (greatest weight attained) - (current weight) where the greatest weight attained value is severely lag filtered, say 2 years or more. The system seems to be very strong in response to rate changes in the error. The integral of the error seems to be pretty strong over a period of say 5-7 days.

Congratulations on your weight loss, does your experience compare to what I've described?


I agree completely. People aren't going to be able to eat all the junk they want just to take a pill and be healthy. No - you have to earn your health. You wouldn't put diesel in a gasoline engine because that will ruin the engine. So why do you put endless amounts of sugar and bread in you? It's just going to do the same.


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There is more to weight gain than lack of willpower. The conscious mind is very little of the problem. The people in the study had all the same opportunity and advice, yet the ones who took the medication lost significantly more weight. What else do you need as proof that it’s not just education and choosing the right thing to do? If that were the case, why wouldn’t both groups show similar improvement?


> There is more to weight gain than lack of willpower.

Is there? The study you quoted suggests the opposite. The drug doesn't directly cause fat to melt off. The fat is lost by eating less. Why is the control group eating more? lack of....


Hold your breath for 3 minutes. This should be doable, with sufficient willpower. Freedivers can go much much longer. You didn't succeed?

Shame on you and your lack of willpower!

Biological urges are powerful, don't be so quick to judge.


No one should be expected to go from eating in an unhealthy fashion to a healthy one, just as one would not learn to hold one's breath for three minutes right away. But there are those who try and get better, and there are those who try and don't, and there are some people who simply don't try. This drug is good for the second group. But is bad for the third, the people who will use this to continue eating badly, just with the consequences less visible. And I think it could also be bad for the first: by hiding the immediate effects of bad habits, it removes the encouragement to get better. The concern that this may allow people to maintain bad diets but not see the effects in the short term is a valid one.


> Why is the control group eating more?

Because they aren't taking an appetite suppressing drug. It's easier to not eat when you aren't hungry, so it's easier to lose weight with the same amount of willpower compared to people that aren't taking an appetite suppressing drug. Willpower has no part in the study, it doesn't "suggest the opposite".


Willpower is exactly why they eat more. They feel a pang of hunger in their grossly stretched out stomach and can't resist eating.

The drug does not remove fat. It removes the feeling of hunger. Assume both groups have little willpower (they are fat after all). The control group feels hunger and continues satisfying that hunger with food as they have no will power. The group with suppressed hunger from the drug also have no willpower, but since they feel no hunger they eat normal amounts.


So we agree that there is more to weight gain than lack of willpower then. It wouldn't be a stretch to then imagine that not all people feel hunger the same (as hormones usually vary from people to people), and thus that for some people, it takes less willpower to maintain a healthy weight.


honestly who cares? it's not a competition. most people eat when they are hungry and stop when they're not hungry anymore. for me this results in being at the lower end of the ideal weight range for a person my size. it takes no willpower at all; I don't even think about it until I read a thread like this. other people, for whatever reason, have an appetite that is out of proportion with what their body needs. why not just let them solve their problem however they see fit? if a drug is part of their weight loss regimen, so be it.


Poverty is solved by earning more money. BAM I just won the war on poverty.

Crime is solved by just not commiting crimes. BAM I just solved crime.

Drug problems is solved by just doing less drugs. BAM I just won the drug war.


You should read "The Hungry Brain" [0]. It's by a neuroscientist, who explains the deep ways that the appetite mechanism is wired into just about every area of our brain, making "willpower" very hard to sustain. As just one example, prisoners placed on a forced starvation diet became obsessed with cooking implements. It also provides strong evidence that physiological mechanisms (not conscious choices) are behind appetite differences and fat mass variations in the population.

[0] https://www.amazon.com/Hungry-Brain-Outsmarting-Instincts-Ov...


If the drug is granting people willpower, then it really is miraculous.


I for one think changing human nature is harder than creating an appetite suppressing drug, and indeed it seems we arrived on the latter earlier. So if it works it works, right?


I think it is better for humans to be able to control themselves than be controlled by pills.


It is my choice to use drugs to assist in achieving my life goals. I've been doing it without drugs for a decade now and it's fucking hard and I don't appreciate assholes who imply otherwise.


By that logic shouldn't we be able to take steroid, or at least HGH, and other performance enhancing drugs that are less dangerous than steroids? Lots of people do less crazy amounts and don't have problems. Plenty of people have lived full lives after juicing, possibly even better lives. I'm not saying either way, just food for thought. If we banned something because you might get cancer alcohol, cigs, and junk food would be banned too.


I'm not shaming you or anyone for taking drugs, not at all. I think drugs can be great and can do great things for a lot of people. I take certain drugs myself on occasion.

What I am trying to say is that someone might not be able to control their appetite, but they do have at least some control over the food they put in their body. I think that education on nutrition can go a much longer way for overall human health than appetite pills.


Having lost over 150lbs and kept most of it off for about a decade, I disagree. Knowledge about nutrition[0] is insufficient. The only reason I was able to do this at all was that I was in a very low-stress period of my life at the start and after that I have had to put a whole lot of effort into not ballooning up again, to the extent that my behavior patterns were described as an eating disorder.

I am hardly unique in this. I would argue that to lose and keep off this kind of weight without chemical assistance (good fucking luck getting a doctor to help there) pretty much necessitates the development of an eating disorder. It takes over a significant portion of your life and is no fucking fun at all.

Give me an apatite pill any day.

[0] this is without even mentioning how difficult it is to find information on nutrition that isn't complete bullshit pushed by people selling fads.


Although a bit preachy, I partially agree with Your comet. If semaglutide mimics a hormone produced in our gut, what microbes produce the hormone and what can be done to encourage them?

That being said, as a person who struggles with weight I can attest to how much better my life was before gaining the weight and being obese compounds the problem in a sort of vicious circle. I'm ashamed of my body so don't participate in fun healthy activities like swimming and dancing, my weight makes it risky to run or skate due to my ankles and knees being strained.

I used to be thin and thought along the same lines of your comment but when I gained the weight I also gained empathy and perspective.


"Toxin" is a weasel word (https://rationalwiki.org/wiki/Weasel_word); be more specific.


>reducing toxic content in foods

can you elaborate on this? The terms toxic/toxins have been so overused when it comes to diet and alternative medicine that it's basically meaningless.


> People want miracle pills rather than educate themselves about...

Yeah, of course we do!

And that is perfectly rational.


That's like telling a depressed person they shouldn't be depressed.


> If you're homeless, why don't you just buy a house?


Do you know people who regularly consume toxic content in food and survive?


lots of foods have toxins in them. usually it's not enough to matter. do you put nutmeg in your alfredo sauce?


Being overweight/obese might be (and might not be) a side-effect of the things you list, but it also that causes its own further side-effects and is worth dealing with in its own right.




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