‘Breakthrough’ obesity drugs that have stunned researchers

https://www.nature.com/articles/d41586-022-04505-7

by pseudolus • 4 years ago

671 1104 4 years ago

nature.com

Tagbert• 4 years ago

That looks like a “one weird trick” headline.

ceejayoz27• 4 years ago

So do quite a few medical advances. "Cure any infection with this moldy bread!" "Don't want polio? Inject some polio!"

gnicholas• 4 years ago

After decades of work, researchers are finally seeing signs of success: a new generation of anti-obesity medications that drastically diminish weight without the serious side effects that have plagued previous efforts.

…

Nutter is concerned that people might start these treatments — whose side effects, such as nausea and vomiting, can be severe — to escape weight stigma, rather than to serve a true health need

So the side effects aren’t “serious” — they’re just potentially “severe”? I’m confused.

ceejayoz27• 4 years ago

They're substantially less severe (and reversible, and more controllable) than the "your heart might stop" ones of the past generation of weight loss meds. (For example: https://en.wikipedia.org/wiki/Fenfluramine/phentermine)

Izkata5• 4 years ago

Leaking medical jargon and mixing it with regular usage: "serious" means needing medical attention, "severe" means hospitalization/long-term disability or worse. They seem to be using medical "serious" and colloquial "severe", which gives the the appearance of reversing their meanings.

derefr4• 4 years ago

Subtly different subjects to those two sentences: the former is talking about the new generation of medications (i.e. the general concept of medications targeting this new receptor); while the latter is talking about one specific treatment (i.e. one specific medication, at one specific dosage, via one specific route of administration, at one specific interval.)

The side-effects of this particular treatment "can be severe", but that doesn't imply anything about the side-effects of any other treatment (combination of medication, dose, RoA, and interval) for drugs in this class. Heck, they could probably fix the nausea/vomiting just by making a pill that contains an adjunct anti-emetic like ondansetron, like they do for cancer drugs.

gumby2• 4 years ago

to escape weight stigma, rather than to serve a true health need

This is an unfair framing by the researchers

For a while I worked in pharma on a drug program for a harmless* "ailment", nail fungus. What I learned is that some people suffer serious psychological consequences, such as marital issues or avoiding situations where they might be barefoot, like the beach. People who have it in their hands may avoid social situations all together, which is even worse and reduces life expectancy.

We have a natural cultural bias in this regard. It's not just the phantom of the opera: in films the hero usually has a clear complexion and the villain often does not (not always to the extent of Darth Vader of course). Now we understand more about disease etiology this bias is no longer helpful, and is in fact destructive.

Losing weight addresses true health needs (increased rates of cancer, cardiac issues etc) but weight stigma has important side effects as well.

* The various fungi that attack skin, scalp, nails etc eat a particular shape of squalene which some people make (referred to unfairly in the medical literature as a "squalene defect"). You're not going to catch it from another person -- there's a good chance you're breathing the spores right now. Either you're genetically predisposed or you're not. And all it does is munch on a tiny amount of your body and causes no other problem.

jobs_throwaway6• 4 years ago

The results astonished researchers: a weekly injection for almost 16 months, along with some lifestyle changes, reduced body weight by at least 20% in more than one-third of the participants

Why would they introduce lifestyle changes alongside the drug? Doesn't that complicate the analysis?

carbocation• 4 years ago

Probably assigned both arms to lifestyle changes, since we know those are beneficial. Assuming that's the case, then yes to your point, but also it's the right thing to do since there is no equipoise about lifestyle.

ceejayoz27• 4 years ago

The control group will have been asked to make the same lifestyle changes, but with a placebo drug.

https://www.nejm.org/doi/10.1056/NEJMoa2032183

Participants were randomly assigned in a 2:1 ratio, through the use of an interactive Web-based response system, to receive semaglutide at a dose of 2.4 mg administered subcutaneously once a week for 68 weeks or matching placebo, in addition to lifestyle intervention...

Tade0• 4 years ago

I suppose it actually makes it simpler, because you control for lifestyle changes.

Who says some participants wouldn't just start eating trash? I know I did after I lost some weight due to a bad case of something my child brought in from daycare.

djur7• 4 years ago

One of the expected benefits of the medication is to make it easier to comply with recommended lifestyle changes. It simplifies the analysis to recommend a specific set of changes rather than letting all of the participants improvise their own diet and exercise changes.

jobs_throwaway6• 4 years ago

Jesus christ, why is nature quoting a psychologist in an article about biology?

However, some researchers worry that these drugs play into some societies’ obsession with being thin. Body size isn’t always a good predictor of health. “I’m really hesitant to be excited about something that I think is potentially harmful from a weight stigma perspective”

ethanbond2• 4 years ago

Because this isn't an article about biology, it's about health, and health isn't unidimensional

jobs_throwaway6• 4 years ago

Helping obese people lose weight is unidimensionally a good thing

__blockcipher__2• 4 years ago

The correct answer is because it's become very taboo, particularly in academic circles, to make any statement that implies that it's not good to be fat. So articles like these always must include at least one generic quote about how being thin is not an end in itself.

carrotcarrot2• 4 years ago

A professor I follow once said Nature isn't as prestigious as people think, they just publish such a high volume that people have gotten that impression

xkbarkar• 4 years ago

I subscribed to Nature for a couple of years and although I am not a proper academic and maybe not the best judge, the articles in Nature sometime looks like they belong on vox.com or wired and not in a scientific paper.

As in opinions presented as evidence, from an almost random person, without actually providing any.

Especially around social subjects like the BLM protests.

One thing I loved about 60 minutes back in the day, was their ability to present a story from multiple points of views.

When I started reading Nature at my former employers, many many years ago, I felt their articles were like that.

At some point it started to look like cherrypicking a single viewpoint, often with obvious political taint.

Maybe it was always like that and I just used to idolize it.

I still very much love the magazine though but stopped subscribing. Its really expensive.

When I get my hands on a copy these days I just filter what I perceive as woke crap from the rest and skip those articles.

I wonder if that is such a good thing… Edit: typo and context

carapace• 4 years ago

Psychology is an epiphenomenon of biology.

gumby2• 4 years ago

My comment on another thread (https://news.ycombinator.com/item?id=34251033) addresses this. Psychological issues are real health issues.

tgv2• 4 years ago

Yes, but this researcher's field is body image and weight stigma, not mental health issues. In the paper that appears first if you google-scholar her name, she writes in the first sentence of the abstract "Weight bias [or the stigma towards and negative stereotypes about individuals who have large bodies] is a form of stigma with detrimental effects on the health and wellness of individuals with large bodies." So making people thinner will actually improve their health and wellness.

If she's worried about other negative outcomes, such as people not being able to afford the drug, she should say so. It might be an editorial fuck-up on Nature's side, of course: they just want to print some soothing words to demonstrate their neutrality.

asdff5• 4 years ago

Its an article about weight loss and that plays into body image which is a huge mental health issue. People purging themselves need a psychologist, not a biologist, and I'm sure a number of people affected with bulimia will be buying this drug.

Izkata5• 4 years ago

They described the details of an investigation of a promising anti-obesity medication in teenagers, a group that is notoriously resistant to such treatment. The results astonished researchers: a weekly injection for almost 16 months, along with some lifestyle changes, reduced body weight by at least 20% in more than one-third of the participants1. Previous studies2,3 had shown that the drug, semaglutide, was just as impressive in adults.

Two immediate thoughts:

How much of it was actually the lifestyle changes? It would be more interesting if there were no lifestyle changes...

This apparently works by suppressing appetite, but doesn't cocaine do the same thing? Constant needle marks from weekly injections might result in more social complications than anything else...

ceejayoz27• 4 years ago

How much of it was actually the lifestyle changes?

That's why the placebo group in the trial also gets the same lifestyle changes.

This apparently works by suppressing appetite, but doesn't cocaine do the same thing?

Sure. If they were otherwise identical, that'd be a good point, but they're not.

Constant needle marks from weekly injections might result in more social complications than anything else...

My daughter has to give herself growth hormone injections every day, and has for nearly a decade now. You don't get needle marks from these sorts of small dosage subcutaneous injection.

Izkata5• 4 years ago

You don't get needle marks from these sorts of small dosage subcutaneous injection.

Ah, my only experience is with things like vaccines and drawing blood; those marks last around a week on me.

carrotcarrot2• 4 years ago

Sure. If they were otherwise identical, that'd be a good point, but they're not.

You can say the same of opium, heroin, morphine, oxycodone, fentanyl, and Naloxone. Many of which have had i ical trials done and all of which are abused and addictive.

I simply don't trust clinical trials by large pharmaceutical companies any longer.

Someone1234• 4 years ago

How much of it was actually the lifestyle changes? It would be more interesting if there were no lifestyle changes...

The article answers this further down:

Those receiving weekly injections of semaglutide lost, on average, 14.9% of their body weight after 16 months of treatment; those who received a placebo lost 2.4% on average.

Per the article still a lot of work to do in this area, but on the face of it this could be an alternative to bariatric surgery for 1/3 of people.

__blockcipher__2• 4 years ago

The line you quoted:

Those receiving weekly injections of semaglutide lost, on average, 14.9% of their body weight after 16 months of treatment; those who received a placebo lost 2.4% on average.

Doesn't really have anything to do with the question about lifestyle changes. That question basically centers around whether the 14.9% weight loss occurred independent of or as a result of lifestyle changes downstream from the semaglutide.

smith7018• 4 years ago

Cocaine does the same thing but it only lasts ~20 minutes. Ozempic is a once a week injection that curbs appetite and makes the user feel fuller faster. It also comes in a pen (like an epipen) and is injected into fat stores so the user probably won't have "track marks."

djur7• 4 years ago

Also, these medications aren't stimulants, which is really important for people who might be at higher risk for heart issues.

PuppyTailWags4• 4 years ago

Have we actually studied if the weight loss is resulting in better health outcomes for the people in question? Outside of diabetics (there is evidence that significant weight loss can relieve the effects of type 2 diabetes), I would like to know if just weight loss benefits the cardiovascular system, blood pressure, etc. These aren't as intuitive as we'd like, for example, it turns out that low fat diets didn't make people less fat, and cholesterol-lowering medication doesn't reduce heart disease.

I'm hesitant to measure weight loss as a pure good in of itself because it isn't evident to me that just losing weight has a causative effect on reducing specific diseases.

ceejayoz27• 4 years ago

My wife lost a hundred pounds via bariatric surgery; resting heart rate dropped by 20, cholesterol dropped into normal range, knee and hip pain disappeared, and it even helped the chronic migraine substantially.

We've got plenty of clear evidence that being significantly overweight has health impacts.

mattbrewsbytes2• 4 years ago

Yup. On a much lesser note, when I lost 10lbs I noticed acid reflux symptoms disappear and blood pressure was lowered. For someone that is borderline on need of medication, the doc basically said lose some weight and these issues could go away (for some time). Its incentive enough for me to keep losing so I can push off the major diseases until much later in life or never.

nscalf• 4 years ago

Yeah, there are a lot of published studies showing this is very impactful. Within certain thresholds, losing weight has been shown to be the biggest change to all cause mortality rates. If you are obese, the most impactful thing on health is losing weight. This obviously isn't true for people with very low BMIs, but there have been a lot of population level studies looking at all cause mortality.

PuppyTailWags4• 4 years ago

What are the certain thresholds? Can we be more specific than lowered all-cause mortality, such as specific diseases we know have causal relationships with obesity specifically? I'm asking because I'm not that educated, but if you know there are studies showing e.g. purely losing weight with no lifestyle changes means less heart attacks, less joint replacements, less cancer, etc. please share.

gadders4• 4 years ago

>it turns out that low fat diets didn't make people less fat

Yeah, but low calorie diets (lower than your daily calories expenditure) always do.

v4dok• 4 years ago

it turns out that low fat diets didn't make people less fat

This is not a "turns out". Anyone who believed that just having a "low fat" diet will make them leaner, didn't really know how losing fat works. Fat is a macronutrient (and quite useful one) just making it lower tells you absolutely nothing on its own.

nextlevelwizard6• 4 years ago

Wtf are you on? Of course losing weight results in a better life. If nothing else it will make moving a lot easier it doesn’t need to reduce any diseases if it does that is pure bonus

iammjm4• 4 years ago

At a risk of being ignorant: Isn’t obesity a function of calories intake and calories burn rate? If so, why do we even need a drug for that? What should a possible drug target here? Assuming no changes in behaviour and thus a continued steady daily caloric surplus, would it even work?

ceejayoz27• 4 years ago

Isn’t obesity a function of calories intake and calories burn rate? If so, why do we even need a drug for that?

Because calorie intake is substantially impacted by things like satiety. As the article's subtitle heavily hints at, "A class of drugs that quash hunger" is beneficial in moving that bit of the equation.

iammjm4• 4 years ago

I understand, but appetite/hunger seems to be just a part of the issue. The second part being people (myself included) using food to comfort ourselves. I feel bad -> I seek tasty food to comfort myself, even if I am not hungry. The whole candy-market is built around. How are drugs to address this?

starkd6• 4 years ago

By using drugs that manipulate specific hormones to alter a person's appetite. So you consume less calories.

0xB31B1B10• 4 years ago

These drugs modulate your hormones to reduce appetite and cravings for unhealthy foods. When people lose weight the normal way, their endocrine system sends out a “you are starving, eat” hormone response that is extremely difficult to overcome and success requires 100% compliance for the rest of your life.

dbspin2• 4 years ago

Success in adjusting diet does not require '100% compliance for the rest of your life'. It requires serious changes yes, but even frequent slips as part of a largely altered diet won't discount it. This perspective - as well as being factually inaccurate - feeds into shame spirals and negative self efficacy. It's also true that virtuous circles can be built on diet and exercise, replacing the endorphin lift provided by sugar / carbohydrate load; and in the longer term homeostasis can be achieved at a healthier weight. It is difficult, but it's absolutely not as impossible as this comment implies.

rootusrootus9• 4 years ago

I think people who think it's "just that simple" have never seriously tried to starve their body. It's truly incredible how far the human brain will go to get food into your mouth when it thinks you're trying to starve it.

awillen2• 4 years ago

Because many people just aren't able to get that ratio to a point that they're at a healthy weight (for numerous reasons - behavioral, medical, etc.).

"Assuming no changes in behavior" doesn't make sense, because the drug makes people feel full after a smaller amount of calories and thus changes behavior.

iammjm4• 4 years ago

Don’t you ever eat sweets despite of not being hungry? I don’t think the issue is people overdosing rice or legumes because they are so hungry. The issue seems to me like quick comfort foods that we eat not to get full but because they just feel so good in our mouths. I don’t think I’ve ever eaten ice cream out of hunger:)

randomdata2• 4 years ago

Isn’t obesity a function of calories intake and calories burn rate?

In the same way that the economy is a function of people trading things, sure. Why do we even need economic policy?

iammjm4• 4 years ago

Indeed, we need an economic policy, not an economic drug. I’m totally for behavioural policies for obesity, such as don’t buy sweets, go for a walk each day, or make sure to eat vegetables each time you are hungry, etc.

megiddo• 4 years ago

It's like treating an addiction by telling the addict "it's ok to have some, just pinkie swear you won't overdo it."

People who are obese or grossly obese often aren't just eating a "little extra" here and there. Imagine more like "extra pizza a day" or "eat a cake once a week because that seems like a good idea".

rhino3692• 4 years ago

The amount of calories to add an extra 50 lbs isn't that crazy. It's around 300 calories a day. So more like 1 *slice* of pizza extra.

That is why weight loss is hard to achieve. If you are hungry, it's hard to--over an entire day--avoid eating 300 extra calories.

cjbgkagh• 4 years ago

It would be if people are calorimeters but they’re not.

pjc503• 4 years ago

Assuming no changes in behaviour

It's the other way round: the point of the drug is to change behavior. By changing the hunger response.

The hunger response is not quite as low-level as, say, the breathing response, but you'll notice that it's very difficult to choose to stop or reduce your breathing below a level that your body will accept, and after a very short while your conscious will will simply be overridden.

kemayo2• 4 years ago

At a really fundamental level, yes, it boils down to calories in versus calories out. However, in practice it's more complicated than that, partially for psychological reasons.

Anyone will lose significant weight on a strict enough diet. Unfortunately, severe calorie restriction does things to your metabolism -- basically, your body notices there's not enough food, and tries to slow everything down so that your existing stores will last as long as possible. This (a) isn't good for you, since major organs are having to limp along, and (b) means your diet gets less effective, as "calories out" aggressively shrinks. There's evidence that this lasts for a fair while after a diet stops, making it really easy to regain weight.

Then, psychologically, most people have a hard time sticking with any sort of long term diet. Unless you have an abnormally low hunger response, ignoring feeling hungry all the time (even just a little bit) is very hard. Cheating on your diet is very alluring, and your body gives you all the rewards for doing things that feel like they're avoiding you slowly starving to death.

The latter point is where these drugs come in. By suppressing hunger signals, dieting suddenly becomes easy, removing the escalating willpower requirement. (Honestly, I'd worry about whether you'd still suffer the metabolic effects of calorie restriction even if you're not noticing the hunger, but hopefully that's being studied and they're only prescribed along with a solid nutritional plan...)

grecy6• 4 years ago

Anyone will lose significant weight on a strict enough diet. Unfortunately, severe calorie restriction does things to your metabolism

Who said anything about "strict" or "severe calorie restriction" ?

To loose weight a person need only regularly eat 100 or 200 calories less than their daily requirement. For many who are obese, we're talking about having one less can of coke per day, or one less slice of a whole pizza or less ice cream every day.

A severely obese person can perfectly well eat McDonald's every single day, and eat more calories than a regular gym junkie and STILL lose weight!

bilsbie• 4 years ago

Let them eat cake (I mean less calories)

drowsspa3• 4 years ago

"Stop being poor"

dougmwne2• 4 years ago

Yes, your instinct is correct, you have vastly oversimplified it in an unhelpful way. The body is not an energy equation to be balanced.

The desire to eat is driven by our hormones and these are not easily overridden by willpower. In fact, study after study shows that willpower is insufficient for most people. Hunger is produced by a complex set of factors that we do not fully understand. What we eat and how we live plays a big part in how hungry we feel.

Calories should not be counted like some fungible currency. Each food is a complex and poorly understood cocktail of organic chemistry. Food is not processed by the body in the same way or at the same speed. In the most simple sense, unprocessed whole foods digest the slowest and provide the most even energy to the body, while highly processed food is digested quickly and leaves you hungry again soon. And above all else, fiber is the most amazing thing that can be in your food to regulate your digestion and make you feel more full.

And the consumption of energy is also not a matter of willpower to go to the gym. The body regulates is caloric burn to suit its environment, again, based on a complex and poorly understood web of signals. But in simple terms, trying to eat less can also caus your body to go into a "low power mode" where you burn less energy, ultimately being counterproductive.

The magic of this drug is that is hijacks one of the important hormone pathways involved in hunger and causes you to eat less calories without a single conscious thought. If proven out as safe and effective, it could be the silver bullet in an obesity epidemic that has never had any easy solutions before.

joe_the_user7• 4 years ago

It's very important to consider "metabolic rate" in these considerations. I have been nearly under-weight my entire life (I'm in my 60s) and I've eaten as much high-calorie food I've felt similarly, usually a large amount (generally consuming the most any gathering I'm at, etc, eating three meal a day, etc).

The one thing I've always done is avoid foods with added sugar and in general processed food. There's good evidence that the consumption of "ultra-processed" food is associated with the obesity epidemic and that these food are what people weight-maintenance processes out of balance.

Given this, adding a drug to solve that problem might not be a panacea. What other bad effects could result from a strong drug plus a crap diet? We'll start another mass experiment to find, I suppose.

hungryforcodes• 4 years ago

The body is an energy equation to be balanced. Physics defines that.

What you are talking about substantially in your post is about willpower with regards to eating and exercise which is totally different.

dcolkitt11• 4 years ago

Modern nutrition science has found that each person, at any given time, has a "metabolic setpoint". This is basically a target weight that their endocrine system is trying to keep them at. There's a feedback loop, where below this weight hunger hormones will nudge them to eat more and metabolic hormones will lower caloric expenditure (lowering body temperature, sleeping longer, fidgeting more). And vice versa above this weight.

Most people will have a +/- 25 lbs window, where the feedback loop is minimal. But once they step outside this window the nudges become increasingly strong. This is why it's generally easy to lose 15 lbs, but really hard to lose 50 lbs. Also why many can lose weight under very targeted lifestyle interventions, but rapidly snap back as soon as they relax even a little bit. Finally it's why the vast majority of normal weight people don't need to count calories, their metabolic setpoint intuitively matches their appetite to their caloric needs.

"Eat fewer calories" is technically a solution, in the same way that "stop drinking alcohol" is a solution for an alcoholic. The problem is someone who has an obese-level metabolic setpoint will literally be ravenous 24/7 once they get down to healthy weight. If you haven't experienced this yourself, try fasting for 48 hours, putting out a bowl of chips on the table in front of you, and resist the urge to eat even one while you try to do something else. That is what it's like to be an obese person trying to lose a large amount of weight.

GLP-1 agonists work by short circuiting the hormones that regulate hunger. It's basically the equivalent of moving your metabolic setpoint 100 pounds lower. The need to explicitly count calories no longer exists, because your appetite will naturally limit itself well below the point of caloric expenditure.

asdff5• 4 years ago

People have trouble dealing with hunger because we frame it all wrong in the western convention. I'm hungry, I should eat a little something, is what most people think. An ascetic from the east who fasts is not immune to the pain of hunger, they just understand that hunger is a sensation that is neither good nor bad, and what they choose to do with that sensation is up to them, and they are not bound to it and do not have to satiate it right then.

I imagine if a prescribed diet from a doctor also came with mental health counseling, that overcoming the satiation issue could be a lot easier for more people. It really is a frame of mind issue that prevents most peoples weight loss from being more successful.

bscphil3• 4 years ago

Modern nutrition science has found that each person, at any given time, has a "metabolic setpoint". This is basically a target weight that their endocrine system is trying to keep them at.

Citation? This goes against everything I've heard from credentialed experts and against my own experience as well. For one thing, it's unclear how you'd explain the weight gain of the median person in the western world over the last 30 years. For another, it's very strange that people like me (previously) gained 5-10 pounds a year, if our bodies were supposedly trying to keep us at a particular set point.

asdff5• 4 years ago

We evolved as hunter gatherers and have been hunter gatherers for most of our history. Continuously moving while collecting resources, even into old age. Today, most people don't continuously move. They go from bed, to work, to the couch at home, then to bed, with as little physical movement as they can possibly do in between.

Maybe if more people at least simulated how much a hunter gatherer moved a day, we'd see a much healthier population versus continuing this sedentary behavior that we have not evolved to do while remaining healthy. Agriculture which enabled a sedentary lifestyle for many people did not happen long enough ago for our species to be well adapted to this behavior; it was only 10,000 years ago, while our ancestors had been hunting and gathering for at least 2 million years, likely foraging even longer still.

bioemerl5• 4 years ago

Drugs can reduce your desire to eat or increase your metabolism.

You don't need a drug, but changing habits is very hard and obesity very deadly.

mattbrewsbytes2• 4 years ago

I had an opinion that this all sounded silly but then watched the 60 Minutes segment on the drugs and what the doc talked about is, in my layman's recollection, the body remembers its weight and wants to get back to that which is why a lot of people end up losing and then gaining most of it back. Genetics play a role in this, I forget how but something to do with what these drugs help change.

I wonder if rather than a placebo they had a control group also try to lose with caloric restriction and defined plateaus where they maintain a weight for some period of time. For example instead of lose 1lb/week for 52 weeks, lose 1lb/week for 12 weeks, maintain weight for 8 weeks, repeat. Maybe the element of the body "remembering" a weight happens when you plateau at a weight for a while? Kinda like giving the body some time to adjust as you lose.

pixl9715• 4 years ago

try to lose with caloric restriction

Other than this is mostly useless in itself.... Calorie restriction really only works well under medical supervision (multiple studies show people suck at calorie counting and avoiding calorie intake). Once the supervision is over, most people gain the weight back.

I have a feeling it may happen with this shot too, and if so I foresee it will have primary treatment to lose weight then a secondary to maintain status.

nextlevelwizard6• 4 years ago

When you are so fat your metabolic maintenance rate hovers around 4000 kcal per day you lose all sense of what to eat and after years of over eating old habits die hard.

On paper dieting is the easiest thing. You literally need to watch one hole and it is right under your nose, but in practice it isnt that easy.

Appetite is great way to control obesity - if you dont want to eat you wont

Kon5ole• 4 years ago

I believe you are correct, but that leaves several possibilities for the drugs to be effective. They could work by either causing you to lose interest in food/improving impulse control so that you eat less, or by increasing your calorie burn rate, or by causing your body to absorb less calories from the same amount of food.

photochemsyn• 4 years ago

There already are quite effective weight-loss drugs but they're not across-the-board medically-approved for that effect (with some exceptions) because they're also drugs of abuse, namely the cocaine and amphetamine drug families. However, many obese people get around this by getting an ADHD diagnosis (any quick search will reveal that 'obesity and ADHD are highly correlated' due to this phenomenon). The WebMD blurb is fairly accurate:

"Sometimes the medicines most often used to treat ADHD can cause weight loss. Stimulant drugs like methylphenidate (Ritalin) and amphetamine/dextroamphetamine (Adderall) make you less hungry and make your body burn calories faster than usual. Some of them are even used to help people lose weight or treat binge eating.Oct 26, 2021"

More technically:

https://pubmed.ncbi.nlm.nih.gov/1523237/

"The effects of amphetamine on body weight and energy expenditure" (1992) Jones et. al

However, in many cases if people stop taking such drugs they can regain the weight, and the drugs can be addictive if dose regimens are not carefully managed (which doesn't seem to be a problem with ADHD). Note also these drugs are much cheaper than this new class, likely by a factor of 10.

In the long run, new behaviors (quitting alcohol and sugary foods, increasing exercise, reducing overall calorie intake, etc.) are probably needed for persistant long-term effects on reducing obesity.

0xB31B1B10• 4 years ago

I’m currently taking one of these drugs and it has been no less than a miracle in my life. I became obese when I was around 5, topping out around a 34 BMI. When I was 20 I lost a substantial amount of weight the old fashioned way (diet and exercise), and within 8 months I was BMI 23. Losing weight was extremely challenging and socially isolating.

7 years later, I had a bad ankle injury and regained weight to about 29 BMI. This time I lost weight by doing an “eat every other day” diet. This was also extremely challenging, but easier than just counting calories and working out. After Covid and a lack of exercise I was back to BMI 30. I started taking tirzeparide this summer and have gone from BMI 31 to BMI 26 and still dropping. This is by far the easiest way to lose weight. The side effects for the first 3 months are quite bad, and include off and on strong nausea, extreme fatigue, brain fog, and constipation. I was eating <1k calories per day for a long time and feeling full. I expect to be on this drug long term. My blood work shows extreme improvements in cholesterol, BP, and other key health indicators. I believe that everyone, even the skinny folks, should be on GLP1 drugs for the longevity effects. They changed they induce in diet reduce the oxidative stress on the human body, even if the person is already thin.

drchickensalad• 4 years ago

What's the drug?

0xB31B1B10• 4 years ago

Trizepatide, brand name is mounjaro. It’s a similar drug to semaglutide.

dmix5• 4 years ago

https://en.wikipedia.org/wiki/Tirzepatide

linsomniac2• 4 years ago

FYI: GoodRX says it costs $1K/month.

hammock2• 4 years ago

For those less familiar with BMI, each point of BMI for a man is about 7 pounds. So 34-->23 BMI = -77 lbs. 31-->26 BMI = -35 lbs

voisin• 4 years ago

It depends on height, so how can you say that?

SystemOut• 4 years ago

Have the side effects stopped? Or have you only been on it 3 months? My wife has been on Ozempic for longer than three months and the side effects haven't stopped. The nausea is typically bad for a few days after taking each dose but some of the others linger most of the cycle. For some I can see that tradeoff being okay but I can't see non-obese, non-diabetic folks making that trade-off for longevity. I know I wouldn't.

hackernewds3• 4 years ago

could you elaborate on the trade-off for longevity? is this based on the supposition that dieting is good for longevity?

0xB31B1B10• 4 years ago

for me, the side effects lessened over time, and are pretty low now. Everyone reacts differently though.

djur7• 4 years ago

How was the process with insurance? About a year ago I tried to get on semaglutide and my insurer shut down every option. It was extremely demoralizing.

hnburnsy• 4 years ago

Check out compounding pharmacies or peptides.

swalsh• 4 years ago

I think the main problem aside from the side effects you listed is the fact that frequent injections sounds really inconvienent, and the cost is pretty prehibitive unless insurance is covering it.

tptacek16• 4 years ago

If you're getting a ~20% weight loss in 6 months, the cost is a steal compared to the alternatives.

I don't think this is the most interesting or curious discussion we can be having about these drugs --- the science story is much more interesting and relevant than HN's general opinions about "big pharma" or the obesity epidemic, and the science story stays interesting even if you think the drugs are not a net good --- but of the non-science discussions we can be having, the pricing seems like the least interesting thing happening here. These are injections whose competition is major surgery.

ceejayoz27• 4 years ago

frequent injections sounds really inconvienent

So's obesity.

the cost is pretty prehibitive unless insurance is covering it

Given the costs of treating the various obesity side-effects, they're pretty likely to. (They'll probably require a few hurdles prior, though.)

paulpauper12• 4 years ago

It is expensive but so is treating health consequences of obesity

Let's hope this changes and insurance companies cover it

notJim3• 4 years ago

I'm taking saxenda, which requires a daily injection and it's totally fine. It takes like 2 minutes. The needle is tiny and most of the time you barely feel it.

hackernewds3• 4 years ago

there's a difference between being full and feeling full. is it still known that the human body is healthy with this level of dieting and lack of nutrition?

clearly can't be the case for someone who is obese so I'm wondering if this is true then if it's limited to folks who are struggling with obesity that can endure this

incongruity• 4 years ago

there's a difference between being full and feeling full.

Implying that something is off if you "feel" but are "not" full? How do you define full? Having a "healthy" amount of food in your stomach? However you define it, with asserting that, you have to acknowledge the closely related idea that there's something off if you are "full" (as you've defined it) but still not feeling full - or satiated. It's that broken state that so many of us are desperate to solve.

I'm on a GLP-1 agonist after years of diets, gym memberships, shame, etc. etc. and this medicine is nothing short of amazing for me. It feels like it has fixed things I didn't even realize were wrong and it has changed my relationship with food in very positive ways. It is now so much easier to eat - some food but not too much food - just like I've seen so many of my friends with healthy BMIs do forever and have always had to consciously fight to do, day in, day out.

But even more than that, it's changed my desire for alcohol and reduced my consumption patterns there as well. Moving is easier -- and that effect happened faster than weightless, suggesting a reduction in systemic inflammation as well.

The side effects were a little rough for the first two weeks, but after ~3 months on it, I'd happily be on this for life given the positive impacts I've seen, barring any unexpected/unseen side effects.

paulpauper12• 4 years ago

Congrats on this drug working

I lost 45 lbs myself with diet and excise, bmi is 25. Hoping it works. If it does not I at least know I have a fallback plan.

Volundr• 4 years ago

Congratulations that's fantastic! Best of luck keeping it up!

nradov2• 4 years ago

I would rather die young than deal with those side effects. And those of us who are competitive endurance athletes need the oxidative stress; it's not necessarily a bad thing depending on timing and volume. Plus we will probably find other harmful side effects after long term use. There is no free lunch when you mess around with basic metabolism; everything has a price (not just in money).

pessimizer5• 4 years ago

You would rather die than suffer through three months of occasional strong nausea, constipation and brainfog? I hope that's hyperbole or that you have someone to talk to.

treeman792• 4 years ago

I was put on topomax for extreme migraines. Turned out a side effect was zero appetite. Unfortunately another side effect was to lose of about 60 iq points. Loved the weight loss. Missed having a brain.

onionisafruit4• 4 years ago

That's why it's called dope-a-max. My wife had the same experience.

antihero• 4 years ago

Was it literally like just being less smart? Or was it sedation/fog?

tyleo3• 4 years ago

Losing weight was extremely challenging and socially isolating.

How was it socially isolating? I’m curious because I exercise and diet and this is not my experience. I understand it being challenging though.

iLoveOncall2• 4 years ago

Because if you want to lose quickly, and once you get the discipline to lose you do want it to be quick, you have to restrict your calories A LOT.

I'm not OP but when I was losing, as a 6"2 male, I was eating between 1200 and 1400 calories a day. This does not allow you to eat anything outside of small meals and drink anything outside of water or diet sodas.

I was still going sometimes to the restaurant with friends but my choice was limited to the unique salad on the menu (which you can't eat whole because it would be too much) and my drink would be a diet coke. Same when we were going to the bar, I would just have diet soda or water.

I was lucky that all of my friends were absolutely supportive and didn't mind at all, but it still limits you. Going to a night club without drinking is not fun at all for example.

omniglottal• 4 years ago

OP commented on a weight-loss scheme of eating every other day. Given the social attitudes around eating (which I suspect to be the #1 most common social activity), this alone has the obvious potential to eliminate ~%50 of the most likely socializing opportunities.

0xB31B1B10• 4 years ago

Eating food and drinking alcohol is a core part of most social activities. When you're losing weight, you can't really fuck up, you really need to stick to your diet. I found it difficult to maintain my diet in social settings (going to a friends party, eating at a restaurant with friends, going to a bar to celebrate something, etc) so I just stopped doing all of those things for 8 months. Like, if you're trying to quit heroin you're not going to go hang out with your old heroin buddies all the time and you're not going to do go near the places that sell heroin. Now, imagine that instead of being addicted to heroin, you're addicted to food, and all of the places that sell heroin are all the places that sell candy or burgers or really anything nowadays, and all of your "heroin friends" are really just your normal friends who have healthy relationships with food. Its really difficult to get away from it. When you're addicted to food, the only real way to improve is to quit it cold turkey style and that means some serious lifestyle changes.

nik282000• 4 years ago

Be overweight, bust out your healthy lunch at work. People will flat out tell you "Oh, it's so good you are trying to be healthy." So already you are being told that they thought you didn't care before and you have finally decided to make the "right" decision.

JamesBarney11• 4 years ago

I get the opposite of brain fog. I feel sharper on semaglutide than off of it.

windpower2• 4 years ago

I'm also on one of these drugs (Tirzepatide) and have been for a few months. The first time I remember knowing I was fat was when a babysitter made fun of me for it at age 6. I've been fat ever since and I'm in my late 30s now.

I've lost significant amounts of weight (60+ pounds) three times in my adult life, through simple calorie restriction (intermittent fasting, including before I'd ever heard the term). Every time, I've gained the weight back. At the beginning of 2022, I was the heaviest I've ever been.

I've accomplished very hard things in my life, including those that take sustained effort. Sufficient willpower isn't a problem for me in general. I honestly only ever hear "it's easy, just eat less and move more" from people that have never actually been fat. "I did it and I lost 15 pounds, no big deal!" and the like. 15 pounds is easy for me to temporarily lose too. I've done it enough times I should know ;)

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full. I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again. "Eat until you feel full" is literally a human experience I had never really had.

On this drug, I finally know what people are talking about. I still like food, and I still get hungry. But it doesn't dominate my thoughts. I eat, and don't feel like eating again for hours. I eat something that I'd normally easily eat all of like a big burrito or whatever, and I feel quite full halfway through with no desire to finish. I'm steadily losing weight, with none of the usual preoccupation with hunger, ascetic adherence to a strict calorie plan, etc. But above all, I feel like I must be experiencing what most thin people experience all the time. I'll be perfectly happy to take the drug for the rest of my life, though I do hope affordability improves.

As for side effects: I've had some heartburn, but none of the other commonly reported side effects.

ilyt8• 4 years ago

What finally got me on right way on controlling hunger was just getting used to eating once a day and dropping a lot of the quick-burning foods that made me go hungry quicker. Not necessarily going super healthy but stuff like eating less bread/pasta and more say baked potatoes so still nice tasty food that doesn't get me into diet sadness mood, just shifting away from carbs

Also figuring out when I'm "brain hungry" (brain is bored and wants to munch on something/get reward for hard day at work) and when I'm "body hungry" (body actually wants some energy and is slowing down, fingers/feet getting colder etc.).

altcognito• 4 years ago

I have gerd, and was like, I was wondering if this would make it easier for me to eat small amounts and not have as much heartburn... then I read this:

As for side effects: I've had some heartburn, but none of the other commonly reported side effects.

And I looked up the less side effects, it is a laundry list of gerd symptoms.

I can confirm, these symptoms will help you lose weight, but I mean that tounge in cheek, I hope this drug helps a lot of people but doesn't have much in the way of side effects.

relaxing2• 4 years ago

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full.

This is what all the common advice doesn’t address.

The only thing that has helped for me in the past was an SNRI (sibutramine) that was later withdrawn from the market. Then all the weight came back.

Izkata5• 4 years ago

I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again.

There's something similar here I've noticed while testing myself in the past: At least for me, it seems like hunger occurs when the stomach empties by a certain percent of its last maximum. No matter if I barely eat anything, or eat until max capacity, hunger starts after my stomach empties a bit further, but it doesn't take until I'm actually empty (tested by the size of the following meal), and the hunger tends to end after reaching the last maximum. To use some made-up numbers to demonstrate, it's like I can bounce back and forth between 60% full and 90% full or 20% and 30% full, and once I've gone a cycle or two on either of those, the low ends of 60% and 20% make me feel equally hungry and the high ends of 90% and 30% equally full, but I've digested more when the baseline is on the higher end.

It can be difficult pushing from the higher range to the lower range though, have to ignore/squelch the hunger long enough to reach it.

loeg• 4 years ago

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full. I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again. "Eat until you feel full" is literally a human experience I had never really had.

I have a similar experience.

danielvaughn4• 4 years ago

I was just saying the exact same thing to my wife yesterday. We’re both trying to lose weight, for the millionth time in the 20 years we’ve been together. Exasperated, I just said “I don’t get it. I was an artist who had no technical background, and was able to teach myself computer science and now I’m a highly successful engineer. I did that. And yet I can’t lose 10 pounds to save my life.”

It’s so hard to eat healthy, I honestly cannot fathom how people do it.

auganov2• 4 years ago

The thing is, I'm never full. I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again. "Eat until you feel full" is literally a human experience I had never really had.

I feel exactly the way you do, and yes, I was fat, lost it in one go and never gained it back. I try to keep my BMI around 18, never went over 20 since losing weight. It's been around 15 years now. I still have the exact same unlimited appetite I have always had. If you put food I like in front of me, I'm going to eat it.

I don't do anything special. I eat the same foods I always have, just less of them. Got really good at counting and never get more food than I need. The trick is to not put yourself in a situation where you have to stop eating in the first place. It's hard to just stop eating something you want to eat. Not that hard to stop yourself from going to the store again or ordering more (especially when other people are around).

I feel like most people never get serious enough about counting, try to eat stuff they don't enjoy, waste effort on exercise or let other people interfere.

notacoward• 4 years ago

people that have never actually been fat. "I did it and I lost 15 pounds

Also people who have never had an older metabolism. It's different. I was also skinny despite eating a ton and hardly exercising when I was 25. Everyone I know over about 30 can identify when their metabolism suddenly changed. Diet (and to a lesser extent exercise) advice from those who haven't hit their own wall yet is worthless for those who have. Those people need to stop over-generalizing their (limited) experience as universal truth.

ashwagary3• 4 years ago

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full. I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again. "Eat until you feel full" is literally a human experience I had never really had.

I hear people following a carnivore diet have had success in dealing with this satiety issue. The only things you can eat with this diet are butter (or ghee), beef, and salt.

There is a claim that nutrient difficiency causes the scenario you are describing. Your body is being deprived of what it really needs with your current diet and requires more consumption to continue its search for a particular set of nutrients.

The carnivore diet is not a silver bullet but worth a try. I will also mention it is high protien, high fat, and zero carb which has been shown to result in massive weight loss in relatively short periods of time (counterintuitive, I know).

heavyset_go7• 4 years ago

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full. I can eat until I physically can't eat anymore (not something I do regularly, of course), and as soon as my stomach has emptied a bit, I feel fairly hungry again. "Eat until you feel full" is literally a human experience I had never really had.

I had this exact same experience when I was prescribed a drug that, as a side effect, blocked receptors in parts of the brain responsible for signalling satiety from food.

I went from having trouble eating enough food to maintain a healthy weight, and just not being hungry, to suddenly being unable to feel full at all. It was like I always had room for more, no matter how much I ate. And I was constantly hungry, felt like I was starving 24/7 and would ruminate about food so much that it impacted my ability to sleep or concentrate. My brain was obsessed with preventing me from "starving" and it ultimately dissolved the illusion of willpower that I thought I had.

No longer take that drug, but it was an eye opening experience. I didn't know that was a thing people could experience, as someone who was always skinny. It really drove home that we are products of our biology and made me more empathetic with those who struggle with food.

ericmcer• 4 years ago

Does your appetite not adjust to your intake?

I did a “dirty bulk” while working at Trader Joe’s in my 20s. At the beginning I could barely eat one frozen mac and cheese. A month of heavy eating later and I could easily finish 2 and still feel hungry.

Im older now so I don’t eat like that anymore, but it is still very noticeable to me how easily I get full when I am dieting hard.

ccvannorman• 4 years ago

I still like food, and I still get hungry. But it doesn't dominate my thoughts.

This is how I feel as a default, I am a perpetually skinny person. Thank you for putting this into words from your perspective in such a crisp way. I wish everyone would have the same (non dominating) relationship with food as a normal occurance (and not some immense mountain to continually climb.)

jononomo15• 4 years ago

Please try eating only liver, eggs, and ribeye steaks and drinking only water. You can absolutely stuff yourself on this diet and you will nevertheless get in shape. It breaks my heart that people have such an upside down idea about what healthy food is -- people think they should avoid red meat and eat fruits and vegetables and "heart healthy grains" when in fact the only thing they should eat is red meat. It is a tragedy almost beyond description -- there are millions of people in your situation who have been thwarted in their weightless journeys at every turn because we've been getting the wrong information about what food is healthy for us to eat. In addition to losing weight, you will also completely eliminate heartburn. Just try it.

kweingar• 4 years ago

If you don’t mind sharing, we’re you prescribed tirzepatide for type 2 diabetes, or was this an off-label prescription for weight loss?

anovikov• 4 years ago

How much weight did you end up losing on that stuff?

vineyardmike• 4 years ago

I've heard people say that the solution is to eat (healthy food) when you're hungry, and stop when you're full. The thing is, I'm never full.

I’ve had a weirdly similar experience due to wildly different histories.

When I was a kid I was on medication that f’ed with my appetite so I literally never learned what hunger was as a kid. As an adult and long off the medication, I just eat and don’t understand the signals my body produces.

When I was younger, I had a healthy and active body and didn’t notice my diet was bad until first I graduated and took a desk job then it accelerated with Covid when I became sedentary and snacks were constantly available. I put on weight very quickly.

paul79862• 4 years ago

Just curious in regards to saying you never really feel full ..have you ever counted daily calories you consumed on average?

adriang133• 4 years ago

I was fat/overweight all my life until I was about 24. I had enough of it and I went from ~94kg to about 85kg quite quickly (through calorie deficit), then over 1-2 years I went to a low of about 72kg. I am about 75-76 now, and have been oscillating in the 72-77 range for the past 5 years or so. It still requires me to be mindful of how much I eat, which has become part of my daily life. I'm not very strict about it, I have days when I eat more and then I compensate by eating less.

I think the mistake people make is they think they can go on a diet temporarily, then go back to the old eating habits and not get fat again. That is nonsense of course, which is why dieting doesn't work. Dieting implies something temporary and you need something permanent.

KirillPanov2• 4 years ago

I expect to be on this drug long term

This is a feature, not a bug.

If this drug produced some kind of permanent physical change, that would be a pretty scary thing.

hutzlibu3• 4 years ago

Erm, the intented permanent physical change for the user is establishing normal weight, at which point you would assume, that you can establish healthy routines and ideally move on without the drug.

But the drug is designed (intentionally or not) in a way, that makes this very hard, keeping the user dependant on it. So I would call this a bug, but I can see people still choosing it over the alternative.

jfk13• 4 years ago

everyone, even the skinny folks, should be on GLP1 drugs

Seriously? No thanks. Think I'll give you all a few decades to see what the long-term effects are like, and let my body largely take care of itself except when specific medical issues indicate that an intervention is in order.

adamrezich3• 4 years ago

it's always really strange to me whenever someone enthusiastically advocates that others use experimental drugs whose long-term side effects have not yet been discovered. if you want to try em yourself then go for it I guess, but I'm good thanks.

it's interesting to take a step back and realize just how much pharmaceutical corporations have got average people to think it's perfectly normal to try putting random chemical compositions into their bodies and see what happens. maybe nothing will happen. maybe you'll get some mild nausea. maybe you'll suddenly develop an urge to kill yourself. but just try it and see what happens! ask your doctor if it's right for you (and if they get any kickbacks from it).

jostmey• 4 years ago

The only proven way to live longer and reduce your risk of essentially every disease is to reduce caloric intake. So unless you are underweight, the benefits could outweigh any side effects. I am not advocating that everyone take these drugs--but I understand why someone might suggest it

MaxHoppersGhost2• 4 years ago

Being a young and very healthy person I felt this way about the COVID vaccine.

hawski• 4 years ago

I'm not exactly skinny as I have some muscle mass, still I'm pretty thin. I do not have to think about restricting calories and I'm still that way. I do not like to eat much sweets, I preferred a schnitzel since I was a child, so that's one thing. But sometimes I get a huge hunger when I feel my body trembling.

I do think that if there would be famine I would just die. I also don't think it would be good for me to restrict caloric intake. There are certainly ways to make my diet healthier, but caloric restriction is not it.

rightbyte• 4 years ago

was eating <1k calories per day for a long time and feeling full.

That sounds like half a days meals? Could it not be some of the side effects were actually from you starving?

gradys• 4 years ago

That’s the effect of the drug.

w1nst0nsm1th• 4 years ago

I'm very skeptical of the 2000kcals/day normal intake.

Mankind has survived with far less than that, and I don't mean in mass hunger period.

If it's like the 1,5l/day of water intake, which is the result of studies funded by... mineral water companies.

It's not hard to believe big corporations in the food sector financing these studies through non-profit organizations.

RedditKon5• 4 years ago

Same - Mounjaro / Tirzeparide is nothing short of life changing.

A question I often get is "how effective is it?"

The SURMOUNT-1 study released in April 2022 showed 22.5% average reduction in weight for people on the highest dose of Mounjaro. For a 250 lbs person who should weigh 150 lbs (so 100 lbs of extra weight), this would result in them losing 56 lbs or 56% of their excess weight.

For context, bariatric surgery has the following success:

- Gastric Band: 35% - 45% of excess weight lost - Gastric Sleeve: 60% - 75% of excess weight lost

The fact that a once a week injection is having results similar to bariatric surgery is insane, and this is only the early innings of this shift. Lilly has another drug in the works (will likely be released in late 2025) that is reporting better results than Mounjaro.

Wild and exciting times!

joedevon• 4 years ago

Oh really? Got any more info on that drug?

machiaweliczny2• 4 years ago

I wonder if somone studied „dragon breath” and „vacuuming” exercise vs surgery. I am 15 pounds overweight but I have a feeling that since doing these I look much better and don’t eat that much

archon8102• 4 years ago

What drug are you talking about? I did some research and I can't find it. Only talk of them ramping up Mounjaro by 2025.

cactusplant73743• 4 years ago

How much do you pay per month?

emmelaich• 4 years ago

So it works by reducing hunger? Bit obvious if you eat less than 1kcal per day you will lose weight.

The article mentions "along with some lifestyle changes". Is what they mean?

Every animal will engorge itself given the chance. All that is happening is the great abundance of cheap food and less activity. Thats it - except maybe for a tiny minority with metabolism / hormone issues.

marcus0x62• 4 years ago

So it works by reducing hunger? Bit obvious if you eat less than 1kcal per day you will lose weight

Yeah, its obvious, even to those who are grossly overweight.

What these drugs do is make it easier, here, on this particular planet, for people who struggle to control their appetite to actually do so.

scarmig9• 4 years ago

Every animal will engorge itself given the chance.

Not every animal. Mice given semaglutide don't gorge when presented with food to feed on freely, to the point where their weight drops >10% compared to control after a month.

Sophistifunk• 4 years ago

Fat guy here: these side effects are pretty scary for somebody like me.

3 months of noticeably extra fatigue on top of my current baseline level of exhaustion seems to threaten serious psychological effects.

3 months of brain-fog sounds like a great way to get fired and really fuck up my life.

If my "gastro situation" was noticeably worse than the unpredictable wildy-swinging nightmare it already is, I honestly have no idea how bad the consequences could be for my social life (I would be the flakiest person anybody knows and everybody hates that guy) and ability to make plans / focus long enough to do any work.

For some reason, I don't know why but I've always been this way, there's nothing my body hates and wants to avoid more than throwing up. I dread it. I'm not so sure I enjoy life enough to get through 3 months of nausea.

asdf333• 4 years ago

it could be the effects of caloric restriction. 3 months, in the context of a whole life plus increased lifespan is not that much time.

raegis• 4 years ago

Another fat guy here. I haven't taken any of these drugs, but I stopped eating processed food (or anything with added sugar), avoided late night snacks, and lost around 30 pounds in 8 months as a result. I had the fatigue and such early in the process, but it sorted itself out eventually. The most important thing I recognized was that if I avoided eating late at night, I didn't feel awful waking up in the morning. I'm embarrassed to say it took more than a year to change my behavior, despite my clear understanding of the harm of snacking all the time.

jesuscript• 4 years ago

Time it properly. Pick the end of the year around December when things are slow. That knocks off a month. Save the vacation time to knock off 2 weeks in January. White knuckle it through February.

You have to try something.

isthisthingon99• 4 years ago

I was quite overweight for 20 years, now I'm just a bit thicc on my way to a lean muscular physique. It feels good. The biggest factor was getting away from the wrong people and habits. I'm not a fan of artificial intervention because I believe I should be able to get my body in line. It takes time for your body to adjust to the absolute shit you did to it for decades. I always said in my head "this is payback for what I did to me for 20 years, how can I expect to just turn on a dime." There is a good chance I will be the sexiest 40 something for miles around (I live in the middle of nowhere, but still!) The best feeling is looking great in clothes. Finding well fitting stuff is now fun.

You can do it. If I can do it.

Be warned that people who know you from the other physique will mock you for taking care of yourself. Be glad they are mocking you, it means you did something right. I felt such a sting the first time, it was traumatizing. "Shouldn't you be happy for me?" Turns out the answer is "no".

Sparkyte4• 4 years ago

I've done keto for three months and my body's ability to process fat has completely changed. I honestly think were never meant to eat as many carbs as we do in a day.

It sounds like a very similar symptoms except only for the first few weeks of Keto. Ketosis is where the body starts to use fats to produce its own sugars for the blood rather than relying on carbs to suppliment.

Anyway I'm off keto now and I find myself capable of burning fat simply by being more physical. It's really weird.

jononomo15• 4 years ago

I'm doing carnivore -- it's like keto but better.

AnIdiotOnTheNet• 4 years ago

Losing weight was extremely challenging and socially isolating

This line alone tells me you're legit be a use nobody talks about this aspect of doing what needs to be done to lose that kind of weight.

From everything I've heard, I'd take this class of drug in a heartbeat if I thought I had any chance at all of getting a prescription. It is apparently a double edged sword that all of my health metrics peg me at above average health, except that I'm a bit overweight again after the COVID times.

qwerty456127• 4 years ago

Are you sure your pancreas is going to live long and prosper under constant stress of incretin mimics pushing it to release more insulin?

tikiman163• 4 years ago

First off, no, not everyone should be on these drugs, there are side effects as well as known drug interactions that can be dangerous and not everyone needs them.

Second, please, please, please stop listing your BMI as if it were a definitive measure of health. To begin with it doesn't correlate well with actual percentage body fat because it doesn't differentiate between fat and muscle. Second, the study which created the BMI was based on a population sample from a single town and all participants were within 4 inches of each other in height, and nearly all were effectively average height with similar lean body masses. If your lean body mass does not conform to the expected range from that study, BMI cannot accurately determine if you are obese, skinny, a body builder or just tall/short.

Finally, rapid weightloss is dangerous, and if you're eating fewer than 1k calories in a day while experiencing extreme fatigue and brain fog, you are more likely to be losing significant muscle mass than fat. This is may be extremely because your heart could be weakened, which could kill you. It's great that your cholesterol and overall weight is down, it's terrifying that you're eating so few calories while being unable to maintain enough physical activity to keep your body from canabilizing vital muscle tissues.

aantix5• 4 years ago

longevity effects

Are you referring to any specific studies?

gadders4• 4 years ago

"The WHO recommends healthier diets and physical activity to reduce obesity, but medication might help when lifestyle changes aren’t enough. The new drugs mimic hormones known as incretins, which lower blood sugar and curb appetite."

Isn't eating less food (whether your appetite is curbed or not) a lifestyle change? It's not that lifestyle changes aren't enough. It's that the size of your change wasn't big enough.

ceejayoz27• 4 years ago

It's not that lifestyle changes aren't enough. It's that the size of your change wasn't big enough.

Sure, and one of the things we conclusively know about obesity is that people struggle enormously to sustain that sort of lifestyle change in the long term.

Hence, medications that help with that. In this case, by reducing hunger.

gadders4• 4 years ago

Yeah. It would probably be more accurate to say that the medicine makes the lifestyle change easier, not that it replaces the lifestyle change.

Communitivity• 4 years ago

I think it's awesome that there's a new use for these drugs. However, obesity kills slowly, when it kills. Diabetes and Chronic Kidney Disease kill more quickly if not under control. These drugs keep diabetes under control..and diabetics like my wife are unable to get their meds because people are buying these off the shelf to lose weight.

I don't pretend to know the solution, but I do think drug availability should be prioritized to those who need it the most, not those who can pay the most (the weight loss brand of the same drug is being marketed for 2x-5x the cost of the diabetic brand, or so I've been told).

pjc503• 4 years ago

I note the reverse applies: my dad was prescribed Metformin for diabetes, and began to lose weight at a significant rate to the point where it became unhealthy.

the weight loss brand of the same drug is being marketed for 2x-5x the cost of the diabetic brand, or so I've been told

Drug pricing is a hell of a drug.

jboy554• 4 years ago

Diabetes and Chronic Kidney Disease kill more quickly if not under control. These drugs keep diabetes under control..and diabetics like my wife are unable to get their meds because people are buying these off the shelf to lose weight.

This seems to be a short term problem, and the solution is to simply make more of the drug to match demand.

charlieflowers2• 4 years ago

and the solution is to simply make more of the drug to match demand

which unfortunately might not align with the incentives of capitalism.

VikingCoder3• 4 years ago

I'm on semaglutide. Was on Saxenda, because I couldn't get access to Wegovy at the lowest dosage. But now I'm on Wegovy, for half a week so far.

I was retching horribly one night at 2 am, but didn't throw up. I've felt clammy and dizzy a few times. (Possibly hypoglycemic?)

I honestly feel like it's changing how I feel about food. I don't want to eat empty carbs, anywhere near as much. Because I feel like they make me feel sick. I'm eager to have more, smaller meals. I'm eager to have protein.

I had previously done a keto diet, except maybe I wasn't really in ketosis? It was medically supervised, doing New Direction complete meal replacements. I lost a bunch of weight, but... gained it back.

So now semaglutide. Dr urging surgery as a possibility. I'm eager to not do surgery. Fingers crossed for Wegovy.

dmix5• 4 years ago

I don't want to eat empty carbs, anywhere near as much. Because I feel like they make me feel sick.

I did a keto diet obsessively for a while and I still have a psychological revulsion to drinking coke or eating cake even a year later. Those sorts of things are long term wins.

VikingCoder3• 4 years ago

When I was trying to slowly increase my calories again, coming off of low-calorie keto, I definitely wanted coke and cake.

I'm happy for you, but I didn't get that benefit you got.

standardUser• 4 years ago

I had the opposite outcome, several months of keto left me avoiding meat and cheese for a long time.

drowsspa3• 4 years ago

I wish I got to this stage where people lose their cravings. While I'm at home I can control my diet pretty well, but as soon as there's junk food in front of me I look like a pig. And I've lost like 30 pounds, to put it into perspective.

cmrdporcupine• 4 years ago

Wait til someone you love develops anorexia or a similar eating disorder (they may already have and you may not know it), and then you will think of "psychological revulsion to X food" in an entirely different light.

Be careful. You'd be amazed at what harm the brain can do to the body.

rajin444• 4 years ago

This drug is a net good for society, but we have to fix the root problem. Much of the food we eat is filled with addictive ingredients (sugar, excess fats/oils, etc) that provide little nutritional value but are highly addictive.

We’re subsidizing companies that create unhealthy addictive food and subsidizing companies to create drugs to counter the unhealthy addictive food. This is an enormous waste of resources.

drjasonharrison• 4 years ago

While we are drowning in quick to consume, non-nutritious, calories, we also have higher levels of anxiety, stress and more distractions.

To your comment, maybe more countries should attempt to implement programs similar to the UK's success in lowering sodium intake by slowly adjusting the sodium content of all manufacturered foods. https://www.nature.com/articles/jhh2013105

WalterBright2• 4 years ago

we also have higher levels of anxiety, stress

Why should that be true? Your kids aren't going off to WW2 to die. You aren't going to starve if bugs ate your crops. You aren't going to get clubbed and robbed if you follow a forest path.

EamonnMR6• 4 years ago

If we're going to treat calories as addictive and addiction as a disease rather than a personal failing it should follow that we treat the disease with a drug.

elcomet• 4 years ago

But not only. It also follow that we need to regulate the industry and stop advertising for sugar for example

hansonkd132• 4 years ago

They didn’t say calories are addictive. They clearly said certain foods are addictive. Those foods should be more regulated like cigarettes and companies take more responsibility as a first or at least concurrent step to everyone taking more drugs.

joe_the_user7• 4 years ago

The problem is that we are plausibly looking at the result of a change over the last thirty or fifty year in the quality of what's considered the normal diet, notably normalizing calories through the consumption of sugary drinks but also a variety of other things. This has had the side-effect of an obesity epidemic.

Now, what are we doing?

* Getting people to stop consuming sugary drinks and other very unhealthy items (maybe that would require drugs at this point)?

* Or offer people drugs so this side-effect of an unhealthy diet can be avoided?

If we're offer a way to continue a bad diet without this effect, it seems very likely further bad effects will appear X many years from now from a combination of the drugs and the bad diet. Because virtually all drugs taken forever accumulate side-effects over since the body did evolve to process them (these drugs may indeed be needed at times but the point remains).

thatguy0900• 4 years ago

If we assume addictions as a disease then we mostly treat them with regulation. Smoking companies would have loved if we just made a pill that mitigates tar in your lungs instead of all but legislating them into obscurity.

kenjackson7• 4 years ago

Isn't all food addictive? Is there something more specific you mean about addition when it comes to these foods? It seems like it may be more about caloric density than addiction.

maxlamb• 4 years ago

You find broccoli addictive?

drdeca4• 4 years ago

In what sense is "all food addictive"?

If you just mean "if you don't eat, you die", I don't think that qualifies as an addiction.

If you mean "if you suddenly eat a lot more for some meal than you usually do, you will likely be more hungry the next day than usual", I also don't think that really qualifies. It's not the same kind of thing?

mensetmanusman5• 4 years ago

No, try the potato only diet and see what happens.

wolverine8769• 4 years ago

These foods are specifically addictive. I mean, water is addictive - I need it every three days, but that's not meaningful.

dcolkitt11• 4 years ago

Disagree. People genuinely enjoy those foods, because they're tasty and flavorful. And there's zero reason to believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus. We know this because we have hunter-gatherer populations who consume 50% of their diets in sugar (e.g. the Hadza) or fats (e.g. Intuit), and they have none of the diseases of abundance found in modern populations because they have near zero obesity.

The problem is not the food. The problem is obesity. The food is only an issue because some people have overly strong appetites relative to the abundance of food. If we can cure obesity, then we can literally have our cake and eat it too.

Humans obviously value tasty and flavorful food, and its existence adds joy to people's lives. That's why they'll pay hundreds of dollars per meal for the best restaurants. In sum total the development of GLP-1 agonists has maybe cost $20 billion in research at most. That's literally less than 0.1% of global GDP, hardly an "enormous waste of resources".

Gatsky3• 4 years ago

There are randomised controlled trials of diets (without caloric restriction). They show that some diets are better than others for real clinical endpoints, eg mediterranean vs low fat diet for secondary prevention of cardiac events [1]. The effect size in that example is not small, it is large, despite most participants already being on a statin. This data shows that diets are biologically active and significantly impact health. Therefore, the philosophy you espouse cannot be correct, or at least needs to be heavily modified.

[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

philjohn• 4 years ago

Does the type of sugar, or type of fat not play a part here?

HFCS is notorious for the bad effects on the body, versus something like honey.

Same for the Intuit, simpler animal fats vs hydrogenated "trans" fats?

I feel like the key difference in their diets is it's not overly processed and full of things we've decided to put in there for cost reasons (corn subsidies making HFCS cheaper than cane sugar, and trans fats are cheaper than more expensive animal products).

joe_the_user7• 4 years ago

I don't think it's half-plausible to compare Hadza or Intuit diets to a Big Mac and a soda. Neither transfats nor processed sugars are in the Hadza diet, just for example.

Aloha• 4 years ago

Peoples appetites are larger than their physical ability level provides for.

We transitioned from a hunter gatherer, to an agrarian, to an industrial society - because most people needed to do much physical activity to survive, even when food was plentiful.

The information age is much more sedentary, but people have evolved needs to eat a certain amount of volume to feel satiated. The fact that our foods are super nutritious/calorie dense makes matters worse.

rychco• 4 years ago

And there's zero reason to believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus.

I have a hard time believing this without some very strong evidence for this claim. There's already existing evidence for greatly varying health effects of differences in cooking method, oil-type, omega ratios in fats, amino-acid ratios in proteins, glycemic index of carbs, sodium content, etc etc. It's hard for me to reconcile the suggestion that the content of food does not affect whether it is "substantially unhealthy"...

mensetmanusman5• 4 years ago

It’s not some people, it’s most people.

We need to tax the ** out of high calorie foods to fund the extreme cost on health care/society that overeating is causing.

myshpa3• 4 years ago

... there's zero reason to believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus. We know this ...

Disagree.

who consume 50% of their diets in sugar (e.g. the Hadza)

"Their diet is made up almost exclusively of food that they forage on the forest and includes fiber rich and highly nutritious berries, bananas and honey while any meat they eat is hunted and caught wild." (https://healthyfocus.org/the-hadza-diet-and-the-key-to-a-hea...)

They don't eat sugar. Fruits & vegetables with lots of fiber, wild game. Nothing like westerners diet ... so not really comparable, imho.

"... the Inuit's bodies have adapted to better handle the process of gluconeogenesis, in which the body turns fat and protein into useable glucose. The Inuit have larger livers and a larger volume of urine than the average human, which helps their bodies to process the byproducts of their diet." (https://oureverydaylife.com/486115-the-inuit-diet.html)

Also ... not applicable to a typical westerner.

The problem is not the food. The problem is obesity.

The food is the problem.

Eat whole foods, mostly plants, minumum fats & sugar, and obesity is problem no more.

the development of GLP-1 agonists has maybe cost $20 billion

What's the total cost of obesity? The cost of diabetes ? It is an enormous waste of resources.

spaginal• 4 years ago

I disagree. Low quality processed foods, typically found in western diets, glysophates, high in industrial seed oils, processed sugars, and salts, are likely one of the biggest reasons for all the negative health effects we are seeing in the western diet, calorie numbers be damned.

Any quantity of this food, long term, is likely the reason for the explosive amount of health issues in the population, including many cancers we now commonly deal with.

One of the biggest changes to my health I ever noticed was a switch not in how I ate, but in WHAT I ate.

When I switched my diet over to high quality foods, organic and garden grown, meat I purchased from a local hunter, it made a substantial impact on my health, helped to fix a lot of my cholesterol and blood sugar numbers, and my overall health shot through the roof. No pills required, just decent ingredients, garden grown food, high quality meat.

sschueller• 4 years ago

You know that if you cut all sugar for just 2 days things with very little sugar will taste very sweet?

We do not need the excessive amount of sugar in our food to fully enjoy it. The general public is just totally numb to it because of over consumption and companies are literally competing on having the sweater product.

mym19903• 4 years ago

Uhhh you're a little disillusioned to think that a very very small subset of humans paying hundred of dollars for a meal is a baseline for why "humans value tasty and flavorful food". Just because some people drive 160mph on a highway does not mean its a good idea. The fact that you're arguing a box of oreos is equally nutritious to a calorie equal amount of say protein and/or vegetables is actually baffling.

steve_adams_864• 4 years ago

We know this because we have hunter-gatherer populations who consume 50% of their diets in sugar (e.g. the Hadza) or fats (e.g. Intuit), and they have none of the diseases of abundance found in modern populations because they have near zero obesity.

The often-cited studies suggesting Inuit populations were protected from heart disease (Bang and Dyerberg, Feldman et al) comes from limited data which has since been refuted as unreliable and insufficient. The hypotheses they generated don't hold up to the greater balance of data we have, and despite attempts to confirm findings, it simply hasn't happened.

Some studies have suggested to a lesser degree that Inuit populations have marginally smaller rates of coronary artery disease (and other cardiovascular complications), but far more have determined that rates are the same or in some cases/time frames even worse, and risk of stroke has generally trended higher as well. These are all incidents of mortality which have a very, very high correlation with diets which are high in animal fats (as well as salt, regarding strokes).

Here is one very good look at this type of data, and if you look you can also find others: https://pubmed.ncbi.nlm.nih.gov/25064579/

I agree that obesity is a major issue (especially in the case of sugar; it appears less harmful to the body when the sugar is needed and thus used immediately, but harmful when it hangs around and gets turned into fat. This is the main cause of the surge in fatty liver disease, for example), but there is very little and often very poor evidence that obesity is what causes atherosclerosis to occur and become a mortal danger. It seems to be dangerous regardless of weight, and exercise doesn't appear to be wholly protective against it either.

Inuits have actually served as a good example as to why this is true. Even when their obesity rates were lower, their lifestyles required more activity than average, and when studies accounted for BMI, their CAD rates were still on par with western populations according to most data.

civilized• 4 years ago

I think "people value tasty food" is an oversimplification. It feels good but we regret it when we get fat, our health deteriorates, and with our health goes our participation in and contribution to everything and everyone we love. For many people, junk food starts to feel more like an addiction than a choice in line with highest values.

Sadly, this means it can be a problem when food tastes too good. The term of art is "hyperpalatable". Studies have shown that even lab animals gorge themselves and get fat and unhealthy when they get human junk food.

I think many people would be grateful to have hyperpalatable food restricted or limited or less visible to them, so the temptation is removed or moderated. How we implement that in society, in a liberal or authoritarian way or somewhere in between, is a separate question.

yodsanklai4• 4 years ago

The problem is not the food. The problem is obesity.

Junk food corporations make profit by selling food, and they are extremely good at this. They rely on intense advertising, making the food addictive, targeting children. As a side effect, people get obese since they consume more calories that what they need.

I don't know about GLP-1, but my intuition tells me that no drug is going to make eating Mac Donald's and drink Coke healthy, even if it doesn't make you obese.

uhtred2• 4 years ago

It seems like you are saying that it would be fine for someone to eat nothing but potato chips and candy bars, as long as they:

a) don't eat so much they get obese, or b) take an anti-obesity drug so they don't get obese

Which is ridiculous. They would still get sick and die early due to lack of nutrition.

tayo42• 4 years ago

believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus.

They are, im not fat (visible flexed abs) I did a blood test and found some issues. I cut out the saturated fats I was eating. Brownies, butter, slow cooked meats. tests were normal again.

csours4• 4 years ago

This analysis lacks proper understanding of the role that hunger and food drive plays.

Imagine that you are at the beach, and you can choose how deep you want to wade or how far you want to swim. If you like the water and the sun and the waves, this is very pleasant to imagine.

Now imagine that you are dropped into the ocean at night 200 meters from shore and you can't see land, you can't see lights. This is very unpleasant to imagine.

Our current food system is much like the second scenario.

Instead of framing it as whether or not it is possible to be healthy in this system, ask if the system is consistent with the goals of being healthy. Is a candy bar and a bag of chips consistent with the goals of being healthy?

If you are dropped in the ocean in the middle of the night, it is possible to swim to land. But it is also very likely that many people will not be able to swim to land in that scenario.

The food is only an issue because some people have overly strong appetites relative to the abundance of food.

Then why is it advertised? Are food advertisements consistent with the goal of health?

ABCLAW• 4 years ago

I think the only way you can make this argument is to have a completely value agnostic perspective and believe that any individual value curve is good. Is Meth good because people clearly value it enough to destroy their lives to get more? No. It isn't - we know individual value assessment isn't always right.

People genuinely enjoy those foods because they're closer to their bliss point than natural analogues. Increasing salt, fat and sugar content of processed foods doesn't mean they're better for consumers. They just mean they're more addictive. People consume more of them and are more likely to purchase them in the future.

https://en.wikipedia.org/wiki/Bliss_point_(food)

We have no issues identifying that restrictions on tobacco are acceptable from a public health standpoint - the same chemical reward hijacking is being done with food.

ddorian43• 4 years ago

Disagree. People genuinely enjoy those foods, because they're tasty and flavorful. And there's zero reason to believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus.

People enjoy drugs, I agree. Some get addicted and die though.

lm284694• 4 years ago

Disagree. People genuinely enjoy those foods, because they're tasty and flavorful. And there's zero reason to believe that they're substantially unhealthy

I mean, there are responsible/functioning heroin users, it doesn't mean heroin is safe for everyone

If we can cure obesity

Or you know, practice self control, which is easily in the top 3 of good traits to have and practice. But that's only a part of the equation, the other being the food industry abusing our monkey brains by adding all kind of additives to their food to trigger the right pathways so that we keep consuming their products.

I for one am happy that I escaped this hellish cycle and mostly consume fresh products, but I completely understand how people get tricked into eating heavily processed food and basically slowly sabotage their whole body

Humans obviously value tasty and flavorful food, and its existence adds joy to people's lives.

We also enjoy all kind of things that cause harm to ourselves or others, this is an extremely weak argument, maybe the weakest of all concerning that topic

ffggvv• 4 years ago

the problem is you are limited in how many calories you can consume. so any unhealthy crap crowds out nutrient rich stuff

gsinclair• 4 years ago

The existence of (active) hunter-gatherer societies living heavily on (natural) fats and sugars seems completely irrelevant to the problem of obesity in sedentary societies eating many processed foods.

imranq2• 4 years ago

I agree that we have incredible waste on both sides, but there is an even greater culprit: people are lacking true meaning and purpose in their lives and are indulging in these foods to distract themselves from their inner emptiness.

mym19903• 4 years ago

This is a pretty big leap, what is even "true meaning and purpose"? The culprit is that this food is literally everywhere and billions of dollars are poured into research everywhere to design systems that entice humans to take the convenient way out. If I was to go along with your hypothesis, I would alter it to say that poor nutrition is what contributes to a person's lack of "true meaning and purpose".

D-Coder• 4 years ago

Reference please?

plutonorm• 4 years ago

I think that toxin exposure - unavoidable in the modern world - is likely the biggest culprit here. There are plenty of ideas about which toxins are causing the problem, but there are so many that it would be nigh on impossible to regulate them all out of the environment.

pixl9715• 4 years ago

I would think you're completely wrong. The green revolution was the first time in history that we were able to continually produce excess food for (excluding distribution issues) the entire earths population. Even more so, the new foods we are able to supply via processing are highly calorically dense.

Simply put if you take mammalian models and allow them to eat all they want they blow up like little balloons. This is no different from bears feasting on salmon for the last millions of years. Creatures are designed to overconsume because the ones that didn't in the past didn't make it thru the lean times.

Eisenstein• 4 years ago

Please define 'toxin' and the mechanism by which they produce harm.

moffkalast3• 4 years ago

That really is the core of the issue, and furthermore once you've used to a sugar diet you crave it more and regular food starts tasting worse in comparison somehow. I bet it's something to do with the gut-brain connection and a large glut of sugar eating bacteria signalling it's time to feed them. Just a theory, but there is some kind of correlated process there.

And the reverse is also true, if you go a while without eating anything high in sugar, what used to taste normal can taste almost unbearably sweet. Exceedingly hard to do with it added to just about all things in absurd amounts though.

CadmiumYellow19• 4 years ago

The first time I tried ketchup after strictly avoiding added sugars for several weeks was a WILD experience. It tasted sweeter than maple syrup. I used to douse my food in ketchup and now I can't even eat it on fries because it's so sickeningly sweet. I noticed the same with most bottled salad dressings and sauces (barbecue sauce and honey mustard being even more egregious than ketchup).

paulpauper12• 4 years ago

Even healthy, nutritious food is packed with calories. Anything that is not a fruit or vegetable can easily cause weight gain. Before civilization, humans had to expend a lot of energy just to get food, what little they could obtain.

grecy6• 4 years ago

This is an enormous waste of resources

Of course it is, which is fantastic for the economy. Like the Industrial War Complex, it's horrifically bad for people and resources, but does wonders for the pockets of those in power

mateo1• 4 years ago

Carbohydrates, fat and protein are the 3 main classes of molecules humans need to survive. Sugar is simply a fast absorbed carbohydrate, glucose is basically the very thing that keeps us alive 99% of the time. We are literally build around glucose. Marking it as "addictive" and without nutritional value is idiotic. A choice of a particular diet high in sugar can have negative affects, but guess what, you can chose a different diet and stop being obese instead of asking for one of the most important nutrients that exist to be banned.

npsimons3• 4 years ago

We’re subsidizing companies that create unhealthy addictive food

People love to bitch about the "diet industry" (which as a whole, seems to be almost entirely bro-science and snake oil), but the profits made there pale in comparison to fast food and processed food. It's really something that we should fix, like we did with tobacco and alcohol.

Fixing food deserts, even though they are not really widespread enough to entirely account for the obesity epidemic, needs to happen as well.

And taking subsidies away from animal products like meat, dairy and corn (specifically for HFCS) would go a long ways to improving the standard American diet (aka, SAD).

twawaaay2• 4 years ago

Just making sure everybody understands that these drugs are not a solution to the problem. Assuming they work, they just make dieting easy.

Look at people who successfully lost weight with diet -- studies show that almost all of them will regain most of their weight within 5 years. And the basic reason is because almost all dieting regimes are shitty, unsustainable way to live and at the end people are left tired of the diet and looking to get back to the eating habits they love and caused the problem in the first place.

Also calorie restriction comes with a host of other problems. You need to provide better nutrition while on a diet -- your body still needs same things but now there is less food with which it has to be delivered. But if you got obese you probably don't know how to eat properly.

Prolonged calorie restriction causes muscle wasting. You can counteract it to a certain degree for some time with exercise. Which if you are obese you probably don't know how to.

Calorie restriction also typically causes basal metabolic rate drop. Which means you have to keep tightening the diet to see results. And when you are off the diet it will be extremely difficult to impossible to keep your weight.

You can still cause a lot of damage to your body by snacking and eating wrong foods even if you are on calorie restricted diet. It is better to learn to not snack and keep your eating window to 4-6 hours every day rather than eat through entire day.

I personally dislike meds like this. It is good it exists but I would never take them or recommend to anybody. There are a lot of medications that are supposed to help (like metformin) but all these meds do not address the main cause of the problem -- which is what you eat, how you eat and when you eat it.

For background, I got obese once and lost weight. Then regained the weight over a decade. Being engineer and problem solver, I vowed to understand the shit out of the problem, loose the weight properly and never regain it back. Which seems to be working. Understanding how to loose weight allowed me to do fantastic things like loose weight at 3 times the rate I did it previously while not feeling hungry or cold.

The previous time I was on calorie restricted diet loosing and I was completely miserable for almost entire year, cold, slow, irritated, unable to focus.

This time I completed the same weight loss in 4 months while actually feeling better than ever (at least most of the time). Most important for me, it is not interfering with my work.

I am also not taking any meds.

I am not preaching any diets here. I am just suggesting that if you are feeling hungry throughout your diet you are probably doing something wrong and it would be worth the while to understand what and how to fix it. And the only way this happens is if you get interested. No drug is going to magically fix it for you.

ceejayoz27• 4 years ago

I think this is too dismissive, and internally inconsistent.

These drugs are not the solution for all people, but they may well be a part of it for many. The interventions you're advising - "don't snack", "exercise more", have the same pattern you're talking about with dieting - alone, they tend to fail in the long-term.

It's easier to learn to eat better (and enjoy things like veggies) if you're not feeling starving all the time. It's easier to learn to exercise (and enjoy it) if you're not obese.

all these meds do not address the main cause of the problem -- which is what you eat, how you eat and when you eat it

"Just don't do that" hasn't historically had a great track record of addressing it, either.

RedditKon5• 4 years ago

100% this. A lot of people on Mounjaro report that one of the benefits is that their internal chatter about food / cravings is silenced. For the first time, when they get hungry they’re able to stop and consider whether they should eat a salad, reduce portion size, etc.

vjk800• 4 years ago

Is the drug a long-term solution either, though? Won't the users regain the weight after stopping the drug, exactly like people who stop dieting do?

The trick with all lifestyle changes is to start as small as possible. Don't try to overhaul your eating and exercising habits overnight, but instead start from something small like "buy some fresh fruits every time you buy groceries" or "go outside for a bit every day whatever time you feel like it".

belltaco• 4 years ago

For background, I got obese once and lost weight. Then regained the weight over a decade. Being engineer and problem solver, I vowed to understand the shit out of the problem, loose the weight properly and never regain it back. Which seems to be working. Understanding how to loose weight allowed me to do fantastic things like loose weight at 3 times the rate I did it previously while not feeling hungry or cold.
The previous time I was on calorie restricted diet loosing and I was completely miserable for almost entire year, cold, slow, irritated, unable to focus.
This time I completed the same weight loss in 4 months while actually feeling better than ever (at least most of the time). Most important for me, it is not interfering with my work.

How did you do it?

twawaaay2• 4 years ago

I would be cautious to give something that could be misconstrued as an actual health advice. I have rather limited medical knowledge and I am only comfortable experimenting on myself.

That said, I red 3-4 dozen books related to weight loss, dieting, habit formation, nutrition, metabolism, diabetes, etc. and countless articles and youtube videos. I made notes of various topics that seemed important and repeated rather frequently and then tried cross-referencing to find which ideas are bunk and which seemed to be well supported.

Starting the process, my goals were to overdetermine the success (ie. do a bunch of things at the same time to ensure success) and to build understanding of topics to the point where I can see how everything fits together and builds confidence I know what I am doing.

Here is an unsorted list of ideas from my memory that I think helped me the most:

* building habits and prepare for what to do after achieving target weight is super important. Weight loss time should be spent learning right habits, building habit chains, discovering/learning healthy dishes, etc.

* managing family is also super important -- if your wife and kids have habits that will collide with your goals they can become worst enemies of the progress achieved,

* become healthy to loose weight rather than loose weight to become healthy -- focus on identifying and fixing health problems and weight loss should more or less come as a consequence

* it is better to do 20% of effort for 80% of benefit in each area rather than try to perfect any one of areas at the cost of others. Don't plan to become an athlete -- it is enough to jog every day for half an hour at comfortable pace. Don't plan for perfect diet -- it is enough to eat "healthy" most of the time. Etc.

* it is better to learn and get to love new, healthy foods and add them to your diet than to try to remove unhealthy things you love. Add new foods/dishes and let them slowly displace bad ones.

* commit to eating a portion of fresh fruit and vegetables, every day, however small. The goal is to build habits so that there is always fresh fruit/veggies at home, so that you automatically search/reach for them at the grocery, so that you have opportunity to test various things and learn new dishes.

* commit to doing any amount of exercise every day. As above, the goal is to build habits, not to become an athlete. The first thing I did was to improve my fitness to the point I could be jogging every day.

* don't start all changes at the same time -- introduce enough delay for each change to get accustomed and to be able to properly focus on that one change

* I found intermittent fasting (4-6 hours eating window, 18-20 hours of fasting) to be probably the single most important thing to improve health and loose weight. It also has benefit of being sustainable and can be additionally combined with calorie restriction and/or keto.

* The best eating window is probably somewhere in the middle of the day. There needs to be enough time before going to bed so that significant portion of fasting happens during sleep (aids recovery) but not too much or it might cause cravings in the evening and make it difficult to adhere.

* I found there are various easy strategies to decrease blood glucose ofter a meal that do not require making huge changes in diet: reduce carb intake during meal, precede carbs with protein/fat, precede carbs with any kind of acid (deactivates enzymes and further reduces blood glucose after a meal).

* A physical exercise like a walk immediately after a meal helps purge blood sugar. While exercise itself does not make the body any less insulin resistant, the effect is as if insulin was more effective.

* I found prolonged fasting and/or keto diet to be good temporary solutions to various problems. After some research I would probably not advise anybody to stay on keto for very long, but spending some time on it gives you superpower of metabolic flexibility, and this ease of being able to hop on and off carbs without ill effects greatly helps with being able to adhere to intermittent/prolonged fasts.

* Carbs make you crave more carbs. If you have problem with hunger while restricting calories, probably the easiest thing you can do is to cut carbs temporarily.

* You probably don't need to get on keto diet to get most of the benefits. MCT oil in morning coffee is enough to generate ketones to stimulate mitochondria to multiply and waste more enrgy.

* The main benefit of keto is that it is darn hard to eat so much fat and cutting carbs suppresses (unhealthy, extra) hunger.

* Running at easy pace (easy = you can still talk easily) for at least 20-30 minutes regularly is ideal to cause mitochondria to multiply. Mitochondria are your friends when loosing weight because this is how your fat gets turned to heat. The more mitochondria you have the easier it is to burn through fat.

* Running at any higher pace or for much longer probably is not advisable. The benefits are incremental but a risk of injury grows significantly making it absolutely not worth it from purely health/weight loss perspective.

andbberger3• 4 years ago

GLP-1 agonists are an incredibly effective pharmaceutical intervention, why are you dismissive of them?

behavorial interventions for weight loss don't work clinically. the only other intervention that comes close to the effect size of GLP-1 agonists is surgery.

you can argue that they treat the symptoms and not the disease, sure. the mechanisms of systemic obesity aren't well understood. but it's inarguable that this is disease of homeostatic misregulation, the set point is too high. which is why behavioral interventions fail.

we don't talk down to the people suffering from other diseases of homeostatic misregulation (eg diabetes) for their moral failings, we treat it. but that's how diabetes is treated now, "just stop being fat".

It is very much in analogous to where depression was 30 years ago. Now, therapy and anti-depressants are widespread and destigmatized.

The difference is that while SSRIs are only marginally better than placebo, GLP-1 agonists are _incredibly_ effective. Huge effect sizes.

I think in 30 years you're going to look back on your opinions now and be embarrassed that you were telling people to avoid a very effective and safe pharmaceutical intervention and "just stop being depressed"

I've been having the same conversation over and over again since GLP-1 agonists were approved and it's always the same. People who are opposed to a very effective pharmaceutical intervention but are not able to articulate any cogent reason as to why. It's just stigma.

sfusato• 4 years ago

I believe that everyone, even the skinny folks, should be on GLP1 drugs for the longevity effects.

Are you for real? Serious question.

0xB31B1B10• 4 years ago

I mean, if you have perfect bloodwork and a marvel movie body probably not necessary but otherwise yes. Heart disease, hypertension, high cholesterol, colon cancer rates are rising amongst everyone, even thin people. These drugs positively impact indicators of these things in everyone. Longevity makers have been betting on metformin for a long time and these drugs are like a supercharged metformin

throwaway5959• 4 years ago

Are they rising across the board or for certain ranges of BMI/weight?

mcculley8• 4 years ago

I think I will wait for some version that does not cause "strong nausea, extreme fatigue, brain fog, and constipation".

watwut3• 4 years ago

I mean yes, the obesity is actually not the only health issue in existence. Your weight and your health are two different somewhat related variables.

But so, the idea that everyone should take drug designed to make you thin by making you not feel hunge including thin people is scary.

mythhouse7• 4 years ago

if you have perfect bloodwork

I see a lot of health influencers always say whatever diet they are doing is best because nothing bad has shown up on their bloodwork.

I am not really sure if bloodwork is all it takes to asses your health.

joe_the_user7• 4 years ago

These drugs positively impact indicators of these things in everyone.

I think people's eagerness to jump from changes in markers to actual longevity is quite unfortunate. Medical "breakthroughs" often founder on such confusion and amateurs approaching things this way. See Goodhart's Law [1] (much as I generally regret the hn/geek tendency to lean these law, here it's reasonable).

https://en.wikipedia.org/wiki/Goodhart%27s_law

yamtaddle2• 4 years ago

these drugs are like a supercharged metformin

No drinking alcohol, like metformin?

If so, I suspect you could get a large fraction of the improvement gained from a population-wide deployment of these drugs, at zero cost, if everyone just stopped drinking alcohol. "But that's unreasonable!" Right, so if that's also required for taking this drug, then....

paulpauper12• 4 years ago

colon cancer rates are rising amongst everyone, even thin people.

Yeah, look at all these super-old people like Alan Greenspan, Warren Buffett, Kissinger, Munger who pretty much have terrible diets, obese, no exercise yet still going strong, productive. Shows the power of genes. "Your BMI is below 23, therefore we will skip the colonoscopy and prostate/PSA exam and blood work," said no doctor ever (unless the doctor wants to get sued, I suppose).

gardenhedge2• 4 years ago

A marvel movie body is made through injecting steorids.. not living healthily.

Ancapistani2• 4 years ago

I'm unfamiliar with the research around GLP1 drugs, but I my past reading about the long-term effects of metformin led me to a similar conclusion. Unfortunately, metformin causes me severe gastrointestinal issues that don't resolve themselves after a few weeks.

There are lots of surprising findings w/r/t pharmaceuticals if you start really digging. Lots of missed opportunity for overall improvement in the human condition that aren't being exploited.

beckingz• 4 years ago

Gets into fun tradeoff questions of "Would you live an extra 20 years but have diarrhea every day"

scifibestfi• 4 years ago

We're seeing the most successful Big Pharma marketing campaign since OxyContin.

The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy

From 1996 to 2001, Purdue conducted more than 40 national pain-management and speaker-training conferences at resorts in Florida, Arizona, and California. More than 5000 physicians, pharmacists, and nurses attended these all-expenses-paid symposia, where they were recruited and trained for Purdue's national speaker bureau.
One of the cornerstones of Purdue's marketing plan was the use of sophisticated marketing data to influence physicians’ prescribing.
Purdue “aggressively” promoted the use of opioids for use in the “non-malignant pain market.” A much larger market than that for cancer-related pain, the non–cancer-related pain market constituted 86% of the total opioid market in 1999. Purdue's promotion of OxyContin for the treatment of non–cancer-related pain contributed to a nearly tenfold increase in OxyContin prescriptions
A consistent feature in the promotion and marketing of OxyContin was a systematic effort to minimize the risk

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2622774/

ceejayoz27• 4 years ago

That article starts with:

Controlled drugs, with their potential for abuse and diversion, can pose public health risks that are different from—and more problematic than—those of uncontrolled drugs when they are overpromoted and highly prescribed.

These drugs are not of that nature.

BurningFrog• 4 years ago

That OxyCOntin turned out to be a mass killer does not imply that these drugs are disasters.

Similarly, that Penicillin turned out to save millions of lives, doesn't mean that these drugs will be very beneficial.

Every day is a new day, every event a potential surprise...

mensetmanusman5• 4 years ago

Those that haven’t heard of Chesterton’s fence might jump at the opportunity to live like no humans in the history of the universe.

sooheon• 4 years ago

All of us already are -- that condition is unavoidable. You just choose your flavor.

mythhouse7• 4 years ago

take GLP1 drugs, NAD , metformin , rapamycin for maximum benefits.

anigbrowl4• 4 years ago

I had the same reaction. I minimize oxidative stress on my body by being selective about what I eat: having a bit less of some delicious things and eating a bit more of some boring foods that I know are good for me.

Also, fuck 'longevity.' The population of the world has doubled during my lifetime and this is a Bad Thing which is wiping out vast numbers of other species. Call me misanthropic if you like but humans are overrated and the maximization of our species' footprint is not a desirable outcome. I expect to live for a shorter time than my parents have (partly due to my own choices, partly environmental factors) and while that's disappointing in some ways I've been fortunate enough to enjoy reasonably good health and resultant quality of life. My idea of biological success is no living to the greatest age possible but having sufficient fitness and autonomy to be physically and mentally active while I'm alive. I have enough experience of injury and near-death situations to know that I'm OK with dying, and have no intention of begging to escape the inevitable.

kiba• 4 years ago

Also, fuck 'longevity.' The population of the world has doubled during my lifetime and this is a Bad Thing which is wiping out vast numbers of other species.

More about our socioeconomic and political structure than raw population numbers.

Every piece of meat, for example, require the conversion of plant matter into meat. There's going to be energy loss. If we eat more plants and less meat, we would pollute less, and less meat animals and presumably more wild animals.

My idea of biological success is no living to the greatest ago possible but having sufficient fitness and autonomy to be physically and mentally active while I'm alive.

Unless you die in an accident, you're going to live longer due to being healthier.

Firmwarrior4• 4 years ago

Man, I'm really sick of this outlook. There's a whole solar system here full of unlimited space and resources. A hundred years from now, if someone feels like it they'll be able to live in an O'Neill cylinder the size of San Francisco by themselves, and it won't be any weirder than /r/vandwellers today

skissane• 4 years ago

I expect to live for a shorter time than my parents have (partly due to my own choices, partly environmental factors) and while that's disappointing in some ways I've been fortunate enough to enjoy reasonably good health and resultant quality of life.

What if we all live forever? https://en.wikipedia.org/wiki/Quantum_suicide_and_immortalit...

dang3• 4 years ago

We detached this subthread from https://news.ycombinator.com/item?id=34247305.

Beaver117• 4 years ago

So does this somehow burn fat or does it just lower your appetite? There are many others drugs that lower appetite, and yet we still have an obesity crisis. Why would this one solve it?

ceejayoz27• 4 years ago

So does this somehow burn fat or does it just lower your appetite?

The article's subheadline is "A class of drugs that quash hunger".

There are many others drugs that lower appetite

Not this well and/or not this safely.

EamonnMR6• 4 years ago

Doctors are reluctant to prescribe stimulants to their patients for various reasons. Also you don't keep the weight off with those.

contravariant• 4 years ago

You don't necessarily need a stimulant, you can also e.g. short the mitochondria using DNP. Doing so does have some fairly predictable downsides.

acuozzo2• 4 years ago

There are many others drugs that lower appetite, and yet we still have an obesity crisis.

Which ones are prescribed in the US, on label, to treat obesity?

jboy554• 4 years ago

There is only one class of drugs that lowers appetite outside of these GLP hormone drugs, those are stimulants like amphetamines. As someone on one of the GLP drugs for 3-4 months, and whose body tolerates it well, this is simply turning off the hunger switch. I will miss meals because I'm not hungry, since starting I have never felt "hangry" and I am satiated with small meals and do not feel hungry later. If I overeat, I will feel nauseous and sick.

I do not feel wired, foggy or feel like my personality or sleep cycle has been affected in the slightest.

ceejayoz27• 4 years ago

There are others; https://en.wikipedia.org/wiki/Topiramate is one. Nowhere near as effective, though.

curation• 4 years ago

Obesity drugs treat a North American symptom - obesity. The cause remains untreated.

partiallypro7• 4 years ago

Obesity is now a global problem; I don't know why people view this as US centric.

nextlevelwizard6• 4 years ago

It will help millions of people in life changing ways. Of course we should also fix the causes, but that is no reason not to pursue easier treatment

glonq• 4 years ago

I lost 100 pounds "the hard way" (diet and exercise) a couple years ago. Gained back 30 and am fighting to burn that off again.

It would be nice to have an affordable, low dose of one of these obesity drugs to make the fight a bit easier.

dang3• 4 years ago

Recent and related:

The FDA will likely approve the diabetes drug tirzepatide for weight loss - https://news.ycombinator.com/item?id=34220996 - Jan 2023 (100 comments)

Tirzepatide delivered up to 22.5% weight loss in obese or overweight adults - https://news.ycombinator.com/item?id=33221121 - Oct 2022 (21 comments)

LarryMullins3• 4 years ago

Why does this headline from Nature read like a scam advert from Facebook?

tptacek16• 4 years ago

Because what's happening in this field is bananas right now, to the point where the results sound like scam adverts from Facebook.

nindalf3• 4 years ago

Because sometimes you’re dealing with the real article. This isn’t a boner pill made of rhino horn. This has been proven in double blind studies, FDA approved and has changed the lives of thousands of people. This could potentially halt the obesity epidemic, preventing many early deaths and improving the quality of life of countless others.

At that point, such headlines are justified. What would you have written instead? Something lukewarm like “Obesity drugs show efficacy in many patients”?

LarryMullins3• 4 years ago

I'm sure it's possible to formulate a headline for this story that doesn't sound like gutter-tier clickbait. Nature must be doing a poor job hiring / directing their editors.

tptacek16• 4 years ago

Too much of this thread is debating whether these drugs are a good thing or a bad thing, and not enough is on the underlying science story, which is what HN "should" be interested in. What's happening with these drugs --- that you can replicate much of the effect of bariatric surgery with an injection --- is super interesting, and didn't seem to be on the horizon 10 years ago.

makeworld• 4 years ago

psychphysic3• 4 years ago

You really need to suppress appetite rather than avoid hunger.

How many have of us have eaten despite not being hungry?

tptacek16• 4 years ago

That's what these drugs do.

psychphysic3• 4 years ago

You're probably right the common side effects are all reason to not eat (nausea, GI upset).

bitwize• 4 years ago

Why use drugs and lifestyle changes when lifestyle changes alone will do the trick? Everybody knows you're not a real Hackernews until you adopt a cold, calculating, "food is fuel" mentality toward eating, with extensive data collection, strict timing, data-driven portion control, and long fasting periods. Once you do that you don't need the drugs and can tell Big Pharma where to shove it.

UI_at_80x24• 4 years ago

Lifestyle change alone is NOT all it takes. I've been fat all of my life, so has everybody in the last 3 generations of genetic contributors.

I can easily drop 20-40lbs if I cut sugar out of my diet. Then it stops. I've cycled 15miles/day for 7 years (on non-snowy days). During that time I went on a water-only fast, (7days on, eat one day, then 14days eat one day, then 7 days more of fasting before I stopped.) I lost 13 lbs during that period. I was doing a keto diet before and after this period. I was killing myself trying to have a high energy output with minimal caloric intake.

In the end, winter came and I stopped. Total weight loss during that time: 35lbs. There is no way I can lose the extra 160lbs that I need to drop. My body just won't drop it.

I'm diabetic now. I take metformin and invokana. As of today I'm down almost 30lbs since august.

Lifestyle changes maybe enough for you. That's awesome, good for you. Don't make blanket assumptions and think that they are true.

mensetmanusman5• 4 years ago

Another option is to not sit at all, all day.

obiefernandez• 4 years ago

Anyone know offhand if these drugs are easily available in Mexico? Having a hard time googling the answer

RedditKon5• 4 years ago

Ozempic is widely available in Mexico (without prescription) and Canada (with prescription). It’s also available throughout Europe.

Mounjaro is not widely available outside the US yet.

thejackgoode3• 4 years ago

How many of obesity cases are caused by eating disorders and addiction psyche in general? Treating the symptom in this case barely helps. You might lose weight, but it'll pop up in some other place in your life. See it as psychological side effect, a swap of coping mechanism. Often enough, IMO you need to go deeper than a pill.

nextlevelwizard6• 4 years ago

Thats such bullshit. Sure, yes, there is 100% mental aspect to every obese person, but some of that shit is old and already dealt with, but since you are already fucked you cant get out from the cycle.

Of course we should deal with the mental side but it will be a million times easier to deal with after you aren’t a fat fuck.

thejackgoode3• 4 years ago

Case in point, "fat fuck" and "old shit that's dealt with" shouldn't normally belong to the same argument

bioemerl5• 4 years ago

In the past, scientists and the public often thought that those with obesity simply lacked the willpower to lose weight. But evidence is growing that most people’s bodies have a natural size that can be hard to change.

In the context where we have gone from obesity rates of 13 percent to 40, to suggest that people have a natural weight and that's the cause of this seems absurd to me.

viro2• 4 years ago

And it makes more logical sense to you that everyone is just weak-willed?

nathas• 4 years ago

How many times do you check HN each day instead of doing work?

bioemerl5• 4 years ago

It makes more sense to point to the fact that we have a far more calorie dense meal palette and a far less active lifestyle.

fxtentacle• 4 years ago

s/weak-willed/addicted/

There. Fixed it for you :) Yes, to me it seems like capitalism creates a society where most people get addicted just trying to cope with everyday life. For some it's alcohol, for some it's OxyContin, for some it's food, for some it's all-nighters in World of Warcraft.

"59.3 million (21.4%) people over age 12 used illicit drugs in the past year."

"Underage [..] 29% reported drinking alcohol"

https://www.verywellmind.com/rates-of-illicit-drug-abuse-in-...

Looks like weed and alcohol already are 50% of all citizens... I don't find it difficult to imagine that the other half ab-uses food.

HDThoreaun6• 4 years ago

Yes, it doesn't to you?

rootusrootus9• 4 years ago

That viewpoint has a strong attraction for people who's natural weight is low, because they get to see themselves as strong willed and morally superior.

AuryGlenz12• 4 years ago

Honestly, yeah?

I know I'll get downvoted to hell for this but I could have absolutely nailed a quiz of "who is going to get really fat after high school." Nobody that I would have defined as a "hard worker" has gotten fat.

whodatbo1• 4 years ago

Absolutely agree. Unironically through the first few paragraphs I though this was some very cleverly put satirical take on modern society. There is a great book about the effects of modern food, primarily on dental health, written back in the 30s - Nutrition and Physical Degeneration by Weston Price. Even though it's almost a century old, the findings are quite fascinating and can be extrapolated to present day. It's quite undeniable that modern life has drawbacks and obesity is just a symptom.

bscphil3• 4 years ago

I think it would be most accurate to say that people's bodies have a natural size given a particular food and social environment. That's a crucial bit of context that's very often neglected. Resisting one's environment is very difficult - it often requires you to have money, time, medicine, workout obsessed friends, or all of the above. Given changes in the environment in western countries over the last 50 years or so, weights are rising to their new "natural" levels as a consequence.

pixl9715• 4 years ago

It's quite undeniable that modern life has drawbacks and obesity is just a symptom.

Yea, people tend to forget pre-green revolution people going hungry for longer periods of time and mass starvation were really common. We made a trade, between the sudden and terrible outcome of starving and hunger to one of long term consequences like obesity and disease.

8note2• 4 years ago

That two people eating the same thing in the same amounts will retain different amounts as weight is something you can experiment on, without assigning a cause.

bioemerl5• 4 years ago

I think we need to really stress here just how bad our situation is. We have an obesity rate of 40 plus percent.

Peoples weight just cannot be said to be a "natural number" in this environment. Something is causing this and your average person is obese because of it, not because of their "natural weight"

buryat• 4 years ago

people previously just couldnt grow to their natural size

pessimizer5• 4 years ago

This caused me uncontrollable laughter and the desire to tell everyone about it.

tootie4• 4 years ago

Prior to the 20th century, it was pretty routine for average people to have inadequate access to nutrition. The rise in obesity corresponded with sweeping changed in agricultural policy that backstopped the prices of staple foods with subsidies and improved land and water management to prevent dust bowls. The result is everybody has enough food available cheaply all the time. Rolling any of that back is likely to replace obesity with malnutrition which is a much worse problem. Pandemic years notwithstanding, life expectancy has increased almost hand-in-hand with obesity rates. Obviously that's correlation, not causation.

krona• 4 years ago

Obesity rates started rising in the 1980's in the US, not the turn of the 20th century. This corresponds with poor diet, not abundant nutrition.

insane_dreamer3• 4 years ago

Rolling any of that back is likely to replace obesity with malnutrition

Based on what evidence? There are plenty of countries where people are not suffering from malnutrition and yet obesity rates are low compared to the U.S.

seneca• 4 years ago

It's just terrible reporting, and equivocation. It being a lifestyle problem and having a natural weight can both be true. People have a natural weight, and it's difficult to drop below it. No one's natural weight is to morbidly obese.

These people are taking a medical finding and blowing it wildly out of proportion to support their agenda. It's an unfortunately common tactic.

I don't quite think it's entirely fair to blame on willpower in modern western society though. We have a food supply that is unnaturally calorie dense, and optimized for hyper strong flavor, shelf stability, and profit, and rarely for health. We're also much more sedentary.

bscphil3• 4 years ago

IMO it's purely a question of perspective. From the point of view of individual health, you need to think like a doctor. The important question is "what can this individual do to improve their health?" From that perspective it's a "lifestyle" problem, as you put it. The individual has a food supply that is unnaturally calorie dense and unhealthy. To lose weight and improve their health the individual must make an effort to shift that; for some it might be impossible. For others it might be possible with a great deal of effort or with drugs.

From the point of view of public healthy, you need to think like a public health expert. From this perspective it makes perfect sense to talk about "natural weights" as something that can change (and has risen) over time. The calorie dense food environment and sedentary lifestyles are things that exist in the background here. Given these background facts, the weights of the great majority of people (who don't have the time, means, willpower, etc to resist) are going to rise to a new higher "natural" point. For some, foods will be so calorie dense and provide so little nutrition or satiety that they experience runaway obesity. These are just predictable downstream effects of the environment, and so the perspective of the public health expert is that individuals aren't to be blamed and you have to fix the environment. Ban soda in public schools, etc etc.

russdill• 4 years ago

There are two problems. One is that some people have a body that drives then incredibly strongly towards a certain size. The other is they there are people that given the opportunity to eat whatever they want whenever they want will slowly gain weight year after year. Gaining 3-4 pounds in a year isn't a problem and a sign that someone has a poor lifestyle. But over 2 or 3 decades, that becomes a serious problem.

ChadNauseam2• 4 years ago

The implication is that something has happened during the last 50-100 years that caused people's "natural weight" to change upward. (Someone's "natural weight" is normally called their "set point".)

The evidence is a little slim (no pun), but there's one theory which I find quite compelling. The theory is that eating foods with high flavor-calorie association increases your set point, and eating foods with low flavor-calorie association decreases your set point.

Flavor-calorie association is when your body knows that a particular flavor results in getting lots of calories in the near future. The flavor-calorie association will be higher for foods that are more flavorful or more calorically dense, and flavor-calorie associations can only be developed for foods you eat regularly. This explains why I lose a bit of weight whenever I go somewhere new – I'm trying new foods, so what I'm eating has doesn't have any flavor-calorie association, so my body's set point goes down, so I get full more quickly, causing me to eat fewer calories overall, causing me to lose weight. And since foods have gotten much more flavorful and calorically dense in the past half-century, it would explain why people's set points have gone up.

There's a simple way to test this theory at home. Extra-light olive oil (not extra-virgin) is tasteless and textureless. So, find a 2-hour window of your day when you don't taste anything with flavor, and have two tablespoons of extra-light olive oil right in the middle of that window. Since the oil has no flavor, it should have no flavor-calorie association, and your set point should go down. I've been doing this, and I've been getting full faster and that's been causing me to lose weight. (If you want to google more info, it's called the shangri-la diet.)

(Note that if you try this, your toothpaste probably counts as a flavor.)

nerdponx• 4 years ago

I'd be sooner to suspect environmental contaminants (changing types of air pollution, microplastics, pesticides on food, stress hormones in factory-farmed meat, et al) as a cause.

Although I suspect there's something to your hypothesis as well. I don't know about a spoonful of oil, but I have gone through phases where food seems less "rewarding" on a physiological level, and as a result I feel more satisfied with less.

eldenbishop• 4 years ago

Haven't heard anyone talk about the Shangri-La diet in ages. I did a slight variation of this for awhile way back in my 30s at it worked great. Recently testing this out with OMAD but haven't been doing it long enough to see if it is workable. I'm in my 50s now and a lot of things that worked wonders in my 30s do not work as well as they once did.

MajimasEyepatch3• 4 years ago

The term "natural weight" as used here is misleading. It does not mean that people are supposed to be a particular weight. It refers to the idea that something—whether it's diet, genetics, environmental factors, or something else—influences the body's weight regulation mechanisms to "prefer" a certain body weight, and changing that is very, very hard.

Think of it like body temperature: normally, your body maintains a certain core temperature, and it will respond in a negative feedback loop when the temperature deviates from that set point. Conditions like infections can induce where your body raises that set point to fight the infection, and it takes time for that set point to come back down.

Something similar appears to happen with people's weight. Hormonal or other changes cause the body to gain weight, and once that happens, it resists losing weight in various ways: increasing appetite, changes to basal metabolic rate, changes to metabolic pathways involved in breaking down nutrients from food, all sorts of things. Deviously, fat cells actually produce hormones that play into these changes, which is one of many reasons why losing weight is usually harder than gaining it. And when people do manage to lose weight, often after a huge exertion of effort and willpower and major lifestyle changes, their set point may not have changed, and so as soon as they slip up even a little bit, they quickly regain back to their set point.

So they're not suggesting that there's some mystical force out there that decides some percentage of the population should be overweight. They're referring to the idea of a set point for body weight that is difficult to change without drugs or bariatric surgery.

bioemerl5• 4 years ago

If this were true I would not expect that changes in our lifestyle would cause broad scale weight increases like they have. I'm very skeptical humans are built with an average set weight way up in the unhealthy range.

Or maybe this is the case, but it is thrown off hard by our modern diets. Our natural set point is in the healthy range, but our meal is x calories per Y food now so it ends up artificially high.

The explanation just doesn't line up with what we've seen. I get that it's hard to lose weight once you've gained it, but that's different. This is absolving us of being responsible for our obesity as a whole.

jdminhbg2• 4 years ago

A sudden change in “natural weight” isn’t any more absurd than a sudden change in willpower.

paulpauper12• 4 years ago

Highly palatable caloric dense food means that people are more incline to gain weight without even trying. 100+ years ago you had to make a more an effort to overeat.

kfarr• 4 years ago

And extremely sedentary lifestyle in US

adamsmith1435• 4 years ago

https://slimemoldtimemold.com/2021/07/07/a-chemical-hunger-p...

TLDR: The modern obesity epidemic is mostly a mystery, things like higher caloric food, western diet bad don't tell the whole story. Most likely answers are chemical contaminants in our foods and water i.e. lithium or PFAS chemicals. Interestingly enough both wild animals and lab animals(rats) have been getting fatter over time as well which clearly invalidates the "bad diet" theory. The Human body has a lipostat, you "natural weight" mechanism if you will and it seems these contaminants increase the lipostat and this results in widespread obesity.

paulpauper12• 4 years ago

TLDR: The modern obesity epidemic is mostly a mystery, things like higher caloric food, western diet bad don't tell the whole story.

I think it tells more of the story than contaminants does. A candy bar is packed with calories and not that filling. This didn't exist a long time ago.

joe_the_user7• 4 years ago

Obesity has increased uniformly across the US and much of the world. But in the US is fairly strongly, negatively correlated with income. And the obvious culprit here is thus processed and cheap food. Now, exactly how that manifests is probably quite complex. I see everyone offering their pet theory and that tends to muddy the waters but the basic outline seems reasonably clear.

JamesBarney11• 4 years ago

https://www.prb.org/resources/for-women-in-the-u-s-obesity-l....

That correlation with income is almost entirely driven by women.

Rich men aren't much thinner than middle class or poor men.

Rich women are just a lot thinner than middle class or poor women.

This tells a different story than cheap processed food.

csours4• 4 years ago

Hunger is like a one way valve - you can gain weight and your body will not stop you, but as soon as you start to incur caloric deficit, your body will turn on lots of alarm bells.

Hunger is also impossible to compare, as it is an internal sensation.

Response to hunger is trained, but it is extremely hard to retrain.

ravenstine• 4 years ago

I've heard this referred to as body "set points", and I've yet to see anything very convincing that set points are a thing. It doesn't really make sense that the body would "prefer" a body weight that is tremendously inefficient and contraindicated. More likely, in my opinion, what may be seen as a "set point" may be more akin to metabolic damage that simply takes time to heal once the pathology is actually being properly addressed.

Also, people simply can't be trusted when it comes to self-reporting of their own regimen. Whether it's not being honest with one's self, or being embarrassed, ill informed, or plain delusional, lots of people will report that they've done "all the right things" to lose weight when they in fact have not. It's far more common that people suffering from obesity remain fat because they are thwarting their own progress, or are being given shitty advice from crackpot dieticians, and less common that there is some chronic hormonal condition that can't be corrected by diet. If your pancreas is still working, as well as your thyroid, your pituitary, your hypothalamus, etc., you probably can correct your obesity without drugs.

But people want the "pill" or the "shot", even though the chances are really good that they could get most of the work done cutting out exogenous sugar and alcohol. And I can't necessarily blame them because I obesity drugs can be a life changing thing for those stuck in the 300+ lbs range. What worries me about these kind of drugs is if people think it's okay to get fat and prediabetic because they can just get a prescription. I guess that's great if they can, but that also seems like a form of low level megalomania of sorts, and results in one fewer thing for people to take personal responsibility over. It's good for the mind to put effort and work into something. It infantilizes the mind to allow it to not have to put rigor into anything.

greggman3• 4 years ago

Is it true there are plenty of places in the world that don't have an epidemic of obesity?

My belief is Japan doesn't have as much of an obesity problem.

Sure, I'd love a drug that lets me eat more calories and not get fat but I'd also love it if we some how managed to stop eating so many cookies, donuts, potato-chips, sugary sodas, giant portion meals, etc.... I'd also love it if we designed more areas to be walkable and bikeable.

I lived ~15 years in Japan. I never missed owning car because the country is designed not to need a car. I also spent a year in Europe and Singapore and again, never missed owning car for the same reasons.

Let me also add that in Japan, at least in big cities like Tokyo, Osaka, Kyoto, you are almost always 1-2 minutes away from junk food. You can walk to a convenience store and find whole aisles of pastries, chips, ice cream, candies, etc and yet somehow the Japanese manage not to pig out.

Similarly there are bakeries all over full of donuts, etc...

Somethings that help are the portions are often smaller. Certainly for potato chips most bags in Japan are 1/3th the size of the average bag in the USA. Similarly cookies are small and come in small portions vs the USA where pretty much any supermarket sells cookies in packages of 20 to 40 cookies and each cookie is giant 300-500 calories each.

I guess this is one of those, we're not going to get people to stop eating too much so we have to find another solution? I can just imagine once I get this drug I'll start eating more because I can and companies will ramp up the portion sizes even more.... TACO TIME!!!!!

waylandsmithers• 4 years ago

Sure, I'd love a drug that lets me eat more calories and not get fat

I think the deal is that the drug suppresses your appetite so you do actually eat less

insane_dreamer3• 4 years ago

to suggest that people have a natural weight and that's the cause of this seems absurd to me

People do have a natural weight, and a fraction of people are genetically predisposed to be overweight regardless of lifestyle. But what I find impossible to accept is that somehow that number has mushroomed in the past half-century and particularly in the U.S.

I've lived and/or worked on every continent over the past 40 years, and nowhere have I seen the degree of obesity that is commonplace in the U.S. (I have not been to the Pacific Islands--I know they have the highest obesity rates there for reasons I haven't researched, but they're also a very small population). Anecdotes aside, the obesite rate in the US is nearly twice as high as some European countries (and not because people in those countries are malnourished).

It's pretty clearly the food. Living in other countries I never had to worry about weight, but as soon as I moved to the U.S. I started gaining weight right away even though I eat quite healthy. It's just very very hard to escape processed foods in the U.S. unless you 1) have money to buy more expensive food, and 2) are very conscious about it and make considerably effort to stick to fresh fruits, veggies, rice, fish, etc., no fast food, sodas, packaged foods, etc. etc.

It's also well documented that obesity is correlated with income, and it's not hard to see why, when the grocery options in low-income areas have very little healthy, minimally-processed food. Nutritional inequality is a huge issue and there's very little action taken about it. Just think about how cheap and easy it is to get unlimited refills of soda -- with a soda fountain nearly everywhere you go, compared to eating fresh food. Many people have neither the time nor money to eat healthy, and despite "be healthy" slogans, etc., nearly everything around us conspires against eating healthy (unless you have lots of $).

I'm happy that obesity-reduction pills are coming on the market because some people are naturally predisposed to gaining weight and will be helped greatly by the pills. But what I hope doesn't happen (but already see happening) is that being used to paper-over this huge problem of nutritional inequality that is the root cause of much (though not all) of the obesity in the U.S. at least.

tchaffee6• 4 years ago

I have also noticed myself and my partner gain weight when we live in the US. I'll make it a little more concerning: I mostly don't eat processed foods. I buy the raw ingredients and cook myself.

Tiktaalik• 4 years ago

The other big difference between the USA (and Canada) and other places in the world is the built environment. NA does have a scattered few walkable cities, but there's a great many places where it's effectively impossible by design to go about the tasks of ones day fueled only by person power and not by getting in a car. This has implications on the amount of calories people are burning every day.

markus_zhang4• 4 years ago

For me it's 80KG. Once it goes over 80KG I would gradually feel all kinds of bad things so I'll start to lose weight, but then it's so easy to get back. I don't really think willpower helps here. I mean unless I can do it for the whole life, it will bounce back quickly.

andromeduck• 4 years ago

This is me exactly. At 80 kg my thighs start bothering me when I sleep. Think 67-70 is my ideal.

pfooti• 4 years ago

The threshold for "obese" and all such labels has changed over the years, in such a way that makes it seem like people are fatter, when in fact the labels have changed.

Some history. https://elemental.medium.com/the-bizarre-and-racist-history-...

tgv2• 4 years ago

It doesn't only seem as if people are fatter. Compare the weight statistics, or just look at pictures from the 1980s. That link is pure self-deception.

tchaffee6• 4 years ago

The environment and our food sources have radically changed in the past hundred years. My grandparents ate a mostly organic diet because that's all that was available back then. They didn't eat food made in a factory. They didn't drink water filled with plastic microparticules. Their work was manual labor. I could easily continue with other environmental factors that are different.

What seems absurd to me is to jump to conclusions instead of taking a scientific approach to eliminating factors until we find causation.

npsimons3• 4 years ago

In the context where we have gone from obesity rates of 13 percent to 40, to suggest that people have a natural weight and that's the cause of this seems absurd to me.

It annoys me too! Human genes haven't changed radically over the last 100 years. We're not dogs or cats where generations can be measured in a year if not months, we're talking roughly 30 years between generations, so no, it's not "genes" or "set point". The answer is obvious for anyone paying even a passing interest to history: we largely went from an agrarian society to a sedentary one, eating more and moving less. It's that simple. Combine this with capitalism pushing the fast food industry to make profits at any externalized cost, and the results are obvious.

As an aside, it always amuses me how people talk about "set point" but never address that it only goes up. If "set point" is a thing, you'd think there would be some people with a lower one, or at a minimum it wouldn't go up (hence it being set), but no one likes to admit that . . .

Cupertino950144• 4 years ago

“I’m really hesitant to be excited about something that I think is potentially harmful from a weight stigma perspective,” says Sarah Nutter, a psychologist at the University of Victoria in Canada, who specializes in weight stigma and body image.

Putting the word "stigma" on things is a sure sign of a grifter. Instead of helping solve it, they're trying to make it a social science problem.

Being overweight is unhealthy. There's no serious dispute about that. So people recognizing that fact is "stigma?"

partiallypro7• 4 years ago

The new idea (mostly in the West) that being obese is/can be a healthy lifestyle is absolutely maddening. People being obese (and I don't mean a few pounds overweight) raises everyone's healthcare cost, because it is incredibly unhealthy and obese people tend to have more complications which requires more treatment, workers and subsidizing.

It's not just an individual problem, it's a societal problem. There's a new "Gatorade Fit" commercial with, easily, a 300lb woman in it...the brand is literally "Fit," being 300lbs is not fit in any way shape or form. Why is this happening? Even when/if I'm 10-20lbs overweight, I don't want someone patting me on the back saying I'm actually "fit" or anything close to it. It's such a weird lie that makes it feel like I'm living in a bizzarro world.

oneoff786• 4 years ago

Is the woman being shown as fit? Or as someone who would like the product with a goal to become more fit?

hirundo• 4 years ago

Telling people what they want to hear is not a novel way to collect cash or votes. It would be bizzarro if there were people who wanted to hear it but nobody willing to tell it to them.

LarryMullins3• 4 years ago

"Gatorade Fit"

1 gram of sugar per half liter https://www.gatorade.com/fuel/hydration/gatorade-fit/16-ounc...

At least it's almost sugar free, relative to normal gatorade anyway. I think advertising regular sugary gatorade to fat people as a fitness product would be tantamount to stochastic murder.

HDThoreaun6• 4 years ago

Japan taxes obesity through a payroll tax, which to my understanding is especially effective because of the peer pressure exerted by your colleagues and even manager. Being fat is seen as letting the team down since you're causing their costs to go up, not just your own.

luckylion4• 4 years ago

raises everyone's healthcare cost, because it is incredibly unhealthy and obese people tend to have more complications which requires more treatment, workers and subsidizing.

Is that actually true? From what I understand, obesity will cost you dearly in life expectancy, and most of the cost comes in the last few years of normal life expectancy. Someone who dies of heart attack at 63 isn't going to run up huge bills from age 77 to 85.

I believe there was a similar calculation for smokers. The health cost in higher cancer rates are outweighed in what you save on costly treatment for the elderly + fewer pension payments.

lazide• 4 years ago

Overton window, and people giving up is why it’s happening.

And yeah, we’re all living in bizarro world.

Frost1x• 4 years ago

The new idea (mostly in the West) that being obese is/can be a healthy lifestyle is absolutely maddening.

We took the extreme of anorexia being healthy to obesity being healthy. The fact is neither extreme is healthy. Being not anorexic is not the same as being obese, there's a huge range of fairly healthy weights in between the two in terms of body fat percentages and muscle ratios.

Rebelgecko2• 4 years ago

Has the health care cost been studied? I wouldn't be surprised if morbidly obese people are cheaper in the long run due to a reduced lifespan (kinda like how smokers can be cheaper than nonsmokers-they may cost more to ensure before retirement age, but it more than evens out when you looked at reduced years after that point)

yowlingcat• 4 years ago

In a way, maybe Gatorade is trying to be honest about lying. After all, a 20 oz bottle of Gatorade has 36 grams of sugar in it and would substantially contribute to type 2 diabetes. It would behoove them to fund a narrative that the product and the outcome associated with the product are indeed "fit" to maximize sales.

Of course, the wrinkle with approach is that that as you mention, the reality is that nothing could be furthest from the truth. Obesity is fastest growing and most deadly American chronic condition. The outsized impact of type 2 diabetes on payer spend, both medical and pharmacy, cannot be overstated.

And when you put that all together, it makes a commercial like the one you mentioned seem banal and sinister at the same time.

paulpauper12• 4 years ago

It does make sense and strikes me as irrational to celebrate something which is clearly harmful to society

tootie4• 4 years ago

That's awfully harsh. For one, the person making that statement is not the developer of the treatment, she's a psychologist expressing concern about the possible downsides. Namely that the drug is expensive, doesn't work on everyone and hasn't been proven to show long-term beneficial outcomes yet (ie lower morbidity). I'm guessing it's also got a high potential for abuse from people with dysphoria. Nobody is saying we should keep it off the market, just that we need to be prepared for potential negative repercussions.

Cupertino950144• 4 years ago

the person making that statement is not the developer of the treatment

and neither is she a doctor or biological scientist. Rather, she's trying to get in on a lucrative field which she has no expertise in.

m0llusk2• 4 years ago

Down's Syndrome is also unhealthy. Should we stigmatize that also? The main issue is control. Many assume that weight is simple and under people's full control. Realistically, though, there are all kinds of reasons why weight gain happens and scientific measurement shows that wild animals are getting bigger too which suggests that pervasive presence of endocrine disrupting agents in the environment may be involved. It is not clear how we might stigmatize exposure to endocrine disruptors.

HDThoreaun6• 4 years ago

Weight is not uncontrollable. It's not easy to control, but neither is any other addiction, and they're certainly stigmatized.

abcc8• 4 years ago

It is rather dishonest to compare a chromosomal disorder with obesity, don't you think? Trisomy 21 is a condition one is born with and has no control over. On the other hand it has been demonstrated time and time again that behavioral and diet changes can be used to control obesity.

joshuahedlund• 4 years ago

scientific measurement shows that wild animals are getting bigger too which suggests that pervasive presence of endocrine disrupting agents in the environment may be involved

Do you have a good source for this?

Cupertino950144• 4 years ago

And here you are, using the very word I called grifting.

It's not "stigmatizing" to call something unhealthy which is, at least potentially, controllable. And you cited no information at all about "endocrine disruptors" for the vast majority of obese people.

Eumenes2• 4 years ago

Last name is Nutter too, literally a nutter.

partiallypro7• 4 years ago

I'm not obese, but am not what I'd consider at my ideal weight. I wonder how/if doctors would even prescribe this to someone like me. I think I've read some Hollywood types are using this to lose weight, but those are edge cases. I imagine for normal people this would not be easy to get prescribed.

happyopossum3• 4 years ago

Previous GLP-1 meds are generally not prescribed if you have below a 30 BMI

bedast• 4 years ago

FDA approves these for use in most people above 30 BMI. Some people may be considered for it at 28 BMI. If you're looking for last mile weight loss, this may not actually be worth it. The side effects, especially getting started, can be really rough.

haywood2• 4 years ago

This is good news (probably?), but wanted to chime in with a tangent.

Also going to preface this by saying I have struggled with weight my entire life and have lost and gained substantial weight through diet alone, always gaining it back and then some — but I think I found something that has worked for me and I have been reflecting on what I wish I was told a long time ago.

It's not necessarily a problem to be "obese", meaning you can have extra fat on top of muscle but also be metabolically healthy. In those cases, the extra weight is just causing your calfs to be huge.

Instead of focusing on getting skinny, I started focusing on getting strong. All of a sudden diet was a supplemental tool to this goal, and not the main thing. I just made sure to eat more protein, and if I had a "bad day" of eating, I chalked it up to my body having more energy to synthesize new muscle :) Before a bad day would "undo" days of suffering on an energy deficit, and I would just give up. But if you frame it as: look, you have struggled your entire life to be 'thin', when in reality, your ability to be obese was a hidden superpower. Stop fighting it and lift weights, you were probably _made_ for this!

In this context I'm weirdly happy with my genetics? there are so many "hard gainers" that do everything in their power to put on 10bs so they can gain muscle. I'm gaining muscle without hardly trying. How many other obese, inactive people are like me and would respond amazingly to resistance training ALONE as well?

I focused on strength training and protein for a long time when I started, that was fun and easy, and my body composition started to change. Then I started to notice the changes, and now I have purposeful short-duration "cuts" in my routine and it seems like at some point I'll eventually not be obese.

Just trying to say that I wonder what would happen if people were told, "hey, you don't need to diet right now, just come in and train twice a week and eat more protein". Of course "energy toxicity" is absolutely real, but lean body mass can improve health markers A LOT before worrying about that.

hsbauauvhabzb• 4 years ago

I too found this valuable, I dropped 15-20kg doing this 5 years ago and slowly put it back on due to health problems. I’ve found recently that even cardio works - if I exercise, I don’t want to waste the effort by eating shitty food, if I do have a bad day or two (Xmas period) then it feels like a bank loan I must pay off before the interest kicks in.

shepherdjerred• 4 years ago

This is really interesting. The idea of intentionally putting on weight terrifies me because I worked so hard in college to lose weight.

What does your plan look like long-term? Are you just going to keep gaining muscle and working out for the rest of your life, or do you plan to stop?

Obviously your TDEE is going to go up with more muscle. I wonder if there's a stable point where you can eat a 'normal' (read: not protein heavy) diet while working out, so that muscle is only maintained.

haywood2• 4 years ago

For the first 6 months I basically didn't worry too much about diet, except getting more protein and working extremely hard on my two workouts (which has since expanded to 3 workouts a week).

What happened was I put on a ton of muscle, and actually lost some weight... in the end I was 12lbs lighter, which doesn't seem like a lot but with the amount of muscle is EXTREMELY noticeable.

For me, seeing my body get more stronger and more muscular was a revelation, it's really fun to see the growth in those areas, much more than suffering to get "skinny fat". So now I'm actually working 4-6 week stints of weight loss into my program where I target 2lbs of fat loss week, while keeping the training intensity high (with lower volume to combat fatigue) to maintain the muscle I have built. I'll follow that with 2-3 months of maybe a slight surplus in calories to build (which comes with some fat gain). A few cycles of that and I'll be golden :)

From a health span and longevity standpoint, having lean body muscle is absolutely crucial for aging, and it's something I plan to not stop doing, even if I fall off the nutrition wagon completely, I'll at least be increasing my bone density and muscle mass which will counteract a lot of whatever bad food habits I'm doing at the time.

The cool thing about muscle vs just pure weight loss, is that muscle isn't super hard to maintain once you have it. The amount of stimulus you need to keep the muscle, especially in an energy balance or surplus environment is surprisingly small it turns out. So to me it's much more rewarding than a crash diet that can be completely erased and then-some in a matter of months.

I wish I had this frame of mind a long time ago, it has personally helped me tremendously.

PuppyTailWags4• 4 years ago

I wonder if, given the cost of the drugs, we're only going to be able moreso to visibly see poorness, i.e. fat people's class will be well known and discrimination to follow.

renewiltord• 4 years ago

There are startups that can simplify the process of getting this drug if you're eligible. They do require you to talk to a doctor and nutritionist to see if this is the best thing you should do first, but then they can get you the drug.

e.g. https://joinmochi.com

glaucon2• 4 years ago

(From a position of significant ignorance) It seems there is not a strong consensus on what has caused the great increase in obesity of the past fifty years, perhaps throwing greater effort in that direction would be a better long term solution ?

To my mind it's strange that there seems to be a circular argument which starts with sedentary life style and "bad" foods cause obesity so exercise and diet control seems like a fix but that is countered by exercise doesn't help (much) and dieting has only temporary effects.

If my summary is reasonably correct it seems to me what's needed is more understanding of the outcome before using drugs to "fix it".

I wonder if a drug is less likely to be lobbied against than the types of changes such investigations might suggest.

luckylion4• 4 years ago

If my summary is reasonably correct it seems to me what's needed is more understanding of the outcome before using drugs to "fix it".

The likely reason is the changes in lifestyle thanks to the changes in technology. Is "let's just get rid of the past 70 years of technological advancement" something that we'll seriously consider?

glaucon2• 4 years ago

| The likely reason is the changes in lifestyle

Agreed, that's the commonly held reason but when one attempts to reverse what the changes seem to have been, by exercising more and eating less, that doesn't seem to work. My point is that perhaps we need to better understand what the changes have been, that perhaps they are more subtle than they are commonly held to be.

curiousllama• 4 years ago

I would encourage you to revise your summary. We don't know what the third-order drivers of obesity are, but we absolutely know that caloric surplus is the primary driver, and that surplus is driven by both lower energy expenditure (sedentary lifestyle) and increased caloric intake (junk food). There are other causes for individuals, but not at a population level.

The question is much more: why did people start moving less & eating more? Each have complex factors (less physical jobs, increased wealth, food addictiveness, cultural shifts, etc.), and on THOSE, there's lots of debate.

But we absolutely know what causes obesity at a population level.

groos• 4 years ago

It's pretty clear by now that the intake of high amounts of fructose, refined carbohydrates and packaged foods has resulted in obesity. The much maligned fat in a healthy diet was never the culprit. The Chinese on a rice diet were never very obese until they became rich and started consuming packaged foods. Now their obesity rates rival the US's.

Uncontrolled insulin levels cause obesity because of insulin's dual role in fat storage. The key is to change one's diet such that insulin levels are lowered and the stored fat can be utilized for metabolic needs.

Exercise is important for general health but trying to lose weight by exercising doesn't work if the diet stays the same. Food is just too calorie rich and the body too calorie efficient. The adage 'get fit in the gym, get slim in the kitchen' applies.

Genetically, a small number of people might have metabolic issues causing obesity.Drugs might be the right choice for them but for the vast majority of us, we just need to take a hard look at our diet.

smooth_remmy2• 4 years ago

Petro Dobromylskyj is one of the foremost experts of fat metabolism. He has a blog called Hyperlipid where he's been blogging about fat metabolism and interpreting research for close to 10 years.

He thinks the GLP-1 inhibitor drugs will be a disaster in the long term because they 1) cause weight loss but also 2) cause the body to create lots of new adipocyte (fat cells). Increasing the number of adipocytes is very unusual after puberty. As long as you are taking the GLP-1 inhibitor drugs you will lose or maintain weight, but as soon as you stop you will gain a lot of weight back.

Here is the blog post: https://high-fat-nutrition.blogspot.com/2023/01/glp-1-agonis...

JamesBarney11• 4 years ago

With every weight loss intervention when you stop you gain back the weight. GLP-1 agonists don't seem to be any different than another other intervention.

smooth_remmy2• 4 years ago

The point is that you could gain back the original weight plus more. Most adults who become obese have not increased their number of fat cells - their fat cells just become larger.

The GLP-1 drugs literally increase the number of fat cells.

paulpauper12• 4 years ago

gastric bypass does not have this problem as bad

ceejayoz27• 4 years ago

With every weight loss intervention when you stop you gain back the weight. GLP-1 agonists don't seem to be any different than another other intervention.

Except for one thing: it's fairly easy to not stop a drug. You just... keep taking it. Long-term use of these drugs for maintenance purposes looks entirely feasible. Not quite as easy to maintain as a gastric bypass, but close enough to be a big deal.

The same isn't true for exercise and diet; it's very easy to fall off those wagons.

post_break• 4 years ago

So drug companies should be seeing alarm bells going off. You can profit off this drug, and it's an endless supply of revenue.

milleramp• 4 years ago

I wonder how breaking old habits and establishing new habits over a year or so would stop a serious rebound?

linsomniac2• 4 years ago

It is, in my personal experience, all to easy to fall back into the old habits.

paulpauper12• 4 years ago

The low success rates of diets suggest very hard to establish new habits

KirillPanov2• 4 years ago

I think the big lesson from Semaglutide is that bad eating habits are not the primary cause of obesity. More likely they are correlated due to common causation.

1024core4• 4 years ago

Given that injections cost ~ $1000/month, you're saying basically that it'll be a great recurring revenue stream for the companies. A CFO's wet dream.

paulpauper12• 4 years ago

consider that treating obesity-related consequences also costs money and enriches companies as well. I think its worth it

nerdawson2• 4 years ago

I did a little bit of research and for people in the UK it appears to be substantially less. I found a few health companies offering it for <$250/mo. I’ll probably wait until it’s readily available on the NHS but it is tempting.

wins32767• 4 years ago

The only thing I see from him on google scholar is about mechanical ventilation for small animals. What's his background?

m_a_g2• 4 years ago

Here is an introduction I found from his blog:

I am Petro Dobromylskyj, always known as Peter. I'm a vet, trained at the RVC, London University. I was fortunate enough to intercalate a BSc degree in physiology in to my veterinary degree. I was even more fortunate to study under Patrick Wall at UCH, who set me on course to become a veterinary anaesthetist, mostly working on acute pain control. That led to the Certificate then Diploma in Veterinary Anaesthesia and enough publications to allow me to enter the European College of Veterinary Anaesthesia and Analgesia as a de facto founding member. Anaesthesia teaches you a lot. Basic science is combined with the occasional need to act rapidly. Wrong decisions can reward you with catastrophe in seconds. Thinking is mandatory. I stumbled on to nutrition completely by accident. Once you have been taught to think, it's hard to stop. I think about lots of things. These are some of them.

rootusrootus9• 4 years ago

Oh man, the first result for him on Google is a link to a YouTube video. That makes my BS meter instantly peg.

wolverine8769• 4 years ago

one of the foremost experts of fat metabolism

Is it correct that the source is a veterinary anaesthesiolgist?

https://news.ycombinator.com/item?id=34252195

jononomo15• 4 years ago

Yes, he is the world's leading expert on this subject because credentials aren't everything

aussiesnack• 4 years ago

one of the foremost experts of fat metabolism.

What makes you say that? In my experience, there are no 'experts' in empirical fields who are no themselves deeply and practically engaged with actual research. Being well-read does not make you an expert. Writing blog posts and appearing on YT doesn't make you an expert. Critics are not experts. To be an expert in anything you have to get your hands dirty.

Nothing I can see from this guys publications or bio make it seems like he's an expert in human fat metabolism at all, let alone a 'foremost' one. I base this on a fairly cursory survey, so I'm happy to be corrected. But convincing corrections would absolutely require details regarding what he has contributed to the field.

JamesBarney11• 4 years ago

I don't know if I'd call a veterinary anaesthetist a foremost expert on fat metabolism. His thoughts on insulin signaling are not consistent with the consensus among obesity researchers. He thinks glp-1 works through uncoupling or fat browning which is just not true.

The consensus among most obesity researchers is the cause of obesity is primarily neurological, not metabolic. Basically the brain can't properly regulate weight in the current obesogenic environment. When you look at GWAS most of the genes related to obesity are active in the brain, (as opposed to genes for diabetes which are more closely related to fat/metabolism etc...).

I'd describe Petro Dobromylskyj as a smart hobbyist with an outsiders views of obesity, not a foremost expert on fat metabolism.

givemeethekeys• 4 years ago

Is human metabolism really so different from other mammalian metabolism?

jononomo15• 4 years ago

He is basically the world's leading expert, but you can only see credentials, lol.

csours4• 4 years ago

N of 1, but I've gone off it for months and maintained my weight.

aantix5• 4 years ago

How much did you lose, how long did you take it, and how long have you been off of it?

koboll• 4 years ago

As long as you are taking the GLP-1 inhibitor drugs you will lose or maintain weight, but as soon as you stop you will gain a lot of weight back.

Sounds like the opposite of a disaster for pharmaceutical companies.

Well, on the upside, the demand for this is so great that cheap generics shouldn't be too far away, right? And it seems like an insurance no-brainer to cover it for life, right?

hollerith• 4 years ago

The cheap generics never appear till the last of the patents have expired regardless of demand.

beloch• 4 years ago

Thought experiment: A drug* that reduces people's weight and massively boosts physical fitness with no negative side effects is discovered. The discoverer of that drug declines to patent it, making it a cheap generic available everywhere. What would your reaction be?

Take a moment to consider what your reaction is before continuing.

...

The comments I'm reading here are diverse and fascinating. Weight loss, diet, and fitness are almost quasi-religious issues that people tend to have strong and personal reactions to. The unfit are desperate for a solution, especially an easy one. The very fit subconsciously resent the notion that people could achieve, with a pill, what they have achieved through discipline and hard work (or genetic luck). Others are keen to point out diverse evils of modern society that they believe are the true culprits which must be tackled instead of masking their effect with a pill.

Nutrition and fitness are classic examples of pseudo-science. Studies that would meet the bare minimum standards of scientific rigour in any other field are practically impossible. Getting a statistically significant sample of people to go on special diets or exercise regimens long term is just not feasible. Whenever an "expert" makes a tentative statement on what they think might be the case, media picks it up and amplifies it. Butter is bad for you. Butter is good for you. Blueberries are superfood. Keto diets. Crossfit. etc. Countless "experts", often with no credentials and no compelling data, are happy to write best-selling self-improvement books. They assume that what works for them (or didn't work, but seems like it should have) will work for everyone. Everyone wants to know how to be healthy, fit, and happy, so there is insatiable demand for books that are, by scientific standards, pure spit-balling.

Then medicine and drug research, which are legally required to be at last somewhat scientific but are always profit-motivated, enter the fray. They can prove a drug meets safety standards and quantify certain specific effects, but interactions with the pseudo-science of the greater health industry eventually become unavoidable.

Perhaps the first step to becoming more objective about drugs like this is to recognize that we really aren't.

*a hypothetical one, not the one being discussed here

uhtred2• 4 years ago

Nutrition and fitness are classic examples of pseudo-science

I think it's pretty well agreed upon in the medical community (and proven) that a healthy diet (lots of fruit and vegetables, not too much sugar, etc) and regular exercise leads to better health. It's not pseudo-science. Neither is the statement that consuming more calories than you burn will make you put on weight.

plopz• 4 years ago

is fruit still considered healthy? i thought they ditched those alongside veg like potatoes and corn

rootusrootus9• 4 years ago

discipline and hard work (or genetic luck)

Let me tell you, the number of thin people I've met who got there through discipline and hard work is vanishingly small compared to those genetically blessed. This is probably why it's such an appealing delusion -- who doesn't want the world to think they're disciplined and hardworking, instead of just lucky?

Invictus0• 4 years ago

I don't think it's so malicious as you make it out: being thin seems like the default option, because that's how it was for most of human history and because you can't become fat without lifting the fork yourself and putting the food in your mouth. That obesity could be a disease questions our notions of free-will and the cascading questions that come along with that are quite uncomfortable.

AuryGlenz12• 4 years ago

How do you know they got it through being "genetically blessed" and not just...putting the fork down? In my experience a lot of skinny people don't outwardly signal that they're "dieting" because they're literally always dieting.

Vt71fcAqt7• 4 years ago

The number of fat people who consume less energy than they expend is literally zero. Nice try redefining "very fit" to mean thin, btw.

lm284694• 4 years ago

instead of just lucky?`

People who stay "fit" and hit a lot are the opposite of lucky, they probably have thyroid issues or other similar issues that will cause more serious problems down the road.

People who think they're lucky are obese with a food addiction problem

jamesgill• 4 years ago

The best 'obesity drug' I've found is low-carb + intermittent fasting. 90 pounds later, I'm not hungry and every aspect of my health has improved dramatically.

andbberger3• 4 years ago

good for you, but that's not a drug. behavioral interventions don't work clinically. GLP-1 agonists work incredibly well.

1024core4• 4 years ago

they also carry a hefty price tag: the injections often cost upwards of US$1,000 each month.

IMHO, it would be much easier to just stop eating processed foods and sugar (and sugar substitutes).

I cut down on sugar drastically and started intermittent fasting, losing 20 lbs in about 5 months without doing anything else.

orblivion• 4 years ago

The headline sounds like a YouTube ad

mirekrusin• 4 years ago

Eat less shit food and excercise more doesn't work anymore nowadays?

Gatsky3• 4 years ago

I have a theory that the Nature group, ostensibly a bunch of academic journals, actually wants to become the NYTimes. They have chosen a custom font, they publish increasingly editorialised political content, and they produce these hype train news pieces which really lack objectivism or scientific rigour. Scientists should consider carefully what is appearing alongside their research, and the ultimate result of an unassailable, centralised academic publisher with opaque editorial practices.

anigbrowl4• 4 years ago

A class of drugs that quash hunger have shown striking results in trials and in practice. But can they help all people with obesity — and conquer weight stigma?

Who cares? Helping half of people with a problem to overcome it is great. Journalists and editors need to push back against simplistic concepts like 'one size fits all' and the urge to rank everything, which just leads to bimodal distributions and the accompanying bad outcomes when they are imposed by economic force.

fswd2• 4 years ago

It appears you can do the same thing with 3g of cinnamon

https://pubmed.ncbi.nlm.nih.gov/19158209/

Conclusions: Ingestion of 3 g cinnamon reduced postprandial serum insulin and increased GLP-1 concentrations without significantly affecting blood glucose, GIP, the ghrelin concentration, satiety, or GER in healthy subjects.

jumpman500• 4 years ago

Isn’t that a dangerous amount?

fswd2• 4 years ago

It's about 1/3 of a tablespoon. It's dangerous to the bottom line of drug manufactures trying to sell a $1000 injection that does the same thing.

exhilaration• 4 years ago

If anyone wants to try this, make sure you're NOT using what's usually passed off as cinnamon in America (Cassia), you want the real thing (Ceylon) -- and from a vendor you can trust. That amount of cassia cinnamon is likely to cause liver damage: https://www.consumerlab.com/answers/cinnamon-coumarin-liver-...

species9606• 4 years ago

Meta comment, I love HN for comments like this. Collectively, this website is a super-brain that’s far more impressive than any language model.

Ayesh• 4 years ago

As someone who is from Ceylon (Sri Lanka), I'd say to be careful of the most commercially available cinnamon that are meant to be used with food and tea too, because they may be flavored to dial down the otherwise strong taste/aroma of cinnamon.

I know because one of my friends has a cinnamon farm, and what he makes at his place is nothing compared to the cinnamon I could buy from supermarkets when I was living in the Netherlands. Look for Sri Lankan markets if you are looking for unaltered stuff.

vimota• 4 years ago

Isn't satiety / ghrelin the mechanism (via GLP-1) for weightloss in semaglutide?

foruhar• 4 years ago

$1000/month seems like a decent amount of money for a lot of people. I'm guessing a large number of folks would love to lose weight miraculously. I wonder how long before we get a bootleg analog that can be bought in the non-medical drug market in the same way as testosterone can be bought. Now that the mechanism is known (GLP-1 inhibition) are these the kind of drug, e.g. LSD, valium, or morphine, that is easy to create a facsimile or analog of?

JamesBarney11• 4 years ago

These drugs are way more difficult to manufacture than testosterone. I'm sure we'll see things branded as a knockoff but I doubt we'll see any true knockoffs.

RedditKon5• 4 years ago

We already have it - you can buy Semaglutide easily on the clear net as it’s relatively easy / cheap to manufacture. r/peptides has more info.

Disclaimer: I’m not advocating this - just sharing info.

maxrev17• 4 years ago

A drug to fix what's on supermarket shelves? Lord help us!

2devnull3• 4 years ago

“when lifestyle changes aren’t enough.”

People don’t want to hear it, but we do nobody any favors by pretending this is more complicated than it is. It’s actually pretty simple. The solution is to adjust calories in vs calories out. Fast a few days a week. Cut out bread, sugar and other simple carbs.

We don’t help alcoholics or opioid addicts by enabling them with statements like “when not getting drunk isn’t enough…”

The pharma industry will enable addicts because it wants money. Fat people need love, though love, and a home without good tasting, or high calorie foods.

epgui• 4 years ago

The pharma industry will enable addicts because it wants money.

This is a little over-simplistic. The "pharma industry" is not a monolith, and is made up in large part by academics who love spending their time thinking about how to make the world better, and by doctors who have no conflict of interest, etc etc.

2devnull3• 4 years ago

It is an industry. It must therefore be optimized to maximize shareholder value, roi, revenue, etc…

Gambling can be fun, and nothing wrong with casinos, but in the long run they are optimized for one thing. A casino that is not optimized for profit will disappear.

Same is true for the healthcare industry. If a corporation is not optimized to make money they disappear.

I think it’s valuable from a financial perspective to avoid casinos. I think it’s valuable from a health perspective to avoid drugs, to the extent possible. But, yes, casinos can be fun, and you can even profit from them if you play your cards right.

mshake2• 4 years ago

While I agree, you're right, nobody wants to hear it. There's no point telling people to have discipline, because discipline is not spread through strangers telling each other to have it. Someone either has the capacity to have discipline (instilled through upbringing or formative events), or they don't. These magic pills are for everyone who doesn't have discipline.

2devnull3• 4 years ago

Maybe. I was fat. I believed various things I heard parroted about, “starvation diets don’t work,” and “it’s not healthy to skip meals.” There are too many of these to list.

I noticed skinny people tended to eat less and skip meals. I noticed bariatric surgery worked, for awhile.

I tried fasting. I’m now quite healthy. Exercise doesn’t help lose weight, but it can be a better way to change your biochemistry than eating tasty food. People should be told these 2 simple things, and none of the other stuff that doesn’t really help. It’s simple. Eat less.

YellOh2• 4 years ago

We actually do often recognize that "just stop having problems" isn't usually useful advice for people with drug addiction, too. Ex. naltrexone for alcohol addiction, methadone for opioid addiction, etc. "Just stop having problems" is usually easy to say as an outside observer, but generally when someone's reward circuit is hijacked by addiction, it takes something more effective to rewire it. Sometimes sheer willpower is enough to exit the cycle, but usually it takes outside changes (drugs, environmental changes, effective therapy) to loosen the grip of addiction.

zmmmmm• 4 years ago

I am curious if drugs that reduce your appetite affect your enjoyment of the food you do eat?

It would be incredibly sad if the price to pay for not becoming obese is not enjoying any food at all.

r00tanon• 4 years ago

Unfortunately just diagnosed type 2. Can't find Ozempic anywhere due to this crazy drug shortage and off label prescribing.

matt32103• 4 years ago

put it in the water!

Vecr• 4 years ago

Not a good idea. Some people are underweight or normal weight, or want to get stronger by lifting weights. Also, it's an injected drug.

matt32103• 4 years ago

Convincing people to not fool around never worked so the birth control pill was invented to allow people to indulge with less consequences. I recall someone (I forget who) said that things that prevent you from eating will never work and the only solution is something that allows you to indulge without the consequences. Does this drug allow you to indulge without consequences or does it make you not want to eat? If its the later, I bet that it won't have long term success.

Edit: A drug that allows you to indulge without consequence in this context would be a bad thing. It would allow people to eat non-stop without the consequences and would increase the demand for food in the modern nations to unreasonable levels. If you think about it, this kind of drug would have the same outcome as bulimia (think, hunger games).

deburo• 4 years ago

Does this drug allow you to indulge without consequences or does it make you not want to eat?

Why wouldn't satiety drugs be helpful?

matt32103• 4 years ago

People WANT to indulge. A drug that kills sex drive would never work but the drug that lets you have a sex drive without consequences already works today.

Edit: It might have novelty support but I'm confident that in the long run people will choose to indulge and get the dopamine.

m_a_g2• 4 years ago

There exists a drug like that called DNP, but it is extremely easy to overdose and die, so it's been banned for almost a century now

jcbcn• 4 years ago

Why do the graphics mention total loss of bodyweight? Surely in those studies they scanned the patients for exact body fat percentages...

totalhack• 4 years ago

I'm curious to see what kind of shape all of these "diet doesn't matter" people are in, on average.

nemo44x• 4 years ago

I’m surprised insurance doesn’t want to cover it. I’d think the cost at scale would outweigh (pun intended) the longer term costs that fat people bring. Or do their hearts just explode at 50 and that’s it?

RedditKon5• 4 years ago

My guess is that they don’t want to cover a $1,000/month drug to save costs that you may not incur for many years / when you’re no longer insured by them.

It only works if all the companies agree to cover it.

karaterobot2• 4 years ago

It's weird that insurance companies won't cover this, considering the cost of treating obesity-related illnesses like diabetes, heart disease, strokes, certain forms of cancer, etc. It's also weird that pharmaceutical manufacturers price this so high, considering the potential size of the market relative to the current size of the market. I guess what I'm saying is: the healthcare industry makes a lot of choices I don't understand. /shrug

zug_zug• 4 years ago

Well... another way of thinking about this is... if it costs 15,000 a year to treat, I wonder what percentage of those people could lose weight another way for less than $15,000 a year (e.g. free gym membership with classes, personal trainer, and $500 a month bonus if you show up twice a week)

karaterobot2• 4 years ago

We know the answer to that, though. Very few morbidly obese adults lose significant amounts of weight and keep it off long term, even with comprehensive lifestyle interventions like calorie counting, gym membership, and therapists. Even people who lose a lot of weight just gain it back at 1-2 kg a year. That's why there's an obesity epidemic.

TEP_Kim_Il_Sung• 4 years ago

I am currently on one of these regimes, and it has been miraculous for my life. I became obese when I was 27, topping a 32 BMI, when I was 35 I gained a substantial amount of mass by just pumping iron and doing cardio, brah.

5 years later, I had a bad knee, and lost most of my gains. Dr. Bronner put me on a steady diet of Carne Asada and Kale, and I've been a wiry lean pooping machine ever since!

He's a miracle worker, send him all your money now!

lonk11• 4 years ago

Related coverage with more graphs: https://erictopol.substack.com/p/the-new-obesity-breakthroug...

valachio• 4 years ago

I discovered a breakthrough technique in fighting obesity.

It's so simple anyone can do it and see results in weeks.

The technique is "eat less"

narrator• 4 years ago

The big elephant in the room is where did everyone's endogenous GLP-1 peptide go? A similar elephant in the room is why is synthetic thyroid hormone to replace all the missing endogenous thyroid hormones such a high selling drug?

What in the environment is slowly poisoning everyone so their bodies don't work normally?

Here's a clue, one of hundreds in the medical literature:

"The endocrine disrupting potential of monosodium glutamate (MSG) on secretion of the glucagon-like peptide-1 (GLP-1) gut hormone and GLP-1 receptor interaction" https://twitter.com/hashtag/AtmosphericRiver?src=hashtag_cli...

There is a huge bias against anyone saying anything in food or otherwise causing anything more than a trivial negative health effect. Everyone says eat healthy, but there's so much more the government in the U.S could do to protect the average consumer from damaging unnecessary food additives. The EU is much better about these food additive issues.

urthor2• 4 years ago

Certainly it's one of the largest issues in society today.

We simply don't have much of an idea how the human hormone system works, or how it reacts to all the chemicals present in the "Standard American Diet."

nervousvarun• 4 years ago

Very interesting post but aren't obesity rates similarly increasing in EU countries?

refurb4• 4 years ago

MSG is very common in Asia and has been for a while (you can buy it in 1 kg bags) yet Asia has low obesity.

lumb632• 4 years ago

I’m sympathetic to anyone who feels they “need” to take these, and wants to encourage others to do the same. I’m sure they work wonders for obesity, and that’s great. But we cannot get something for nothing, so I have to wonder: at what cost?

A poster below me said that, at a population level, diet and exercise do not work. That’s mostly true. Most people don’t permanently change their diet and other lifestyle long term. I think that ignoring that they do work in the short term, and could work in the long term if adherence were better, overlooks something important.

Moving past that, we are an obese population. Or, at least, very overweight. Supposing diet and exercise do not work, what are we to do? I’d propose we look toward rectifying the causes. There are innumerable environmental factors today that make us fat: pollution, drug side effects, food advertising, alcohol, social pressure, widespread sedentary jobs and lifestyle, etc., etc., etc. If we focused on solving the problems that are making us obese, we wouldn’t need these drugs (or at least, not nearly to the extent we do). We used to live in a world like that. We know what it looks like. We know the consequences. We know our bodies and society can tolerate that world, and that it would solve our issues. Why not aim for a return?

Instead we will opt for another technical solution to our technical problem of obesity, causing all manner of unknown risks later on, and falling back to another technical solution to that technical problem. We will continue to layer on technique after technique to patch holes in the solutions we left in our last layer of solutions. The holes will grow larger and larger as we stack on more layers with more holes, and solutions will grow smaller and smaller as technology grows ever more specialized. The cycle is not sustainable.

ITB• 4 years ago

The whole idea that obesity is a “stigma” is overplayed. Obesity is unhealthy. If I see an obese young child, I might form a negative opinion about their parents. If an adult is obese, they should want to lose weight because it will make them healthier.

jononomo15• 4 years ago

For anyone that wants to lose weight without taking drugs, just try eating only eggs, liver, and ribeye steaks with salt and drinking only water. You can eat to satiety on this diet - in fact you can just stuff yourself as much as you want - and you will lose weight and get in shape. Also, you'll find that it is impossible to eat a more nutrient dense and nutritionally complete diet than liver, eggs, and ribeye steaks. Remember never to drink a calorie.

unixbotnuke• 4 years ago

You fat fucks just eat less and go for a walk.

dang3• 4 years ago

We've banned this account for repeatedly breaking the site guidelines.

If you don't want to be banned, you're welcome to email hn@ycombinator.com and give us reason to believe that you'll follow the rules in the future. They're here: https://news.ycombinator.com/newsguidelines.html.

elil17• 4 years ago

Am I right that, if I (early twenties, 36 BMI) have no other health complications, it makes sense to wait to see what the long term effects of these drugs are?

If I knew it was safe in the long term I’d take it in a heartbeat. However, I’m concerned that there could be long term issues with the drug (perhaps a resistance/“yo-yo” effect where the potency wears off and I gain back my original weight plus more than I would have otherwise over, say, 10 or 20 years).

Is that the sort of thing that’s in the realm of the possible/plausible or is this more like a vaccine where there are some strong theoretical reasons why we don’t expect it to have long term issues?

idealmedtech• 4 years ago

As a diabetes researcher, results like this don't surprise me one bit, but I'm glad they're getting national coverage! A publication in Nature is an incredible achievement, congrats to the teams involved.

We think good glucose control is at the center of a whole host of medical issues, inside and outside the hospital. Bringing critically ill patients under control has been found to reduce mortality rates by up to 30%, results which have been repeated several times in thousands of patients. These drugs, which are less intense than insulin therapy, confer similar glucoregulatory effects, which has all sorts of cascading hormone benefits etc.

Exciting stuff, thanks for sharing!

hoseja• 4 years ago

"conquer weight stigma"? No, it should be stigmatized.

sacnoradhq• 4 years ago

My doc is trying to get me on these kind of meds.

I'm on high dose (60 mg) mirtazapine motivates immense weight gain as a side-effect.

I'm +30% overweight (260 lbs vs. 200 / 117 kg vs 90) and the hunger for carbs is beyond ravenous.

Stimulants are nonstarters because I'm already on a beta blocker for inappropriate sinus tachycardia, and other meds for "physiological" anxiety (can never relax).

zupa-hu2• 4 years ago

I’m a skinny / athletic person. The reason is a doctor told my parents not to feed me any sugar until age 2-3, as fat cells are created up to that age. After that, they only change in size.

I don’t know if that’s a scientifically proven thing, but indeed i simply can not gain weight, whatever i eat. As if i had zero fat cells.

The only downside is that I’m often cold, which is of course far easier to manage. I’m not a water person though, as its nontrivial to “dress up” for swimming.

It’s a miracle, please spread it. The next generation could avoid the fatness problem alltogether.

a4a4a4a4• 4 years ago

The reason is a doctor told my parents not to feed me any sugar until age 2-3

What I take from this is that the actual reason is, "I had parents that were concerned enough with my nutrition to not feed me much sugar as a child, and those healthy eating habits probably didn't stop after age 2-3. I now cannot gain weight, even if I eat what I perceive as a lot of food (because I grew up eating healthy food and portion sizes)."

I was one of those "I can't gain weight/put on muscle" people for a long time. I eventually tried eating literally double what I would normally eat, and as expected, I started gaining weight.

zupa-hu2• 4 years ago

Once I was working in London as a contractor, a colleague looked at my lunch after a while of working together, shook his head and told me "you are going to kill yourself". I hope that was indeed the worst 6mo in my life pretty much living on fast food, but I did not gain a penny in weight.

I think healthy eating habits would be the last thing that came to my friends minds when describing me.

I totally agree I'm only a sample of one that I know of, but the fact that this doctor relative of ours told my parents the cause-and-effect relationship beforehand, and it worked out, makes me believe the theory. Either way, I keep recommending it to my friends getting babies, so I'll be able to collect more data in the next 50 years. ;)

The thing is, that's the kind of gamble that costs nothing and might have immense upside, so it would be kinda silly not to apply it. My 2c.

cstross• 4 years ago

I'm 58, have type II diabetes, and BMI over 30, which is the criterion for NHS Scotland to offer semaglutide (currently in the formulation Rybelsus, which is a once-a-day tablet rather than an injection).

I've been on Semaglutide for 6 months now. Weight is down from 97kg to 83kg, blood HbA1C is down into pre-diabetes levels. (Also, my knees don't hurt!)

The down side of semaglutide:

1. Continuous low-grade nausea, as in, "am I going to throw up?" levels of stomach upset. Feeling nauseous for six months is No Fun Whatsoever.

2. Appetite suppression: it's like a chemical gastric band. My stomach capacity is way down. It makes family meal planning pretty much impossible: it makes the rare celebratory restaurant meal difficult (I'm limited to either two starter-sized portions or a main portion, and expect to leave some on the plate or feel bloated for 12-18 hours afterwards).

3. Muscle loss, not just fat loss. There's a pandemic surge and the health service here is in crisis so I'm not going to the swimming pool (my main form of exercise -- low joint impact). Consequently I'm not getting enough exercise. I have noticed that on semaglutide you lose weight from all tissues -- not just white adipose, so I'm losing muscle density as well. (New Year's Resolution: once the current COVID peak passes, go back to the pool during off-peak hours.)

Upshot: I'm going to persist for a while longer then when the weight loss slows off I'll talk to my GP about a medication review and maybe reducing the dosage to a maintenance level (in hope of keeping the benefits and reducing the side-effects). I would not recommend this medication to someone who is only a bit overweight -- it's a first-generation GLP-1 agonist, and like H2 antagonists in the 1970s and 1980s there will be a deluge of me-too drugs over the next few years that are cheaper/better/have fewer side-effects. If you can wait, wait.

bratwurst3000• 4 years ago

My diet pill is aderall. Works like charm.

amai• 4 years ago

Don‘t cigarettes and nicotine also suppress hunger quite effectively? It also has side effects, but are these more severe than from these drugs?

MagicMoonlight• 4 years ago

If weight gain was genetic then we’d have fat ancestors. Nobody has fat ancestors.

So sure we can drug everyone to try and fix it, but that’s not actually fixing the cause.

TheGeminon• 4 years ago

Available food/calorie supply has dramatically increased over time[0] so many ancestors probably didn’t have the opportunity to get fat even if they had the genes.

[0] https://ourworldindata.org/food-supply

martin82• 4 years ago

Eat a keto diet and you won't be obese.

Why does THAT not stun researchers? Oh... can't make any money from selling people unprocessed foods and even less from not selling carbs...

‘Breakthrough’ obesity drugs that have stunned researchers

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