8 ms·

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 possi

by iammjm 4y 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?

ceejayoz 4y 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.
- iammjm 4y 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?
  - ceejayoz 4y ago
    One drug can't address every situation. You might add in an anti-depressant for this aspect, or some sort of behavioral therapy. Consider, though, that quite a few obese people "feel bad" at least in part because of the health and social impacts of their weight.
  - djur 4y ago
    One effect of these drugs appears to be weakening that "comfort -> food" urge. There's some evidence that it also affects similar urges for alcohol.
starkd 4y ago
By using drugs that manipulate specific hormones to alter a person's appetite. So you consume less calories.
0xB31B1B 4y 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.
- dbspin 4y 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.
- rootusrootus 4y 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.
awillen 4y 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.
- iammjm 4y 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:)
  - awillen 4y ago
    Yeah, I agree with all of that, but I would differentiate slightly between not being hungry and being full. I snack when I'm not necessarily hungry, but I don't snack right after I've eaten a full meal and am actively full. Anyway, semantics of hunger/fullness aside, the effect of the drug is behavioral - people taking it do end up eating significantly less, which leads to substantial weight loss.
    - Ekaros 4y ago
      Also it is much easier to pass those snacks and other stuff when you are full or not hungry. If this is consistent state, it can also effect how accessible at other times snacks and such are.
randomdata 4y 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?
- iammjm 4y 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.
  - ceejayoz 4y ago
    > 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. So are physicians, and most patients. It's just a lot harder than it sounds to sustain. There's the old adage that "the definition of insanity is trying the same thing over and over expecting different results"; attempting to cure obesity by telling patients "exercise more, eat less" is precisely that.
    - robertlagrant 4y ago
      This is too absolutist. People aren't immutable, unable to control themselves at all without drugs. Anyone who gives up smoking without a patch has to decide to never pick up a cigarette again. They may have "given up" a few times before, and the last time they succeeded. By your logic they shouldn't have tried more than once.
      - ceejayoz 4y ago
        At a population level, we know how effective the various kinds of behavioral interventions for obesity are. The numbers aren't good. https://www.cbc.ca/news/health/obesity-research-confirms-long-term-weight-loss-almost-impossible-1.2663585 https://www.cbc.ca/news/health/obesity-research-confirms-lon... > But if we check back after five or 10 years, there's a good chance they will have put the weight back on. Only about five per cent of people who try to lose weight ultimately succeed, according to the research. Those people are the outliers, but we cling to their stories as proof that losing weight is possible. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ > In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years more than 80% of lost weight was regained. "Just eat right and exercise more" may work for a small number of people, but for most it's setting folks up to fail. It's good that we're starting to get medication options that can help folks achieve those changes; bariatric surgery works, but it's a big deal for the body.
megiddo 4y 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".
- rhino369 4y 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.
  - thefz 4y ago
    ... nah. 1Kg of human fat is around 8000kcals give or take. 50lbs is 22Kg. 176000kcal. It's 586x "extra slices of pizza", almost two years of overeating every day.
    - rhino369 4y ago
      That's exactly what I said. 300 cals indefinitely. I obviously didn't mean you eat one slice of pizza and gain 50lbs. It's easy to say "put down the pizza," but pizza is just an example. 300 calories is also 1/4 a cup of rice (50 cals), 1/3 service of chicken (100 cals) an egg (78 cals), a teaspoon of olive oil (40 cals), and a toast (75 cals). There are lot of reasons its hard to cut weight. Measuring calorie intake to 300 calories is hard enough. But also, its easy to eat a bit more at each meal if you are hungry (and it adds up).
cjbgkagh 4y ago
It would be if people are calorimeters but they’re not.
pjc50 4y 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.
kemayo 4y 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...)
- grecy 4y 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 4y ago
Let them eat cake (I mean less calories)
drowsspa 4y ago
"Stop being poor"
dougmwne 4y 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_user 4y 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 4y ago
dcolkitt 4y 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.
- asdff 4y 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.
asdff 4y 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.
bioemerl 4y 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.
mattbrewsbytes 4y 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.
- pixl97 4y 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.
nextlevelwizard 4y 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 4y 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 4y 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/ 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.

by iammjm 4y ago

ceejayoz 4y 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.

iammjm 4y 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?
- ceejayoz 4y ago
  One drug can't address every situation. You might add in an anti-depressant for this aspect, or some sort of behavioral therapy. Consider, though, that quite a few obese people "feel bad" at least in part because of the health and social impacts of their weight.
- djur 4y ago
  One effect of these drugs appears to be weakening that "comfort -> food" urge. There's some evidence that it also affects similar urges for alcohol.

starkd 4y ago

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

0xB31B1B 4y 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.

dbspin 4y 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.
rootusrootus 4y 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.

awillen 4y 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.

iammjm 4y 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:)
- awillen 4y ago
  Yeah, I agree with all of that, but I would differentiate slightly between not being hungry and being full. I snack when I'm not necessarily hungry, but I don't snack right after I've eaten a full meal and am actively full. Anyway, semantics of hunger/fullness aside, the effect of the drug is behavioral - people taking it do end up eating significantly less, which leads to substantial weight loss.
  - Ekaros 4y ago
    Also it is much easier to pass those snacks and other stuff when you are full or not hungry. If this is consistent state, it can also effect how accessible at other times snacks and such are.

randomdata 4y 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?

iammjm 4y 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.
- ceejayoz 4y ago
  > 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. So are physicians, and most patients. It's just a lot harder than it sounds to sustain. There's the old adage that "the definition of insanity is trying the same thing over and over expecting different results"; attempting to cure obesity by telling patients "exercise more, eat less" is precisely that.
  - robertlagrant 4y ago
    This is too absolutist. People aren't immutable, unable to control themselves at all without drugs. Anyone who gives up smoking without a patch has to decide to never pick up a cigarette again. They may have "given up" a few times before, and the last time they succeeded. By your logic they shouldn't have tried more than once.
    - ceejayoz 4y ago
      At a population level, we know how effective the various kinds of behavioral interventions for obesity are. The numbers aren't good. https://www.cbc.ca/news/health/obesity-research-confirms-long-term-weight-loss-almost-impossible-1.2663585 https://www.cbc.ca/news/health/obesity-research-confirms-lon... > But if we check back after five or 10 years, there's a good chance they will have put the weight back on. Only about five per cent of people who try to lose weight ultimately succeed, according to the research. Those people are the outliers, but we cling to their stories as proof that losing weight is possible. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764193/ > In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years more than 80% of lost weight was regained. "Just eat right and exercise more" may work for a small number of people, but for most it's setting folks up to fail. It's good that we're starting to get medication options that can help folks achieve those changes; bariatric surgery works, but it's a big deal for the body.

megiddo 4y 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".

rhino369 4y 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.
- thefz 4y ago
  ... nah. 1Kg of human fat is around 8000kcals give or take. 50lbs is 22Kg. 176000kcal. It's 586x "extra slices of pizza", almost two years of overeating every day.
  - rhino369 4y ago
    That's exactly what I said. 300 cals indefinitely. I obviously didn't mean you eat one slice of pizza and gain 50lbs. It's easy to say "put down the pizza," but pizza is just an example. 300 calories is also 1/4 a cup of rice (50 cals), 1/3 service of chicken (100 cals) an egg (78 cals), a teaspoon of olive oil (40 cals), and a toast (75 cals). There are lot of reasons its hard to cut weight. Measuring calorie intake to 300 calories is hard enough. But also, its easy to eat a bit more at each meal if you are hungry (and it adds up).

cjbgkagh 4y ago

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

pjc50 4y 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.

kemayo 4y 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...)

grecy 4y 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 4y ago

Let them eat cake (I mean less calories)

drowsspa 4y ago

"Stop being poor"

dougmwne 4y 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_user 4y 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 4y ago

dcolkitt 4y 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.

asdff 4y 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.

asdff 4y 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.

bioemerl 4y 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.

mattbrewsbytes 4y 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.

pixl97 4y 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.

nextlevelwizard 4y 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 4y 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 4y 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/ 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.