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Mounjaro is not an obesity drug. It's a type 2 diabetes drug. Do not call it an obesity drug.

The headline is editorialized. The linked article's headline: The ‘next Ozempic’ became a social media sensation. Then everything changed

The coupon didn't go away. The coupon's terms changed. I'm using the coupon now. Because I have type 2 diabetes. The coupon changed because people were using it to get the drug for off-label use. The drug wasn't taken away from people trying to lose weight by jacking up the cost. The drug shouldn't have been dispensed in this way to begin with.

Lilly is seeking to get approval of tirzepatide under a different label as a weight loss drug, similar to how Ozempic and Wegovy exist, as well as Victoza and Saxenda.

If you want a GLP-1 RA (this drug class) for weight loss, go get Wegovy or Saxenda, which are a version of these drugs approved for weight loss for those with a BMI over 30, or wait for the tirzepatide version. Leave the diabetes drugs alone.

And to be clear: This drug isn't helping diabetics by helping them lose weight. It helps diabetics regulate blood glucose. It slows the release of glucose from the liver as well as promotes the release of insulin from the pancreas. Weight loss due to slowed stomach emptying is a side effect.

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> Mounjaro is not an obesity drug. It's a type 2 diabetes drug. Do not call it an obesity drug

This is an absurd argument. It's a drug. It has specific metabolic affects in humans that are valuable to people's health, among which are the control of blood glucose levels, and control of appetite and nutrient uptake, leading to loss of excess weight. That it is currently labeled only for Type 2 diabetes is a marketing decision by the manufacturer, not a characteristic of the drug.

Or, to put this another way: the drug is doing exactly the same thing whether you measure its effectiveness with a glucometer, or with a bathroom scale.

> That it is currently labeled only for Type 2 diabetes is a marketing decision by the manufacturer, not a characteristic of the drug.

Regulatory approval. It is a diabetes drug because it has been evaluated as such, including understanding the primary effects and side effects at various dosing levels. Mounjaro is prescribed to diabetics from 2.5mg to 15mg in increments of 2.5mg and titrated based on needs and goals.

Typically, weight loss versions of these drugs (Saxenda and Wegovy) are dosed higher than their diabetes counterpart, and are just titrated to maximum dose over time to maximize weight loss benefits. So evaluation is based on this, and approval follows this.

Various drugs do get used for off-label purposes, but the drug makers can't promote this because their marketing claims are regulated. This is why the coupon terms were changed.

Coupon terms changed because drug makers can't promote this? Can you help me understand why the ability to promote would have any bearing on a coupon's terms?

Coupons for products or services are considered a form of promotion.

Allowing the coupon to be used for the treatment of obesity is an implicit approval for the drug to be used in this way, and coupons are a form of marketing. Lilly cannot approve nor market this drug in a way that is off-label. This is why when Lilly talks about testing tirzepatide for weight loss, they say tirzepatide and not Mounjaro. Whenever you see articles mentioning Mounjaro for weight loss, these are statements not originating from Lilly.

Mounjaro will have FDA approval for obesity this year. GP’s dogmatic stance that “Mounjaro is not an obesity drug!!” is soundly rejected by the available evidence.

Mounjaro will never be approved for obesity. The documentation for dosing is for diabetes. If the trend follows with how Novo Nordisk has released their versions of this, dosing for weight loss will be different than dosing for diabetes care, and so it must be under a whole new label.

Mounjaro is a trade name for a diabetes drug and that won't change. So no, it is not soundly rejected.

It's not as simple as "SQUIRT JUICE INSIDE ME GET THINNER AND CURE DIABETES". There's a lot more to this than you seem to understand.

>It's not as simple as SQUIRT JUICE INSIDE ME GET THINNER AND CURE DIABETES

It kind of is that simple. Tirzepatide has three main functions: Hunger suppression, slower digestion, and increased insulin sensitivity.

For a large portion of people who are overweight, this will get them thinner and in some cases reverse t2 diabetes.

Tirzepatide will have FDA approval for obesity this year. GP’s dogmatic stance that “Mounjaro is not an obesity drug!!” is overwhelmingly rejected by the available evidence.

Sometimes you need to examine subtext a little closer.

Obviously this person is (reasonably) upset* that off-label use is muscling out on-label use, when the two uses are of two very different classes.

Their issue isn't just the fact that the common vocabulary has switched to focusing on weight loss, it's the general shift in where the supply is going that's accompanies said shift in vocabulary

Being overweight is a serious health issue, but Type 2 diabetics were using it in a way that was much more acutely pressing, with much fewer alternatives. It's not hard to understand why diabetics would feel upset/threatened by a secondary off-label use of such a different class.

* I read it as upset as the situation, not at those who are overweight to be clear

I'm aware that you're upset because of shortages in the medicine you need.

I think your beef should be with the pharma company seeking to maximize profits by constraining supply such that they are easily overwhelmed by off-label use, not with people seeking effective medical treatment.

There's a common meme among what I've seen from diabetics complaining about the shortages: that this is a tik-tok thing, or prompted by some celebrity, and the medicine is being take by people trying to lose ten lbs. I don't think any of that is true. Doctors are prescribing this for people who have medical conditions that make them dramatically overweight. My mother found relief from lipedema after decades of pain thanks to mounjaro, and she's facing the same shortages you are. She's done the half-doses and the quarter-doses and stretched them out until the pain came back.

Mounjaro is the best drug for a number of conditions, both the approved diabetes and some number of not-yet-approved conditions. Eli Lilly is maximizing profits in a way that leaves people with Type 2 diabetes and other painful conditions suffering. There's no need to blame social media for Eli Lilly's shortcomings.

>Doctors are prescribing this for people who have medical conditions that make them dramatically overweight

I know multiple people < 150 lbs who have gotten scrips for it with no history of diabetes.

How many? Enough to make this comment anything other than a meaningless anecdote? I'm over 375lbs and nobody will prescribe it for me. There's my counter-anecdote.

More than 10.

There are online providers that are effectively just pill mills for these drugs if you're actually interested. They're' expensive though... https://joinnextmed.com/weight_loss

How tall are these <150lbs people? How old? Are they men or women? Do their doctors think they show signs of possibly getting diabetes in the future? Obviously if there's a 5'10" 25 year old male with negligible risk of diabetes, they should keep their current weight or even increase it slightly by changing their body composition from majority fat to majority muscle by doing exercise. If someone's short, old, can't exercise for some reason, and might get diabetes at some point, there could be a role for a drug there.

pharma company seeking to maximize profits by constraining supply

They have a monopoly on the drug, what's the evidence they are constraining supply? It makes no sense, the price is set, the more they supply the more money they make.

I swear people just say things without a shred of thinking.

I think what's meant here it's that the manufacturer chose to target specific patient groups (T2D) and commercial insurances to get the highest profit per dose. About 40% of adults in the US are obese, they could have made the drug available at much lower cost and get their profits from economies of scale. Instead, the production is low and the focus is narrow.

It's not always the case that production is made intentionally low. There are actual limits to how much times a chemical/biochemical production process can be run in a given year. I'm actually learning this the hard way with one biotech project.

The alternative might be a $200 million dollar production facility which may not even be feasible to cater to the excess of consumers. Or which may be too excessive for the excess of consumers targeted.

They also probably don't want to put significant investment in boosting production knowing that will be temporary since the weight loss effects aren't permanent. As someone who has been on GLP-1 RA for a decade, starting with Victoza, and now on Mounjaro, those weight loss benefits have no effect on me anymore. Delayed gastric emptying and appetite suppression is so far reduced that it might as well not be a thing anymore. But I don't use this drug for weight loss, I take it for glycemic management, and it still works great for that. I have to do the work to continue my weight loss and maintenance.

Yeah, these drugs aren't new but the wide world is just learning about the weight loss aspect. So they don't know this is a temporary solution.

Perhaps the weight loss would be more permanent with the higher doses that are being approved for the weight loss use case?

You might get a good few years from the drug. You have to still do the work to make the changes permanent.

"Diabetes patients think people with obesity are stealing their drug, as it’s currently only approved for the treatment of T2D (though FDA approval for the treatment of obesity may come as soon as this summer.) People with obesity are angry that obesity isn’t recognized as a disease. And users who can’t afford it say they’ve been abandoned by Big Pharma."

Always amazing when an article is verified in real time

It's weird for anyone to "feel abandoned by Big Pharma" when you abused a coupon to get a drug for off-label use, and terms were changed to match its on-label use. Especially when there's versions of these drugs with on-label use for weight loss.

Why should anyone need to use a coupon in the first place? Just charge a reasonable price, don’t make people jump through hoops for medicine.

Brand new drugs tend to take a while to get on insurance formularies. I believe Mounjaro is still missing in most formularies. Lilly wants people on their drug, not the competition.

So just yet another case of the American healthcare/insurance system being absolutely bottom tier in usability, profits for middlemen over all else.

This is not only an American issue. I've seen people in the UK struggle to get access to treatments and devices through the NHS. Canada tends to follow what the US is doing even though they have their more socialized system. It all tends to be a bit of a mess with brand new drugs and devices. And Mounjaro is new as of last year (approval less than a year ago?).

No, drug approval takes time everywhere with a health care system. Heck I've been on methylphenidate for my ADHD for almost 15 years now, and it's still off-label when prescribed to an adult in the UK according to the NICE.

Did we read the same comment?

> If you want a GLP-1 RA (this drug class) for weight loss, go get Wegovy or Saxenda, which are a version of these drugs approved for weight loss for those with a BMI over 30, or wait for the tirzepatide version. Leave the diabetes drugs alone.

Definitely think it's forgiveable and even rational to be upset that droves of people are creating shortages of a medicine you need with off-label use, however legitimate.

I'm not saying that the feelings are unjustified. I just thought it was interesting to see the article confirmed so quickly. If I needed a medication intendeded for my illness and couldn't get it I would feel the same way.

With very few exceptions obesity is simply the result of eating more calories than needed for a long time. Very obese people eat a LOT of food. 10,000 calories/day for years is not uncommon.

Thermodynamics obviously holds, but I'm unsure what you implication is. If it is that the obese should simply eat less, that doesn't seem terribly useful though it is completely true.

The implication is that obesity is not a disease, it is actually the human body working as intended by storing the excess energy as fat for future use.

A friend that is a doctor specialized in metabolic problems told me that around 5% of the cases of obesity have some medical cause, not eating too much. 5% is low, but it is a lot more than "very few exceptions". (Disclaimer: the number is for Europe, I have no idea what is in US)

All obesity is fundamentally caused by eating too much because fat contains energy that HAS to come from food.

Technically right is the most reliable kind of right, but in this case “too much” means that someone’s body responds differently than expected to the same amount of food.

It’s true that the extra stored fat might must come from calories not used or excreted elsewhere, but that might be because their body is very poor at making immediate use of the calories as energy or is unusually efficient at storing energy that might otherwise be used. To put a number to it, a 2000 calorie diet as normally recommended may leave them depleted of energy and increasingly fat.

It can take years to discover that kind of “outside the norm” issue, and obesity can easily set in before its recognized let alone addressed. And of course, once obesity does become a part of someone’s life, there’s a whole spiral of challenges that make it hard to overcome. Even moreso when your body doesn’t work normally.

Well, blood sugar contains energy that has to come from somewhere, too, but one would hardly say this means type 2 diabetes is fundamentally caused by eating too much. Shoot, tumors contain energy that has to come from somewhere...

Of course, you could rightly reply that there are a lot of complicated things that happen between the food and the problem, and while those diseases require an energy surplus, that neither causes them, nor does trying to naively eliminate the energy surplus fix them. Contrary to popular wisdom, the same is true of obesity.

The idea that obesity could be avoided or cured with a little bookkeeping and self control is laughable to just about anyone who has tried. Telling obese people to eat less is like telling depressed people to get over it. You'd be astonished by how ultimately impossible that is if you haven't been there.

Type 2 diabetes is fundamentally caused by eating too much of carbohydrates. Most type 2 diabetics can put the condition into remission by changing their diet.

https://www.virtahealth.com/research

There are many people who have cured their obesity with a little bookkeeping and self control. Sue Reynolds and David Goggins are a couple of prominent examples, but there are many others. It's not easy, but it's certainly possible.

https://suereynolds.net/book/ https://davidgoggins.com/book/

> Type 2 diabetes is fundamentally caused by eating too much of carbohydrates. (Emphasis mine)

Fructose, specifically, is the going theory. And I'm a big fan of Virtahealth specifically, and Dr. Fung's approach for treating type 2 diabetes generally. :)

However, I'd disagree that we know that that's what causes it. We know that treats it. Cancer is not caused by a lack of chemotherapy, and I think chemotherapy is a good analogy for the fasting and low carb approach in this situation. It is a treatment, not a generally normative lifestyle.

But my point is actually more limited, and you actually sort of made it for me by adding the detail about carbohydrates. To wit: just because sugar requires energy, does not mean that you got too much sugar by bringing in too much energy. It's not that simple. You won't get the disease by eating too much protein, for example (you'll get protein poisoning ;) ). You get the disease as a result of liver dysfunction, which you exacerbate and possibly cause by eating too much fructose. It's a control mechanism problem and an injury problem -- the fact that energy is involved (even required!) does not make that the central issue.

Cancer requires energy for growth, but that doesn't make energy the central problem. Blood sugar requires energy for dysregulated high levels, but that doesn't make energy the central problem. Fat requires energy for dysregulated growth, but that doesn't make energy the central problem. That's something you have to demonstrate, and rigorous attempts to demonstrate it fail.

> There are many people who have cured their obesity with a little bookkeeping and self control ... David Goggins

Citing David Goggins as an example of "a little bookkeeping and self control" is hilarious to me. I've read his book. I love his talks. But the guy is about as heroic and extreme as it is possible to get, and that is far from the only thing he did.

I have yet to see a type 2 diabetic who didn't eat excessive quantities of carbohydrates before developing the condition. The details of the exact causative mechanism are interesting, but largely irrelevant from a prevention perspective.

My point is that David Goggins is nothing special. He isn't a superhero from the planet Krypton. Anyone can choose to do those things (or at least lesser versions of them). Some people just prefer to sit on the couch eating cookies.

> but one would hardly say this means type 2 diabetes is fundamentally caused by eating too much.

Eating too much is literally what causes type 2 diabetes.

The entire purpose of fat is to store excess energy for future use because over human evolution food supply was unreliable enough for this to create an evolutionary advantage. Getting fat from eating a lot of food is completely predictable.

"The idea that obesity could be avoided or cured with a little bookkeeping and self control"

It absolutely can. Again people just don't want to feel bad about not having enough self control.

> It absolutely can

It can’t. There are many people who, if they simply scaled down their diet without otherwise modifying their nutrient intake/lifestyle, start having health problems well before they lose weight. Hot flashes, fainting, severe stomach pains, nausea.

This sounds false to me. I suppose for someone used to eating 10 to 20 thousand calories per day suddenly going to 1500 would be stressful but if gently tapered no one should have any issues.

I mean the obvious counterexample is someone who eats 1500 calories of real food and 2500 calories of junk food a day. If you scale that down by half you start getting all sorts of nutrient deficiencies well before hitting your target weight.

But there are subtler versions of this. People who live in food deserts, only have access to iceberg lettuce and freezer-burned tomatoes as produce are gonna have a tough time getting all the nutrients they need in 2000 calories or less. There’s also others who have very specific dietary needs that they’re not yet aware of.

What's the issue with iceberg lettuce?

Nothing wrong with it but it’s pretty devoid of nutrition compared to other greens.

> The entire purpose of fat is to store excess energy for future use

That isn't true. Though it's a primary use, the opening paragraph of the wikipedia article on fat outlines that it actually has many biological functions (and is properly thought of as an organ!): https://en.wikipedia.org/wiki/Adipose_tissue

> ... because over human evolution food supply was unreliable enough for this to create an evolutionary advantage. Getting fat from eating a lot of food is completely predictable.

Not at all. While fat does have a primary function as an energy reserve, that does not mean that unregulated growth is a simple matter of putting too much energy into the system. After all, just as in nature there are times of famine, there are also times of feast. It would be pretty disadvantageous for animals to have no regulation on their fat growth in times of abundance. Something more has to go wrong to cross the line from "saving for a rainy day" to "killing you". Animals don't eat until they damage their stomachs, do they? Not generally. Why does it make any more sense that they should eat until they damaged their endocrine systems?

An interesting counterpoint: bears hibernate. In preparation for doing so, they become fat by eating a lot. Now, they do this, not just any time of the year when food is abundant, but specifically in the fall as they prepare for the winter. Are they just lucky that food happens to be abundant every fall? Or is something else going on? What happens in years of famine? Do they still manage to get fat so they can hibernate?

Another interesting counterpoint: Pregnant women eat a lot and put on weight. Why do they do that? Is it because more food is available? Or is something else going on?

One last counterpoint. Bodybuilders put on a lot of muscle, which also takes energy, and they eat a ton to support that growth. Why is it that if I eat an extra steak, my flab gets bigger, but when Ahnold eats one, his biceps get bigger?

Obesity is dysregulated growth. While growth does require energy, it is in the failed regulation of that growth that you will find the best explanation for the disease.

" It would be pretty disadvantageous for animals to have no regulation on their fat growth in times of abundance. Something more has to go wrong to cross the line from "saving for a rainy day" to "killing you". ""

I really can't blame you for assuming this, but it actually turns out that food was scarce enough in human history that humans never actually evolved a limit on how much fat we will store. If we keep consuming a caloric surplus the body will keep creating fat to store it. This is the body working as intended. Things would be different if humans had a more reasonable max body fat percentage.

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

You have mixed up a few facts with a lot of "bro-science" there. What you have described is not consistent with our current understanding.

https://peterattiamd.com/rickjohnson2/

Anyone can build muscle instead of flab if they do sufficient resistance training and eat enough protein. Gains will tend to be slower for women and older people. Arnold Schwarzenegger used a lot of steroids and other PEDS which can certainly accelerate gains, but aren't worth the side effects and legal risks for most people.

https://www.essentiallysports.com/us-sports-news-bodybuildin...

>>"The idea that obesity could be avoided or cured with a little bookkeeping and self control"

> It absolutely can.

No it can't. ;)

Well, not always. I've experienced both sides of this: an effortless loss of 60 lbs with easy diet changes and bookkeeping over the course of a year and a half. And a few years later, an abject failure as the same strategy -- a moderate calorie restriction -- resulted in such profound physical distress that I developed psychological problems long before I made any physical progress.

Sometimes it's easy. Sometimes it's impossible.

My story is far from atypical. It's common. Practically universal. Everyone, just about everyone, who tries to lose weight, using any strategy, succeeds over a period of months, and fails over a period of years. The reason is that the underlying control mechanism is in a different condition, in different people who may be the same weight.

> people just don't want to feel bad about not having enough self control.

I know you're really attached to the energy imbalance theory of obesity. People often are. But I'd like to suggest that this comment suggests you may have a different motivation for believing in it than just that you find the evidence persuasive.

I often wonder why people get so attached to a theory that I think is in such obvious evidential crisis. A need to believe a simple solution will be there when they need it? A traumatic dieting experience that they need to believe was necessary and useful and healthy? Maybe it worked for them once and they're universalizing their experience? A desire for moral superiority? The fact that deliberately oversimplifying things makes for slam dunk messages on forums?

I don't know, but diet is one of those weird topics where people are attached to their opinion with the religious fire of a thousand suns. While I know I won't change your mind, it does seem fair to point out that your statements are both hyperbolic and inaccurate, and that's not a good sign.

"I know you're really attached to the energy imbalance theory of obesity. "

It isn't a theory, it is a fact. It is basic thermodynamics. The human body requires a constant amount of energy for basic operation and activity. Any excess is stored as fat for future use. Creating fat requires calories that HAVE to come from food. Eat few enough calories and you WILL lose weight. Eat zero and you WILL die. Eat 20,000/day for a year and you WILL get very fat.

A good example of this is this man went 382 days without eating

https://www.diabetes.co.uk/blog/2018/02/story-angus-barbieri...

He had a calories surplus for long enough to weigh 207kg. While not eating his body consumed energy in his fat to stay alive and he got down to 81kg. ((207-87)kg * 7700 calories/kg)/382 days = 2539 calories/day, which is a very plausible number.

The problem, which I can't work out if you know about but ignoring or are ignorant of, is that humans have inordinately strong control systems to maintain some state, as well as hugely influential effects from e.g. a gut biome.

To say "it's just thermodynamics" might be right as far as the physics goes, but it doesn't recognise that biological drives overwhelm everything. It's hugely complicated how energy expenditure and steady state energy consumption interacts with weight gain, not least because the body will invariably work to make your actions as efficient as possible to maintain weight. For example, observational studies of hunter societies that might travel large distances daily, energy requirements bear little relation to daily activity after any transition time has elapsed when compared to relatively inactive Western counterparts. These people can't just will their activities to be less efficient if they hypothetically wanted to consume more energy.

Ultimately, the biology will decide what the effect of any intervention is, regardless of how motivated or not you are. Any advice that doesn't explicitly factor that in is just hot air.

"humans have inordinately strong control systems to maintain some state"

If energy intake matches energy needs then body fat percentage stays the same.

If energy intake exceeds energy needs then body fat percentage increases as the body stored the excess as fat.

If energy needs exceed energy intake then body fat percentage decreases as fat is used as fuel.

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

"The human body requires a constant amount of energy for basic operation and activity. "

no, it doesn't. the amount it uses for basic operation and activity will change. shrinking in response to your attempts to lose weight.

This is absolutely false. The human body must always consume a minimum amount of energy for basic maintenance. See https://en.wikipedia.org/wiki/Basal_metabolic_rate. While it does vary it also has a hard lower limit.

The basic metabolic rate varies between individuals. One study of 150 adults representative of the population in Scotland reported basal metabolic rates from as low as 1,027 kilocalories (4,300 kJ) per day to as high as 2,499 kilocalories (10,460 kJ); with a mean BMR of 1,500 kilocalories (6,300 kJ) per day.

you said "constant" not minimum. don't move the goal post.

https://www.ncbi.nlm.nih.gov/books/NBK572145/

When I typed that I was thinking of the basal metabolic rate, which is relatively constant for a person. Think of it as the calories a coma patient would need to stay alive.

Calories In Calories Out (CICO) doesn't explain obesity. You are dealing with biochemical machines (humans). CI enters this biochemical machine; here, the signal system should be effective to 'equalize'. Otherwise, you get all kinds of problems: obesity, t2d, cardiovascular events, etc.

These new generation of drugs (semaglutide, tirzapatide) deal with the signaling system (endocrine signaling, that is).

"Calories In Calories Out (CICO) doesn't explain obesity."

Yes it does, because it is basically just repeating basic laws of thermodynamics. Obesity is actually just the body working as intended by storing the excess energy for future use during a famine. CICO is why obesity used to be very rare in past when calories were expensive and is now common when calories are very cheap and artificially delicious.

Well, two conceptions of human beings are in conflict: (a) humans are controlled by their own "will" (b) signaling system (biochemical interactions) control stuff. (a) is a cultural intuition. Now many life sciences researchers sell us a hybrid version: both (a) and (b) are true.

https://www.diabetes.co.uk/blog/2018/02/story-angus-barbieri...

No. Absorption rates are different. Liquefied fat of the same calories translates to more fat then plant with the same calories.

That's just an extreme example. The real culprit is processed foods.

The difference should not be enough to be the difference from a body fat percentage of 15% to 80%.

https://www.theatlantic.com/health/archive/2015/09/why-it-wa...

You don't know that.

I very much doubt the accuracy of calorie consumption data that article is based on. CICO is so fundamental that I would propose that the current rate of obesity is proof that average net calorie surplus has increased.

let's keep it to one thread. I'm ending it here.

https://www.diabetes.co.uk/blog/2018/02/story-angus-barbieri...

Do you think depression is a disease? I would argue obesity is certainly a symptom of depression in some people.

Great. Now answer why they eat that much.

Addiction to the dopamine rush it gives them.

I agree with you, but have a few qualifiers about it.

I decided I want to lose weight for the third time in my life. A few weeks I was probably eating 5,000 calories a day. I’ve lost 15 pounds in three weeks. Basically before every day I’d eat and eat and never ever feel full. My stomach would hurt, I’d throw up every day, I felt tired and shitty every single day.

Now I can barely managed to eat 1400 calories a day. I’m eating red meat and kimchi, basically. That’s my diet. Once a week I’ll crave a nice big salad with mushrooms and olives and ranch dressing. I feel great. If I try to exceed that calorie amount I’ll feel super satiated (not full, like physically full) and stop mid bite, and save the rest for later. It feels like a long dormant part of my mind that controls calorie intake suddenly has a voice again and that voice has been drowned out for years.

So I mean it’s easy to say “it’s just calories”, but why when I eat a standard American diet am I craving thousands of extra calories per day and that stops when I eat like this? Even stranger, why do I relapse into these habits when I eat even a small amount of food like French fries or ice cream, over and over again? I know precisely why I’m fat, exactly what to do to lose weight, it’s not even difficult, but unless I have a very strong motivation to lose it I just don’t.

Most people don’t even have the requisite knowledge of how to deal with hunger cravings and get themselves in a state where they’re losing at all. They’ll eat chicken breast and a salad with no dressing then wonder why they feel awful because they’re not getting nourishment, then binge on ice cream. So how is the average person supposed to lose weight?

From high school through nearly all of my adult life I’ve been obese. For the last several years my weight has barely fluctuated, but it’s fluctuated between caution about being underweight and a few pounds “overweight” that barely even count. I’ve eaten almost exactly the same the whole time. The two factors which changed:

- I take ADHD meds, amphetamines, which are appetite suppressants. They haven’t made me eat less, and they’ve reinforced “bad” eating habits I used to have before I lost so much weight, specifically reinforcing my tendency to eat one, large, meal per day.

- I’m much more active than I used to be, because I got a pup who needs the activity and with whom I like to be active.

My caloric intake is about the same as it’s always been. Once I actually paid attention to it I realized it wasn’t even very high. I very seldom reach the recommended 2000 calories diet metrics are based on. I still don’t understand how eating that way made me obese, but I have to assume now I was just absurdly sedentary.

I got lectures like this about caloric intake for years and always found it interesting but confusing! How was I so fat and never eaten much?

I’m not saying this applies to anyone else, but it’s bothered me for decades that I’d been told calories in -> obesity meanwhile my own caloric intake had next to nothing to do with my body mass.

Odds are you are consuming more than 2000 kcal/day. Most people underestimate. Have you tried weighing and recording everything you consume for a couple weeks?

Anyone who wants to lose weight should start with a resting metabolic rate test in order to establish a baseline. You just sit in a chair for a few minutes while a machine measures your inhaled and exhaled gasses to calculate energy expenditure. If you consume fewer calories than your RMR then it is impossible to not lose weight.

This is a confusing response. I do not want to lose weight. I had to pay more attention so I could stop losing weight. Your advice might be good for someone with a different problem, but (1) I don’t have that problem and (2) I addressed the problem I did have by eating more.

People are notorious for underestimating how many calories they are eating. Modern food is so cheap and delicious it isn't hard to eat 1000 calories in a few minutes. I lost weight by only eating food with accurate calorie information available that I could weight to the gram. I then used MyFitnessPal to track it and keep a 1000 calorie/day deficit.

I’m eating basically the same food, basically the same quantities, and I did start paying attention to the calories. Amusingly I started paying closer attention when I was worried about losing too much weight, and when I found myself frequently craving sweets (which I very seldom have since I was a kid).

The simple act of tracking things - even with no intent to change - typically makes me eat far less, or do the activity far more. Anecdotes with friends makes me believe this is quite common.

There is literally no way to take in more calories than you expend and not gain weight - short of hyper-specific and exceedingly rare medical conditions you'd be quite aware of.

Some people find this easier or harder than others due to a whole host of factors. Physics is physics though, and there is no way to run a calorie deficit and not lose weight. It's why this drug class is so interesting/popular - it lowers the bar for many people, making the effort of taking in less calories than they expend much easier to achieve.

> The simple act of tracking things - even with no intent to change - typically makes me eat far less, or do the activity far more.

When I started tracking things so closely, I was already concerned that I’d been losing weight and feeling very strong cravings for sweets which I don’t usually care for. The effect wasn’t that I ate less: I started making an effort to eat more, again much like I used to eat. The biggest change is that eating enough has been a concerted effort rather than fairly automatic.

Have you every reached 600 pounds? 800? If not why do you think that is? It is because you simply didn't eat enough food to do so.

I reached about 350 lb, and my current weight is just shy of 190. I’m eating almost exactly the same, with some minor adjustments for taste changing over time. What I eat now would still be ill advised for anyone trying to lose weight. The thing that changed is I burn a lot more calories than I used to. Everyone pointing out this basic fact is right, but the focus on calories in is wrong in my case, and I find it pretty odd to totally dismiss the calories burned factor.

No one is dismissing calories burned, it is the calories out part of CICO but it is vastly easier to reduce caloric intake than to increase caloric burn. as an example for me it takes an hour of walking to burn 400 - 600 calories.

1 in 3 people in the US are obese. It is not just about eating more calories than needed for a long time. The story is much much more complicated then that given that 1 in 3 people are obese.

It's like saying an overdose on heroin is simply someone doing too much heroin at a time.

"It is not just about eating more calories than needed for a long time."

Yes it is. It really is as simple as that, people just don't want to hear it. Historically food was scarce that it was nearly impossible to sustain a calorie surplus long enough to get fat. But some people did, that is why the rich used to be called "fat cats" but now calories are so cheap and delicious and lifestyles are so sedentary that it is very easy for almost anyone to sustain the caloric surplus needed to become very fat. I had a cousin who reached 650 pounds and then died. He would spend hours every day eating and almost as long shitting.

>Yes it is. It really is as simple as that, people just don't want to hear it. Historically food was scarce that it was nearly impossible to sustain a calorie surplus long enough to get fat. But some people did, that is why the rich used to be called "fat cats" but now calories are so cheap and delicious and lifestyles are so sedentary that it is very easy for almost anyone to sustain the caloric surplus needed to become very fat.

I'm skinny so I'm unbiased. There is nothing I "don't" want to hear because I'm literally not affected by it. Thus, I assure you I have more information than you. Read below:

https://www.theatlantic.com/health/archive/2015/09/why-it-wa...

Your reasoning is on anthropological timescales, which while technically true, doesn't explain why people were still skinny in the 80s and before. There was an actual turning point AFTER the 80s... A huge shift in weight gain where MODERN and well-fed people suddenly got heavier. Something happened with the food supply starting with the US.

We only have correlative studies that match a number of things with the sudden change in weight. Thus no causative confirmation on the exact source. Our educated guess says that it has to do with processed foods. Processed foods streamline calorie absorption to unnatural levels leading to unnatural weight gain.

The article above mentions a number of other factors that I think are possible.

Self-reported calorie consumption is worthless.

But a reader questions the methodology of the researchers: “My main concern is that the calories are almost assuredly self-reported, which is notoriously unreliable.” Another reader agrees:

    In the 1980s, we weren’t walking around with a computer in our pockets to look up accurate calorie counts for everything that allowed us to store an accurate list of everything we’ve eaten and compute the calories based on that database. It was 100% self-reporting and calorie lookups “from memory” or done manually (complete with calculations) long after the fact. So the reports based on that old data might be suspect.

But another reader notes:

    The study authors addressed that point somewhat:

    Whether self-reported dietary intake accurately reflects an individual’s true dietary intake has been questioned. Indeed, doubly-labelled water studies typically show that individuals underreport their energy intake, and that the magnitude of the underreporting may be larger in people who are obese.

Lots of stretching of the imagination here in attempt to fill in the gaps in your bias. I mean you had to dig for this stuff in order to support your stance. Why not let the facts change your conclusions as an unbiased person should?

The fact of the matter is, people weighed less in the 80s then they do today. No amount of stretching can change this quantitative measurement. So something must've changed. What changed?

You can continue to talk about calories in and calories out just like we can blame the overdose problem on people doing too much heroin. Again, while YOU can do that, it's not a very useful position.

My bias is for basic laws of thermodynamics.

https://www.diabetes.co.uk/blog/2018/02/story-angus-barbieri...

"The fact of the matter is, people weighed less in the 80s then they do today. "

Because they ate less. Portions were smaller, Food wasn't marketed as much.

"No amount of stretching can change this quantitative measurement."

Self-reported calorie intake is not a reliable quantitative measure.

"You can continue to talk about calories in and calories out just like we can blame the overdose problem on people doing too much heroin."

I really don't understand why you think this statement proves. A heroin overdose IS caused directly by an excess amount of heroin in a given time interval, just like obesity IS caused directly by excessive calories in a given time interval. The time interval for obesity is years instead of hours.

Heroin and obesity are indirectly caused by people getting addicted to the dopamine levels consuming them cause.

You sound a tad like a 9/11 truther insisting on some over complex conspiracy theories to explain something fairly straightforward.

>I really don't understand why you think this statement proves. A heroin overdose IS caused directly by an excess amount of heroin in a given time interval, just like obesity IS caused directly by excessive calories in a given time interval. The time interval for obesity is years instead of hours.

This is the part you're not getting. You DIRECTLY say you don't understand here, and I am here to confirm that you in actuality DO NOT understand.

A heroin overdose IS directly a result of too much heroin within a time interval. But that answer is too obvious and PEDANTIC. You would be stupid to characterize the opiate epidemic as just people doing too much heroin and that they should do less to improve their health. "Yeah that's the problem with opiates in America, people doing too much of it, I know you guys don't like to hear it, but it's the truth. Just control yourself and do less"

Obviously it's more than that. There's a problem with tolerance, with addiction, the fact that opiates were introduced as addictive pain killers by Purdue Pharma under the name Oxycontin. The story of heroin is much more then the completely idiotic characterization of just "doing too much."

So to bring it back around. The the situation is MUCH more complex then people eating more and becoming fatter.

>You sound a tad like a 9/11 truther insisting on some over complex conspiracy theories to explain something fairly straightforward.

I'll just be blunt. You sound like a fucking idiot for regurgitating something SO OBVIOUS. Look, you're not actually an idiot, so stop acting like one and stop calling me a 9/11 truther.

What's even stupider is that when I tell you that while TECHNICALLY more calories in does make you fatter there's clearly something else going on. Do you see the connection with the metaphor here with heroin? Heroin isn't just about people doing too much of it. There's many underlying reasons here for WHY something happens.

I have experience in this area with people who are overweight. Even the simple answer of calorie density in processed foods increasing due to industrial food manufacturing after the 80s leads to fatter people is a better characterization here.

However that answer above ^^ is inline with your simplistic calorie in-out logic so maybe that explanation can help you "get it".

"I'll just be blunt. You sound like a fucking idiot for regurgitating something SO OBVIOUS"

First, don't be so rude. You think what I'm stating is obvious but there is an entire industry built to deny it. Even on this thread there are people who deny it.

Don't be rude? You compared me to a 9/11 truther. We're done here. I'm rude in response to your rudeness. I'm wrong though, I shouldn't be rude in response to you.. The proper thing to do is to end the conversation. Good day.

"You compared me to a 9/11 truther."

Just because you honestly reminded me of their need for overly complicated explanations of well understood things.

Same here, you honestly reminded me of an idiot.

Your explanations are simplistic you fail to see nuance and complexity within reality. I find your outlook on things to also be delusional. You think things are simple and well understood but that's just a reflection of your ignorance.

Not trying be insulting or anything like that but this is just what it is.

Just to drill it home. How stupid does a person have to be to think that comparing someone to a 9/11 truther isn't rude? You have to be pretty stupid.

Again not being rude. Just telling it like it is.

People aren’t stupid. Mounjaro is the most effective weight loss drug in existence. Better than wegovy and the other brand name semaglutides. If you think FDA approval is going to stop people from wanting and getting it you’re sorely mistaken.

Yeah, feel free to spend the $1200/mo for it then. Because that's off-label use when there are drugs in this class with on-label weight loss use. And sometime this year, tirzepatide is expected to be among them.

The coupon was changed because people were abusing it. This drug is approved for diabetes, not weight loss.

Don't worry, it will be approved for the latter soon enough, perhaps under a different brand. No way to put this genie back in the bottle, sorry.

Yes, this is what Novo Nordisk did with Victoza around 2014 with the release of Saxenda. And then again with Ozempic around 2021 with Wegovy. These weight loss versions exist. And there will be one likely this year based on tirzepatide from Lilly (I haven't looked up if they have a name for it yet).

Why are you defending the price gouging of the american healthcare system? Do you really only care about yourself?

I care that many people I know are losing glycemic control because they're going on a waiting list for their medication while Kim K and Elon Musk and TikTok promote easy mode cosmetic weight loss.

if someone is 'losing glycemic control' because they can't get a specific new en-vogue med, then their doctor is doing a poor job.

there is a very big problem with blaming the suffering who find relief with this drug -- regardless of what their ailment is -- rather than blaming the systems and processes that lead to a supposed shortage that urged a price adjustment.

forgive me for diving into conspiracy for a second here..

do you really think for a second that the pharmaceutical groups responsible for this class of drug do not have the facilities to ramp up production?

They absolutely do -- the problem here is that since it's a gold-mine there is even more cash capture to occur with an added scarcity element, hence the price adjustment.

The price adjustment wasn't to champion the diabetics over the obese, it was to make more MONEY.

You are among the people just learning about this class of drug. It's been around since 2004 (Byetta). I've been taking it since 2012 (Victoza). Even then, it was known to promote weight loss (Saxenda approved around 2014).

This is not a new hotness. And many diabetics have used this drug class for a long time.

And yeah, you're jumping into conspiracy theory. Ramping up production would likely take significant investment. Do they have the resources? Probably. But given the weight loss benefit is temporary (seriously, it is, ask anyone who has used one of these drugs for a significant amount of time), do you think they're going to sink significant investment into production when demand is going to wane in a few years? Well, you see, their investors are going to say no, and they hold the final say.

Seems like the problem is that not enough is produced to meet real demand instead of mere regulator-approved demand.

> Leave the diabetes drugs alone.

Is artificially partitioning what is almost certainly the same medication (with the same manufacturing process) into two separate product lines actually a Good Thing? This means that when Mounjaro has supply problems even with the split, diabetics won't be able to get it because part of the supply is inaccessible to them since it is dedicated to a different "product".

Instead we should advocate for the real solution, which is to demand the manufacturer drastically increase production - Mounjaro along with Semaglutide have literally capital-S Solved one of the most urgent health epidemics of the 21st century, and the solution isn't to shame people for using it, the solution is to make it available to anyone who needs it.

Who is this 'we'?

I'm quite certain a large fraction of the HN userbase still believes that people can do independent business without being forced along one direction or another.

What in the world are you talking about

> Instead we should advocate for the real solution, which is to demand the manufacturer drastically increase production -

Significantly increasing production for a temporary benefit is going to require significant investment. Since it is a temporary benefit, it's probably not worth that significant investment. Because eventually the demand will falter.

And yeah, the weight loss benefit is a temporary benefit. It may last a few years, but it fades. This is not a new drug class. The weight loss aspect to it is also not new (Saxenda, the weight loss variant of Victoza, released in 2014). Liraglutide was in trials for weight management when I started Victoza. That was a decade ago. I'm on Mounjaro now for glycemic management and it works great for that. But it's not doing anything for appetite, delayed gastric emptying, etc.

The diabetes and obesity versions are pharmacologically identical, the only difference is the name and price.

Off label prescribing is extremely common, to treat specific drugs as special in that regard is silly.

And dose. The doses are different. You need a much higher dose than is typically prescribed for diabetes to get the full weight loss benefits.

Part of getting approval for on-label use of these drugs is understanding this part of it.

>Mounjaro is not an obesity drug. It's a type 2 diabetes drug. Do not call it an obesity drug.

Mounjaro is a drug that causes weight loss. Is that better?

> Mounjaro is not an obesity drug. It's a type 2 diabetes drug. Do not call it an obesity drug.

It's in round 2 of phase 3 clinical testing as an obesity drug, and will probably have full approval this summer.

Tirzepatide is in testing. The weight loss variant will not be called Mounjaro. If they follow similar patterns from Novo Nordisk with Saxenda and Wegovy, dosing will be different for the weight loss variant, which means it won't carry the same label.

They're the same chemical.

The manufacturing process seems to be reasonably efficient. See "Kilogram-Scale GMP Manufacture of Tirzepatide Using a Hybrid SPPS/LPPS Approach with Continuous Manufacturing"[1] Yields are apparently good. There are drugs which require many processing steps with low yields at each step, and those really are expensive to make. But not this one, it seems. A kilogram of the stuff is about 100,000 to 200,000 doses, so this is not an inherently expensive material.

Patent expiration in 2036.

[1] https://pubs.acs.org/doi/10.1021/acs.oprd.1c00108

I feel like you're splitting hairs. The intended purpose of GLP-1 drugs is to improve A1C in existing diabetic patients. Weight loss is directly correlated with that, because if your body is properly expending glucose, then the excess will not be stored as fat, or sit around in your blood stream in the case of diabetics.

Do you even know what A1c is? Or how GLP-1 RA achieves this goal?

GLP-1 RA does NOT achieve a reduced A1c through weight loss. It achieves improved glycemic control by slowing the release of glucose into the blood as well as promoting increased production of insulin in response to glucose. The overall result is a reduction in blood glucose.

A1c is a measure of your glycemic health that spans around 90 days with heavier weight on more recent trends. It's like a longer blood glucose average measurement. There are actually algorithms that can calculate an estimate of your A1c based on blood glucose trends, which is referred to GMI (glucose management indicator).

The gastric effects leading to feeling full sooner and longer are a side effect and is what leads to weight loss. It also fades with time. Having been on various GLP-1 RAs over a decade, they don't provide this benefit to me anymore. Even with Mounjaro also being a GIP, it's just doing its primary job for me.

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