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Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

independent.co.uk

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Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#251

Post by Dove »

HyperSane wrote: post #242
Dove wrote: post #187

Earlier quoted context omitted.

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…

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 se…

> 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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#252

Post by Animats »

bedast wrote: post #235
Animats wrote: post #214

Earlier quoted context omitted.

> 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

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#253

Post by Dove »

HyperSane wrote: post #242
Dove wrote: post #187

Earlier quoted context omitted.

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…

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 se…

>>"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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#254

Post by Dove »

nradov wrote: post #207
Dove wrote: post #187

Earlier quoted context omitted.

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…

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…

> 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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#255

Post by perfecthjrjth »

HyperSane wrote: post #209
perfecthjrjth wrote: post #188

Earlier quoted context omitted.

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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#256

Post by telotortium »

bedast wrote: post #232
fakedang wrote: post #223

Earlier quoted context omitted.

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 e…

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 an…

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

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#257

Post by Rury »

Retric wrote: post #224
Rury wrote: post #200

Earlier quoted context omitted.

You're entitled to find his or anyone's answer not interesting, but what he said is not a tautology. Just because it's obvious does not make it tautological. But in any case, the matter really is as simple as people eating too much nowadays. Evolutionary speaking, we didn't eat 3 meals every day, let alone all highly calorie packed ones. Food was also relatively quite scarce for much of civilization, until modern pre…

Our ancestors often had an abundance of food and ate quite a lot every day even if it was relatively more expensive. But, it’s harder to be obese and have by todays standards an extremely active lifestyle. Not only do you run into limits on the digestive system but carrying extra weight means spending more energy moving that weight around. The classic lumberjack breakfast is just an insane amount of food, but you did…

Our ancestors did not often have an abundance of food or eat a lot every day. Most Romans only ate 1 meal a day, and our evolutionary ancestors regularly faced days without food. Fatness was historically a signal of wealth. It was even rare to find someone fat as recent as the 1800s as you noted (and the reason had less to do with exercise than caloric intake). Really, the abundance of food didn't start happening until recent times with modern preservation techniques, industrial farming, and food processing (which also allowed for more calorie packed foods). The tractor wasn't even widespread until the 1910s, when it took 1.5 hours for horses to plow an acre of farmland. Nowadays it takes 5 minutes.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#258

Post by JaimeThompson »

finneganscat wrote: post #169
JaimeThompson wrote: post #154

Earlier quoted context omitted.

>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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#259

Post by HyperSane »

Dove wrote: post #253
HyperSane wrote: post #242

Earlier quoted context omitted.

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 se…

>>"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 ph…

"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.

Re: Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month

#260

Post by HyperSane »

Dove wrote: post #251
HyperSane wrote: post #242

Earlier quoted context omitted.

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 se…

> 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 adva…

" 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

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