Diabetes drug Mounjaro was available at $25/month, then increased to $1k/month
independent.co.uk
independent.co.uk
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.
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.
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.
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 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.
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 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.
I know multiple people < 150 lbs who have gotten scrips for it with no history of diabetes.
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.
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.
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.
Always amazing when an article is verified in real time
- 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.
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.
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.
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.
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?
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.
"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.
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.
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.
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.
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.
no, it doesn't. the amount it uses for basic operation and activity will change. shrinking in response to your attempts to lose weight.
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.
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.
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://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...
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.
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.
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/
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.
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.
Eating too much is literally what causes type 2 diabetes.
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.
These new generation of drugs (semaglutide, tirzapatide) deal with the signaling system (endocrine signaling, that is).
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.
That's just an extreme example. The real culprit is processed foods.
You don't know that.
It's like saying an overdose on heroin is simply someone doing too much heroin at a 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.
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.
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.
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.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.
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.
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".
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.
Just because you honestly reminded me of their need for overly complicated explanations of well understood things.
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.
> 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.
The coupon was changed because people were abusing it. This drug is approved for diabetes, not weight loss.
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.
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.
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.
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.
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.
Off label prescribing is extremely common, to treat specific drugs as special in that regard is silly.
Part of getting approval for on-label use of these drugs is understanding this part of it.
Mounjaro is a drug that causes weight loss. Is that better?
It's in round 2 of phase 3 clinical testing as an obesity drug, and will probably have full approval this summer.
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.
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.
These new weight loss medications are the solution to obesity. Imo this is one of the biggest medical advances of the century and at least in urban areas of wealthy countries, I don’t think we’ll see obese people anymore in 10 years.
The pharma companies realized they’ve got something truly revolutionary so they took the old tried and true drug dealer strategy. Get ‘em hooked for free/cheap and then bump the price to capture the value. Can’t say it’s surprising, they’re just following the incentives. And as the link goes through, these drugs have the potential to be worth many billions of dollars over their lifespan.
This is pretty much it. Zero side effects (other than the side effects from losing weight too fast, still have to pay attention to diet). We'll see if there's long term pancreatic/other issues down the line; but comparing risk against obesity, I still feel like I come out ahead on risk.
I expect to be taking some low level of a GLP/GIP/next-twincretin/next-tricretin forever. If I didn't now; I figure I'd keep running and dieting and meditating to steel my willpower; continue slighty overeating and slowly gaining fat and insulin resistance. And then I'd still end up taking a GLP/GIP years down the line after I finally developed T2DM.
I'd gladly spend $12k/year for the extra healthspan, and it seems many, many people are prepared to do the same.
If you have to do it anyway to have a long healthspan, and it generally has the side effect of assisting in controlling weight, then why lean on the costly drug?
Because it's man made and completely avoidable. Look at tobacco for example, it was the exact same thing until it wasn't because we woke up and decided to act on the issue
Helping currently obese people to get out of the loop is good, breaking the system we built that make more and more people obese would be better.
Also, being obese is only a part of the complications of eating shit and not exercising, the rest of the symptoms will catch up eventually, there are no magic pills
The system exists because people like it. I don't think it's possible to break it at this point considering how people normally react to having their life made worse. You can't stop people from eating what they want, but these drugs make it possible to change what they want.
You can certainly stop advertising junk food to kids, that would be a good start. You can also regulate things you know, like not having your entire daily sugar requirement in a single can of soda
Btw if you still eat the same garbage you'll still absolutely wreck your body, obese or not, you'll need a diabetes pill, a cardiovascular disease pill, a blood pressure pill, a kidney boosting pill, &c. You are what you eat, quite literally.
This will never happen in the US. I wouldn't mind, by anyone who votes for this would be dead in the water politically.
The main problem to my mind is that cheap, easy, accessible foods are high in both fat and carbs. Fat is satiating, but super calorie dense. Carbs are less calorie dense, but spike your blood sugar. After your blood sugar levels drop, your body signals that you're hungry again in spite of the fact that you've eaten plenty of calories. So now you're starving again and you've surpassed the number of calories you can reasonably utilize without storing it as fat. Add in the fact that evolution hasn't even begun to catch up with the current situation where calories are not a scarce resource (in the US and similar countries) and your body is screaming to eat while the eating's good. This causes you to comsume way too many calories and nowhere near enough vitamins and minerals.
It's a lot of work to eat right anymore. You're working 40 hours a week if you're lucky, you're exhausted and feel like shit and you may not even be able to afford what you need to be eating to maintain a healthy weight.
And, just to make things more fun, there's 1000 sources telling you 1000 different things about what you should and shouldn't eat to be healthy. Cholesterol is bad for you - wait, no it isn't. Eat whole grains. No, don't, that's sugar! Eat fruit. Oh no, fruit is basically all sugar. No it isn't, it's full of fiber and that cancels out the sugar. Don't eat fats, except unsaturated fats, but those are calorie dense. Vegetable oil is unsaturated, but that's bad for you too in a different way.
It's damn frustrating. If it were as easy as just eating less, no one would be obese. Back to the point of the article, however, I don't think it's as simple as taking a magic pill. How many miracle weight loss drugs have come and gone over the last decade? I'm not holding my breath that this is the one that will turn out to work forever with no severe downsides.
But people act like I have three heads when they ask me how I lost weight and I answer honestly. They just feel like it has to be a net negative somehow, that it’s not allowed that I eat prime ribeyes (just one, I’m not that hungry m) every night and lose weight.
A month ago I was throwing up every day and eating 5000+ calories per day. I hope I don’t go back this time.
Realistically, none. These are the only ones that have ever been found to actually work, everything else is either homeopathy or has terrible side effects. I agree that having food that tastes better is the main culprit for the obesity epidemic, but I don't think the answer is making tasty, addictive, food harder to access. Those foods are popular because people like them, they bring people happiness. It absolutely is a lot of work to eat right, but it doesn't have to be with these drugs.
As far as there being no severe side effects, it looks like semaglutide was looked at for medical use in 2012 and didn't go to clinical trials until 2016. Then there's tirzepatide, which I think is the part that's the big breakthrough recently, wasn't approved for use until the end of 2021. I don't believe we have the data yet to really say that it's safe long-term. I sure hope it is, but this is a very new treatment.
I wonder what the long-term health outcomes would be between two groups: one group that was obese the whole time, and another group whose obesity was delayed by ten years.
I suspect the latter group would end up having fewer negative health outcomes over the course of their life - 10 years of essentially “reduced wear and tear” on different systems in their bodies. That is to say - even if it’s a bandaid, it may still be really useful for public health.
Yep, that.
My understanding of this argument (which for the record, I'm loosely convinced is probably true, but probably isn't the only, and maybe not the main, factor) is that your body's hungry signal is it needs non-calorie nutrients, but our food is less nutrient dense so you get a lot more calories than your body is prepared to handle for a given quantity of nutrients.
Pharma companies arent allowed to have copay programs for off label use.
Promoting off-label use is why Pfizer was fined $3B. Its illegal.
This is just the next step in the ultimate dream, losing weight without putting in effort necessary. If you need to keep taking pills to keep your healthy weight, you're just suppressing symptoms of something bigger.
Making people chemically dependent on a drug to keep themselves healthy is optimising for the wrong solution. It's quick and easy but it mostly serves to keep insurance and drug company profits up.
I certainly believe that these drugs can be useful as a means of gaining an intermediate result (which can significantly reduce the immediate risk of many diseases) during treatment, but that's not how people treat them; people treat them as a magical fix for obesity and that's simply not healthy.
> Medicating obesity is like taking pills to make smoking healthy.
This is wrong though. Eating is not unhealthy. Overeating is. These drugs stop people from overeating.
It's not a measure of willing, it's about access to treatment that isn't a nice, quick, profitable pill that you end up hooked on.
This doesn’t seem worth it to me. I’m sure a lot of people would like to lose 25lbs but you’re making a deal with the devil to get it. It almost makes me think they design these drugs to make a recurring revenue stream instead of fixing the issue permanently.
I was put on Ozempic last year for a short amount of time. That, combined with changing of diet and starting an exercise routine, lead me to lose ~60 pounds in a relatively short amount of time (~8 months). I'm not taking the medication anymore and I did gain about 20 pounds back, but it's a lot easier going on a walk or run when you're carrying net 40 fewer pounds.
Willpower and discipline are simple things but they're not easy. In my opinion, it's important that the patient uses it as boost instead of a crutch and don't get too discouraged if/when they wean off and gain some weight back.
To be clear, I'm not intending to shame or throw shade at those who take or need the drugs, I just want to do all in my power avoid them as much as I can.
Other people just have a disorder, where they literally don't feel the full signals that normal people do, so they only feel "full" when their stomachs are stuffed to discomfort. These people are already consigned to a life of suffering, either from being obese or from constant hunger and an inability to have a normal relationship with food. In this case being on a medication for the rest of your life is the lesser of two evils.
If you take the perspective of someone who has struggled with weight loss in the past (especially if prior results were not great and had trouble keeping the weight off anyways) - it’s not so much of a deal with the devil, if the drug actually works.
I mean surely that can't be a 100% always the case, I would think it is either continue to take the medication or do a strenuous weight reduction program / eat less + exercise.
but why is that important, because some people might be so obese that they need to lose 25 lbs (maybe more, just following what was written) to get to a point where the exercise part of that equation is at all doable.
That would require a major cultural shift, we're far far away from that
This is one of the biggest things people with obesity struggle with. This is seen as a miracle cure for obesity because it doesn't require work, just a weekly injection and watch the weight melt off. But making lifestyle changes (changing eating habits, increasing activity, etc) is the most reliable way to make this a permanent fix.
But that's putting the patient to work and they don't want that.
Of course will power and environment changes can keep you at a lower weight but it's a constant struggle against your body.
Given that I can go for months without those "bad habits", but if I stop taking it they come back, I think they're more than habits. Habits break if you stop doing them for a while, these compulsions don't. Until I took this drug, I didn't know what it was like to be able to not constantly think about food and being hungry. I've been overweight for nearly my entire life since I was a breastfeeding baby, and this is the first time in my life that I don't feel like I'm being held hostage to my hunger.
I have lost weight and maintained a healthy weight for periods of time, but I'm just hungry the whole time and eventually the hunger starts beating my willpower.
For what it's worth I also have problems with anxiety. Similarly I tried years of therapy/mediation/mindfulness/etc. to get rid of my anxiety but it never went away until I took sertraline. Now, I live a pretty much anxiety-free life as long as I take a pill a day.
I probably need to see a therapist that can help with my eating habits, and this has highlighted that for me.
It's also interesting that they were designed to treat diabetes then we also discovered they reduce hunger. My guess is that we may have assumed the cause-effect relationship is more straightforward than it actually is.
I also want to see what happens if we take the people who criticise us for relying on a drug instead of willpower/mental conditioning, then give them a drug that does the opposite of these ones. My guess is they'll overeat and get fat. Much like animals do in animal studies. Ignoring your body constantly telling you to eat is almost impossibly hard over the long term.
Humans have a tendency to assume that we have much more free will than any kind of scientific evidence tends to show.
I've taken various GLP-1 RA over a decade for glycemic management (I'm on Mounjaro now). They still work great for this. But I have to do the work to maintain my body, now.
The real problem with using it as a weight loss is that it doesn't solve the underlying problem. Mounjaro makes it so that you can't eat. Eat too much and you get sick (seriously like 2 bites and you're done eating). Overeating is a psychological problem. The drug doesn't fix you wanting the food, it just makes it so that you can't eat it. Take the barrier away, and you're back to where you started.
Many would argue that drugs like this and Ozempic are showing that overeating is more of a hormone problem then a psychological problem.
While I’ve know some people experience more severe GI issues or nausea with the drug, this is quite the exaggeration. A drug that made it difficult or impossible to actually consume enough food to survive (more than “two bites”) would be wildly unsafe to prescribe.
The comment I was replying to was talking about Mounjaro, which is a weekly injectable - and thus no way to do it for only three days a week. In that context, if Mounjaro made it impossible to eat to the degree the commenter described, it would be wildly unsafe (because of how long each shot lasts).
Shouldn't it _eventually_ have a pavlovian effect where you associate all food with nausea?
There are side effects, especially initially with loose stool and some nausea, but generally they don't last. I'm sure they persist with some but that's effectively every medication. The goal isn't to change the relationship with food where it makes one physically ill when seeing or eating food
EDIT: My experience is with Ozempic, not Mounjaro. They may work differently
The Mounjaro patent appears to be until '39, with no generics available at the moment.
As one of the patients states in the article, obesity may very well lead them to diabetes. People will die. And with the shortage affecting current diabetics, they are dying now.
How scary! If only there was a reliable way for patients to prevent this disease :-(
I agree with your that's why you see many obese people in parts of the world with food shortages.
And the food industry, the real root cause of all of this
So we 1000% should deal with the amount of crap that's in our food but I don't think it'll be the cure-all that people expect.
> I eat pretty much nothing but garbage food -- pizza, wings, burgers, subs: just salt and grease. And I went from 220 to 120 and stayed there doing it
Fast forward 10 years later and you'll get a very concerning blood work result. (I don't wish it on you but the web is full of "fat/skinny/I only eat junk food and I was healthy until I hit 45 and discovered XYZ is 5 times over the recommended limit" stories)
Also you might have a damaged thyroid or other similar health issues, I know a few people coming from an industrial region known for pollution, they have more thyroid issues than the average, as a result they can eat 6+ times a day and much more calories than you'd expect while not packing a gram of fat.
Once your body is ravaged by years of junk food you're an addict in the medical sense of the term. When you give a soda that contains 2x the daily recommended amount of sugar to a kid because "it tastes good" you're sabotaging their future health.
They don't make the food taste good to make you enjoy good food, they make food addictive to make you keep consuming.
It tastes bad compared to junk food the same way caffein is bland compared to cocaine, ie. you have to be addicted and in denial to believe it
I would say properly cooked, fresh healthy food tastes better than junk food. But most people don't have time for that.
But again, if the best economical system of the galaxy in the richest country of the universe can't guarantee basic things such as feeding yourself properly I'd say you have quite a big problem
When do we start acting ? 50% obesity ? 75% ? It's already the top 1 cause of death (cardiovascular disease). What does it say about our society ? Looking at it from the outside makes it look like sabotage if not suicide, very few people profit from it, and in the long run everybody loses
When you factor in junk food marketing targeted to kids it starts to be a bit different. Then you add lobbies fighting to keep fast food in schools, the sugar industry, "fat makes you fat" and other clearly bs takes ...
What happened between the 50s and today that made < 12 year old obesity for from 5% to 20% ? https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6002a2.htm
Is it because 5 years old kids can't put the box of oreo down ? They must be stupid right ? Why can't they possess high level long term thinking ??? Don't they know about insulin resistance ? and calories ?
Sorry for that rant I am a bit traumatized by my experiences trying to do business in the US healthcare industry.
I also let my doctor know that I was extremely displeased about his referral to that facility when there were cheaper alternatives.
Maybe they can capture the $1000/mo market first and then offer something very similar to those who are interested at $100/mo. Or they have capacity constraints where they can't scale up manufacturing to supply everyone who would buy it at $100, but they can validate their process at the higher price first.
$25 was the patient support program for diabetes. That still exists.
The drug isnt approved for obesity, so they dont get access to the program. Its actually illegal for the company.
This is a case of the company stopping people from doing something they shouldnt have been doing in the first place.
Seems like a supply chain problem
That’s sure to make everything better for everyone.
Mounjaro Linux
We already force people to go to school and in some countries you have to join the military but after that we are free to never exercise again and stuff our face with any kind of food we want the year round. If we are financially successful we will never have to use our brain. Can get drunk and stoned every day.... wonderful? You can smoke, drink coffee and watch tiktok indefinetly... at least until any kind of challenge presents it self. Then ur fucked. Not very funny in a personal context but as a society or a culture things should get rather bizarre as we pile up more and more convenience. We already have to import people to do the work.
It seems cheap universal healthcare isn't as hard as it seems. Putting out a small fire and cleaning up is cheaper than letting the entire city burn down before doing anything.
I also hope we can agree that not everyone attains meaningful weight loss with just diet and exercise. The human body is incredibly complex, with a spectrum of natural compositions, metabolisms, etc. Your post dismissing these nuances risks being interpreted as “thin privilege” (my wife is a Dietitian and taught me the concept).
For what it’s worth, I’m against treating drugs like this as a first line of defense against obesity; it should be seen as the last step before bariatric surgery, and only used under the direction of a competent and ethical health professional.
This is easier for some people but not a solution for the general population.
Similarly, eating less is easier for some people while others are genetically or psychologically predisposed to eating more than they need.
Regardless, I am very happy to see that there are effective weight-loss treatments that will be available soon, because losing weight is incredibly hard, and it's been shown definitively at this point that something is causing most Americans to be fat (not just Americans anymore either), it negatively impacts their lives, and for one reason or another they are unable to lose the weight without help.
The fact that these drugs exist and work demonstrates the hormonal link that decades of research has shown is there.
Also, the prices of healthy food is much higher than the prices of unhealthy food thanks to subsidies and scale. But that's secondary to the fact that many people actually can't just "eat less" the way others can.
Let me give you an example of something that humans really can't do. "Humans can't breathe unassisted underwater". See the difference?
You could read about catabolism and metabolic suppression, or lupus, or lipedema, or just carry on, but please, don't be mean to people in real life.
Capitalism, ho!
(If you accept that obesity kills, reducing obesity saves everyone’s money and lives)
That seems like a ... strange argument.
If that is a very poorly phrased way of saying that reducing obesity will extend peoples' working lives, that's certainly true.
But otherwise, everyone dies in the end. Is it really that much more expensive to die as a middle aged overweight person than a healthy weight old person?
And those higher costs get socialized through insurance and taxes.
Supply chain issues
edit now the title here has changed, but it's still strange The Independent list that as the most important part. Guess it's normal click bait tactics.