FDA Approves Lilly's Zepbound (Tirzepatide) for Chronic Weight Management
investor.lilly.com
investor.lilly.com
Cheap, effective interventions like this are incredible for our future populace.
I want to point out, I disagree with the HAES people, you are not healthy at every size.. you're going to have some people who are more healthy than others regardless of some amount of weight... But not obesity, not that size.
Companies selling $500-$1,000/mo drugs to counteract the garbage food and "food products" other companies are producing and marketing to us.
But now, through farming technologies, food has never been more abundant. Yes we've saved people from dying of famine, but then the corn producers grew so much more corn that were beyond America's daily dietary need, they then could use much of it for HFCS, say. Or you know, Taco Bell's fourthmeal.
It's absolutely a willpower problem. These medications won't fix that for you. You stop taking them and you will gain weight again.
I've heard this called "food noise" by those who are obese. GLP-1 agonists reduce the so called food noise -- that's all it does.
In that light your argument is like trying to tell schizophrenics, "Hey, stop hearing those voices in your head!" I think we tried that for over a century.
I hit my 30's, and became a dad, I lost my ability to run as much as I did. Now a decade later that's changed. But in that time I gained a lot of weight. I started running again. I'm a distance type of runner so I'm talking 6-15km a day, 6-7 days a week.
With that out of the way. After doing that for 6 months I was wondering WHY am I not losing weight? Like basically nothing. I counted every calorie, kept myself in a caloric deficit, used a TDEE spreadsheet to keep readjusting my daily caloric needs. Nothing was working.
Went to the doctor, he did blood work, it was all pretty much normal for someone obese. He asked me how hungry I am. I said I'm constantly hungry and it's just willpower alone that keeps me from eating, unless I had a drink, so I usually refused to drink.
I was put on Ozempic/Wegovy.
Pretty much two weeks later, I stopped thinking about food. Gone. Just gone. Before I would wake, and I'd be planning every meal.. when, what. How much, etc. If anything got in the way of a meal, I would be super irate. I was counting down seconds... Every single thought in my head was food.
Now gone.
I sometimes forget to eat.
So yeah. Food noise is real, and it suuuucks.
Side note: the weight loss helped my running a lot! And the weight loss seems to have stalled... But I don't care. I'm just happy to have this extra energy from not thinking about food every second of every day. :)
The evolutionary human condition was primarily hunger. Animals fought over food. Humans fought, went to war over it. Nature has been that way for millions of years.
So now only in the past 100 years food has become abundant. Do you expect our evolution to change with it to be that quick too? That's really only 4 or 5 generations.
One data point here. In the 1700's, 1800's the rich were the ones that were fat, because they were the ones that had the abundance.
Different levels of anxiety, depression, focus, pain, sexuality. All that we can manipulate with medication, to bring within a range we find suitable.
So why can't ones inner experience of hunger be vastly different from someone else?
Eating right, exercising, taking this medication - if you stop any of these, yes, you will gain back weight.
I would happily continue to be on this med for the rest of my life, side effects and all.
What we need is a radical change in the food we eat and how we live our lives. It's easier than ever to not move all day. Sugar in one form or another is our primary diet. These problems won't go away.
The issue with that thinking is it's super black and white, that willpower alone is the cure to weight loss.
So let's do a little thought experiment , what about all those naturally thin people, like really thin.. they can eat what they want and remain thin, find it hard to put on muscle. If it's really really hard for them to gain weight... Then isn't the inverse also true? Aren't there also people who are trying to do everything they can but for similar get inverted reasons just cannot lose weight?
The problem with relying on willpower alone is there's a finite amount of it.
Yes, for some people they have terrible willpower, they have terrible diets, and they do not work out. But they aren't the only ones. There's definitely others who are trying but failing... And you can only fail for so long before you give up.
So going back to my first point. I hope these drugs enable a new option, to get them past a certain point where they can lose weight without the failure... Begin to make better choices... Gain more confidence and willpower.
My own mother struggled with her weight and opted for surgery at one point while I was in college. It did help her lose weight and keep it off. However, I honestly believe that surgery was a large factor in her death many years later. She was never the same after it. She lost the weight, but I would say she never obtained a healthy body and mind.
I don't say those things lightly. Surgery and other interventions are fine, but they shouldn't become our goto solution for these problems. There are absolutely other problems at play here. Willpower may be one of them, but the way food is mass produced and our usage of sugar additives seems to be a huge factor (we now have obese children...).
This lecture changed my mind on many arguments in this space: https://www.youtube.com/watch?v=dBnniua6-oM
That for sure would obviate the need for such pharmaceutical countermeasures, but achieving such radical change would be very difficult and time consuming. I'm glad we have some options to improve the quality and quantity of peoples lives while we work on that.
Dieting makes you hungry, truly revolutionary research.
Ever try working on a tricky coding project while starving? Take a math test when all you can think about is finding something, anything, to eat?
Losing significant amounts of weight the natural way isn’t so much a test of willpower as a test of how well you can function under a constant sense of hunger (or, how good you are at tricking your way out of it).
Bonus tip: when you are so hungry you can’t sleep and don’t want to drink a bunch of water right before bed, sugar-free jell-o has only 10 calories and can silence the feeling long enough to fall asleep.
If we're talking raw with no sauce I can't say there's any vegetable I'm keen to snack on, certainly none on your list.
https://www.reuters.com/business/healthcare-pharmaceuticals/...
https://www.nejm.org/doi/full/10.1056/nejmoa2107519
I think retatrutide might be the current leader for weight loss from clinical trials.
If I remember correctly, you lost the same amount of weight on retatrutide vs tirzepatide, but over a shorter time span.
What's new is that tirzepatide is now FDA approved for treatment of obesity, which will make it possible for insurance to cover it without a type 2 diabetes diagnosis.
Also just like Ozempic/Wegovy, Mounjaro is still indicated for type 2 diabetes. Zepbound will be the weight loss drug.
The doctor can certainly prescribe it though.
The various subreddits concerned with this certainly talk about whether or not insurance should be legally compelled to cover obesity.
Just to tack this on to "what's the gold standard", the gold standard is GLP-1 receptor agonists, and nothing before that has been anywhere near as effective without serious side effects. Things have basically been stimulants (phentermine, ephedrine), bulking agents (like fiber), things that mess with fat absorption (orlistat, which prevents it; olestra, which is a fat substitute), or treatments that reduce the active area of your stomach (bypass, stapling, sticking a balloon in your stomach). All are either ineffective or come with really bad side-effects.
GLP-1 receptor agonists are really the only game in town, like Viagra was when it came out. The evolution has basically been (as I understand it):
* Liraglutide / Victoza / Saxenda (works OK)
* Semaglutide / Ozempic / Wegovy (works well)
* Tirzepatide / Mounjaro / Zepbound (works great)
In each case, they've been a diabetic medication that turns out to be great at weight-loss.
Lilly has the so-called "Triple-G" shot in trials right now. Retartrutide shows even better weight loss potential than Tirzepatide
I've only read a few papers and articles but what I've seen is that all of the hormone triggering leads to 1) decreased appetite 2) slowed gastric emptying which also decreases appetite.
Patients lose weight due to eating less but usually regain the weight when stopping the drug since they then go back to their normal level of eating.
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Are these drugs fixing/replacing a system failure where people don't feel satiated normally?
Can the same effect be replicated by eating a higher fiber and higher fat diet with more whole foods to feel full longer and slow gastric emptying?
Those are definitely the key routes, but I suspect from my experience (and so the do the drug companies!) that there's some kind of mediation of reward system going on there too. Simply put: I no longer get a massive dopamine hit from sugary food. A candy bar still tastes great, but I don't immediately want to eat another one like I used to, even if I'm genuinely hungry. My addictive response to food is gone.
My favourite foods still taste great, I just no longer have to expend all of my energy in not having three portions.
> Can the same effect be replicated by eating a higher fiber and higher fat diet with more whole foods to feel full longer and slow gastric emptying?
No. Like many people who've been on a perpetual diet, I have tried -- at length -- virtually every style of eating known to man. The food noise always comes back. Even before I started, I was eating very healthily as a base-line, mostly vegetables, mostly vegan, mostly whole foods, tracking my fiber to make sure it was high. But I've also tried and sustained for many months keto, paleo, "slow carb", all sorts.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396640/
- Another study - there was a 16% weight loss for those that received semaglutide/diet/exercise/counseling versus a loss of 5% for placebo those that received diet/exercise/counseling without semaglutide.
But they didn't control for calories, so it may just be proving that dietary adherence with the medication is better than without.
I think it simply takes a long time for your body to adjust back to where it should be after a period of extended binging and these drugs make it happen much faster. The only time I consistently lost weight in my life was when I lived in a food desert and had no car and not much money, so I was forced to only buy the cheapest vegetables and meats (usually chicken) and make what I could out of that and make it last for the week. Even then it took more than 6 months before I felt normal eating that way.
Of course, it's extremely easy to fall off the wagon when your body works this way too. Even a day can wipe out weeks of gains and you can always 'relapse' even after months of doing the right thing, and end up stagnating or completely reversing any progress you've made. In a way it seems that food is the most addictive drug of all. You can easily quit alcohol, cigarettes, hard drugs with a couple weeks of willpower (and I have multiple times). You can't ever stop eating food if you want to be around to experience life.
And oh, by the way, we also happen to be introducing a very very very slightly different molecule that qualifies for a brand new patent. No side effects this time, we promise, and see you in 20 years.
Who is they?
> And oh, by the way, we also happen to be introducing a very very very slightly different molecule that qualifies for a brand new patent
Presuming “we” is the companies that own the current patent, what does this have to do with the older molecule’s patent that is expiring?
"Evergreening" is a very common practice among pharmaceutical companies. In its purest form, it looks like this:
* About 10 years after a drug has been approved, they will seek approval for a replacement version which is very similar, but different enough to qualify for a different patent.
* Then they have a few years to get everyone onto the new drug, claiming that the new one is safer, or more effective, or (in some cases) that the original one is horribly dangerous or has abuse potential which is somehow solved with the new drug[0].
* Around 15 years after the first drug was first approved, once enough people are on the second drug, they'll withdraw the first one from the market entirely, forcing everyone still using the first drug to switch to the second.
* Then, when the patent for the first drug expires (year 17), there's "no market" for it, because nobody is currently prescribed that drug, so no manufacturers will bother producing any generic versions of it.
Rinse and repeat.
[0] Heroin™ was one of the first examples of this: it was developed and marketed by Bayer as a "less addictive" version of morphine.
Why are other companies not jumping on this opportunity before 10 years?
>Then, when the patent for the first drug expires (year 17), there's "no market" for it, because nobody is currently prescribed that drug, so no manufacturers will bother producing any generic versions of it.
So the cost of educating consumers (marketing) is not offset by the difference in cost of selling the generic and the cost of selling the new patented version?
They do, when they can. But often they can't. A patent covers not just the molecule, but the treatment. Often, they would need to license the original patent even if they have the more advanced molecule, and they can't get the license.
So the cost of educating consumers (marketing) is not offset by the difference in cost of selling the generic and the cost of selling the new patented version?
Patients aren't really equipped to make this decision. It's made by doctors and by insurance companies. They are often reluctant to prescribe/pay for the "almost as good and a lot cheaper" drug, for fear of exposing themselves to risk. Generics manufacturers don't usually have the influence to convince them otherwise.
There's also the regulators. If the drug manufacturer can convince the regulator that the old drug is dangerous, they can simply forbid it.
That sounds crazy. How can someone patent the process of healing? What else could patenting the “treatment” mean? Are there any examples of this?
> Patients aren't really equipped to make this decision. It's made by doctors and by insurance companies. They are often reluctant to prescribe/pay for the "almost as good and a lot cheaper" drug, for fear of exposing themselves to risk.
Why would they have risk, if the government has already declared it legal to sell? Insurance companies and government are known to prefer cheaper, generic medicine, and a common complaint is insurance companies and government requiring prior authorization for brand name medications.
> There's also the regulators. If the drug manufacturer can convince the regulator that the old drug is dangerous, they can simply forbid it.
This would be pretty big corruption. Are there examples?
There's much less oversight over the production of compounded drugs, and people who purchase them may not be getting what they expect, with no way to tell the difference.
https://www.fda.gov/drugs/postmarket-drug-safety-information...
https://medicalxpress.com/news/2023-10-links-popular-weight-...
But its still pretty exciting.
I've lost 60+lbs with Mounjaro and never experienced any of the side effects listed.
I lost cravings for alcohol, sugars.
I was tired once jumping from 2.5->5, but we also have four kids, so..
These are my most recent blood work numbers. My A1C was 4.7
I'm at 55 lbs lost since July 1. No side effects at all.
Remember to eat, and you don't get gastroparesis.
It is a GLP-1 agonist as well and is considered a well-tolerated, long-term weight loss agent.
I've seen great success stories, but I'm kind of nervous of the long-term effects of taking a drug like this for your whole lifetime (i.e. what's implied by the "chronic" in "chronic weight management").
It seems like it might be a great off-ramp from obesity to a body weight where the risk of injury in exercise is greatly diminished and the degree of enjoyment in exercise goes way up. If you could go off the drug and then use exercise to maintain the caloric deficit (instead of under-eating, as the drug induces you to do), that sounds like it would be kind of miraculous.
Exercise is great for dozens of reasons, but weight loss is probably at the bottom of the list (if it's on the list at all). The asymmetry between the ease of consuming calories and the effort of exhaling calories during exercise is too great.
I, and many many other overweight people, have successfully lost a lot of weight in the past. There's no off-ramp when you look at the data, you always gain it back.
Mounjaro is no different from any other way of losing weight in that respect, except it doesn't rely on willpower, so you can keep taking it, and keep the weight off.
If the public sector doesn't help, I imagine that insurance companies are doing what they can to put downward price pressure on these drugs. If I can pay x now to avoid 10x in payout costs to medical providers for obesity complications (while keeping rates the same), I'm going to take that trade (subject to actuarial data and discount rates).
The insurance companies basically think 1 year at a time for drug coverage and only care about keeping you alive for that 1 year at the cheapest possible price. Long term care and planning is something medicare/medicaid may better be able to utilize in their economic model to justify coverage.
The weight loss number surpass that of semaglutide alone. https://www.nejm.org/doi/full/10.1056/nejmoa2107519
From: https://www.nytimes.com/2023/11/08/well/zepbound-mounjaro-we...