This is definitely a historic moment in US public health. Today we look at photos and marvel at how prevalent smoking was 50 years ago (in restaurants, in hospitals, in airplanes, etc.). 40 years from now people will look at photos from the last decade and be in disbelief at how widespread obesity was.
It also hopefully opens up the door to responsibly talk about how obesity will shorten your life significantly. There isn't a concept of "healthy obesity" when you look at your body's bloodwork. My buddy lost a friend who was only 38 due to complications from morbid obesity. It was tragic.
Cheap, effective interventions like this are incredible for our future populace.
Sadly that "healthy obesity" or HAES (Healthy At Every Size) people are very much against this or any kind of weight loss. It kind of undermines their whole movement.
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.
I'll note: HAES, at least initially, was about living a healthier lifestyle regardless of weight, especially recognising that without this latest batch of weight loss drugs, sustainable weight loss is incredibly difficult, and that weight loss in general can have some paradoxical effects such as increased appetite and lowered BMR.
This cannot be understated. Obesity is being changed from a willpower problem to a chronic disease that is treatable. The follow-on effects of this are huge.
It slows down gastric emptying as one of the primary ways it helps people feel full longer, so there a slew of possible GI side effects (nausea, constipation, diarrhea). In general they are manageable due to being able to adjust dosages to where patients still lose significant weight and minimize the impact of those side effects.
Possibly none. These drugs are bringing our appetite under control in an environmental that is full of readily available, appetizing, easy to digest, high-calorie foods.
Well... when we were like cave men and calories were hard to get, hunger pangs make more sense from an evolutionary standpoint.
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.
Should be noted: Basically nothing is a "willpower" problem, in reality. Psychological research is fairly clear on this: People who make good decisions are people who don't even consider the bad decisions, not people who have some higher level of "willpower."
All forms of contraception are also solving a "willpower problem". Food is even more of a basic need compared to sex, so evolution has it made it so that it's really hard to eat less.
Hunger is caused by not enough glucagen-like peptides (GLP-1, etc) being distributed to the brain from the gut. Obesity is not so much a food "addiction" as it is the body's failure to properly regulate it's own fullness.
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. :)
Fully agree with you. I think the unknown that still remains is why that noise is created. It must be related to modern food processing, besides the abundance of food.
I don't necessarily agree with that premise it's modern food processing.
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.
The amount of willpower required to maintain differs from person to person. So yes you can willpower your way to a healthy weight, but the amount of mental energy required is going to vary significantly between people. The drug proves it as it basically flips people with a high willpower requirement to feel more in the normal range where it is easier to eat less.
How? You give an obese person a pill and they shrink. They will go back to obese when they stop taking the pill and resume the diet and lifestyle that got them obese to begin with.
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.
What I do hope these drugs do, is offer people ways to get themselves into healthier lives. One of the things I hear/read all the time is how "people just need to stop eating bad" or some such.. it's practically your comment here.
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...).
> What we need is a radical change in the food we eat and how we live our lives.
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.
It seems obvious but the “just eat less” crowd needs to hear it.
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.
To fight off hunger while dieting, you eat lower calorie density, fiber-rich vegetables and unsaturated fats. Potatoes, avocados, legumes, there are a lot of options. They just don't fulfill the same psychological need that less healthy food does.
Free school breakfasts are a thing because kids will go home on Friday and not eat anything til Monday. The second hunger is no longer an issue, the kids perform much better.
There are quite a few veggies that are low calorie, filling, and are tasty enough to snack on without dip. The ones I eat when I just want to feel full without a bunch of calories are carrots (45 cal/100g), cucumbers (14 cal/100g), sugar snap peas ( 42 cal/100g), and yellow bell pepper (27 cal/100g).
I'm specifically talking about when you're hungry and want to eat, but your calorie budget is very small. Obviously you should still be eating an appropriate amount of protein over the course of a day.
Call it what you want but for some unlucky people when they run a deficit they completely shut down mentally. Their ability to lose weight is entirely dependent on how long they're able to avoid doing any mentally taxing activity.
The active ingredient, tirzepatide, isn't what's new here. It was patented in 2016 and has been on the market for treating type 2 diabetes since 2021.
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.
It should also be noted that during those original studies significant weight loss was observed, which is why doctor's were prescribing tirzepatide off-label.
Also just like Ozempic/Wegovy, Mounjaro is still indicated for type 2 diabetes. Zepbound will be the weight loss drug.
With these drugs, is there any mechanism at work beyond "patients have a lower appetite and eat less food"?
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?
GLP-1 affects a lot of systems beyond just appetite and gastric emptying. For instance it acts in the pancreas to promote insulin secretion. GLP-1 receptors are also found in a lot of other tissues, including heart, tongue, adipose, muscles, bones, kidneys, liver and lungs. The effects of GLP-1 in these tissues are an area of intense research.
> With these drugs, is there any mechanism at work beyond "patients have a lower appetite and eat less food"?
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.
- 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.
> 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?
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.
As I understand it, as the patents begin to expire, they suddenly discover that the old formulation has serious side effects that make it too dangerous to keep making.
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.
> 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.
>* 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.
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?
Why are other companies not jumping on this opportunity before 10 years?
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.
> Semaglutide is available in compounded form by pharmacies due to a shortage (without end in sight) being declared.
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.
Absolutely. My comment was more pertaining to patent's being partially suspended, which is not the same as generic fully regulated drugs being available.
I have illegally ordered generic pharmaceuticals from overseas and I will do it again. Sometimes the right answer to unreasonable market constraints is simply the black market. See also: recreational drugs, sex
This appears to be a GIP and GLP-1 agonist. Recently I read there might be some severe side effects with this class of med in diabetic and non-diabetic patients:
Lost 35 (I didn't start too high so this was all I needed), and actually side effects almost entirely positive. Stopped all smoking, better quality sleep, less immune system issues.
Has anybody here taken this category of drug, lost significant weight, and kept it off after dropping the drug?
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.
While personally I'd like to see a reduction in obesity rates by focusing on causes (e.g., "sugar taxes" and the like), it's hard to deny the positive impact of these drugs. Obesity is such a destructive epidemic in my country (US) that I see an argument for providing these drugs either for free or at substantially reduced costs via government subsidy. Despite vaccine skepticism, free COVID vaccinations might be a model worth following.
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).
While I agree on your points of the benefits, the one place who is not advocating for them is insurance. People switch insurance frequently, so there is no benefit to help this year what causes a significant disease to their customer in 10 years as that benefit will likely acrue to some other insurance company.
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.
"Semaglutide simulates a single hormone in the body, while tirzepatide [active ingredient in Zepbound] mimics two, which experts say may be why it’s often more effective at triggering weight loss."