1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC419497/
Take a country like Singapore where obesity rates are low (11%) but type 2 diabetes rates are high (9%).
Compare that with the US with much higher obesity rates (40%+) but only slightly higher type 2 diabetes rates (11%).
Plenty of skinny fat older men in Singapore. Slightly overweight but it’s all visceral fat.
There are many GLP-1 agonists approved now. Some are approved for type-2 diabetes as one trade name, and may also be approved under another trade name at a higher dosage. For example, Lixisenatide came off-patent for diabetes in 2020 but it doesn't have an obesity formulation in the US. The various GLP-1 agonists have slightly different risk profiles of causing pancreatitis and/or thyroid cancers.
I don't know though maybe the freezing method (cryolipolysis) could potentially be useful for some people, but it's probably still too soon to characterize its long-term risks and other benefits.
Also, CagriSema (cagrilintide (long-acting amylin analogue) & semaglutide) is promising for obesity.
Maybe in the future there will be a temporary immunotherapy target to get the immune system to attack adipose cells but then terminate/unlearn before it gets too carried away.
If there is a legitimate hormonal imbalance or genetic defect, I get it. But short of that, are there not only two root causes left? Which in my opinion would be:
1) Poor diet, which includes poor quality in food supply
2) Poor choices being made, or made for people. This includes car-centric cities, sedentary lifestyle and similar well known ailments of modern life.
The root cause isn't being solved, only the adverse effects are temporarily inhibited so long as people continue to afford dependency on the pharmaceutical industry. How can any medical professional support this?
It is already so hard to trust American medicine; doctors having intimate financial relationships with pharma is already a public secret. This certainly doesn't help. They already ruined generations by blaming weight gain on fats instead of sugar because of these corrupt relationships with pharma and other corporate types. I don't doubt the efficacy of the medicine, but the disease is not fatness, it is the reason we get fat that needs to be solved. Rarely do shortcuts result in long term solutions. Why is this different? How do I know this won't expose us to higher cancer risks, new types of diseases like nutrition absorption disorders or becoming over dependent on these medicines and developing malnutrition?
I just don't get the lack of skepticism.
A friend of mine who works in primary care has a policy of not prescribing semaglutide unless a patient has tried at least three months of diet/exercise first. She now has a long list of patients who decide to screw that and self-refer to a specialist who'd write them the script. I don't work in primary care myself, but this more or less matches my own experience - 95% of people do not want to put in the effort of changing diet, exercise, and other lifestyle habits. They want a quick fix.
In the words of Ronnie Coleman, "Everybody wants to be a bodybuilder, but nobody wants to lift no heavy-ass weights."
So I really do think the popularity of semaglutide is a bottom up phenomenon. There is has been huge consumer demand for a weight loss drug for decades, and pharma is only now meeting that demand.
> doctors having intimate financial relationships with pharma is already a public secret
A small number of elite doctors have intimate relationships with pharma. The other 99% who are prescribing semaglutide do not profit from it. In fact, it's the other way around. You can't bill for the act of prescribing medications, but there are dedicated billing codes for counseling a patient on diet/lifestyle modification.
I lost a bunch of weight when I moved to Dublin and started walking everywhere. Then I moved to the Netherlands and lost even more, and got stronger. I didn't particularly try, I just lived somewhere where I used my own body to get around and the "normal" portion sizes were actually somewhat sane (a bag of Doritos here is maybe a third the size of one in the US).
I was 280 pounds when I lived in suburban California. I'm 180 pounds now.
Build bike lanes and public transport, put schools where kids can walk to them, and maybe don't sell a thousand calories of chips in a personal-sized and marketed bag, and it should get better.
As an added bonus you get a lot less air pollution (and noise pollution, etc.) and less people being run over!
If the genetic / hormonal explanation is right, it would mean the "effort" is not the same for everyone. So expecting people on the wrong side of the equation to not go for a solution to right the scales demonstrate a lack of empathy.
Would you call cochlear implants a quick fix for people who have problem hearing?
This ozempic study seems to suggest something similar.
Self-discipline is a noble concept, and probably important in the grand scheme of things, but sometimes medicine and technology outpaces what is naturally possible, which inevitably results in a moral backlash.
Well yes obviously that is difficult to do. Our society (American society, that is) is about “me” and convenience.
Nobody seems to want to say what is obvious to me: ban junk food. Sugary white bread, Cheez Its, Oreos, candy, ice cream, highly processed frozen burritos, frozen pizza, Little Debbie’s, potato chips , all of it.
It is crazy to me the C levels of poison food companies do not rot in jail for the rest of their lives for knowingly selling poison and lying about it. It is crazy to me how a group of people can conspire to harm the citizens of a nation in the name of profit and not receive any consequences. It’s crazy to me the governments of that nation actually enjoy it and don’t care.
The data however shows that diet and exercise fails for most people though. I don't see it as entirely irrational to go strait to the more effective drugs.
Many are unlucky to have unforgiving disorders.
This is easily seen in T2D which is mostly diet related and fixable.
This is untrue, you can stop taking the drug and the effects will persist, most people keep weight off after coming off the drugs.
I've assembled some stuff on this here:
https://glp1.guide/content/do-people-regain-all-the-weight-l...
There are anecdotal reports of astounding levels of hunger returning (more than before perhaps) but this can be solved by a more gradual wean-off (like the ramp up).
> I just don't get the lack of skepticism.
There has never been such a con-free, researched solution to weight loss (and originally these drugs were meant to treat type 2 diabetes, so it's more like we have a viagra situation on our hands).
Don't read what the media puts out, go back and read the research papers. It's not magic -- it's well researched, and while it's not clear exactly every effect, there is a growing body of evidence.
Hold up, how is impermanence such a black-mark when it's also true of everything else? Exercising must be continued indefinitely, or else the benefits fade, and the same is true of dieting.
Your post suggests that there is some kind of superior one-and-done weight-loss fix that is being overlooked or neglected, but I don't think we even have consensus on what this "root cause" is, and it's not clear why we should expect a perma-fix to be just around the corner.
Is the root problem "humans aren't calibrated for abundant food"? Is the single-event fix a form of gastric-restriction surgery? Genetic editing?
> I just don't get the lack of skepticism.
Simple answer is people like to eat, lack discipline, and want to look good. None of these will ever change, and so the economic pressure is immense and unstoppable. Until it's proven that these drugs have serious side effects (and that's a real possibility), people will gamble on the risk/reward.
I wouldn't touch them yet myself, but I can see it's a fait accompli. As for solving the root cause, doctors and policy makers have tried everything, to little or no avail. And so we're back to those 3 variables that won't change.
this is not the answer to the question they asked, just a useless triviality. They are not asking _why_ people would like this, it's obvious, they are asking how is this possible to continue eating garbage and living a bad lifestyle, and keep losing weight, and is it then still a health positive or not?
In June 2008, a phase II clinical trial began studying semaglutide, a once-weekly diabetes therapy as a longer-acting alternative to liraglutide
This is indeed a simple answer, and way over simplified. You can walk into any grocery store in the US and most of the floor space is dedicated to packaged poison and chemicals masquerading as food.
For someone who is 100+ pounds overweight, losing a big chunk of that has a whole set of knock on effects (lower appetite, ability to actually exercise without pain, more general energy, fewer depressive episodes, etc.), that help make permanent weight loss a lot more achievable. In addition, semaglutide can be tried before a doctor would normally do a gastric bypass (and probably makes that operation a lot easier even if it doesn't completely work).
And, before you go blaming everyone that their dietary choices are their own fault, do be aware that the total number of fat cells is highly conserved in the human body. In addition, fat cells "remember" the weight when they were created and only turn over at about 20-25% per year. If you were obese in adolescence and teenage years due to the habits your parents taught you, that can be really difficult to correct as an adult.
Sure, these kinds of drugs are wrong for losing those 20 pounds that you should remove via diet, some extra exercise and some lifestyle changes. Yeah, a lot of people are stupidly using these drugs from dumb reasons instead of what they should be using them for.
That doesn't make the drugs useless.
The body wants to maintain whatever weight it usually has, if you can keep that weight lower using drugs, there is absolutely a way to stop using the drug and keep the weight loss. You need lifestyle changes, of course, and that is something these GLP-1 agonists do for you. They make you not want to eat.
Ideally, we could allow everyone enough time off enough exercise, rest, and so on, to emulate what has shaped us for the first however many millennia, but we haven't.
Using a medication to compensate for that seems reasonable, provided we've accurately estimated it's negatives, etc...
2. Your argument boils down to "if there exists a traditional way to solve a problem then we should keep doing things the old way, even if the old way costs more time, energy, and money; for example it's better to use a sickle instead of combine harvester because combine harvesters are evil because they make people lazy" which is exactly how you avoid civilizational progress.
> Rarely do shortcuts result in long term solutions.
This sentence is so ridiculous it deserves a witty insult but the etiquette of this website stops me.
No.
Let me paraphrase the conversation I had with the head of obestity at one of Europe's leading research hospitals (top 5 in EU):
Once you get a certain amount of overweight, regardless of the cause, there are so many regulation systems in your body (at least 20 that we know of) which kick in to keep you overweight that it is not possible to diet and exercise your way back to a healthy weight without picking up a new disease (eating disorder, exercise additiction, etc.). The people who manage it spend the rest of their lives obsessively weighing everything they eat, exercizing every day, and even then if they slip up or lose mobility or something, inevitably they will become overweight again.
The only known medical treatment is operating on the stomach. This changes enough of the regulation systems (including the hormonal ones) that it has a reasonable chance of sticking. GLP-1 seems to offer a second option.
It continues to astonish me that eating disorders which result in weight loss are (correctly) accepted by society as diseases with complex causes which can include lifestyle and self-control but also mental health and innumerable other things, but if you're overweight clearly you are a sad sack of shit that just can't open their mouth without shoving food in it.
The legitimate hormonal imbalance and genetic defect is being human. Our brains and bodies were never intended to operate in a setting with a surplus of extremely nutritious food.
To me, it is clear that food can be extremely addictive, maybe even more so than traditional avenues of addiction like nicotine or alcohol. It's obvious that modern day foods are constructed in such a way to ensure this addiction.
They have appropriate amounts of fat, sodium, and sugar to give an immediate good feeling to people, as well as increase their dopamine for a while.
The reality is that the obesity epidemic is the primary killer in the first world. We have moved past the point where we can close our ears and yell "bootstraps! bootstraps!!!"
Clearly this is bigger, more complex, and more sinister than online armchair doctors will have you believe. Look around you. I see a society of sickness. Did everyone magically, at the same time, become lazy? Is everyone just stupid? I don't think so.
'No Way to Prevent This,' Says Only Nation Where This Regularly Happens.
First of all this is just blatantly disregarding the first order quality of life benefits, which is beyond inexcusable. The second chance at an elevated quality of life counts as legitimate rationale in and of itself. Even a 'season' of improved quality of life needs to matter to those of us who value health and life.
But secondly, as a consequence of the above, it can dramatically shift the odds of maintaining good habits in a positive direction. It's easier to initiate and sustain momentum from a position of strength, of enjoying a benefit that's already in hand, than it is to try and summon the extraordinary willpower necessary to initiate and power through a long-term health journey. I don't see any reason to force people to take path that except for a confused desire to impose pull-yourself-up-by-your-bootstraps moralizing.
Third, it appears to come with the benefit of moderating cravings for alcohol, which in and of itself is such a critical health benefit is that it could compensate for even quite serious side effects, if it had them.
Fourth, it does address significant root causes. Unlike a bariatric surgery or gastric sleeve, it is an intervention that impacts cravings and metabolic processes at their source. Different people are born with different exposures to the risks given our reward and addiction systems. Our relationships to those risks is not more or less healthy, more or less attestament to our self-control, many of us are getting those benefits for free and aren't truly challenged. Nor should we be. Whatever our initial state we didn't "earn" that and once again I think it's confused moralizing true require people to essentially rewire their reward systems out of a subjective belief that that's more pure path to self regulation.
Fifth, it is a medicine and medicines involve tradeoffs. Being qualified to prescribe medicines involves being trained to think coherently about a trade-offs. If you're not trained, then ignoring benefits and focusing on negatives might feel like it's some form of enlightened skepticism. But it's just as much malpractice to ignore the benefits of medicine as it would be to ignore negative side effects. Even it's necessary to maintain a lifelong relationship with the specific form of medicated intervention, that can be a net positive trade-off for long-term quality of life.
A number of other things you mention are pretty subjective. It's just as hard for me to diet and exercise when I'm BMI 19 or BMI 25. In fact, that's true for 90+% of people, because everyone almost universally rebounds to bad habits, in all studies. This "power through a long-term health journey" is your whole life, always, there is no start or stop to this until we die or give up, even with this pill. The pill may help with the BMI part, but it obscures the fact that there is still very real health damage from bad diet and bad lifestyle no matter what your BMI or even visceral fat is.
* the observable weight loss seems real based on reports - that's easy to measure, and harder to fabricate like "blaming fats" conspiracies of the past. Unless there is truly massive numbers falsification in all these studies, which i doubt. So that's kind of exciting.
* stuff like this article about visceral fat might also be true, so that's also easy to get excited about, and might even be true.
Major downsides are transparent and predictable - this is not magic, or willpower replacement for health, because:
* if you keep eating garbage, you will still suffer health damage despite losing weight. If I eat nothing but twinkies for a year, and this pill makes me feel full after two twinkies a day, I will lose weight, I will also kill my liver and suffer severe malnutrition - you are right! A less extreme, average American food will also produce health damage while losing weight on this pill.
* if you live a bad lifestyle while on this pill, you will still lose weight, but will damage your health exposing yourself to things like diabetes, CVD, etc.
* the big unknown for me - curious about that - do people develop tolerance for this pill? and another big one, do they rebound violently (much worse than usual) once they stop taking it after a while? or not. This is easier to cover up and harder to measure.
* other more subtle things like is there a link to higher cancer risks over time, etc, but the first two "cons" points are big enough for me already.
TLDR: this is a way to look better and soften some effects of obesity, but does not help with continuing health damage that still needs to be addressed in a more traditional way unfortunately. Lack of skepticism is not because the massive downsides are unknown or absent, but because apparently they are less of a concern to users+marketers.
It works in mice and probably works in humans but was not the main focus of the study so they didn't have a good control group to be able to prove it.
There's just been nothing so effective (and relatively side-effect free and cheap, believe it or not) up until now.
Note that the wider class of drugs are called GLP1 Receptor Agonists.
I've found a good vitamin a boosting skoncare regime and general face moisturiser application goes some way to noticeably reducing the flakiness and dryness.
(disclaimer: armchair logic)
The problem with your computation is that the body is not stupid, when you stop eating, it stops burning. I don't know the exact numbers, but it is absolutely not linear like that.
> Here, we present data from a proof-of-concept study on 30 individuals with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks.
They compared weight loss medication to a sleep apnea treatment and the weight loss medication group lost fat... which happens when your appetite is suppressed and you eat less - you lose some muscle and some fat, some of the fat you lose is visceral, some isn't.
I've been on the lookout personally for more negative side effects (it's almost suspicious how little there are, though it varies by person to person), but also excited to hear of benefits.
Some of the benefits recently led 23andMe to get into GLP1s:
https://glp1.guide/content/23andme-gets-into-glp1/
They even a paper on some possible benefits with Alzheimers, though I think the research is in it's infancy. I think the plastic story is a bit more compelling though.
I've got a rare one for you. "Realistic dreams"
It wouldn't matter the content of the dreams, (they weren't all bad); but every night my dreams were so vivid that I wouldn't be rested in the morning.
A caloric deficit leads to a loss of visceral fat. It wouldn't suprise me, if we see the same VAT activity if we had a control group with the same caloric deficit. Only then we could calculate the direct effect of GLP-1 to the VAT acitivity.
If the wealth of anecdotal experience isn't enough for you, read the published research and trials.
Source: https://www.fda.gov/news-events/press-announcements/fda-appr...
For what it's worth, it's also one of the only classes of weight loss drugs the FAA has felt was safe enough to approve for pilots to use. (The only other one being metformin, which has a much more modest effect.) They tend to be very picky about the safety profile of drugs that are used by aviators.
This is a big deal for folks in aviation, because until now there has been no other options available other than lifestyle modification - which is always preferable when it works, but statistically has an abysmal success rate.
So the safety profile has a different baseline risk.
If you're morbidly obese, and don't yet have diabetes, it's still so likely that you will develop it, and a host of other issues, that it's probably still better to lose weight with ozempic. Morbidly obese people also have an extremely shortened lifespan.
If you're only a little overweight and you're trying to get a lean physique. That's where you should really think if taking a risk is worth it.
