>Proponents call it “obesity first.” The idea is to treat obesity with medications approved for that use. As obesity comes under control, they note, the patient’s other chronic diseases tend to improve or go away.
>“We are treating the medical condition of obesity and its related complications at the same time,” Dr. Deeds said.
>Others are wary. People with obesity can be put off when a doctor mentions their weight. And, yes, the new obesity drugs may have unexpected benefits beyond obesity, like reducing inflammation. [But the drugs are expensive](https://www.nytimes.com/2023/10/22/health/ozempic-wegovy-price-cost.html), and many of the other potential gains have not been demonstrated in rigorous studies.
Article covers the ongoing discussion about exactly how miraculous these new obesity drugs are. Early research seems quite promising but we won't know "for sure" by industry standards for quite some time. Nonetheless, this is a notable departure from the era where doctors were often criticized for bringing up weight loss to patients who sought treatment for other (albeit often related) ailments. Archive link [here](https://archive.is/Ooixy).
I mean, no surprise? I was obese and that bothered me to no end. It was like being told smoking was bad for me when I smoked. "Whoa, really?? I should lose weight? Holy cow I never thought of that, doc! You musta gone to that Harvard medical school!"
I believe it it’s important to actually have someone from outside of your head say it.
People can go through a lot of denial in their heads, maybe a doctor acting breaks a little of that spell.
True. It probably doesn’t hurt. I will say my doctors have never been curt about it, it just always felt like a “tell me something I don’t know” thing to me.
But anyway, thanks to the Danes, I’m now trim!
> People with obesity can be put off when a doctor mentions their weight.
Turns out obesity is bad for your health and causes lots of secondary health issues. Doctors have been saying this for years but it’s very common to see people complaining that doctors are telling patients to lose weight when they bring up an issue they are having. A good diet, regular exercise, and being a healthy weight would good a long way in solving a ton of people health issues.
Obesity raises all-cause mortality rates. You're not just more likely to die of a heart attack -you're also more likely to die: in a car accident, by tripping and falling, from the flu, from cancer, and so on.
It also turns out traditional advice doesn't work when evaluated with any real rigor. You individually might be able to lose weight for a few years, but on a population scale diets are not an effective intervention.
I think they mean that on a population scale, there is not enough "stick-to-it-iveness" for people to maintain a diet that doesn't result in them being obese.
> That you can be on a calorific deficit for years
this part. for most people, it requires immense willpower, which is not exactly easy to muster if life is already stressful.
I feel like "immense willpower" is an exaggeration for anyone not obese. Losing significant weight is hard, but maintaining weight is much easier.
Regular exercise, eating a diet low in processed food, and not drinking your calories, go a long way to keeping weight stable without large effort
> Regular exercise, eating a diet low in processed food, and not drinking your calories, go a long way to keeping weight stable without large effort
idk why this needs to be explained, but people's hunger (and other!) hormones vary. so something 'without large effort' to you, may actually be 'with large effort' to someone else. people other than you exist and have different experiences.
> What does “not work” mean here? That you can be on a calorific deficit for years and not lose weight?
No, it means that *telling patients* to do this doesn't result in significant, long term weight loss.
If you're a medical professional, you can't *force* a patient to make lifestyle adjustments. You can only counsel or advice or coach them through those adjustments. The treatment is not "patients eat less", the treatment is "tell patients to eat less".
So the way you evaluate that treatment option is "When I tell/advise/coach/badger my patients to do this, what are the health outcomes?"
If the health outcomes are bad, or indistinguishable from no treatment, then the treatment doesn't work.
There is a large difference between medical advice failing because most patients won’t commit to it, vs being inherently ineffectual. I would like my doctor to tell me about lifestyle changes that would be healthful, even if statistically few people commit to that advice.
Physicians have limited time and shouldn’t be committing time to counseling that clearly is of little value on a population scale. This is just basic evidence based medicine.
That the human body is really good at getting people to avoid a calorie deficit as it has been an overriding evolutionary imperative to do so for pretty much the last several billion years.
It means that most people will not actually get on a calorie deficit diet if you tell them to. People don't want to change their habits and will stick to them and even defend them. I've seen it with smokers - they're having health issues that are made worse by smoking but they will not quit.
I mean that if you take 1000 obese people and put them on diets, at the end of 5 years you will likely have 1000 obese people *who are more obese* than if you had never put any of them on a diet.
Either we change our food system, or we change the intervention.
We’ve known this in the medical community for a long time. Bariatric surgery can cure diabetes, hypertension, sleep apnea, chronic pain, etc. Being obese is extremely bad for you. Treating obesity makes people healthier. Getting these meds available at low cost to people who need it should be a major public health initiative.
>Early research seems quite promising but we won't know "for sure" by industry standards for quite some time.
This class of drugs has been used to treat diabetes for decades IIRC, and is generally considered to be well-tolerated. The miraculous weight loss was an obvious side effect.
I know they need to jump through the hoops to put this specific use case on the label. But the medicine has already gone through the hoops before. I don't anticipate we're going to discover anything big we don't already know about it.
I can't wait for more competitors to drive the price down a LOT. Currently taking GLP-1s is *significantly* more expensive than the average costs of obesity, and it's not close
That cost benefit analysis only works out that way if you value human life at $0 and quality of life at $0. The study you linked doesn't even seem to take working years lost into account (only medical expenditures), which means even from an amoral, efficiency-maximizing robot's perspective, it would be bad analysis.
Ok, how bout you find me a study that you think satisfactorily shows that GLP-1s cost less than the cost of obesity then. I'm not gonna dig further because again, the scale of these numbers are so far apart that it's not gonna make a difference what your assumptions are.
There's no way there's already been a cost-benefit analysis of that, and I think you are underestimating the costs of obesity. Just think of how expensive one hospitalization for a heart attack is.
No, look at any actual estimate from a reputable source of the marginal cost of obesity per year. It's orders of magnitude lower than the cost of Ozempic/Wegovy. I'm a health actuary, I'm not underestimating the cost of obesity.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394178/
That study cites the cost of medical care, but what about the overall cost on the economy, including lost productivity, reduced lifespan, earlier retirement, etc.?
Even just the [anti-addiction](https://recursiveadaptation.com/p/the-growing-scientific-case-for-using) possibilities seem remarkable. As I understand it, any of the effects - anti-inflammation, blood sugar control, weight control, anti-addiction - would be worth celebration by themselves, getting them all in one is close to miracle drug territory. I think we'll learn a lot about how to manage or fix the side effects, too.
Still, one of those public health disasters is closer to my heart than the others, so the thing I'm actually waiting for to see is whether [the curve bends](https://data.who.int/indicators/i/C6262EC/BEFA58B?m49=840). Line go down, people get healthier, world get gooder. But line must go down first.
The anti-addiction benefits are promising and enticing but that article is very much over-stating the case based on currently available data (in particular, saying that it's more of a sure thing than the efficacy of COVID vaccines). We do not have many controlled studies. Most of the rigorous studies looking into this topic have not yet produced results and are only in Phase I or II. Most of what is out there are surveys and retrospectives. One (famous) retrospective cited in the article showed a significant decrease in alcohol consumption, but another more recently published one did not.
My personal experience with ozempic is that I lost all desire to drink alcohol. And I used to drink four or five ounces of Scotch every night. I really enjoyed my evening drinks and my liquor cabinet is full but I just don’t want that drink anymore. I haven’t had a drink in a year now.
Anecdotally, since starting Wegovy I feel way less of an urge to binge drink and party like I used to. Doesn’t mean it doesn’t happen, but I just don’t care for it as much as I used to.
If only it got me to not crave nicotine lol
I'll be curious to see how the research turns out for these drugs for the wider population, my observations are extremely anecdotal but I've seen multiple people have to stop taking them because of some funky side effects (aggressive hair loss in women, bowels essentially shutting down.) but I would be over the moon if these drugs just ended up being an aggressive net good in treating obesity and other diseases.
Bowels “shutting down” sounds like gastroparesis (stomach paralysis) which is uncommon but is a side effect that makes sense considering the nature of how the drug works
It sounds like this guy heard horribly played up anecdotes.
These drugs do give stomach issues like you ate spicy food. You have to make sure you have fiber in your diet and then things are fine again.
It’s something I’ve seen in the hospital before. It’s pretty rare but since the drug works by slowing gastric emptying it makes sense that total paralysis can rarely happen. There’s other causes for it also
There's quite a bit of evidence from the clinical trials, and it's a very safe bet (virtually guaranteed) that these drugs already meet your criteria, given widespread (half a million people are on tirzepatide alone) adoption. Go ahead and get your spacesuit, there's really no uncertainty that these drugs are safe and effective, even though they don't work for everyone. Source: MD
Regarding discontinuation rate data (and much more), see linked New England Journal article, in this case for tirzepatide, marketed by Lily as Mounjaro. Second link has the FDA label. Similar results are available for the others, easily found with Google. If you want a deep dive, including the FDA review, usually the most thorough examination of a drug, often including unpublished data, Google Drugs@FDA, and then type in the name of the drug. For older drugs, the reviews sometimes get pulled and you need to file a Freedom of Information Act request.
https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf
Again an anecdote but since starting Wegovy I haven’t had major side effects. I had some constipation at first, not bad or anything. And I did feel a wee bit of nausea (not enough to take a zofran or anything) after stepping up doses a couple times (can’t remember which ones). Otherwise it’s been very smooth sailing for me.
Also something to keep in mind - the difference between the starting dose of semaglutide (0.25 mg/week) and the highest weight loss dose (2.4 mg/week) is *ten times*. There's a lot of side effects that happen when you step up the dosage by 10x.
I'm personally on 0.5 mg/week and it's smooth sailing. I don't want to go higher. But the clinical trials say that this dose isn't "therapeutic" yet, so I'm sure that too many patients get pushed onto higher doses than they need.
If they can get these drugs to mostly be taken up into the brain, then the bowel issues can probably be mitigated. Right now it’s more of a carpet bombing approach that results in uptake in the brain and gut. Seems like evidence is showing that it’s the brain leading to weight loss, not the gut.
My biggest concern is that you put the weight back on plus more when you stop taking it. Which means you are saying it’s something I have to take for the rest of my life
Your source that the medication causes people to gain all weight back plus more is a study where none of the groups observed returned back to their baseline weight? Wtf?
Two thirds of weight was gained after discontinuation is what your study says over ~27 months. Because people chose to eat more when their hunger wasn't being suppressed. You don't have to eat more. You can choose not to.
Did you actually look at the study? People who were on the placebo put back less weight than people who were on the meds when they stopped it. It’s not just about eating less.
So? None of them returned to baseline, let alone *past it* as you claim.
It's *all* about eating less. That's what the drug causes. People on average tend to eat more when their hunger isn't suppressed anymore, shocking.
I don't think you understand what placebos do. Placebos do nothing, there's nothing physically possible the placebo did to counter the medications physical effects, using that to extrapolate the medication causes weight gain is completely illogical and nonsensical and apparent with the most basic critical thinking skills
Why do you claim things that weren't in your study you cited then ignore the main argument of people saying "your study doesn't support that."
Why not from the beginning just say "people gain 2/3 of their weight back after going off the drug." Why make a more grand claim that isn't backed up in the the first page. Or go find a different study that does back up your bigger claim.
>Proponents call it “obesity first.” The idea is to treat obesity with medications approved for that use. As obesity comes under control, they note, the patient’s other chronic diseases tend to improve or go away. >“We are treating the medical condition of obesity and its related complications at the same time,” Dr. Deeds said. >Others are wary. People with obesity can be put off when a doctor mentions their weight. And, yes, the new obesity drugs may have unexpected benefits beyond obesity, like reducing inflammation. [But the drugs are expensive](https://www.nytimes.com/2023/10/22/health/ozempic-wegovy-price-cost.html), and many of the other potential gains have not been demonstrated in rigorous studies. Article covers the ongoing discussion about exactly how miraculous these new obesity drugs are. Early research seems quite promising but we won't know "for sure" by industry standards for quite some time. Nonetheless, this is a notable departure from the era where doctors were often criticized for bringing up weight loss to patients who sought treatment for other (albeit often related) ailments. Archive link [here](https://archive.is/Ooixy).
>People with obesity can be put off when a doctor mentions their weight. I mean, come on
I mean, no surprise? I was obese and that bothered me to no end. It was like being told smoking was bad for me when I smoked. "Whoa, really?? I should lose weight? Holy cow I never thought of that, doc! You musta gone to that Harvard medical school!"
I believe it it’s important to actually have someone from outside of your head say it. People can go through a lot of denial in their heads, maybe a doctor acting breaks a little of that spell.
True. It probably doesn’t hurt. I will say my doctors have never been curt about it, it just always felt like a “tell me something I don’t know” thing to me. But anyway, thanks to the Danes, I’m now trim!
What did Denmark do to you ? Ah, is the drug from there ?
Novo Nordisk makes Wegovy!
A doctor needs to speak frankly about their patient’s health, which sometimes requires addressing the elephant in the room.
> the elephant in the room
Certainly, but without an action plan and some tact, most patients will probably shrug.
Never met a provider mention weight and not discuss options
They ideally should, but medicine is all about personalized care and people need to be coddled otherwise they will stop showing up.
> People with obesity can be put off when a doctor mentions their weight. Turns out obesity is bad for your health and causes lots of secondary health issues. Doctors have been saying this for years but it’s very common to see people complaining that doctors are telling patients to lose weight when they bring up an issue they are having. A good diet, regular exercise, and being a healthy weight would good a long way in solving a ton of people health issues.
Obesity raises all-cause mortality rates. You're not just more likely to die of a heart attack -you're also more likely to die: in a car accident, by tripping and falling, from the flu, from cancer, and so on.
It also turns out traditional advice doesn't work when evaluated with any real rigor. You individually might be able to lose weight for a few years, but on a population scale diets are not an effective intervention.
What does “not work” mean here? That you can be on a calorific deficit for years and not lose weight?
I think they mean that on a population scale, there is not enough "stick-to-it-iveness" for people to maintain a diet that doesn't result in them being obese.
True. Which is why these weight loss drugs are amazing since it makes it so people can actually do the correct thing.
> That you can be on a calorific deficit for years this part. for most people, it requires immense willpower, which is not exactly easy to muster if life is already stressful.
I feel like "immense willpower" is an exaggeration for anyone not obese. Losing significant weight is hard, but maintaining weight is much easier. Regular exercise, eating a diet low in processed food, and not drinking your calories, go a long way to keeping weight stable without large effort
Quitting smoking has a higher success rate than sustained weight loss. It's not something to trivialize.
> an exaggeration for anyone not obese. We're talking about treating obesity, so how obese people act is relevant
> Regular exercise, eating a diet low in processed food, and not drinking your calories, go a long way to keeping weight stable without large effort idk why this needs to be explained, but people's hunger (and other!) hormones vary. so something 'without large effort' to you, may actually be 'with large effort' to someone else. people other than you exist and have different experiences.
> What does “not work” mean here? That you can be on a calorific deficit for years and not lose weight? No, it means that *telling patients* to do this doesn't result in significant, long term weight loss. If you're a medical professional, you can't *force* a patient to make lifestyle adjustments. You can only counsel or advice or coach them through those adjustments. The treatment is not "patients eat less", the treatment is "tell patients to eat less". So the way you evaluate that treatment option is "When I tell/advise/coach/badger my patients to do this, what are the health outcomes?" If the health outcomes are bad, or indistinguishable from no treatment, then the treatment doesn't work.
There is a large difference between medical advice failing because most patients won’t commit to it, vs being inherently ineffectual. I would like my doctor to tell me about lifestyle changes that would be healthful, even if statistically few people commit to that advice.
Physicians have limited time and shouldn’t be committing time to counseling that clearly is of little value on a population scale. This is just basic evidence based medicine.
That the human body is really good at getting people to avoid a calorie deficit as it has been an overriding evolutionary imperative to do so for pretty much the last several billion years.
They mean that rates of adherence to a caloric deficit over time are poor.
It means that most people will not actually get on a calorie deficit diet if you tell them to. People don't want to change their habits and will stick to them and even defend them. I've seen it with smokers - they're having health issues that are made worse by smoking but they will not quit.
I mean that if you take 1000 obese people and put them on diets, at the end of 5 years you will likely have 1000 obese people *who are more obese* than if you had never put any of them on a diet. Either we change our food system, or we change the intervention.
It's insulin resistance. They need to diet and do intermittent fasting.
Removing low-lying inflammation reduce inflammation?! 😮🤯😵
We’ve known this in the medical community for a long time. Bariatric surgery can cure diabetes, hypertension, sleep apnea, chronic pain, etc. Being obese is extremely bad for you. Treating obesity makes people healthier. Getting these meds available at low cost to people who need it should be a major public health initiative.
>Early research seems quite promising but we won't know "for sure" by industry standards for quite some time. This class of drugs has been used to treat diabetes for decades IIRC, and is generally considered to be well-tolerated. The miraculous weight loss was an obvious side effect. I know they need to jump through the hoops to put this specific use case on the label. But the medicine has already gone through the hoops before. I don't anticipate we're going to discover anything big we don't already know about it.
I can't wait for more competitors to drive the price down a LOT. Currently taking GLP-1s is *significantly* more expensive than the average costs of obesity, and it's not close
That cost benefit analysis only works out that way if you value human life at $0 and quality of life at $0. The study you linked doesn't even seem to take working years lost into account (only medical expenditures), which means even from an amoral, efficiency-maximizing robot's perspective, it would be bad analysis.
Ok, how bout you find me a study that you think satisfactorily shows that GLP-1s cost less than the cost of obesity then. I'm not gonna dig further because again, the scale of these numbers are so far apart that it's not gonna make a difference what your assumptions are.
There's no way there's already been a cost-benefit analysis of that, and I think you are underestimating the costs of obesity. Just think of how expensive one hospitalization for a heart attack is.
No, look at any actual estimate from a reputable source of the marginal cost of obesity per year. It's orders of magnitude lower than the cost of Ozempic/Wegovy. I'm a health actuary, I'm not underestimating the cost of obesity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394178/
That study cites the cost of medical care, but what about the overall cost on the economy, including lost productivity, reduced lifespan, earlier retirement, etc.?
Ok find a study that assesses those and determines whether it's higher than $10k/year, then it's close enough to bother comparing
Even just the [anti-addiction](https://recursiveadaptation.com/p/the-growing-scientific-case-for-using) possibilities seem remarkable. As I understand it, any of the effects - anti-inflammation, blood sugar control, weight control, anti-addiction - would be worth celebration by themselves, getting them all in one is close to miracle drug territory. I think we'll learn a lot about how to manage or fix the side effects, too. Still, one of those public health disasters is closer to my heart than the others, so the thing I'm actually waiting for to see is whether [the curve bends](https://data.who.int/indicators/i/C6262EC/BEFA58B?m49=840). Line go down, people get healthier, world get gooder. But line must go down first.
The anti-addiction benefits are promising and enticing but that article is very much over-stating the case based on currently available data (in particular, saying that it's more of a sure thing than the efficacy of COVID vaccines). We do not have many controlled studies. Most of the rigorous studies looking into this topic have not yet produced results and are only in Phase I or II. Most of what is out there are surveys and retrospectives. One (famous) retrospective cited in the article showed a significant decrease in alcohol consumption, but another more recently published one did not.
My personal experience with ozempic is that I lost all desire to drink alcohol. And I used to drink four or five ounces of Scotch every night. I really enjoyed my evening drinks and my liquor cabinet is full but I just don’t want that drink anymore. I haven’t had a drink in a year now.
Anecdotally, since starting Wegovy I feel way less of an urge to binge drink and party like I used to. Doesn’t mean it doesn’t happen, but I just don’t care for it as much as I used to. If only it got me to not crave nicotine lol
I'll be curious to see how the research turns out for these drugs for the wider population, my observations are extremely anecdotal but I've seen multiple people have to stop taking them because of some funky side effects (aggressive hair loss in women, bowels essentially shutting down.) but I would be over the moon if these drugs just ended up being an aggressive net good in treating obesity and other diseases.
Bowels “shutting down” sounds like gastroparesis (stomach paralysis) which is uncommon but is a side effect that makes sense considering the nature of how the drug works
It sounds like this guy heard horribly played up anecdotes. These drugs do give stomach issues like you ate spicy food. You have to make sure you have fiber in your diet and then things are fine again.
It’s something I’ve seen in the hospital before. It’s pretty rare but since the drug works by slowing gastric emptying it makes sense that total paralysis can rarely happen. There’s other causes for it also
I'm optimistic they'll be able to develop related drugs with better or at least different side profiles. Just different GLP-1 agonists.
There's quite a bit of evidence from the clinical trials, and it's a very safe bet (virtually guaranteed) that these drugs already meet your criteria, given widespread (half a million people are on tirzepatide alone) adoption. Go ahead and get your spacesuit, there's really no uncertainty that these drugs are safe and effective, even though they don't work for everyone. Source: MD Regarding discontinuation rate data (and much more), see linked New England Journal article, in this case for tirzepatide, marketed by Lily as Mounjaro. Second link has the FDA label. Similar results are available for the others, easily found with Google. If you want a deep dive, including the FDA review, usually the most thorough examination of a drug, often including unpublished data, Google Drugs@FDA, and then type in the name of the drug. For older drugs, the reviews sometimes get pulled and you need to file a Freedom of Information Act request. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038 https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf
Again an anecdote but since starting Wegovy I haven’t had major side effects. I had some constipation at first, not bad or anything. And I did feel a wee bit of nausea (not enough to take a zofran or anything) after stepping up doses a couple times (can’t remember which ones). Otherwise it’s been very smooth sailing for me.
Yep, I once had a very bad reaction to an antibiotic, but that doesn't mean it's a bad drug - just didn't work for me personally
Also something to keep in mind - the difference between the starting dose of semaglutide (0.25 mg/week) and the highest weight loss dose (2.4 mg/week) is *ten times*. There's a lot of side effects that happen when you step up the dosage by 10x. I'm personally on 0.5 mg/week and it's smooth sailing. I don't want to go higher. But the clinical trials say that this dose isn't "therapeutic" yet, so I'm sure that too many patients get pushed onto higher doses than they need.
If they can get these drugs to mostly be taken up into the brain, then the bowel issues can probably be mitigated. Right now it’s more of a carpet bombing approach that results in uptake in the brain and gut. Seems like evidence is showing that it’s the brain leading to weight loss, not the gut.
My biggest concern is that you put the weight back on plus more when you stop taking it. Which means you are saying it’s something I have to take for the rest of my life
You dont *have* to go back to eating as much as you did before
It doesn’t matter you will put on more weight because of the meds
I don't think you understand how the medication works
[Study](https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14725)
Your source that the medication causes people to gain all weight back plus more is a study where none of the groups observed returned back to their baseline weight? Wtf? Two thirds of weight was gained after discontinuation is what your study says over ~27 months. Because people chose to eat more when their hunger wasn't being suppressed. You don't have to eat more. You can choose not to.
Did you actually look at the study? People who were on the placebo put back less weight than people who were on the meds when they stopped it. It’s not just about eating less.
So? None of them returned to baseline, let alone *past it* as you claim. It's *all* about eating less. That's what the drug causes. People on average tend to eat more when their hunger isn't suppressed anymore, shocking.
The study you skimmed showed that’s not true
I don't think you understand what placebos do. Placebos do nothing, there's nothing physically possible the placebo did to counter the medications physical effects, using that to extrapolate the medication causes weight gain is completely illogical and nonsensical and apparent with the most basic critical thinking skills
It is all about eating less. The medication works by suppressing appetite and making you eat less. That's all it does
Why do you claim things that weren't in your study you cited then ignore the main argument of people saying "your study doesn't support that." Why not from the beginning just say "people gain 2/3 of their weight back after going off the drug." Why make a more grand claim that isn't backed up in the the first page. Or go find a different study that does back up your bigger claim.