I am always incredibly worried anytime a new breakthrough drug type is found and a race is on to get it patented and approved for every hypothetical use case and then some. We don't know what the...
I am always incredibly worried anytime a new breakthrough drug type is found and a race is on to get it patented and approved for every hypothetical use case and then some.
We don't know what the long term effects of this will be. For people whom are seeing immediate tangible benefits where risk of dying in < 10 years without is much higher than baseline it makes sense.
Remember smoking itself was seen as a medical treatment with no downsides early in the 20th century. It wasn't until decades of heavy use started demonstrating the harms. Our tooling is better now, but our drug interactions are also getting exponentially more complicated as well.
All I'm saying is proceed with caution. This kind of miracle drug rarely comes without some heavy unforseen side effect discovered 10-20 years later.
Just to be clear, Ozempic got FDA approval in 2017. Semaglutide’s first clinical trials started in 2008. Just wanted to point that out because unfortunately, a lot of people see the media craze...
Just to be clear, Ozempic got FDA approval in 2017. Semaglutide’s first clinical trials started in 2008.
Just wanted to point that out because unfortunately, a lot of people see the media craze about Ozempic and Wegovy and assume they’re brand new and largely untested.
If you’re someone who’s overweight, there’s very little reason to “proceed with caution” because of the overhyped specter of “long term side effects” compared to the damage being overweight or obese is doing to your body right now.
When I say "proceed with caution," I'm talking within the scope of prescribing GLP-1's for addictions and other things that are almost certainly in the pipeline. Also, I hadn't bothered to look at...
When I say "proceed with caution," I'm talking within the scope of prescribing GLP-1's for addictions and other things that are almost certainly in the pipeline.
Also, I hadn't bothered to look at the side of the box, but
WARNING: RISK OF THYROID C-CELL TUMORS
In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined [see Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1)].
While I'm not a domain expert, "we haven't determined if there's human relevance for tumors" is a worrying sign, one that likely won't rear its head for 20-30 years. If these meds are only used for short durations (< 5 years) for severe weight loss? Yea they're probably fine. But for addiction treatment, where it's likely to be in perpetuity? I'd be quite concerned.
Hi I'm a clinical pharmacist. The data we have currently makes me far less concerned about the existing black box warning. That risk is not actually proven in humans and there is no known...
Exemplary
Hi I'm a clinical pharmacist. The data we have currently makes me far less concerned about the existing black box warning. That risk is not actually proven in humans and there is no known mechanism.
The reason for the warning is because animal studies have shown dose-dependent and treatment duration-dependent harmful effects in rodents but not primates, thereby indicating that proliferative C-cell effects of liraglutide may be rodent specific. Humans have far fewer C cells than rodents, and expression of the GLP-1 receptor in human C cells is very low. Source article
Edit: here's an article from this year as well that further reinforces my point. The incidence of thyroid cancers was not significantly higher
Agreed, based on what I know of rodent toxicology. And even if the risks in primates were comparable, thyroid cancer is much more treatable than colon and pancreatic cancers, for which obesity...
Agreed, based on what I know of rodent toxicology. And even if the risks in primates were comparable, thyroid cancer is much more treatable than colon and pancreatic cancers, for which obesity causes well-established significant increases in risk.
I'm inclined to trust your gut, but sadly that paper isn't on sci-hub (edit: doh its free access, reading now, see end edit), so I'm having to roll off the abstract: I'd really like to see what...
I'm inclined to trust your gut, but sadly that paper isn't on sci-hub (edit: doh its free access, reading now, see end edit), so I'm having to roll off the abstract:
The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk.
I'd really like to see what those incidence rates were, for both the patients and non-patients.
According to this, thyroid cancer in the USA is at about 13.5/100000. If I'm doing my math correctly, with the total population of 14,550 participants, would mean about 2 cases expected, or 0.013%. If they saw even 0.1% incidence, that's a 10x increase over baseline, and something might be up.
Edit: After reading:
It seems if their data tables have all the data, 4 patients in all the studies with thyroid cancer. If none were in the control group, that seems worth investigating, though not too alarming. Also I'm going to drop this quote from a study they reference in the discussion.
A total of 2,562 case subjects with thyroid cancers were included in the study and matched with 45,184 control subjects. Use of GLP-1 RA for 1–3 years was associated with increased risk of all thyroid cancer (adjusted hazard ratio [HR] 1.58, 95% CI 1.27–1.95) and medullary thyroid cancer (adjusted HR 1.78, 95% CI 1.04–3.05).
I appreciate your thoughts, but I still am less concerned about the black box warning. All of those tiny percentages you have mentioned are miniscule and more likely due to chance/external factors...
I appreciate your thoughts, but I still am less concerned about the black box warning. All of those tiny percentages you have mentioned are miniscule and more likely due to chance/external factors versus some unknown GLP-1 driven mechanism. If there was such a mechanism, the rates would be far higher than <1%, which further leads me to believe these are chance occurrences versus something directly driven by GLP-1's. Sure, these drugs could affect some people that way, but I can confidently tell patients that the risk of GLP-1 associated thyroid cancer is minimal, and has never had a positive correlation established
Something you are forgetting to consider as well I think are the positive benefits to the drug, which I completely believe that the benefits of GLP-1's outweigh the risks. Every single medication has positive and negative side effects. You can split hairs all day to try to make your case when you have a negative bias against something, but at the end of the day you really have to look at the big picture
What's a bigger deal, the statistically significant health benefits that elderly obese patients get from losing weight, or the <1% risk of thyroid cancer that is not statistically significant?
I'm thankful for your breakdown. Within the scope of what its already approved for, that risk makes sense. However, I feel it makes much less sense if you're talking about expanding use across the...
I'm thankful for your breakdown.
Within the scope of what its already approved for, that risk makes sense.
However, I feel it makes much less sense if you're talking about expanding use across the entire population for things that are more readily treatable without medicine, like addiction.
That's going to vary greatly from individual to individual. I say something because blanket statements like this put expectations on people with addictions (or even diabetes, etc.) that they...
That's going to vary greatly from individual to individual. I say something because blanket statements like this put expectations on people with addictions (or even diabetes, etc.) that they should be handling their medical issues in a particular way. And addictions (and immune disorders too oddly) have a lot of shame associated with them socially, so those statements can be harmful.
I'm not sure I understand your argument. The shame around addictions is real, but that's why we should speak honestly and openly about them, right? The harms of alcohol addiction are well...
I'm not sure I understand your argument. The shame around addictions is real, but that's why we should speak honestly and openly about them, right?
The harms of alcohol addiction are well understood, so I feel like we should be hopeful and promote new treatment options.
Being hopeful is great, blanket saying it's (almost certainly) worth the risk is doing that math for (almost) everyone. Particularly in response to the point about not knowing the full risks yet....
Being hopeful is great, blanket saying it's (almost certainly) worth the risk is doing that math for (almost) everyone. Particularly in response to the point about not knowing the full risks yet.
It is hopeful, even if I'm deeply suspicious of magic pills/shots. But it's a potentially lifelong expensive medical intervention and may not be manageable for many. I am already seeing a blanket assumption from some folks that all fat people should take this med. Because of course it'll solve all of our medical problems (they really only care about the "fat" part.).
I don't want to see the same about addiction for the reasons I mentioned originally. Perceived "failure" is a relapse trigger. A way to phrase something in a hopeful way would be that it seems like it's anecdotally really helping people who are using it. If it is affordable and low risk it could hopefully be incredibly useful as one tool to help people dealing with addiction.
And all this is more effort than I want to put into an ozempic post. The base drug has been around a while, I don't think it's curing all addiction and is really prefer it not be shorted from diabetic folks who need it to maintain their glucose levels while it's being flagged as the solver of all the West's problems.
So I have a base bias against that from the jump, but I would say the same about AA or a specific therapy, etc. avoiding blanket statements with "shoulds" implicit or otherwise, is for the better.
I think that one thing that needs to be said more often is that endemic health issues like obesity and drug addiction are part of a host of public health problems that have their roots in the way...
I think that one thing that needs to be said more often is that endemic health issues like obesity and drug addiction are part of a host of public health problems that have their roots in the way our society is organized. People are getting obese, diabetic, and circulatory problems because of the way our society addresses food. Anyone who has ever done drugs will tell you there's a social aspect to it.
It's great that we've found a drug that can help with some of these things, but I feel more and more that it is just putting a bandage on the problems rather than actually fixing them. When we discovered the health affects of radiation, we didn't just ignore it until we could invent real-world Rad-Away. We took steps to control radiation so people wouldn't get sick. Granted, fixing the societal problems causing these issues are much more complex, but it seems like it would be much better for everyone in the long-term to fix them. And now that we do have Ozempic, the efforts to get those changes made just became much more difficult.
It's important to note that taking these medications for weight loss is not "take them for short durations and stop". Almost all of the clinical trials have demonstrated that you gain the weight...
It's important to note that taking these medications for weight loss is not "take them for short durations and stop". Almost all of the clinical trials have demonstrated that you gain the weight back when you stop taking the medications.
When you're eliminating a medical condition that causes fertility problems (obesity), this is expected. The question comes when we use the medicine for things that don't cause fertility problems....
When you're eliminating a medical condition that causes fertility problems (obesity), this is expected.
The question comes when we use the medicine for things that don't cause fertility problems.
Though it's a crapshoot anyway when it comes to arbitrary gambles like that. After a bit more cursory glancing, "mass thyroid disruption/cancer" seems much more likely.
Considering alcohol, nicotine, and opiates all have well-known negative effects on fertility (especially pregnancy), I think it's safe to assume that any potential risks from Ozempic are less...
Considering alcohol, nicotine, and opiates all have well-known negative effects on fertility (especially pregnancy), I think it's safe to assume that any potential risks from Ozempic are less important.
Would that actually happen, though? Say it takes 10 years to determine for sure that it has an effect - there are plenty of people who won’t be on it (even if that’s 0-10 year olds) and who will...
Would that actually happen, though? Say it takes 10 years to determine for sure that it has an effect - there are plenty of people who won’t be on it (even if that’s 0-10 year olds) and who will be able to have babies in that time, and also there’s a possibility that those who were on it could come off and have some fertility restored. I’d imagine a medicine that is both voluntary and likely to be cost-prohibitive for at least some portion of the population would fail to cause mass fertility issues, right?
You have to consider: "Who profits?" According to the Social Security Administration, the ratio of old people (i.e. beneficiaries) to workers has gone from 5.1:1 to a projected 2.1:1 in 2040,...
You have to consider: "Who profits?" According to the Social Security Administration, the ratio of old people (i.e. beneficiaries) to workers has gone from 5.1:1 to a projected 2.1:1 in 2040, which is unsustainable unless we raise the retirement age. If a quarter of the population is 65+, and—at the other end of the age number line—there is even a small drop in fertility rates (which we already saw post-2020), the math starts collapsing pretty quick. The golden number for population maintenance is a fertility rate of 2.1 babies per woman having babies, and a ton of countries are way below that already (US is 1.79). So it wouldn't take a giant drop in fertility to cause serious financial concerns for wealthy boomers, who make the vast majority of corporate and governmental policy decisions in America. So basically if ozempic or anything else looks like it might threaten that even a little, then yeah I'd bet my proletariat ass it would get yanked pretty quick.
There almost certainly will be. Check this population chart. Note that Genration Alpha is still being born. The oldest Boomers are 78 now, the youngest 60. Notice that they're still a giant...
The oldest Boomers are 78 now, the youngest 60. Notice that they're still a giant cohort, despite entering the die-off phase of the generation, even with COVID. Also, many of them are just now entering retirement in their 70s. Once the boomers die off, it'll be much less bad, especially if we plan ahead, knowing that X is smaller, Millenials are bigger, and that Millennials and younger are spacing out their childrearing more and having less kids despite any fertility issues.
I think anybody saying that the retirement age needs raised is being shortsighted. What needs to happen first is removing dumb caps on Social Security taxes and maybe increasing required work hours for earning social security. That'll solve many of these supposed "not enough workers/money" problems.
It definitely feels like I'm taking crazy pills when there is all this talk of the "social security" problem but raising the social security income taxable cap is a popular solution that never...
It definitely feels like I'm taking crazy pills when there is all this talk of the "social security" problem but raising the social security income taxable cap is a popular solution that never seems to be on the table for some reason.
My offbeat bet is that the average person becomes more physically attractive and capable. This leads to them engaging in more sexual activity. Maybe fertility gets dragged upwards along the way. I...
My offbeat bet is that the average person becomes more physically attractive and capable. This leads to them engaging in more sexual activity. Maybe fertility gets dragged upwards along the way.
I recall there's a strong association between BMI and sexual activity. When people feel less confident about their bodies, especially when comparing to their younger, probably fitter selves in their memories, they feel less confident about initiating and engaging in sexual activity.
As a fat person, I honestly think you're missing a bigger factor -- sex is physical activity and being obese or otherwise out of shape can make it more difficult or exhausting.
When people feel less confident about their bodies, especially when comparing to their younger, probably fitter selves in their memories, they feel less confident about initiating and engaging in sexual activity.
As a fat person, I honestly think you're missing a bigger factor -- sex is physical activity and being obese or otherwise out of shape can make it more difficult or exhausting.
I'd like to add another layer; Fertility, particularly women's fertility can also be directly impacted by the medical conditions that ozempic treats, or the commonly co-occurring conditions. And...
I'd like to add another layer;
Fertility, particularly women's fertility can also be directly impacted by the medical conditions that ozempic treats, or the commonly co-occurring conditions. And getting diabetes under medical control is really necessary for safe pregnancies which would encourage interested folks to intentionally try for pregnancy by increasing sexual activity or stop using contraceptives.
Idk that I've not engaged in sex due to my weight, so that hasn't been my experience. But there's a host of "medical conditions" that you're likely to have (half of which seem to have the qualifications of "you have the other ones" and very few of which have actual causes rather than risk factors) as a woman who's fat and diabetic, that impact fertility and that the only medical treatment for is "lose weight.". It's rather infuriating tbh.
That's explicitly what I was stating was infuriating. Thanks for demonstrating it. I don't consider a medication for fatness that I'd have to take for the rest of my life to be useful. I also...
That's explicitly what I was stating was infuriating. Thanks for demonstrating it.
I don't consider a medication for fatness that I'd have to take for the rest of my life to be useful. I also don't consider "you have fatty liver, we dont know why some people get it, though probably lots of people have it but we only look in certain people, but the only solution is weight loss... And if you still have it, the only solution is weight loss. And if you still have it...". Rinse and repeat for "metabolic syndrome" and the like. Fatness is associated with those but not all fat people have it and not only fat people have it. And doctors don't know why so they just tell us to lose weight. Generally by suggesting treatments with huge failure rates, including this one.
Not eating due to lack of appetite is not helpful for my diabetes either. As I already take a med that changes my focus/impulse control/impacts my appetite and thirst.
Remove the stigma against my body in society and particularly in medical care first - so I know I'm getting actual medical care - and then let me decide if I want to change said body or not.
(It's wild how hard we're restricting certain hormone treatments in society in the name of morality while basically shoving another one down people's throats in people's arms, also in the name of morality. )
I sorta follow. I guess we're just coming at this from different angles. I absolutely don't want to judge anyone or blame obesity on a "moral failure" or any other dumb talking points. In my view,...
I sorta follow. I guess we're just coming at this from different angles. I absolutely don't want to judge anyone or blame obesity on a "moral failure" or any other dumb talking points.
In my view, it's just a medical condition, plain and simple. Obesity is inherently associated with dramatically increased risks for a wide variety of conditions as you've said. People should never be made to feel any sense of shame or judgement; it's just the medical reality of it.
I don't think it's a moral judgement for doctors to suggest a treatment for a medical condition which is the underlying cause or contributor to a wide variety of ailments.
Suggesting a treatment that isn't effective in 95% of people (most diets and programs) is unethical in my opinion. Idk the drop out rate/failure rate of things like ozempic yet so I can't speak to...
In my view, it's just a medical condition, plain and simple. Obesity is inherently associated with dramatically increased risks for a wide variety of conditions as you've said. People should never be made to feel any sense of shame or judgement; it's just the medical reality of it.
I don't think it's a moral judgement for doctors to suggest a treatment for a medical condition which is the underlying cause or contributor to a wide variety of ailments.
Suggesting a treatment that isn't effective in 95% of people (most diets and programs) is unethical in my opinion. Idk the drop out rate/failure rate of things like ozempic yet so I can't speak to it, but lots of people do not continue taking it for a variety of reasons. And the history of diet pills is one where the long term safety of the patient is consistently disregarded.
It's between a person and their doctor as needed to decide what approaches are right for them, but most of these disorders and diseases are much more complex than a causation between weight and diagnosis. There are heavier people than me running marathons, there are thinner people than me with unmanaged Type 2 diabetes. No one knows what causes PCOS or "fatty liver disease", they're just correlated with a number of things... But the treatments are often boiled down to "lose weight." (And some of this doesn't even get into how losing 10% of your bodyweight, the standard some obesity treatments use, might still leave you obese... So then what? )
And on top of that, we hear it all the time - I have undiagnosed joint pain. We don't know what it is, but my first primary care doctor said it wasn't my joints it was muscles and also described how my "breasts are large and pendulous" and that the hospital had a weight loss clinic. My wrists and elbows, which are definitely joints, definitely didn't start aching/throbbing in pain off and on, together, due to my weight. And the rheumatologist I saw from my new PCP agreed that it's something systemic but that the flares likely weren't lasting long enough to catch it in the bloodwork yet.
There's a "joke" that you can walk in the ER with a knife in your stomach as a heavy woman and get asked if you had considered a diet or exercise to relieve the pain.
For me, my body size is the absolute least of my problems. My diabetes is managed with medication, my cholesterol and such are great (my prescription insurance's doctors tried to tell me I needed a statin because I'm diabetic and I told them politely to go approve someone's prior authorization and leave me alone. My blood work is fine.) if society could let me buy clothes, sit in chairs (especially plane seats), and the like in peace, I'd be content.
All of this is why I'm suspicious of magic 🪄 obesity cures. And why I find, "but this med will fix your X and you won't be fat anymore" to be deeply hurtful and infuriating. My body is fine. I've worked hard to love it. I'm lucky my meds fix my X already. If they didn't I'd work with my doctor in what did, but IDGAF if it makes me skinny. I don't need that.
I'm happy you're comfortable in your body. Please don't take anything I've said as personal criticism because it's definitely not intended as such! I guess we may just not see eye to eye on...
I'm happy you're comfortable in your body. Please don't take anything I've said as personal criticism because it's definitely not intended as such!
I guess we may just not see eye to eye on obesity treatment. Everything I've ever seen says Ozempic is a very safe and effective drug which helps people lose weight and become healthier.
The only other thing I want to address is your comments about diseases correlated with obesity are a bit misleading. In medicine, most things are correlation and don't have direct 1:1 causes. It's not surprising there are such a broad range of outcomes with obesity or even things we know are super unhealthy like cigarettes. That doesn't make obesity any safer though. It's objectively bad for your health. (Also, it's called fatty liver disease for a reason, excess fat is the primary risk factor for non-alcoholic fatty liver disease).
For the folks it works for, sure. However it's specifically a drug for diabetes. Wegovy is the drug intended for weight loss. Regardless I don't have any specific concerns about the drugs, other...
I guess we may just not see eye to eye on obesity treatment. Everything I've ever seen says Ozempic is a very safe and effective drug which helps people lose weight and become healthier.
For the folks it works for, sure. However it's specifically a drug for diabetes. Wegovy is the drug intended for weight loss. Regardless I don't have any specific concerns about the drugs, other than my general suspicion of magic cure alls and desire for diabetics to have access to it. It's not a magic cure all though.
The only other thing I want to address is your comments about diseases correlated with obesity are a bit misleading. In medicine, most things are correlation and don't have direct 1:1 causes. It's not surprising there are such a broad range of outcomes with obesity or even things we know are super unhealthy like cigarettes. That doesn't make obesity any safer though. It's objectively bad for your health.
What? No. Who could guess. A thing fat people are never told. This sub conversation started because I expressed that it is infuriating to be told to lose weight rather than get medical treatment. And your response was "yay you get to lose weight and thus treat your medical thing." I appreciate how respectful you're trying to be, but you're repeating the exact same behavior in response to my comment. I want treatment for the actual thing.
Focusing on the weight is why fat people get praised for their eating disorders. If anyone wants to take these meds, that's 100% their (and their doc's) decision. but there're reasons only 1/3 of patients kept filling their script after a year and, 22% of diabetics keep filling their script after 2 years - side effects, efficacy and cost.
1 out of 4 isn't bad compared to 1 in 20, but that is for Ozempic not Wegovy, so those are more likely to be diabetics who need the meds for blood glucose than only weight loss. I don't see those numbers discussed as often, especially as it's touted as solving addiction or whatever else it'll do in the news tomorrow. And 2 years is usually the time frame assessed for weight loss which is not particularly useful when the reality is a yo-yoing effect over time.
(Also, it's called fatty liver disease for a reason, excess fat is the primary risk factor for non-alcoholic fatty liver disease).
Yeah, it is but mostly only when carried in the stomach - which is just something certain bodies do and others don't. And we have no idea why not all fat people with apple shaped bodies don't get it, or why thin people do, and the prevalence numbers vary widely because most people aren't checked for it (and mostly only fat people are checked so that probably skews numbers too)
But then NAFLD is an almost totally asymptomatic disease with no actual treatment. Just a "try to lose 10 percent of your body weight to reduce your risk." Which means if you're 300 lbs and you drop to 270... You'll just get told to do that again because you're still fat. That's not helpful nor a treatment but that's it. I'm not sure it even counts as its own disease vs being a warning sign for NASH but I'm not a doc.
But if your only treatment option for anything, NAFLD, or PCOS, or metabolic syndrome, is something that actively tanks your mental health, (particularly in my case when I'm already on a med that suppresses my appetite and have to be reminded to eat during the day,) and has very low success rates, it doesn't give you a lot of trust in the people that recommend it, especially as a blanket recommendation. Fat people are told to lose weight all the time, either directly or by societal pressure. Maybe if we don't get told to lose weight for a cold, or don't get praised for weight loss caused by an eating disorder or cancer, it might feel like actual useful medical advice in certain situations.
It's sort of like how another treatment recommendation is reducing stress. In a vacuum this is not a treatment, this is not even really useful. Because it does nothing to actually help you reduce your stress and probably increases it if you're already swimming in cortisol from every day life.
Anyway, I know I'm rambling, running on a lack of sleep led me to crash for six hours after work and now I'm awake again at a stupid time. (I should get better sleep, and be less stressed) But if I'm to sum this all up, I replied because the previous posts in the thread about fertility omitted that many things ozempic treats directly impact fertility in women. Treating our medical problems is generally the goal beyond weight loss. Weight loss is not something that any fat person hasn't heard of before. Which is why this repetition of the cycle is infuriating. Also Ozempic and its peers are not miracle drugs, especially if most people don't or can't keep taking them. It may not be worth the risk for a lot of people.
Per the CDC, the success rate of quitting smoking is only 7.5%. Unless you are also willing to say it’s unethical to encourage people to quit smoking for similar reasons, this isn’t a good...
Suggesting a treatment that isn't effective in 95% of people (most diets and programs) is unethical in my opinion.
Per the CDC, the success rate of quitting smoking is only 7.5%. Unless you are also willing to say it’s unethical to encourage people to quit smoking for similar reasons, this isn’t a good argument.
"Quitting smoking" isn't a treatment. "quitting smoking with Chantix" is. And I believe the success rate is higher there. But just telling people to quit smoking is absolutely setting them up for...
Per the CDC, the success rate of quitting smoking is only 7.5%. Unless you are also willing to say it’s unethical to encourage people to quit smoking for similar reasons, this isn’t a good argument.
"Quitting smoking" isn't a treatment. "quitting smoking with Chantix" is. And I believe the success rate is higher there.
But just telling people to quit smoking is absolutely setting them up for failure, yes. That's not medical treatment and it's not particularly ethical as a doctor IMO to not attempt to provide something better or to help the patient understand exactly how hard that is.
So yeah I'm arguing that "losing weight" isn't even really a treatment, and the ones they do prescribe generally still have quite low success rates especially long term.
Evidence that GLP-1 treatments like Ozempic and Mounjaro have strong anti-addictive effects across substances and behaviors has been mounting every month. This article reviews the published studies in the field, including two new randomized controlled trials in humans, as well as the strategic opportunity they present to reduce addiction at a society-wide level. The strength of the anti-addictive effect of GLP-1s appears so clear that some physicians are already using these treatments off-label for patients with substance use disorders (SUD), despite ongoing shortages (particularly for Mounjaro / Zepbound) and complications with insurance coverage.
...
Because GLP-1 drugs are not opioid-based treatments and are not primarily SUD treatments, they are positioned to completely bypass the culture wars surrounding substance use treatment, which will enable them to have a dramatic impact on the global prevalence of addiction, at a scale that existing treatments cannot reach.
...
If upcoming studies confirm existing data, GLP-1 drugs will be, by a wide margin, the most widely deployed anti-addiction medications. In fact, because of the scale of prescribing for obesity, far more people with alcohol use disorder (AUD) are already taking GLP-1s than existing indicated anti-addiction medications, as we examine below.
I kind of wonder what sort of effect it has on other, more quasi-pro-social but also kind of addictive behaviours. For example, workaholics or obsessive athletic training. I'm certainly not going...
I kind of wonder what sort of effect it has on other, more quasi-pro-social but also kind of addictive behaviours. For example, workaholics or obsessive athletic training. I'm certainly not going try ozempic, but would it make me "lazy"?
I’ve written on Tildes before about my experience with semaglutide and addiction before. I love that you brought this up, because in my experience I feel like it has changed my overall behavior...
I’ve written on Tildes before about my experience with semaglutide and addiction before.
I love that you brought this up, because in my experience I feel like it has changed my overall behavior like you mentioned.
For example, I’m an overachiever workaholic who works in the emergency department.
I used to feel fantastic at work riding adrenaline highs and felt great about productive I was. Now… I don’t feel any rush, even during codes. Not burnt out, but i’m not nearly as motivated to maintain the high standard that I used to hold myself to. I don’t feel disinhibited either, though. I still get the stuff that needs to be done, done.
I describe it as feeling….more balanced. I don’t get the same highs from shopping, saying something witty in conversation, winning a game, etc. So, as a result, I guess I am much lazier.
All of that sounds horrible and depressing but it doesn’t feel like that to me, I just feel like I’m simply content for the first time in my life and I don’t have to go to extremes anymore to get that.
I really can’t wait until more information comes out about semaglutide and its psychological effects.
I am always incredibly worried anytime a new breakthrough drug type is found and a race is on to get it patented and approved for every hypothetical use case and then some.
We don't know what the long term effects of this will be. For people whom are seeing immediate tangible benefits where risk of dying in < 10 years without is much higher than baseline it makes sense.
Remember smoking itself was seen as a medical treatment with no downsides early in the 20th century. It wasn't until decades of heavy use started demonstrating the harms. Our tooling is better now, but our drug interactions are also getting exponentially more complicated as well.
All I'm saying is proceed with caution. This kind of miracle drug rarely comes without some heavy unforseen side effect discovered 10-20 years later.
Just to be clear, Ozempic got FDA approval in 2017. Semaglutide’s first clinical trials started in 2008.
Just wanted to point that out because unfortunately, a lot of people see the media craze about Ozempic and Wegovy and assume they’re brand new and largely untested.
If you’re someone who’s overweight, there’s very little reason to “proceed with caution” because of the overhyped specter of “long term side effects” compared to the damage being overweight or obese is doing to your body right now.
When I say "proceed with caution," I'm talking within the scope of prescribing GLP-1's for addictions and other things that are almost certainly in the pipeline.
Also, I hadn't bothered to look at the side of the box, but
While I'm not a domain expert, "we haven't determined if there's human relevance for tumors" is a worrying sign, one that likely won't rear its head for 20-30 years. If these meds are only used for short durations (< 5 years) for severe weight loss? Yea they're probably fine. But for addiction treatment, where it's likely to be in perpetuity? I'd be quite concerned.
Hi I'm a clinical pharmacist. The data we have currently makes me far less concerned about the existing black box warning. That risk is not actually proven in humans and there is no known mechanism.
The reason for the warning is because animal studies have shown dose-dependent and treatment duration-dependent harmful effects in rodents but not primates, thereby indicating that proliferative C-cell effects of liraglutide may be rodent specific. Humans have far fewer C cells than rodents, and expression of the GLP-1 receptor in human C cells is very low. Source article
Edit: here's an article from this year as well that further reinforces my point. The incidence of thyroid cancers was not significantly higher
Agreed, based on what I know of rodent toxicology. And even if the risks in primates were comparable, thyroid cancer is much more treatable than colon and pancreatic cancers, for which obesity causes well-established significant increases in risk.
I'm inclined to trust your gut, but sadly that paper isn't on sci-hub (edit: doh its free access, reading now, see end edit), so I'm having to roll off the abstract:
I'd really like to see what those incidence rates were, for both the patients and non-patients.
According to this, thyroid cancer in the USA is at about 13.5/100000. If I'm doing my math correctly, with the total population of 14,550 participants, would mean about 2 cases expected, or 0.013%. If they saw even 0.1% incidence, that's a 10x increase over baseline, and something might be up.
Edit: After reading:
It seems if their data tables have all the data, 4 patients in all the studies with thyroid cancer. If none were in the control group, that seems worth investigating, though not too alarming. Also I'm going to drop this quote from a study they reference in the discussion.
I appreciate your thoughts, but I still am less concerned about the black box warning. All of those tiny percentages you have mentioned are miniscule and more likely due to chance/external factors versus some unknown GLP-1 driven mechanism. If there was such a mechanism, the rates would be far higher than <1%, which further leads me to believe these are chance occurrences versus something directly driven by GLP-1's. Sure, these drugs could affect some people that way, but I can confidently tell patients that the risk of GLP-1 associated thyroid cancer is minimal, and has never had a positive correlation established
Something you are forgetting to consider as well I think are the positive benefits to the drug, which I completely believe that the benefits of GLP-1's outweigh the risks. Every single medication has positive and negative side effects. You can split hairs all day to try to make your case when you have a negative bias against something, but at the end of the day you really have to look at the big picture
What's a bigger deal, the statistically significant health benefits that elderly obese patients get from losing weight, or the <1% risk of thyroid cancer that is not statistically significant?
I'm thankful for your breakdown.
Within the scope of what its already approved for, that risk makes sense.
However, I feel it makes much less sense if you're talking about expanding use across the entire population for things that are more readily treatable without medicine, like addiction.
Depending on what the addiction is to, it's almost certainly worth the risk.
That's going to vary greatly from individual to individual. I say something because blanket statements like this put expectations on people with addictions (or even diabetes, etc.) that they should be handling their medical issues in a particular way. And addictions (and immune disorders too oddly) have a lot of shame associated with them socially, so those statements can be harmful.
I'm not sure I understand your argument. The shame around addictions is real, but that's why we should speak honestly and openly about them, right?
The harms of alcohol addiction are well understood, so I feel like we should be hopeful and promote new treatment options.
Being hopeful is great, blanket saying it's (almost certainly) worth the risk is doing that math for (almost) everyone. Particularly in response to the point about not knowing the full risks yet.
It is hopeful, even if I'm deeply suspicious of magic pills/shots. But it's a potentially lifelong expensive medical intervention and may not be manageable for many. I am already seeing a blanket assumption from some folks that all fat people should take this med. Because of course it'll solve all of our medical problems (they really only care about the "fat" part.).
I don't want to see the same about addiction for the reasons I mentioned originally. Perceived "failure" is a relapse trigger. A way to phrase something in a hopeful way would be that it seems like it's anecdotally really helping people who are using it. If it is affordable and low risk it could hopefully be incredibly useful as one tool to help people dealing with addiction.
And all this is more effort than I want to put into an ozempic post. The base drug has been around a while, I don't think it's curing all addiction and is really prefer it not be shorted from diabetic folks who need it to maintain their glucose levels while it's being flagged as the solver of all the West's problems.
So I have a base bias against that from the jump, but I would say the same about AA or a specific therapy, etc. avoiding blanket statements with "shoulds" implicit or otherwise, is for the better.
I think that one thing that needs to be said more often is that endemic health issues like obesity and drug addiction are part of a host of public health problems that have their roots in the way our society is organized. People are getting obese, diabetic, and circulatory problems because of the way our society addresses food. Anyone who has ever done drugs will tell you there's a social aspect to it.
It's great that we've found a drug that can help with some of these things, but I feel more and more that it is just putting a bandage on the problems rather than actually fixing them. When we discovered the health affects of radiation, we didn't just ignore it until we could invent real-world Rad-Away. We took steps to control radiation so people wouldn't get sick. Granted, fixing the societal problems causing these issues are much more complex, but it seems like it would be much better for everyone in the long-term to fix them. And now that we do have Ozempic, the efforts to get those changes made just became much more difficult.
It's important to note that taking these medications for weight loss is not "take them for short durations and stop". Almost all of the clinical trials have demonstrated that you gain the weight back when you stop taking the medications.
e.g., SURMOUNT-4 trial
https://jamanetwork.com/journals/jama/fullarticle/2812936
Well shit I'm just having flashbacks to my early childhood when they just used aphetimines for weight loss.
I agree with this. As someone who works in biopharma, I'm just waiting for the long term effects of Ozempic to be known, but that will take time...
My money (as a layperson) is on reduced fertility rates, leading us to a "Children of Men" situation.
So called “Ozempic babies” seem to indicate the opposite https://www.cnn.com/2024/05/08/health/ozempic-babies-pregnancy/index.html
When you're eliminating a medical condition that causes fertility problems (obesity), this is expected.
The question comes when we use the medicine for things that don't cause fertility problems.
Though it's a crapshoot anyway when it comes to arbitrary gambles like that. After a bit more cursory glancing, "mass thyroid disruption/cancer" seems much more likely.
Considering alcohol, nicotine, and opiates all have well-known negative effects on fertility (especially pregnancy), I think it's safe to assume that any potential risks from Ozempic are less important.
Would that actually happen, though? Say it takes 10 years to determine for sure that it has an effect - there are plenty of people who won’t be on it (even if that’s 0-10 year olds) and who will be able to have babies in that time, and also there’s a possibility that those who were on it could come off and have some fertility restored. I’d imagine a medicine that is both voluntary and likely to be cost-prohibitive for at least some portion of the population would fail to cause mass fertility issues, right?
You have to consider: "Who profits?" According to the Social Security Administration, the ratio of old people (i.e. beneficiaries) to workers has gone from 5.1:1 to a projected 2.1:1 in 2040, which is unsustainable unless we raise the retirement age. If a quarter of the population is 65+, and—at the other end of the age number line—there is even a small drop in fertility rates (which we already saw post-2020), the math starts collapsing pretty quick. The golden number for population maintenance is a fertility rate of 2.1 babies per woman having babies, and a ton of countries are way below that already (US is 1.79). So it wouldn't take a giant drop in fertility to cause serious financial concerns for wealthy boomers, who make the vast majority of corporate and governmental policy decisions in America. So basically if ozempic or anything else looks like it might threaten that even a little, then yeah I'd bet my proletariat ass it would get yanked pretty quick.
surely this is the other way around (workers to beneficiaries)? this is saying there will be more workers per beneficiary in the future
There almost certainly will be. Check this population chart. Note that Genration Alpha is still being born.
The oldest Boomers are 78 now, the youngest 60. Notice that they're still a giant cohort, despite entering the die-off phase of the generation, even with COVID. Also, many of them are just now entering retirement in their 70s. Once the boomers die off, it'll be much less bad, especially if we plan ahead, knowing that X is smaller, Millenials are bigger, and that Millennials and younger are spacing out their childrearing more and having less kids despite any fertility issues.
I think anybody saying that the retirement age needs raised is being shortsighted. What needs to happen first is removing dumb caps on Social Security taxes and maybe increasing required work hours for earning social security. That'll solve many of these supposed "not enough workers/money" problems.
It definitely feels like I'm taking crazy pills when there is all this talk of the "social security" problem but raising the social security income taxable cap is a popular solution that never seems to be on the table for some reason.
That is a popular solution that Biden called out as an option in the presidential debate as something he wants to enact.
My offbeat bet is that the average person becomes more physically attractive and capable. This leads to them engaging in more sexual activity. Maybe fertility gets dragged upwards along the way.
I recall there's a strong association between BMI and sexual activity. When people feel less confident about their bodies, especially when comparing to their younger, probably fitter selves in their memories, they feel less confident about initiating and engaging in sexual activity.
As a fat person, I honestly think you're missing a bigger factor -- sex is physical activity and being obese or otherwise out of shape can make it more difficult or exhausting.
I'd like to add another layer;
Fertility, particularly women's fertility can also be directly impacted by the medical conditions that ozempic treats, or the commonly co-occurring conditions. And getting diabetes under medical control is really necessary for safe pregnancies which would encourage interested folks to intentionally try for pregnancy by increasing sexual activity or stop using contraceptives.
Idk that I've not engaged in sex due to my weight, so that hasn't been my experience. But there's a host of "medical conditions" that you're likely to have (half of which seem to have the qualifications of "you have the other ones" and very few of which have actual causes rather than risk factors) as a woman who's fat and diabetic, that impact fertility and that the only medical treatment for is "lose weight.". It's rather infuriating tbh.
On the bright side, if we have a medication that treats obesity, we'd be able to take out a lot more than two birds with one drug!
That's explicitly what I was stating was infuriating. Thanks for demonstrating it.
I don't consider a medication for fatness that I'd have to take for the rest of my life to be useful. I also don't consider "you have fatty liver, we dont know why some people get it, though probably lots of people have it but we only look in certain people, but the only solution is weight loss... And if you still have it, the only solution is weight loss. And if you still have it...". Rinse and repeat for "metabolic syndrome" and the like. Fatness is associated with those but not all fat people have it and not only fat people have it. And doctors don't know why so they just tell us to lose weight. Generally by suggesting treatments with huge failure rates, including this one.
Not eating due to lack of appetite is not helpful for my diabetes either. As I already take a med that changes my focus/impulse control/impacts my appetite and thirst.
Remove the stigma against my body in society and particularly in medical care first - so I know I'm getting actual medical care - and then let me decide if I want to change said body or not.
(It's wild how hard we're restricting certain hormone treatments in society in the name of morality while basically shoving another one
down people's throatsin people's arms, also in the name of morality. )I sorta follow. I guess we're just coming at this from different angles. I absolutely don't want to judge anyone or blame obesity on a "moral failure" or any other dumb talking points.
In my view, it's just a medical condition, plain and simple. Obesity is inherently associated with dramatically increased risks for a wide variety of conditions as you've said. People should never be made to feel any sense of shame or judgement; it's just the medical reality of it.
I don't think it's a moral judgement for doctors to suggest a treatment for a medical condition which is the underlying cause or contributor to a wide variety of ailments.
Suggesting a treatment that isn't effective in 95% of people (most diets and programs) is unethical in my opinion. Idk the drop out rate/failure rate of things like ozempic yet so I can't speak to it, but lots of people do not continue taking it for a variety of reasons. And the history of diet pills is one where the long term safety of the patient is consistently disregarded.
It's between a person and their doctor as needed to decide what approaches are right for them, but most of these disorders and diseases are much more complex than a causation between weight and diagnosis. There are heavier people than me running marathons, there are thinner people than me with unmanaged Type 2 diabetes. No one knows what causes PCOS or "fatty liver disease", they're just correlated with a number of things... But the treatments are often boiled down to "lose weight." (And some of this doesn't even get into how losing 10% of your bodyweight, the standard some obesity treatments use, might still leave you obese... So then what? )
And on top of that, we hear it all the time - I have undiagnosed joint pain. We don't know what it is, but my first primary care doctor said it wasn't my joints it was muscles and also described how my "breasts are large and pendulous" and that the hospital had a weight loss clinic. My wrists and elbows, which are definitely joints, definitely didn't start aching/throbbing in pain off and on, together, due to my weight. And the rheumatologist I saw from my new PCP agreed that it's something systemic but that the flares likely weren't lasting long enough to catch it in the bloodwork yet.
There's a "joke" that you can walk in the ER with a knife in your stomach as a heavy woman and get asked if you had considered a diet or exercise to relieve the pain.
For me, my body size is the absolute least of my problems. My diabetes is managed with medication, my cholesterol and such are great (my prescription insurance's doctors tried to tell me I needed a statin because I'm diabetic and I told them politely to go approve someone's prior authorization and leave me alone. My blood work is fine.) if society could let me buy clothes, sit in chairs (especially plane seats), and the like in peace, I'd be content.
All of this is why I'm suspicious of magic 🪄 obesity cures. And why I find, "but this med will fix your X and you won't be fat anymore" to be deeply hurtful and infuriating. My body is fine. I've worked hard to love it. I'm lucky my meds fix my X already. If they didn't I'd work with my doctor in what did, but IDGAF if it makes me skinny. I don't need that.
I'm happy you're comfortable in your body. Please don't take anything I've said as personal criticism because it's definitely not intended as such!
I guess we may just not see eye to eye on obesity treatment. Everything I've ever seen says Ozempic is a very safe and effective drug which helps people lose weight and become healthier.
The only other thing I want to address is your comments about diseases correlated with obesity are a bit misleading. In medicine, most things are correlation and don't have direct 1:1 causes. It's not surprising there are such a broad range of outcomes with obesity or even things we know are super unhealthy like cigarettes. That doesn't make obesity any safer though. It's objectively bad for your health. (Also, it's called fatty liver disease for a reason, excess fat is the primary risk factor for non-alcoholic fatty liver disease).
For the folks it works for, sure. However it's specifically a drug for diabetes. Wegovy is the drug intended for weight loss. Regardless I don't have any specific concerns about the drugs, other than my general suspicion of magic cure alls and desire for diabetics to have access to it. It's not a magic cure all though.
What? No. Who could guess. A thing fat people are never told. This sub conversation started because I expressed that it is infuriating to be told to lose weight rather than get medical treatment. And your response was "yay you get to lose weight and thus treat your medical thing." I appreciate how respectful you're trying to be, but you're repeating the exact same behavior in response to my comment. I want treatment for the actual thing.
Focusing on the weight is why fat people get praised for their eating disorders. If anyone wants to take these meds, that's 100% their (and their doc's) decision. but there're reasons only 1/3 of patients kept filling their script after a year and, 22% of diabetics keep filling their script after 2 years - side effects, efficacy and cost.
1 out of 4 isn't bad compared to 1 in 20, but that is for Ozempic not Wegovy, so those are more likely to be diabetics who need the meds for blood glucose than only weight loss. I don't see those numbers discussed as often, especially as it's touted as solving addiction or whatever else it'll do in the news tomorrow. And 2 years is usually the time frame assessed for weight loss which is not particularly useful when the reality is a yo-yoing effect over time.
Yeah, it is but mostly only when carried in the stomach - which is just something certain bodies do and others don't. And we have no idea why not all fat people with apple shaped bodies don't get it, or why thin people do, and the prevalence numbers vary widely because most people aren't checked for it (and mostly only fat people are checked so that probably skews numbers too)
But then NAFLD is an almost totally asymptomatic disease with no actual treatment. Just a "try to lose 10 percent of your body weight to reduce your risk." Which means if you're 300 lbs and you drop to 270... You'll just get told to do that again because you're still fat. That's not helpful nor a treatment but that's it. I'm not sure it even counts as its own disease vs being a warning sign for NASH but I'm not a doc.
But if your only treatment option for anything, NAFLD, or PCOS, or metabolic syndrome, is something that actively tanks your mental health, (particularly in my case when I'm already on a med that suppresses my appetite and have to be reminded to eat during the day,) and has very low success rates, it doesn't give you a lot of trust in the people that recommend it, especially as a blanket recommendation. Fat people are told to lose weight all the time, either directly or by societal pressure. Maybe if we don't get told to lose weight for a cold, or don't get praised for weight loss caused by an eating disorder or cancer, it might feel like actual useful medical advice in certain situations.
It's sort of like how another treatment recommendation is reducing stress. In a vacuum this is not a treatment, this is not even really useful. Because it does nothing to actually help you reduce your stress and probably increases it if you're already swimming in cortisol from every day life.
Anyway, I know I'm rambling, running on a lack of sleep led me to crash for six hours after work and now I'm awake again at a stupid time. (I should get better sleep, and be less stressed) But if I'm to sum this all up, I replied because the previous posts in the thread about fertility omitted that many things ozempic treats directly impact fertility in women. Treating our medical problems is generally the goal beyond weight loss. Weight loss is not something that any fat person hasn't heard of before. Which is why this repetition of the cycle is infuriating. Also Ozempic and its peers are not miracle drugs, especially if most people don't or can't keep taking them. It may not be worth the risk for a lot of people.
Per the CDC, the success rate of quitting smoking is only 7.5%. Unless you are also willing to say it’s unethical to encourage people to quit smoking for similar reasons, this isn’t a good argument.
https://www.cdc.gov/tobacco/data_statistics/fact_sheets/cessation/smoking-cessation-fast-facts/index.html
"Quitting smoking" isn't a treatment. "quitting smoking with Chantix" is. And I believe the success rate is higher there.
But just telling people to quit smoking is absolutely setting them up for failure, yes. That's not medical treatment and it's not particularly ethical as a doctor IMO to not attempt to provide something better or to help the patient understand exactly how hard that is.
So yeah I'm arguing that "losing weight" isn't even really a treatment, and the ones they do prescribe generally still have quite low success rates especially long term.
From the blog post:
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I kind of wonder what sort of effect it has on other, more quasi-pro-social but also kind of addictive behaviours. For example, workaholics or obsessive athletic training. I'm certainly not going try ozempic, but would it make me "lazy"?
I’ve written on Tildes before about my experience with semaglutide and addiction before.
I love that you brought this up, because in my experience I feel like it has changed my overall behavior like you mentioned.
For example, I’m an overachiever workaholic who works in the emergency department.
I used to feel fantastic at work riding adrenaline highs and felt great about productive I was. Now… I don’t feel any rush, even during codes. Not burnt out, but i’m not nearly as motivated to maintain the high standard that I used to hold myself to. I don’t feel disinhibited either, though. I still get the stuff that needs to be done, done.
I describe it as feeling….more balanced. I don’t get the same highs from shopping, saying something witty in conversation, winning a game, etc. So, as a result, I guess I am much lazier.
All of that sounds horrible and depressing but it doesn’t feel like that to me, I just feel like I’m simply content for the first time in my life and I don’t have to go to extremes anymore to get that.
I really can’t wait until more information comes out about semaglutide and its psychological effects.