As the authors admit, this needs more research. I find the following portion to be the most questionable: This facility is a hospital. So their entire sample looked at people who most likely came...
As the authors admit, this needs more research. I find the following portion to be the most questionable:
They analyzed the medical records of about 17,000 Mass Eye and Ear patients dating back to 2017, when the first semaglutide-based medication Ozempic was approved for use as a treatment for type 2 diabetes.
This facility is a hospital. So their entire sample looked at people who most likely came to them knowing they had some form of vision issue. So the research isn't really representative of the general population, but of a group of people who visited a hospital with a known issue of some sort.
How is this a sampling issue? If a drug has a rare chance of causing a vision impairment, you will of course discover that by analyzing medical records of patients treated for vision impairments....
How is this a sampling issue?
They focused on nearly 1,700 patients who were diagnosed with diabetes or with being overweight/obese but who had no prior history of NAION. Then they tracked NAION diagnoses between similarly matched groups of patients who were prescribed semaglutide or who were prescribed other diabetes or obesity medications.
The patients were tracked for about three years. During that time, 46 NAION cases were diagnosed among the matched groups of patients. But those prescribed semaglutide were significantly more likely to be diagnosed with NAION, the researchers found. This pattern was seen across both groups of patients, though the risk appeared higher for those prescribed the drug for weight loss. Compared to people taking other obesity medications, the risk of NAION was over seven times higher for those prescribed semaglutide.
If a drug has a rare chance of causing a vision impairment, you will of course discover that by analyzing medical records of patients treated for vision impairments. That doesn't mean they have a sampling bias. However, I haven't read the underlying paper to look at their stats myself, so who knows. But detecting statistically significant correlations through an intrapopulation retrospective study is perfectly normal and acceptable science, and a starting point for many lines of investigation.
This is actually mentioned in the paper in the "Limitations" section. Might as well post the whole section so we don't have to wonder about what the paper authors covered or not. I highlighted the...
This is actually mentioned in the paper in the "Limitations" section. Might as well post the whole section so we don't have to wonder about what the paper authors covered or not. I highlighted the section I think is relevant to this point.
There are several limitations to our study. Our tertiary care institution specializes in ophthalmology and includes a specialized neuro-ophthalmology service that evaluates a large proportion of the region’s NAION cases; therefore, our findings may not be fully generalizable to other settings. Second, our retrospective study does not allow inquiry into potential biases related to decisions about which patients were prescribed semaglutide or which of those patients were referred and evaluated in our neuro-ophthalmology clinic, although notably our hospital system and our service do not exclude any patient based on insurance coverage. Third, our study could not assess whether all patients actually took the drugs as prescribed; nonadherence is a common phenomenon, even for GLP-1 RA drugs,27 and this may have led to an inaccurate estimation of a semaglutide-associated risk. We did, however, confirm that prescribed doses of semaglutide were dispensed for all patients with NAION. Fourth, our study also is limited in that the severity of confounding factors could not be adequately assessed, as our attempt to substratify the relatively small number of NAION cases in the semaglutide-exposed cohorts (n = 17 and 20) produced wide 95% CIs and less statistical precision. Our analyses were also hindered by laboratory data that were not retrievable from outside institutions. Although we uncovered an association between prescribed semaglutide and NAION, our study did not enable definitive inquiry into relatedness. Although we showed temporal proximity between prescribed semaglutide and NAION, the highest level of confidence to assess relatedness suggested by the FDA also requires establishing risk reduction on stopping a medication and a dose-dependent association.28 Given that our cohorts were composed of relatively small percentages of patients of races other than White (in particular, of the 16 827 patients in our eligible cohort, 5.7% were listed in the medical record as being Black or African American vs 22.5% of individuals who in 2022 self-identified similarly in the greater Boston area), our results should be considered with caution for the general population, especially given that Black individuals generally have a lower risk of NAION.
I don't think the post I responded to was an accurate summary of those limitations. There is always caveats around the extrapolation from sub populations to a general population, and the portion...
I don't think the post I responded to was an accurate summary of those limitations. There is always caveats around the extrapolation from sub populations to a general population, and the portion you highlighted is disclaiming the possibility of unknown biases in the practice of prescribing drugs or referring to specialist care. Those limitations are not the same as sampling bias due to study methodology. Edit: meaning, there's no reason to assume that sampling from this pool of people suffering from NAION should have a lower or higher rate of prescription of the drugs in question. It's possible, hence the disclaimers, but there isn't a systemic or structural bias in the study that would lead one to assume that.
For reference, most every retrospective study has a set of inclusion criteria. Typically medical records from a hospital system will be screened for inclusion criteria, and matching subjects will be consented into the study. That inclusion criteria and selecting of hospital system per force limits the study to a subset of the population. Once a statistically significant correlation is found, the results can be translated to a subsequent phase of discovery, such as examining the larger population of drug recipients through a prospective study and controlling for limitations in the retrospective, such as partnering with clinics across many hospital systems in a multi site study.
However, none of that should give the takeaway of sampling bias or untrustworthy science or findings.
Useful research, though I don't imagine a small risk of blindness in diabetic patients will be a major concern for most people. However, with all drugs that are administered systemically, there is...
Useful research, though I don't imagine a small risk of blindness in diabetic patients will be a major concern for most people.
However, with all drugs that are administered systemically, there is no such thing as only flipping one switch (so to speak). If it has a dramatic biological effect that you like, it's also having other dramatic effects that you might not like. Most of which will be discovered decades down the road.
I thought the same thing. This is a clear case of pros outweigh* the cons for most people. Being overweight has a direct influence on your health. Possibly going blind is not. It all depends on...
I thought the same thing. This is a clear case of pros outweigh* the cons for most people.
Being overweight has a direct influence on your health. Possibly going blind is not. It all depends on how frequent the problems occur and whether or not it can be halted (or reversed) before someone goes fully blind. But considering it affects a subset of a subset I'm going to assume, and before proven otherwise, it's probably rare enough it won't be a deterrent.
Since these are drugs that many patients are prescribed with the intent to take for the rest of their life, it will be important to determine if the risk of these side effects increases with time...
Since these are drugs that many patients are prescribed with the intent to take for the rest of their life, it will be important to determine if the risk of these side effects increases with time or use. Even something with a fixed chance of happening per year can become worrisome after 50 years. So we will be seeing many of these retrospective studies.
However, I suspect the people who need it will still elect to take the drug, but the risks may rightfully deter people from taking it for cosmetic weight loss. Though some people do turn down lifesaving medication because of the side effects.
This is the ways of medicine after all. Aspirin was a miricle drug. Until we learned about all of the side effects that come with it. Namely how its not safe for kids.
This is the ways of medicine after all. Aspirin was a miricle drug. Until we learned about all of the side effects that come with it. Namely how its not safe for kids.
I don't know how this drug works, but is it the kind of drug whose aim is that once someone has decreased enough mass that they can make other lifestyle adjustments on their own, perhaps they can...
I don't know how this drug works, but is it the kind of drug whose aim is that once someone has decreased enough mass that they can make other lifestyle adjustments on their own, perhaps they can have the dosage lowered?
The short answer is no. It is the type of drug where if you stop taking it, you gain the weight right back. I'm not an expert in how it works but my understanding is that it decreases...
The short answer is no. It is the type of drug where if you stop taking it, you gain the weight right back. I'm not an expert in how it works but my understanding is that it decreases appetite/food cravings. Someone taking it for weight loss is expected to remain on it for the rest of their life.
See I got hte impression you gain your apetite back so if you can willpower yourself through the apetite the weight gain doesn't come back. But the caveat here is if you are some one who needs...
See I got hte impression you gain your apetite back so if you can willpower yourself through the apetite the weight gain doesn't come back. But the caveat here is if you are some one who needs medication to keep you from eating too much, that probably is a hard ask so without the medicine people who needed it to lose weight are highly likely to just go back to eating badly (and weight does come back quicker if you have been losing it no matter what way you used to lose it).
But to be fair it may be an easier ask to change eating habits to sustain your current weight then to eat little enough to actually lose weight so it still might be a positive thing to try even if you don't want it to be a lifelong thing. Especially if they are very happy with the weight they are (I know when I lost 90 lbs through counting calories I kept it off for five years cause I was so happy to have it gone I feared gaining it again... unfortunately I got out of that habit and back into bad ones after I got into a motorcycle accident).
The vast majority (like overwhelming) of people who lose weight on any diet or intervention gain it back. I've heard folks that take these meds for diabetes share that they have since realized...
The vast majority (like overwhelming) of people who lose weight on any diet or intervention gain it back. I've heard folks that take these meds for diabetes share that they have since realized that they were in fact actively using their willpower all the time prior to the medication. Stopping it just reverts to that status quo.
I remain untrusting of a "magic pill" that "fixes" weight and would rather we stop stigmatizing fatness than push everyone into a fix. I don't begrudge anyone what they do with their bodies, I just want that expectation to apply equally.
Oh wow then that's a serious concern - I don't know how I would be able to make that trade between the condition vs the side effects, which will stack over my life time.
Oh wow then that's a serious concern - I don't know how I would be able to make that trade between the condition vs the side effects, which will stack over my life time.
I've not seen any indications that this is the case. Some medications are only effective if you're taking them consistently and stop working when you go off of them. If I went off my thyroid...
I've not seen any indications that this is the case. Some medications are only effective if you're taking them consistently and stop working when you go off of them. If I went off my thyroid medication, I would start gaining weight uncontrollably (...again). This wouldn't be something I could keep from happening based on being aware of it, because the thing the medication is doing is providing things my body needs to actually do certain biological processes correctly and efficiently. Without those things, my body goes back to not doing those things properly.
I don't know what the actual biological mechanisms involved are in the case of Ozempic, but it seems pretty widely known and accepted by doctors that you will regain the weight if you go off of it. If there were a way to avert that outcome and take Ozempic only temporarily but keep the weight off, doctors would almost definitely be prescribing it that way, because they are generally averse to putting someone on lifelong medication if there are other effective options.
But what these weight loss drugs do from what I understand is severely depress your apetite. You aren't losing weight cause they are burning the calories for you, you are losing weight simply...
But what these weight loss drugs do from what I understand is severely depress your apetite. You aren't losing weight cause they are burning the calories for you, you are losing weight simply cause you don't want to eat more (like they make you feel so full eating more feels like you'll just get sick). Which is entirely different from your thyroid medications which are affecting your metabolism (or rather your thyroid not working properly affects it badly and the medications make it work like it's supposed to).
So.. if you can resist the hunger pangs and wanting to eat more again after you lose the weight it shouldn't be a problem to go off the drugs? Unless some action of the drugs when you stop taking them do something to your metabolism (more than losing weight does, cause no matter how you lose weight, once you do it is even easier to gain it back).
If these people have struggled to lose weight enough in the past despite their willpower that their doctor thinks Ozempic is an appropriate treatment, it seems unlikely that pure willpower will be...
If these people have struggled to lose weight enough in the past despite their willpower that their doctor thinks Ozempic is an appropriate treatment, it seems unlikely that pure willpower will be enough keep weight off when you take it off of it.
If I go off my ADHD meds, I will struggle to focus regardless of how much willpower I put into it. Taking ADHD meds helps me focus, but if I stop taking them I don't magically gain the ability to focus better with enough willpower.
Appetite suppression and controls blood sugar. I used to take it to raise my blood sugar, so I'm pretty convinced that it normalizes it rather than only lowering it. Makes me wonder how many...
Appetite suppression and controls blood sugar. I used to take it to raise my blood sugar, so I'm pretty convinced that it normalizes it rather than only lowering it. Makes me wonder how many people have chronic low blood sugar like I do but don't know it.
Diabetes also has a risk of blindness (high blood sugar will damage the retina over time). How does this risk compare to that? The /r/medicine thread seems pretty dismissive of the study...
Diabetes also has a risk of blindness (high blood sugar will damage the retina over time). How does this risk compare to that?
True but this isn't a concern for people who are taking it just for weight loss. It's still a good thing to figure out the risk cause it may be better for people with diabetes cause the risks'...
True but this isn't a concern for people who are taking it just for weight loss. It's still a good thing to figure out the risk cause it may be better for people with diabetes cause the risks' cancel each other out but not good for people who just want to lose weight who don't have that risk int he first place.
It depends on what sort of weight loss. You could in theory also be preventing or delaying future diabetes. Almost 30% of Americans over 65 are diabetic, so depending on the relative ratio, even...
It depends on what sort of weight loss. You could in theory also be preventing or delaying future diabetes. Almost 30% of Americans over 65 are diabetic, so depending on the relative ratio, even providing it for weight loss could still result in less blindness.
I take a common medication that's got known, significant risks for retinal toxicity. Hydroxychloroquine has a long history of use. The risk factors, side effect detection, and prevention are...
I take a common medication that's got known, significant risks for retinal toxicity. Hydroxychloroquine has a long history of use. The risk factors, side effect detection, and prevention are well-understood. If there is an increased risk of NAION with semaglutide, it may be just as easily manageable with further research to delineate the causes, early symptoms, and timeline.
There's no reason to put a spectacularly useful drug on the shelf just because of a rare non-lethal side effect, especially if that side effect is manageable and preventable.
I think being glib about people who have persistently struggled to lose weight to the extent that their doctors are prescribing them weight loss medication potentially having unexpected severe...
I think being glib about people who have persistently struggled to lose weight to the extent that their doctors are prescribing them weight loss medication potentially having unexpected severe side effects is in poor taste.
The risks of being overweight are pretty well understood and also pretty serious. It doesn't seem like the risk of going blind is really that high based on this. Personally I'd rather take a small...
The risks of being overweight are pretty well understood and also pretty serious.
It doesn't seem like the risk of going blind is really that high based on this. Personally I'd rather take a small risk of going blind over the large risk of a heart attack, cancer, diabetes, or any of the other serious complications associated with obesity.
As with everything, these risks are meaningless without actually comparing statistics though.
As the authors admit, this needs more research. I find the following portion to be the most questionable:
This facility is a hospital. So their entire sample looked at people who most likely came to them knowing they had some form of vision issue. So the research isn't really representative of the general population, but of a group of people who visited a hospital with a known issue of some sort.
How is this a sampling issue?
If a drug has a rare chance of causing a vision impairment, you will of course discover that by analyzing medical records of patients treated for vision impairments. That doesn't mean they have a sampling bias. However, I haven't read the underlying paper to look at their stats myself, so who knows. But detecting statistically significant correlations through an intrapopulation retrospective study is perfectly normal and acceptable science, and a starting point for many lines of investigation.
This is actually mentioned in the paper in the "Limitations" section. Might as well post the whole section so we don't have to wonder about what the paper authors covered or not. I highlighted the section I think is relevant to this point.
I don't think the post I responded to was an accurate summary of those limitations. There is always caveats around the extrapolation from sub populations to a general population, and the portion you highlighted is disclaiming the possibility of unknown biases in the practice of prescribing drugs or referring to specialist care. Those limitations are not the same as sampling bias due to study methodology. Edit: meaning, there's no reason to assume that sampling from this pool of people suffering from NAION should have a lower or higher rate of prescription of the drugs in question. It's possible, hence the disclaimers, but there isn't a systemic or structural bias in the study that would lead one to assume that.
For reference, most every retrospective study has a set of inclusion criteria. Typically medical records from a hospital system will be screened for inclusion criteria, and matching subjects will be consented into the study. That inclusion criteria and selecting of hospital system per force limits the study to a subset of the population. Once a statistically significant correlation is found, the results can be translated to a subsequent phase of discovery, such as examining the larger population of drug recipients through a prospective study and controlling for limitations in the retrospective, such as partnering with clinics across many hospital systems in a multi site study.
However, none of that should give the takeaway of sampling bias or untrustworthy science or findings.
Sampling bias is a bitch. Definitely needs more research. I expect fear mongering in the meantime though.
Most likely. Although then again Viagra is associated with NAION and no one seems to be fear-mongering about it, haha.
Useful research, though I don't imagine a small risk of blindness in diabetic patients will be a major concern for most people.
However, with all drugs that are administered systemically, there is no such thing as only flipping one switch (so to speak). If it has a dramatic biological effect that you like, it's also having other dramatic effects that you might not like. Most of which will be discovered decades down the road.
I thought the same thing. This is a clear case of pros outweigh* the cons for most people.
Being overweight has a direct influence on your health. Possibly going blind is not. It all depends on how frequent the problems occur and whether or not it can be halted (or reversed) before someone goes fully blind. But considering it affects a subset of a subset I'm going to assume, and before proven otherwise, it's probably rare enough it won't be a deterrent.
*Not intended
Since these are drugs that many patients are prescribed with the intent to take for the rest of their life, it will be important to determine if the risk of these side effects increases with time or use. Even something with a fixed chance of happening per year can become worrisome after 50 years. So we will be seeing many of these retrospective studies.
However, I suspect the people who need it will still elect to take the drug, but the risks may rightfully deter people from taking it for cosmetic weight loss. Though some people do turn down lifesaving medication because of the side effects.
This is the ways of medicine after all. Aspirin was a miricle drug. Until we learned about all of the side effects that come with it. Namely how its not safe for kids.
I don't know how this drug works, but is it the kind of drug whose aim is that once someone has decreased enough mass that they can make other lifestyle adjustments on their own, perhaps they can have the dosage lowered?
The short answer is no. It is the type of drug where if you stop taking it, you gain the weight right back. I'm not an expert in how it works but my understanding is that it decreases appetite/food cravings. Someone taking it for weight loss is expected to remain on it for the rest of their life.
1/6 patients can successfully come off it and not gain weight back. Not a great number, but at least some.
See I got hte impression you gain your apetite back so if you can willpower yourself through the apetite the weight gain doesn't come back. But the caveat here is if you are some one who needs medication to keep you from eating too much, that probably is a hard ask so without the medicine people who needed it to lose weight are highly likely to just go back to eating badly (and weight does come back quicker if you have been losing it no matter what way you used to lose it).
But to be fair it may be an easier ask to change eating habits to sustain your current weight then to eat little enough to actually lose weight so it still might be a positive thing to try even if you don't want it to be a lifelong thing. Especially if they are very happy with the weight they are (I know when I lost 90 lbs through counting calories I kept it off for five years cause I was so happy to have it gone I feared gaining it again... unfortunately I got out of that habit and back into bad ones after I got into a motorcycle accident).
The vast majority (like overwhelming) of people who lose weight on any diet or intervention gain it back. I've heard folks that take these meds for diabetes share that they have since realized that they were in fact actively using their willpower all the time prior to the medication. Stopping it just reverts to that status quo.
I remain untrusting of a "magic pill" that "fixes" weight and would rather we stop stigmatizing fatness than push everyone into a fix. I don't begrudge anyone what they do with their bodies, I just want that expectation to apply equally.
Unfortunately it is how insurance companies look at it. BMI drops?. You're cured!
Oh wow then that's a serious concern - I don't know how I would be able to make that trade between the condition vs the side effects, which will stack over my life time.
I suppose it depends a lot about the side effects specifically, which is why it's important to study stuff like this as we become aware of it.
I’m guessing that’s not destiny, but it’s what usually happens? Perhaps there are ways to keep it from happening if you’re aware of the issue?
I've not seen any indications that this is the case. Some medications are only effective if you're taking them consistently and stop working when you go off of them. If I went off my thyroid medication, I would start gaining weight uncontrollably (...again). This wouldn't be something I could keep from happening based on being aware of it, because the thing the medication is doing is providing things my body needs to actually do certain biological processes correctly and efficiently. Without those things, my body goes back to not doing those things properly.
I don't know what the actual biological mechanisms involved are in the case of Ozempic, but it seems pretty widely known and accepted by doctors that you will regain the weight if you go off of it. If there were a way to avert that outcome and take Ozempic only temporarily but keep the weight off, doctors would almost definitely be prescribing it that way, because they are generally averse to putting someone on lifelong medication if there are other effective options.
But what these weight loss drugs do from what I understand is severely depress your apetite. You aren't losing weight cause they are burning the calories for you, you are losing weight simply cause you don't want to eat more (like they make you feel so full eating more feels like you'll just get sick). Which is entirely different from your thyroid medications which are affecting your metabolism (or rather your thyroid not working properly affects it badly and the medications make it work like it's supposed to).
So.. if you can resist the hunger pangs and wanting to eat more again after you lose the weight it shouldn't be a problem to go off the drugs? Unless some action of the drugs when you stop taking them do something to your metabolism (more than losing weight does, cause no matter how you lose weight, once you do it is even easier to gain it back).
If these people have struggled to lose weight enough in the past despite their willpower that their doctor thinks Ozempic is an appropriate treatment, it seems unlikely that pure willpower will be enough keep weight off when you take it off of it.
If I go off my ADHD meds, I will struggle to focus regardless of how much willpower I put into it. Taking ADHD meds helps me focus, but if I stop taking them I don't magically gain the ability to focus better with enough willpower.
The effect is in the brain, yes, but so is behavior. The things these medicines change also change a person's "ability" to effect their behavior.
Appetite suppression and controls blood sugar. I used to take it to raise my blood sugar, so I'm pretty convinced that it normalizes it rather than only lowering it. Makes me wonder how many people have chronic low blood sugar like I do but don't know it.
Diabetes also has a risk of blindness (high blood sugar will damage the retina over time). How does this risk compare to that?
The /r/medicine thread seems pretty dismissive of the study https://old.reddit.com/r/medicine/comments/1duxfng/risk_of_nonarteritic_anterior_ischemic_optic/
True but this isn't a concern for people who are taking it just for weight loss. It's still a good thing to figure out the risk cause it may be better for people with diabetes cause the risks' cancel each other out but not good for people who just want to lose weight who don't have that risk int he first place.
It depends on what sort of weight loss. You could in theory also be preventing or delaying future diabetes. Almost 30% of Americans over 65 are diabetic, so depending on the relative ratio, even providing it for weight loss could still result in less blindness.
This study compared the rates to other diabetes and obesity medications and did point out that rates were elevated for diabetics overall, iirc.
I take a common medication that's got known, significant risks for retinal toxicity. Hydroxychloroquine has a long history of use. The risk factors, side effect detection, and prevention are well-understood. If there is an increased risk of NAION with semaglutide, it may be just as easily manageable with further research to delineate the causes, early symptoms, and timeline.
There's no reason to put a spectacularly useful drug on the shelf just because of a rare non-lethal side effect, especially if that side effect is manageable and preventable.
People taking these just for weight loss are going to be quite surprised when they go blind
I think being glib about people who have persistently struggled to lose weight to the extent that their doctors are prescribing them weight loss medication potentially having unexpected severe side effects is in poor taste.
The risks of being overweight are pretty well understood and also pretty serious.
It doesn't seem like the risk of going blind is really that high based on this. Personally I'd rather take a small risk of going blind over the large risk of a heart attack, cancer, diabetes, or any of the other serious complications associated with obesity.
As with everything, these risks are meaningless without actually comparing statistics though.