Ozempic keeps wowing: trial data show benefits for kidney disease(nature.com)
nature.com
Ozempic keeps wowing: trial data show benefits for kidney disease
https://www.nature.com/articles/d41586-024-01564-w
99 comments
I'm starting to think somebody has a bunch of truckloads of this stuff they gotta unload.
You'd be wrong. On multiple accounts - people can't "fake" clinical trial results like this to sell medication.
And there is global shortage right now.
And there is global shortage right now.
> people can't "fake" clinical trial results like this to sell medication
Many clinical trials are controversial when they are positive.
Most clinical trials are subcontracted. The subcontractor has a deep interest in pleasing his client. You can select patients at the beginning of the trial, or during the trial you can report that a patient with a "bad" result, just dropped out of the study. And indeed in most clinical trials there is no strong adverse effects (just weak) reported except when patients die.
Moreover, the hospitals that implement the trial often only do the minimum to satisfy the principal investigator
Just look at the field of neurodegenerative diseases or ask patients how negligently they have been treated.
Many clinical trials are controversial when they are positive.
Most clinical trials are subcontracted. The subcontractor has a deep interest in pleasing his client. You can select patients at the beginning of the trial, or during the trial you can report that a patient with a "bad" result, just dropped out of the study. And indeed in most clinical trials there is no strong adverse effects (just weak) reported except when patients die.
Moreover, the hospitals that implement the trial often only do the minimum to satisfy the principal investigator
Just look at the field of neurodegenerative diseases or ask patients how negligently they have been treated.
It is fine to be sceptical, but I think you should have taken a few minutes to read the method chapter in the study, seeing as that possibly could have eased your doubts. The first sentence cites the previously published design of the study. In the method chapter it is reported to be an "international, double-blind, randomized, placebo-controlled trial" with 3533 participants and a mean median follow-up of 3.4 years[0]. The cited article on the study of the trial states that "Participants were enrolled from 418 trial locations across 28 countries." [1]
[0]: https://www.nejm.org/doi/full/10.1056/NEJMoa2403347#sec-1
[1]: https://pubmed.ncbi.nlm.nih.gov/36651820/
[0]: https://www.nejm.org/doi/full/10.1056/NEJMoa2403347#sec-1
[1]: https://pubmed.ncbi.nlm.nih.gov/36651820/
I think they were responding to the general claim that clinical trials can’t be faked, not the specific one from the article.
> Many clinical trials are controversial when they are positive.
Which isn't the same as being "faked".
> Most clinical trials are subcontracted.
They are not subcontracted, clinical trial sites are identified. They are basically doctors interested in running a trial. Usually done at academic hospitals.
> The subcontractor has a deep interest in pleasing his client.
No they don't. They have no vested interest beyond their own careers and publications. Doctors only put a few hours into a clinical trial each month, usually their own patients. Most of the work is done by clinical trial staff. The costs of the trials are paid for by the sponsor, but that money doesn't go into the doctor's pocket, it's the hospital.
> You can select patients at the beginning of the trial, or during the trial you can report that a patient with a "bad" result, just dropped out of the study.
But pretty much every trial is triple blinded. The company, doctor and patient don't know if the patient got the drug or the placebo. Placebos are chosen to pretty much be identical to the drug (people get injections, take pills that look exactly the same).
And no, you can't just "say a patient dropped out". There is a predefined set of criteria that the doctor needs to follow. The patient needs to agree to follow them as well. But again, the doctor doesn't know who received what so how they can they "tweak" the results?
Plus if a patient drops out, the results are penalized. The data doesn't just disappear. All data needs to be reported to the FDA for every patient, including all follow ups.
> And indeed in most clinical trials there is no strong adverse effects (just weak) reported except when patients die.
This is 100% false. All adverse events need to be reported, whether caused by the drug or not. This is why relatively innocuous drug have weird side effects like "diarrhea, constipation". The top adverse events have to be reported, even if it's 0.01% who had them.
> Moreover, the hospitals that implement the trial often only do the minimum to satisfy the principal investigator
No, the hospital doesn't know which patient received the drug or not. If the patient needs a blood test, they get a blood test like any other patient.
And again, the process needs to be followed or else the deviation reported. All of that is reported to the FDA. If enough deviations happen, the FDA can say they won't approve the drug.
> Just look at the field of neurodegenerative diseases or ask patients how negligently they have been treated.
What are you talking about? Can you provide a source?
You've already made many statements that are clearly false, which you would know if you had done even basic research into the field using google. You clearly don't know the field very well, so I'm not sure why you feel like your "ideas" of how trials are run are of any value.
Which isn't the same as being "faked".
> Most clinical trials are subcontracted.
They are not subcontracted, clinical trial sites are identified. They are basically doctors interested in running a trial. Usually done at academic hospitals.
> The subcontractor has a deep interest in pleasing his client.
No they don't. They have no vested interest beyond their own careers and publications. Doctors only put a few hours into a clinical trial each month, usually their own patients. Most of the work is done by clinical trial staff. The costs of the trials are paid for by the sponsor, but that money doesn't go into the doctor's pocket, it's the hospital.
> You can select patients at the beginning of the trial, or during the trial you can report that a patient with a "bad" result, just dropped out of the study.
But pretty much every trial is triple blinded. The company, doctor and patient don't know if the patient got the drug or the placebo. Placebos are chosen to pretty much be identical to the drug (people get injections, take pills that look exactly the same).
And no, you can't just "say a patient dropped out". There is a predefined set of criteria that the doctor needs to follow. The patient needs to agree to follow them as well. But again, the doctor doesn't know who received what so how they can they "tweak" the results?
Plus if a patient drops out, the results are penalized. The data doesn't just disappear. All data needs to be reported to the FDA for every patient, including all follow ups.
> And indeed in most clinical trials there is no strong adverse effects (just weak) reported except when patients die.
This is 100% false. All adverse events need to be reported, whether caused by the drug or not. This is why relatively innocuous drug have weird side effects like "diarrhea, constipation". The top adverse events have to be reported, even if it's 0.01% who had them.
> Moreover, the hospitals that implement the trial often only do the minimum to satisfy the principal investigator
No, the hospital doesn't know which patient received the drug or not. If the patient needs a blood test, they get a blood test like any other patient.
And again, the process needs to be followed or else the deviation reported. All of that is reported to the FDA. If enough deviations happen, the FDA can say they won't approve the drug.
> Just look at the field of neurodegenerative diseases or ask patients how negligently they have been treated.
What are you talking about? Can you provide a source?
You've already made many statements that are clearly false, which you would know if you had done even basic research into the field using google. You clearly don't know the field very well, so I'm not sure why you feel like your "ideas" of how trials are run are of any value.
I think GP may be referring to CROs who generally do most of the ops of a clinical trial. Their incentive isn’t to have positive results though, it’s to milk the trial contract (cost plus contracting w/ ~no incentive to operate them quickly and efficiently) and then to have the results never get disputed by FDA. A CRO that fakes data is a CRO that will not survive very long.
Agreed on all your other points though, GP has no clue what they’re talking about.
Agreed on all your other points though, GP has no clue what they’re talking about.
nah, OP is an internet expert, lets just listen to them instead of this study
There is a global shortage.
[deleted]
Here's a potentially better alternative to Ozempic: glucose control.
Let people buy CGMs without a prescription, increase education about healthy habits from the point of view of minimizing glucose spikes [1][2], and the importance of metabolism for everything, including physical and mental health [3].
Yes, diet and exercise helps, but what you eat is also important, as well as when, and in what order. Once you learn about it (and have a CGM showing the effects in your body in realtime) you can't unsee it.
[1] Glucose Revolution, by Jessie Inchauspe https://www.amazon.com/Glucose-Revolution-Life-Changing-Powe...
[2] Brain Energy, by Dr. Christopher M. Palmer MD - https://brainenergy.com/
https://www.psychologytoday.com/us/blog/advancing-psychiatry...
Let people buy CGMs without a prescription, increase education about healthy habits from the point of view of minimizing glucose spikes [1][2], and the importance of metabolism for everything, including physical and mental health [3].
Yes, diet and exercise helps, but what you eat is also important, as well as when, and in what order. Once you learn about it (and have a CGM showing the effects in your body in realtime) you can't unsee it.
[1] Glucose Revolution, by Jessie Inchauspe https://www.amazon.com/Glucose-Revolution-Life-Changing-Powe...
[2] Brain Energy, by Dr. Christopher M. Palmer MD - https://brainenergy.com/
https://www.psychologytoday.com/us/blog/advancing-psychiatry...
Why is it a better alternative? Does more data actually make a difference for something like this? Do you know anyone on Ozempic?
It's on the way. Abbott (makers of the Freestyle Libre CGM) are trying to get a general use version sold under the Lingo brand name.
https://www.abbott.com/corpnewsroom/products-and-innovation/...
https://www.abbott.com/corpnewsroom/products-and-innovation/...
This is nonsense. There's no evidence that "glucose control" is helpful for anyone but actual diabetics. Glucose spikes are completely normal physiology and nothing to be concerned about unless your actually diabetic.
This whole "all sickness is metabolic disorder, caused by glucose" is a fringe grifter youtube quack theory. On the other hand, semaglutides have actual science behind them.
This whole "all sickness is metabolic disorder, caused by glucose" is a fringe grifter youtube quack theory. On the other hand, semaglutides have actual science behind them.
Echoing the other reply, there is a raging scientific debate between the energy balance model and the carbohydrate insulin model of obesity and diabetes. There are large cohorts of very smart scientists on both sides of this debate.
No there isn't. There's no serious debate and no evidence for the carbohydrate insulin model of obesity.
It seems you're unable to add something to debate, rather than shallow dismissals.
FYI, per HN guidelines, so you can reflect on your future contributions:
- Comments should get more thoughtful and substantive, not less, as a topic gets more divisive.
- Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something.
FYI, per HN guidelines, so you can reflect on your future contributions:
- Comments should get more thoughtful and substantive, not less, as a topic gets more divisive.
- Please don't post shallow dismissals, especially of other people's work. A good critical comment teaches us something.
There absolutely is not. There is raging internet debate, not scientific debate.
> There's no evidence...
I just pointed to an entire book written by a psychiatrist and Harvard professor, with citations to hundreds of studies linking metabolism to metal disorders, insulin resistance, the effect of diet on mitochondrial dysfunction, and your argument is "trust me bro, it's quack theory"?
Don't you think you're being overly reductionist and close-minded, without even reading the evidence provided?
I just pointed to an entire book written by a psychiatrist and Harvard professor, with citations to hundreds of studies linking metabolism to metal disorders, insulin resistance, the effect of diet on mitochondrial dysfunction, and your argument is "trust me bro, it's quack theory"?
Don't you think you're being overly reductionist and close-minded, without even reading the evidence provided?
There are books for every theory, this isn't one that any scientist in the actual field takes serious.
But fringe theories are always popular among certain people, same as conspiracy theories.
But fringe theories are always popular among certain people, same as conspiracy theories.
Ozempic? Or just eating less?
Probably the latter, but "just eating less" is next to impossible for a non-trivial minority of people much the way "just stopping heroin" would be for someone battling addiction.
An aid to help clear the noise in the brain seems to be unsurprisingly useful, then, in achieving these outcomes.
An aid to help clear the noise in the brain seems to be unsurprisingly useful, then, in achieving these outcomes.
Sure, but Ozempic is not the only drug that suppresses appetite. So if the underlying benefits are from “just eating less,” then the study should also examine the effects of other pharmaceutical interventions that suppress appetite.
It's not the only drug that suppresses appetite, but GLP-1 agonists (Ozempic, Zepbound, etc) appear to work for a larger percentage of the population, and significantly outperform previous appetite suppressants.
There's also findings that suggest that it goes beyond simply suppressing appetite, but also manipulates the "reward" center in the brain. Individuals who take it to lose weight find that they have reduced desire to drink or smoke, suggesting it's less that they struggle with appetite and more the medicine helps overcome addictive behavior.
There's also findings that suggest that it goes beyond simply suppressing appetite, but also manipulates the "reward" center in the brain. Individuals who take it to lose weight find that they have reduced desire to drink or smoke, suggesting it's less that they struggle with appetite and more the medicine helps overcome addictive behavior.
Nicotine suppresses appetite as well and that has been used by humans for thousands of years.
That’s so silly, these drugs aren’t even anywhere near the same league of effectiveness. There’s plenty of fat people who take nicotine all day.
Hmmm...if as many people consumed semeglutide you would have examples of fat people in that population as well.
You certainly would, because not every case of obesity results from the same mechanisms. But just as with all the other what-about comments, this comment misses the point: this class of drug is wildly successful, and it's the most specific drug for this problem that's been developed so far
https://www.healthline.com/health-news/ozempic-glp-1-drugs-m...
Here's a good piece running through the failure modes in lay terms.
https://www.healthline.com/health-news/ozempic-glp-1-drugs-m...
Here's a good piece running through the failure modes in lay terms.
This is genuinely one of the stupidest conversations I’ve been involved in. If nicotine was as effective as Ozempic at appetite suppression then everyone would know about it, it would be commonly used in medicine to treat obesity and Ozempic would never have been created. I hope for your sake this is pedantry instead of ignorance.
Sure, it's just not as good as Ozempic at doing that particular job.
> Ozempic is not the only drug that suppresses appetite
If there were a drug that is equally as effective with the same or fewer downsides, then it would've been just as popular for that use case already.
Someone else mentioned nicotine. There are still a lot of "unsuccessful" nicotine users compared to Ozempic.
If there were a drug that is equally as effective with the same or fewer downsides, then it would've been just as popular for that use case already.
Someone else mentioned nicotine. There are still a lot of "unsuccessful" nicotine users compared to Ozempic.
Funding tends to be a constraint with larger studies, and it's best to keep studies focused anyway — less confounding variables.
Here, I'll pontificate a bit. For instance, study 1 finds that Ozempic is associated with a reduced risk of X. Study 2 is now funded to see if the association can be experimentally reproduced to establish a causative relationship. Competing institution gets Study 3 funded to test competing drug Mounjaro, reaches same conclusion. Study 4 by another institution finds same conclusion with a drug that acts in an entirely different manner, Buproprion. Study 5 by yet another institution finds similar results with amphetamines. Study 6 is funded on the premise that there's an underlying mechanism that needs to be explored, gets funding to study caloric restriction, gets similar results. Meanwhile, study 2 finds a causative relationship between Ozempic and X, concluding experimentally that Ozempic achieves X by inducing calorie restriction, which concurs with study 6.
I'm oversimplifying. But you see where I'm going with this. Much easier to both control and fund the smaller studies than a giant one, and you develop more knowledge in the process.
---
Also, I'm not an academic, so I could be wildly off base. Would appreciate a gut check by someone who actually does this for a living.
Here, I'll pontificate a bit. For instance, study 1 finds that Ozempic is associated with a reduced risk of X. Study 2 is now funded to see if the association can be experimentally reproduced to establish a causative relationship. Competing institution gets Study 3 funded to test competing drug Mounjaro, reaches same conclusion. Study 4 by another institution finds same conclusion with a drug that acts in an entirely different manner, Buproprion. Study 5 by yet another institution finds similar results with amphetamines. Study 6 is funded on the premise that there's an underlying mechanism that needs to be explored, gets funding to study caloric restriction, gets similar results. Meanwhile, study 2 finds a causative relationship between Ozempic and X, concluding experimentally that Ozempic achieves X by inducing calorie restriction, which concurs with study 6.
I'm oversimplifying. But you see where I'm going with this. Much easier to both control and fund the smaller studies than a giant one, and you develop more knowledge in the process.
---
Also, I'm not an academic, so I could be wildly off base. Would appreciate a gut check by someone who actually does this for a living.
Just to hammer the point home, imagine suggesting a cure for heroin addiction is to amputate the arms so they can't shoot up. Then look up what gastric bypass surgery is.
For some reason we don't take food addiction seriously at all. You can't walk anywhere without seeing a picture of a Big Muck or something. Heroin addicts don't have to see their vice everywhere they go. Even cigarette addicts don't.
For some reason we don't take food addiction seriously at all. You can't walk anywhere without seeing a picture of a Big Muck or something. Heroin addicts don't have to see their vice everywhere they go. Even cigarette addicts don't.
"Just eating less" may be very difficult, psychologically, in the context of an otherwise stressful and distracting life. However, I find that if you are able to eliminate those issues and focus on your own health and diet -- a big "if", I will grant -- then it's actually not that hard, on its own. You get used to it.
That GLP-1 agonists are as successful as they are and appear to modulate the reward center of the brain (per the latest research on the same class of drugs and smoking/alcohol cessation) suggests that it's certainly not just a psychological matter.
That's why I made the heroin comparison. People underappreciate the addictive properties of refined sugars.
Edit: people also looked at the opiate angle too, apparently. https://pennstatehealthnews.org/2024/04/qa-can-weight-loss-d...
That's why I made the heroin comparison. People underappreciate the addictive properties of refined sugars.
Edit: people also looked at the opiate angle too, apparently. https://pennstatehealthnews.org/2024/04/qa-can-weight-loss-d...
My wife takes full dose. Shes lost 60 pounds in six months.
I have been taking the smallest dose.
Normally i can eat a full meal, and be hungrier at the end of it, then when i started.
For a couple of days after taking the small dose. I get full after a small amount. Then feel full for most of the day. I need to go up to a higher dose as this effect fades before next dose.
Normally i can eat a full meal, and be hungrier at the end of it, then when i started.
For a couple of days after taking the small dose. I get full after a small amount. Then feel full for most of the day. I need to go up to a higher dose as this effect fades before next dose.
> Normally i can eat a full meal, and be hungrier at the end of it, then when i started.
how?! what exactly are you eating that's making you feel hungrier, not full?
how?! what exactly are you eating that's making you feel hungrier, not full?
Rinzler89(1)
It would be interesting to see a comparative study of glp1 agitators to intermittent fasting. It surprises me that people will spend huge amounts on a drug which makes them feel less full, rather than have the tiny amount of willpower it takes to just not eat.
Don't be so fast to assume that your willpower isn't just from genetic luck. You might as well be surprised some people are short. I mean, look how much better your life is as someone tall.
We humans are very quick to assume our positive traits and outcomes come from conscious decisions to make things that way. It's why every successful person has a book about how they chose to become successful. They just worked hard. It's something we want to believe rather than admit anything came down to luck of the draw.
We humans are very quick to assume our positive traits and outcomes come from conscious decisions to make things that way. It's why every successful person has a book about how they chose to become successful. They just worked hard. It's something we want to believe rather than admit anything came down to luck of the draw.
You’re right in your argument about “just do this” suggestions without considering how hard it can be based on intrinsic factors.
I feel there is a point in the thread you’re commenting on though. It would be scientifically interesting to know whether the desired(positive) outcomes of this drug can be replicated by consciously controlling the quantity or quality of food without the use of the drug(by those who can). Still, presenting the result in a useful way rather than stating the drug is useless.
If you had a way to get the same results without any pharmaceutical intervention, and you’re a lucky one that _can_ do it, wouldn’t you want to know how?
I feel there is a point in the thread you’re commenting on though. It would be scientifically interesting to know whether the desired(positive) outcomes of this drug can be replicated by consciously controlling the quantity or quality of food without the use of the drug(by those who can). Still, presenting the result in a useful way rather than stating the drug is useless.
If you had a way to get the same results without any pharmaceutical intervention, and you’re a lucky one that _can_ do it, wouldn’t you want to know how?
It has been tested, Ozempic wins. These drugs are usually tested specifically on people who have tried and failed dieting and exercise interventions. I doubt any doctor is prescribing this without first asking, “have you tried diet and exercise?” The side effects can be pretty gnarly for some people and it’s very expensive and hard to obtain.
And not just genetic luck, but luck of childhood circumstances. Lots of people were given a deranged relationship to food as a child by their parents, leading in many cases to actual metabolic derangement as well.
The common theme in normal weight individuals is their comparative lack of food drive, not an outsized capacity for willpower.
When you talk to "skinny" people you'll hear things like they just forgot to eat or I just had a couple bites of cake then felt full/had enough.
Alternatively when you speak with heavier people you'll realize that they're white knuckling their entire lives (because calories are so abundant). On average they're actually exerting more willpower around food than skinnier people.
Not everyone of course, there are folks in either camp, but at population scale lack of food drive is what keeps people skinny in a calorie rich, low activity environment.
When you talk to "skinny" people you'll hear things like they just forgot to eat or I just had a couple bites of cake then felt full/had enough.
Alternatively when you speak with heavier people you'll realize that they're white knuckling their entire lives (because calories are so abundant). On average they're actually exerting more willpower around food than skinnier people.
Not everyone of course, there are folks in either camp, but at population scale lack of food drive is what keeps people skinny in a calorie rich, low activity environment.
I definitely could have worded this better. I'm NOT suggesting that people who struggle with weight just don't have willpower. I was suggesting that it would be interesting to see a study comparing 2 modalities.
I'm not going to explain it but "ozempic" sounds exactly like the type of wonder drug that turns out be really unfortunate years later.
I wonder how long until these medicines are freely available and no longer in shortage.
It’s encouraging that there is competition.
I’m guessing it might be three or four years till I could just go the the chemist and get it.
It’s encouraging that there is competition.
I’m guessing it might be three or four years till I could just go the the chemist and get it.
It’s pennies on the dollar if you go to a peptide specialist and measure out individual syringes instead of using the auto injectors.
[deleted]
robomartin(6)
It sounds like a miracle drug until you hear prolonged use turns your stomach into stone. They haven't been around long enough to fully understand the side effects unfortunately.