There should be trials directly comparing intermittent fasting vs. this drug for the same population. We know that decades long Type Two Diabetes patients have 50% reversal of their diabetes in one year simply staying on intermittent fasting of one to two meals a day without snacking when directly compared to those treated with traditional medical interventions! That’s monumental achievement!
Semaglutide has been wonderful for our patients! It gives them hope and incentive to change their behaviors. They start losing weight immediately which is positive motivation to look at their diet and start an exercise (strength training) program. The con to this medication is patients who look at it as a quick fix and do not make any effort to change their diet or exercise. These patients will lose muscle mass which can lead to instability and falls in the elderly population. For patients taking this medication, it's so IMPORTANT to help them with diet and exercise and not just write a prescription and send them on their way. It's common sense that these drugs will improve outcomes. Get rid of the fat covering all of your organs and clogging your vessels, the better your outcomes will be long term. However, they can also effect other outcomes such as falls, instability, and frailty in elderly patients if they don't change the way that they eat and exercise.
The agriculture industry is not changing any time soon. Probably never. Too many people have too many financial incentives to keep our food unhealthy. I think this class of medications opens the door for more in depth discussion about diet and exercise along with the medication. This is what we do in the office where I work and we use an In-Body scan to assess muscle loss vs. fat loss. So far, our patients are very happy and are all working on diet and strength training.
I disagree John. We need to incentivize healthy behaviors and remove toxic junk food from the environment if we are really going to move the needle.
Ultra-processed foods make up most of the diet in the developed world. They contain three ingredients - processed added sugar, highly processed grains, and seed oils. These foods have no nutrition in them.
Denmark has a program where if you earn a lower income, you get a food card and you're incentivized to buy whole food. But in the US, if you’re on a lower income, you get a food stamp, and you can buy Coke. In fact, 10% of all that money goes towards Coke and sugary drinks, 70% goes towards ultra-processed food.
Instead, the US government subsidizes drugs like Ozempic to the tune of $10,000 per patient per year and it’s the reason why people are doing cartwheels on Wall Street right now - because obesity drugs are the largest target market. Much of that money should be invested in regenerative agriculture and better food, particularly for lower income kids.
I’m not impressed but check my math. At the beginning of the trial, I see 100 adults age ~62 in the room each hoping to get the drug v. placebo. 3 years later, we find out 93 had no CV event but 12 had an adverse reaction. Of the 7 who had CV event, 3 we’re taking drug and 4 were taking placebo. Presumption is that any benefit will continue after 3 years. Cost is too high for the possible long term benefit, especially if paid by third party. Nevertheless, John, keep these interesting articles coming . These are so good, they should be integrated and formalized into continuing education credits.
The final scientific word on obesity has not been written.
Some people erroneously dismiss that it has genetic precursors and that is to dismiss the fact that humans have stopped evolving, we are no longer evolutionarily "fit" because we no longer die of un-fitness, we now have medical interventions for nearly everything, and neonates who should be dead are forced to live and procreate, further spreading un-fitness.
We have sedentary lifestyles
We have junk-food lifestyles
We have high anxiety lifestyles (yes, the rat race is more anxiety causing than palaeolithic tribe survivalism)
I think Vinay has the final word on this.
Just like he says the purpose of cancer drugs should not be to defeat the cancer but to extend the life, the same must be said for anti-obesity drugs.
The criteria should NOT to "reduce obesity".
The criteria should be: did it delete the life shortening effects of obesity?
Honestly, for Big Pharma to be acceptable in its conclusions, the studies need to be run long enough to demonstrate life extension.
That's where the bar should be.
I had a friend a while back who'd been on Fenfen, she LOVED it and was incredibly disappointed when it stopped. I'd trust Fenfen before I'd trust these semaglutides. Because Fenfen acted by raising your baseline. Semaglutides reduce digestion, that just sounds like a catastrophe waiting to happen.
Me: "Well Doc, if I take this pill, will it help me live longer?". Doc: "Well no, not really, maybe 3 week longer if you didn't take it, but if you do maybe you won't suffer a heart attack or stroke - and you'll wake up 3x per week with this weird leg pain"
The girl who eats a saucer full of food and fells full is sensitive to leptin. Individuals who consume lots of fructose or are overweight are insensitive to leptin and they remain hungry.
All good points. The major problem facing the clinician is this. What will people do? How can I really help them deal with these challenges in realistic ways. The bottom line is: you can't outrun a spoon. You must walk a mile to work off the 100 calories in a piece of white bread. I have drastically reduced carbs and almost eliminated sugar. I go to the Y and do 30 min of progressive resistance exercise three times a week. Most people can do that and many of them will.
The problem is the prospect of "gym exercise" is most depressing to so many of us. Before we became wall-E sedentary slugs, our NORMAL life used to provide us with enough varied exercise to keep us somewhat fit.
But because we're addicted to tech (appliances, etc) we've replaced all our manual labour with machine labour.
This is unsustainable.
Our lives as in the film wall-E is inevitable.
I lived in Ecuador for a while, and I re-learned to perform household chores by hand. It was fukin amazing. I loved it.
Your points are valid. I am talking about a specific issue. Once you pass 65, muscle wasting begins due to oxidant imbalance. Too much oxidant production. Too few antioxidants. Ordinary housework is good but it will not stop frailty. The most effective tool against frailty is moving as much weight as you can 15 times. It takes 30 min three times a week and enables everything else you love to do longer.
I have been in internal medicine since 1973 and I am 76 years old now. I am still active and contributing to society. New medical science and systems mean we can live longer, healthier, productive lives. That is important to me and others like me. It is fine if that is not important to you
I'm nearing 60. So a bit younger indeed. Well past menopause. You and I can have our ideas about things.
What I'm talking about is PH policy. I am quite angry that in countries with *Public ACCESS private PROFITS* healthcare, we are more and more focused on extending the death of the old instead of improving the quality of life of the generations of living age.
We are wasting billions of dollars making Big Pharma rich, because geriatrics is a golden goose of never ending profits.
Making youth chronically sick is the other golden goose of Big Pharma.
On the PH policy front, we are going in the WRONG direction.
Surprisingly, we have some agreement here. I have been writing on Substack for two and a half years at Slowaging, and Delay Chronic Disease. There are medical protocols for type 2 diabetes that extend HEATHIER life by eight years for about $31. Our system rewards expensive interventions late in the disease process. Other developed countries are healthier longer in part because the have a system that is anchored in primary care and health maintenance. They also eat whole real food and they don't depend on cars as much. The current discussion is actually a great example. By taking metformin for $4 a month and eating real food by limiting sugar and carbs, you can double the reduction in heart attack risk produced by Wegovy. If you combine generic drugs in a protocol to address diabetes with lifestyle measures you reduce heart attack risk 4 fold compared with the care that most Americans receive. There is no one to pay for the advertising to promote that and that is why I write about it.
I hope people will do that. Even for those intimidated by “working out” they need to know that all it takes to get started is getting out in the sun in the morning and walking for 30mins a few times a week.
Obesity is not a disease. A disease is a physical and/or biochemical alteration that causes a body organ or organ system to malfunction. Nothing that can be eliminated through the exercise of will power is a disease and to call it such is a disservice to those who suffer from true diseases and causes people to have unrealistic expectations about what doctors and the practice of medicine are really all about.
The hormonal disfunction that underlies obesity is certainly a physiological process, whether you want to call it a disease or not. No one is choosing to be fat. And you can’t fight hormones through will power. You CAN intervene in the cycle through dramatic changes in diet - eg, significantly cutting back on carbs. But unfortunately all our official dietary guidelines tell people the opposite.
My comment was in response to the author's claim that "It (obesity) is a disease." I certainly agree with you that obsession with eradication of disease and death is a recipe for disaster.
You seem to have either missed or ignored that 2/3rds of the patients had an A1C > 5.7% and were thus prediabetic and that the drug worked better in those prediabetic than those that were not. It’s not surprising a GLP-1 helps obese hyperglycemic patients with preexisting atherosclerosis. Maybe this will awaken cardiologists to normalize blood sugars instead of trying to suppress LDL to < 1st percentile thru multiple drugs, some of which (evolocumab and bempedoic acid) are constantly associated with more cardiovascular and all-cause mortality.
Gastric bypass essentially had the same impact for pre-diabetics and diabetics. Basically semaglutides could be described as a chemical gastric bypass.
That's another thing: A1c greater than 5.7 = pre-diabetic? Funny how that upper bound keeps getting lowered. Now who, I wonder, who could possibly be benefiting from that widening net of pre-diabetes? Why don't we just say everyone is pre-diabetic? I'm predicting that A1c of >4.0 will be the new pre-diabetic by 2030.
The problem is not the goal-post A1c shift, but rather the use of glucose-centric metrics. The paradigm shift that is needed is to move towards insulin-centric metrics. Insulin resistance is the target. The are many studies showing the link between insulin resistance and the plagues of prosperity. It is impossible to be healthy if one has insulin resistance. The big elephant in the room primary cause is hyperinsulinemia which is also a consequence of insulin resistance. And the big cause of hyperinsulinemia is the high percentage if hyperpalatable, highly processed junk food that the US consumes
Your questions and comments are right on the money. I published a short article several years ago on junkscience.com on this topic. It was titled "Creating Disease Through Redefinition". Unfortunately I can't link to it because the website was taken over a few years ago and they didn't archive the previous articles. I kept copies but, being technologically limited, I don't know how to transmit them. It is a fairly short article and I can retype the relevant parts for you here if you are interested. Basically I described how the "normal" levels for cholesterol were progressively ratcheted downward in order to create a large class of new "patients" out of the normal population. Subsequently the same process was followed for blood glucose values in order to create a new (and entirely fictitious) disease called Type 2 diabetes and, then the absurd label of "pre-diabetic". The same pattern was then followed for Body Mass Index in order to swell the ranks of those labelled obese.
I'd love to read what you wrote about this. My husband and I read "The Cholesterol Delusion" and really found that informative. It's astonishing to me how gullible Americans are. I think what we're talking about is "disease mongering". Every time some new "fill-in-the-blank Syndrome" hits the news I search for the wonder drug ads that will surely cure that. Like "Restless Leg Syndrome". There's gold in them thar hills!
I agree with your points generally. But “restless leg syndrome” is a bad example as it is unfortunately very real. I had it for a while and it’s pretty awful. I was able to treat it through a combination of medication and addressing food allergies.
I've had restless legs myself. It is horrible. For me it was a result of meds for asthma. My point was that once pharma zeros in on a "syndrome", the patent meds will appear that are directed specifically at that "syndrome'" and they won't be cheap. And they may not be necessary at all. It's just another way to come up with products that can be directly advertised to consumers who will be encouraged to "ask your doctor about ____,".
Disease mongering is a very accurate term. I will quote part of the article I referred to: Creating Disease Through Redefinition.
The first part pointed out that the government likes to "solve" problems by redefining them and I used unemployment statistics and inflation figures as typical examples. Following that introduction:
"Redefinition is thus a useful tool for "solving" certain problems. But it can also be used to create the appearance of a problem where none really exists. Nowhere has this technique been more profitably employed than in the medical field.
Probably the most flagrant use of fraudulent redefinition can be seen in the history of blood cholesterol levels. Forty years ago the normal range for an individual's blood cholesterol level was 150-350 mg/dl. Over the past 20-30 years this "normal" level has been ratcheted down so that the highest number considered to be normal or "acceptable" is now 200 mg/dl or less. Of course the net effect of this is to create a large number of "patients" out of the normal healthy population. And, of course, all of these new patients need treatment in order to reduce their cholesterol numbers down to the new acceptable levels. Most people naturally assume that these changes were made in response to new scientific data showing that these lower levels would significantly reduce the risk of heart disease. Nothing could be further from the truth.
These changes were wrought by panels of "experts" usually convened under the auspices of the National Institute of Health (NIH), a government bureaucracy that is responsible for funding the great majority of what passes for medical research in this country. On the cholesterol question a number of "consensus conferences" were held and out of these came the recommendations to ratchet down the normal or acceptable cholesterol levels to where they are today----considerably below the mean level of the normal population. Of course the participants invited to the consensus conferences did not include any of those who seriously questioned the veracity of the cholesterol theory of heart disease. Excluding such troublemakers and heretics assured a smooth and easy path to a proper consensus. The panel members were mostly those whose careers were closely tied to the cholesterol theory and many had financially remunerative relationships with drug companies and other groups with a vested interest in expanding the public's anxiety over cholesterol and heart disease.
Many people put the bulk of the blame on the pharmaceutical companies. These companies certainly put out a lot of misinformation and promote it to a fare-thee-well but they didn't really instigate it. That was mostly done by academics and researchers who tied their reputations and careers to the cholesterol theory and were aided and abetted by organizations such as the NIH and the American Heart Association who have a vested interest in exaggerating the extent of heart disease and fooling people into thinking that they are on the front lines fighting it.
But medical redefinition is not confined to cholesterol and heart disease. The so called "epidemics" of obesity and diabetes were also created this way.
A few decades back a person was diagnosed as diabetic if their fasting blood sugar (FBS) was greater than 160. Much like the cholesterol story, this has been ratcheted down to where people with FBS levels as low as 110-120 are being told they are diabetic and often put on medication. In addition a whole new category of "pre-diabetics" has been created to provide an even larger number of people in need of close medical monitoring. And just as with cholesterol, there has been no compelling scientific data to justify any of these changes. Diabetic researchers, drug companies and groups like the American Diabetes Association and some endocrinology trade organizations that all have a vested interest in creating more diabetics have driven the process.
Years ago a Body Mass Index (BMI) greater than 30 would earn a person the label of "obese", Now one's BMI must be below 25 in order to avoid being branded with this derogatory label. Since a substantial proportion of the population over the age of 35 have BMIs in this 25-30 range, it has naturally swelled the ranks of the obese by quite a bit. Just like heart disease and diabetes there are analogous interest groups who profit from creating this "epidemic". Obesity researchers and anti-obesity organizations abound. The internet is full of people describing themselves as "anti-obesity activists". It is ironic that so many people who are properly critical of the role that drug companies play in these fraudulent schemes are helping to promote the interests and profits of an enormous diet and weight loss industry that dwarfs the pharmaceutical companies in size and scope
Ths same techniques of redefinition have been used to increase the number of those with hypertension, autism, and many other conditions. And we mustn't forget the pseudo-diseases such as attention deficit disorder, fibromyalgia, chronic fatigue syndrome, and a whole litany of addictions. They all have their own advocacy groups and hordes of researchers trying to get on the research grant gravy train."
I agree with many of your points. As someone who has had chronic fatigue syndrome (also known as ME/CFS) since 1987, I strongly disagree with your characteristic of it as a “pseudo-disease.” This is misinformation that has been circulated for many years (HHS was one of the main perpetrators). I know many people with ME/CFS - in addition to my personal experience - and this disease is all too real, and very disabling.
Perhaps the term "pseudo-disease" was a poor word choice on my part. I didn't intend it to be insulting. I just wanted to show that it didn't fit my definition of disease which is something that can be diagnosed via biochemical testing and/or physical observation. Perhaps some of those I listed will be shown to be diseases in the future but, at this time, they don't fit the definition. There are lots of things that bother people for which there is no known cause and that doesn't mean they are not real; they just don't fit the definition of disease.
Thanks! You sum it up pretty well. My fasting glucose was 101 last test I took and that got flagged. I've read enough to know how asinine that is but along with the flag came the "consider metformin" notice. My A1c was 5.8 and you know that got flagged. My BMI is 25 but I'm a weight lifter so that means nothing but I still hear mention of "that's an upper bound" for normal weight. I feel really bad for people who trust the various organizations, the AHA etc, and live in fear, and discomfort because of the horrible meds. Now here comes semaglutide and it's stunning how it's trumpeted as just what we need. At some point no one is going to listen to any advice from doctors.
You are very welcome. It is a pleasure to communicate with people who have their head on straight. It gives me some hope for the future for my children and grandchildren. I think the medical profession lost a lot of whatever credibility they had with the Covid scam. I'm glad I got out when I did. And thank you for the kind words about my book. It was the first thing I ever wrote and that was several years after I retired from active medical practice. So I'm glad that you found it to be fairly coherent.
Or we could jail the entire C-suite occupants of P&G, Conagra, etc, and every FDA and CDC jackoff who lies day in and day out to unassuming Americans and profits off the chronic diseases we’ve all been set up for with the soybean oil, HFCS, red-40 laden garbage that is virtually the only “food” that’s even legal to sell in this country anymore. Put those trials on PPV, and you could buy a lot of Ozempic and/or grass-fed beef from those ticket sales.
Well that's just peachy keen. These people were in their early 60's and so what will be the outcome if they live another 10, 15, 20, 25 or 30 years? And the cost to the patient and profit to pig pharma? Perhaps about $300-400 thousand over 15-20 years. Thanks for ramping up my insurance costs. Just how many retirees can afford to play an out-of-pocket $20K/year get out of obesity card?
This looks like lifestyles will go down the tubes as we now have more drugs to do the job and fix the problems. Eat, drink and smoke anything you want. Don't matter, no more. Coach potatoes are now saved from over-couching. And fast food junkies can "fast-food" all they want.
I will never give up the belief that most solutions for many medical problems do not involve endless drugs for life.
What's better: A society in which people are sedentary and fat, or a society in which people are sedentary and not fat?
We can cry all day long (and believe me, I've done that) about how people don't take responsibility for their health, but the facts are that any treatment which helps people be less sick over their lifetime is a net positive.
You're assuming the cost of that treatment is low. But we don't know the long term effects of semaglutide. And the short term side effects are not trivial. I think semaglutide will turn out to make people less healthy over their lifetimes.
Fair enough, we don't know the long-term effects, though these types of drugs have been on the market for about 20 years without much concern.
However, we do know the long-term effects of obesity, among which is a significantly reduced life span and death.
The most common short-term side effects are gastrointestinal in nature and mostly due to people continuing to eat past when they feel full. There really are very few side effects of this drug when compared to other treatments for obesity (exercise and dieting not included).
Given that almost everyone who uses semaglutide for weight loss is going to be taking it for the rest of his life, what's happening is a mass long term test. The long term side effects will be known, eventually, but this present cohort will be paying full price. I think people should be able to do whatever they want to lose weight. But semaglutide should be last ditch.
Seeing this kind of marketing in the hrt domain, where estrogen is considered almost toxic. Now there's "Veozah", which directly targets the neurons that control body temperature. It's just there are those side effects, among which, if you believe the FDA release on the study that resulted in its approval (a study of 1100 women for maybe a year), can include more than twice the relative risk of insomnia as for the placebo arm. That's just short term. What are the long term side effects? No one knows. Tampering with neurotransmitters long term doesn't seem like a good idea, but the pressure is on to push this.
Again, we're faced with either the long-term effects of semaglutides or the long-term effects of obesity, which are better or least worse?
I agree that semaglutides should be a final resort option, similar to gastric bypass. However, we already know that nearly 50% of people have been incapable of making the necessary lifestyle changes to not be obese, so we are likely to see the majority of obese individuals using this drug.
I see this much like you do with respect to HRT, but in the other direction. GLP-1 is a naturally produced hormone, like estradiol, and we are creating a synthetic version called semaglutide, like synthetic estradiol, to supplement low levels of the naturally produced hormone. As opposed to other weight loss drugs which effect neurotransmitters, like stimulants, or raise basal metabolic rates, such as levothyroxine, synthetically produced GLP-1 receptor agonists have so far shown relatively few side effects. The jury is still out on long-term effects, but compared to the scope of the problem that is obesity and the societal problems it causes, we'd have to see major and severe long-term side effects to offset its benefits.
Not to mention that new versions of these class of drugs are being researched and tested which can prove more effective and with potentially fewer side effects.
Will you still be against this drug if it demonstrates minor side effects over long-term use?
It depends on what you call minor. If it's short lived constipation or flatulence that's one thing. But it's going to be more than that, because severe side effects are already showing up near term. I would not want to deny this to someone willing to take those risks with full knowledge. And most of the obesity we see now is a consequence of poor choices in food and exercise, unlike low estrogen. But I would put this in the same class as amphetamines for weight loss.
Is semaglutide's effect on appetite a product of its action on monoamine neurotransmitters? I know there have been reports of suicide on semaglutide, and most diet drugs in that category, including some amphetamines, have been flagged as dangerous and withdrawn:
The more I think about this, the more I think amphetamines were really no worse than semaglutide. People lost weight on them because they killed the appetite. To keep the weight off you had to stay on them indefinitely. Maybe pharma would rather not go back to "diet pills" because they're available in generic form. But they sure sounded like a lot more fun than flatulence, belching, constipation, and gastroparesis and ileus. 🤔
For the record - Ohio is just as fat as Kentucky.... maybe we start banning advertisement for anything containing sugar or fructose - similar to what was done with cigarettes. while we're at banning ads-- we could stop letting pharma run direct to consumer ads as well - if I see a pharma ad -- pretty sure the product doesn't work very well or you would not need the ad to sell it.
There should be trials directly comparing intermittent fasting vs. this drug for the same population. We know that decades long Type Two Diabetes patients have 50% reversal of their diabetes in one year simply staying on intermittent fasting of one to two meals a day without snacking when directly compared to those treated with traditional medical interventions! That’s monumental achievement!
Improving 1% seems minimums, in my opinion.
Semaglutide has been wonderful for our patients! It gives them hope and incentive to change their behaviors. They start losing weight immediately which is positive motivation to look at their diet and start an exercise (strength training) program. The con to this medication is patients who look at it as a quick fix and do not make any effort to change their diet or exercise. These patients will lose muscle mass which can lead to instability and falls in the elderly population. For patients taking this medication, it's so IMPORTANT to help them with diet and exercise and not just write a prescription and send them on their way. It's common sense that these drugs will improve outcomes. Get rid of the fat covering all of your organs and clogging your vessels, the better your outcomes will be long term. However, they can also effect other outcomes such as falls, instability, and frailty in elderly patients if they don't change the way that they eat and exercise.
The agriculture industry is not changing any time soon. Probably never. Too many people have too many financial incentives to keep our food unhealthy. I think this class of medications opens the door for more in depth discussion about diet and exercise along with the medication. This is what we do in the office where I work and we use an In-Body scan to assess muscle loss vs. fat loss. So far, our patients are very happy and are all working on diet and strength training.
Yup. Pretty basic and sensible advice.
It is odd. They smoke and live longer. Our toxic food and inactivity seems to be an offset.
I disagree John. We need to incentivize healthy behaviors and remove toxic junk food from the environment if we are really going to move the needle.
Ultra-processed foods make up most of the diet in the developed world. They contain three ingredients - processed added sugar, highly processed grains, and seed oils. These foods have no nutrition in them.
Denmark has a program where if you earn a lower income, you get a food card and you're incentivized to buy whole food. But in the US, if you’re on a lower income, you get a food stamp, and you can buy Coke. In fact, 10% of all that money goes towards Coke and sugary drinks, 70% goes towards ultra-processed food.
Instead, the US government subsidizes drugs like Ozempic to the tune of $10,000 per patient per year and it’s the reason why people are doing cartwheels on Wall Street right now - because obesity drugs are the largest target market. Much of that money should be invested in regenerative agriculture and better food, particularly for lower income kids.
Oh wonderful... let’s put half the country on this so that we can continue to see the stocks rise and profit off of this real pandemic.
The real problem lies with what people are eating. Until that is fixed, American will continue down the path of morbid living and addicted to drugs.
wait till gastroparesis really rears its ugly head?
what was All Cause Mortality?
I’m not impressed but check my math. At the beginning of the trial, I see 100 adults age ~62 in the room each hoping to get the drug v. placebo. 3 years later, we find out 93 had no CV event but 12 had an adverse reaction. Of the 7 who had CV event, 3 we’re taking drug and 4 were taking placebo. Presumption is that any benefit will continue after 3 years. Cost is too high for the possible long term benefit, especially if paid by third party. Nevertheless, John, keep these interesting articles coming . These are so good, they should be integrated and formalized into continuing education credits.
The final scientific word on obesity has not been written.
Some people erroneously dismiss that it has genetic precursors and that is to dismiss the fact that humans have stopped evolving, we are no longer evolutionarily "fit" because we no longer die of un-fitness, we now have medical interventions for nearly everything, and neonates who should be dead are forced to live and procreate, further spreading un-fitness.
We have sedentary lifestyles
We have junk-food lifestyles
We have high anxiety lifestyles (yes, the rat race is more anxiety causing than palaeolithic tribe survivalism)
I think Vinay has the final word on this.
Just like he says the purpose of cancer drugs should not be to defeat the cancer but to extend the life, the same must be said for anti-obesity drugs.
The criteria should NOT to "reduce obesity".
The criteria should be: did it delete the life shortening effects of obesity?
Honestly, for Big Pharma to be acceptable in its conclusions, the studies need to be run long enough to demonstrate life extension.
That's where the bar should be.
I had a friend a while back who'd been on Fenfen, she LOVED it and was incredibly disappointed when it stopped. I'd trust Fenfen before I'd trust these semaglutides. Because Fenfen acted by raising your baseline. Semaglutides reduce digestion, that just sounds like a catastrophe waiting to happen.
Me: "Well Doc, if I take this pill, will it help me live longer?". Doc: "Well no, not really, maybe 3 week longer if you didn't take it, but if you do maybe you won't suffer a heart attack or stroke - and you'll wake up 3x per week with this weird leg pain"
The girl who eats a saucer full of food and fells full is sensitive to leptin. Individuals who consume lots of fructose or are overweight are insensitive to leptin and they remain hungry.
All good points. The major problem facing the clinician is this. What will people do? How can I really help them deal with these challenges in realistic ways. The bottom line is: you can't outrun a spoon. You must walk a mile to work off the 100 calories in a piece of white bread. I have drastically reduced carbs and almost eliminated sugar. I go to the Y and do 30 min of progressive resistance exercise three times a week. Most people can do that and many of them will.
The problem is the prospect of "gym exercise" is most depressing to so many of us. Before we became wall-E sedentary slugs, our NORMAL life used to provide us with enough varied exercise to keep us somewhat fit.
But because we're addicted to tech (appliances, etc) we've replaced all our manual labour with machine labour.
This is unsustainable.
Our lives as in the film wall-E is inevitable.
I lived in Ecuador for a while, and I re-learned to perform household chores by hand. It was fukin amazing. I loved it.
Your points are valid. I am talking about a specific issue. Once you pass 65, muscle wasting begins due to oxidant imbalance. Too much oxidant production. Too few antioxidants. Ordinary housework is good but it will not stop frailty. The most effective tool against frailty is moving as much weight as you can 15 times. It takes 30 min three times a week and enables everything else you love to do longer.
Life past menopause is a modernity social construct. People used to work in their day to day act of living.
Civilisation medicine pushed people to live past menopause and now calls "illness" everything that is simply old age.
Yes, ordinary living stopped frailty to a reasonable age.
Fountain-of-youthism is a real freakin problem in PH policy.
I have been in internal medicine since 1973 and I am 76 years old now. I am still active and contributing to society. New medical science and systems mean we can live longer, healthier, productive lives. That is important to me and others like me. It is fine if that is not important to you
I'm nearing 60. So a bit younger indeed. Well past menopause. You and I can have our ideas about things.
What I'm talking about is PH policy. I am quite angry that in countries with *Public ACCESS private PROFITS* healthcare, we are more and more focused on extending the death of the old instead of improving the quality of life of the generations of living age.
We are wasting billions of dollars making Big Pharma rich, because geriatrics is a golden goose of never ending profits.
Making youth chronically sick is the other golden goose of Big Pharma.
On the PH policy front, we are going in the WRONG direction.
Surprisingly, we have some agreement here. I have been writing on Substack for two and a half years at Slowaging, and Delay Chronic Disease. There are medical protocols for type 2 diabetes that extend HEATHIER life by eight years for about $31. Our system rewards expensive interventions late in the disease process. Other developed countries are healthier longer in part because the have a system that is anchored in primary care and health maintenance. They also eat whole real food and they don't depend on cars as much. The current discussion is actually a great example. By taking metformin for $4 a month and eating real food by limiting sugar and carbs, you can double the reduction in heart attack risk produced by Wegovy. If you combine generic drugs in a protocol to address diabetes with lifestyle measures you reduce heart attack risk 4 fold compared with the care that most Americans receive. There is no one to pay for the advertising to promote that and that is why I write about it.
I hope people will do that. Even for those intimidated by “working out” they need to know that all it takes to get started is getting out in the sun in the morning and walking for 30mins a few times a week.
Obesity is not a disease. A disease is a physical and/or biochemical alteration that causes a body organ or organ system to malfunction. Nothing that can be eliminated through the exercise of will power is a disease and to call it such is a disservice to those who suffer from true diseases and causes people to have unrealistic expectations about what doctors and the practice of medicine are really all about.
The hormonal disfunction that underlies obesity is certainly a physiological process, whether you want to call it a disease or not. No one is choosing to be fat. And you can’t fight hormones through will power. You CAN intervene in the cycle through dramatic changes in diet - eg, significantly cutting back on carbs. But unfortunately all our official dietary guidelines tell people the opposite.
It's not "obesity" that's a disease, but obesity is a symptom of a diseased society.
In the natural world, un-fit individuals die. Death drives evolution and fitness.
But our civilisation is obsessed with disease eradication and death eradication. That is a diseased way of thinking.
Diseased thinking leads to diseased living which leads to Pharma profits.
My comment was in response to the author's claim that "It (obesity) is a disease." I certainly agree with you that obsession with eradication of disease and death is a recipe for disaster.
You seem to have either missed or ignored that 2/3rds of the patients had an A1C > 5.7% and were thus prediabetic and that the drug worked better in those prediabetic than those that were not. It’s not surprising a GLP-1 helps obese hyperglycemic patients with preexisting atherosclerosis. Maybe this will awaken cardiologists to normalize blood sugars instead of trying to suppress LDL to < 1st percentile thru multiple drugs, some of which (evolocumab and bempedoic acid) are constantly associated with more cardiovascular and all-cause mortality.
Gastric bypass essentially had the same impact for pre-diabetics and diabetics. Basically semaglutides could be described as a chemical gastric bypass.
That's another thing: A1c greater than 5.7 = pre-diabetic? Funny how that upper bound keeps getting lowered. Now who, I wonder, who could possibly be benefiting from that widening net of pre-diabetes? Why don't we just say everyone is pre-diabetic? I'm predicting that A1c of >4.0 will be the new pre-diabetic by 2030.
The problem is not the goal-post A1c shift, but rather the use of glucose-centric metrics. The paradigm shift that is needed is to move towards insulin-centric metrics. Insulin resistance is the target. The are many studies showing the link between insulin resistance and the plagues of prosperity. It is impossible to be healthy if one has insulin resistance. The big elephant in the room primary cause is hyperinsulinemia which is also a consequence of insulin resistance. And the big cause of hyperinsulinemia is the high percentage if hyperpalatable, highly processed junk food that the US consumes
Your questions and comments are right on the money. I published a short article several years ago on junkscience.com on this topic. It was titled "Creating Disease Through Redefinition". Unfortunately I can't link to it because the website was taken over a few years ago and they didn't archive the previous articles. I kept copies but, being technologically limited, I don't know how to transmit them. It is a fairly short article and I can retype the relevant parts for you here if you are interested. Basically I described how the "normal" levels for cholesterol were progressively ratcheted downward in order to create a large class of new "patients" out of the normal population. Subsequently the same process was followed for blood glucose values in order to create a new (and entirely fictitious) disease called Type 2 diabetes and, then the absurd label of "pre-diabetic". The same pattern was then followed for Body Mass Index in order to swell the ranks of those labelled obese.
I'd love to read what you wrote about this. My husband and I read "The Cholesterol Delusion" and really found that informative. It's astonishing to me how gullible Americans are. I think what we're talking about is "disease mongering". Every time some new "fill-in-the-blank Syndrome" hits the news I search for the wonder drug ads that will surely cure that. Like "Restless Leg Syndrome". There's gold in them thar hills!
I agree with your points generally. But “restless leg syndrome” is a bad example as it is unfortunately very real. I had it for a while and it’s pretty awful. I was able to treat it through a combination of medication and addressing food allergies.
I've had restless legs myself. It is horrible. For me it was a result of meds for asthma. My point was that once pharma zeros in on a "syndrome", the patent meds will appear that are directed specifically at that "syndrome'" and they won't be cheap. And they may not be necessary at all. It's just another way to come up with products that can be directly advertised to consumers who will be encouraged to "ask your doctor about ____,".
Disease mongering is a very accurate term. I will quote part of the article I referred to: Creating Disease Through Redefinition.
The first part pointed out that the government likes to "solve" problems by redefining them and I used unemployment statistics and inflation figures as typical examples. Following that introduction:
"Redefinition is thus a useful tool for "solving" certain problems. But it can also be used to create the appearance of a problem where none really exists. Nowhere has this technique been more profitably employed than in the medical field.
Probably the most flagrant use of fraudulent redefinition can be seen in the history of blood cholesterol levels. Forty years ago the normal range for an individual's blood cholesterol level was 150-350 mg/dl. Over the past 20-30 years this "normal" level has been ratcheted down so that the highest number considered to be normal or "acceptable" is now 200 mg/dl or less. Of course the net effect of this is to create a large number of "patients" out of the normal healthy population. And, of course, all of these new patients need treatment in order to reduce their cholesterol numbers down to the new acceptable levels. Most people naturally assume that these changes were made in response to new scientific data showing that these lower levels would significantly reduce the risk of heart disease. Nothing could be further from the truth.
These changes were wrought by panels of "experts" usually convened under the auspices of the National Institute of Health (NIH), a government bureaucracy that is responsible for funding the great majority of what passes for medical research in this country. On the cholesterol question a number of "consensus conferences" were held and out of these came the recommendations to ratchet down the normal or acceptable cholesterol levels to where they are today----considerably below the mean level of the normal population. Of course the participants invited to the consensus conferences did not include any of those who seriously questioned the veracity of the cholesterol theory of heart disease. Excluding such troublemakers and heretics assured a smooth and easy path to a proper consensus. The panel members were mostly those whose careers were closely tied to the cholesterol theory and many had financially remunerative relationships with drug companies and other groups with a vested interest in expanding the public's anxiety over cholesterol and heart disease.
Many people put the bulk of the blame on the pharmaceutical companies. These companies certainly put out a lot of misinformation and promote it to a fare-thee-well but they didn't really instigate it. That was mostly done by academics and researchers who tied their reputations and careers to the cholesterol theory and were aided and abetted by organizations such as the NIH and the American Heart Association who have a vested interest in exaggerating the extent of heart disease and fooling people into thinking that they are on the front lines fighting it.
But medical redefinition is not confined to cholesterol and heart disease. The so called "epidemics" of obesity and diabetes were also created this way.
A few decades back a person was diagnosed as diabetic if their fasting blood sugar (FBS) was greater than 160. Much like the cholesterol story, this has been ratcheted down to where people with FBS levels as low as 110-120 are being told they are diabetic and often put on medication. In addition a whole new category of "pre-diabetics" has been created to provide an even larger number of people in need of close medical monitoring. And just as with cholesterol, there has been no compelling scientific data to justify any of these changes. Diabetic researchers, drug companies and groups like the American Diabetes Association and some endocrinology trade organizations that all have a vested interest in creating more diabetics have driven the process.
Years ago a Body Mass Index (BMI) greater than 30 would earn a person the label of "obese", Now one's BMI must be below 25 in order to avoid being branded with this derogatory label. Since a substantial proportion of the population over the age of 35 have BMIs in this 25-30 range, it has naturally swelled the ranks of the obese by quite a bit. Just like heart disease and diabetes there are analogous interest groups who profit from creating this "epidemic". Obesity researchers and anti-obesity organizations abound. The internet is full of people describing themselves as "anti-obesity activists". It is ironic that so many people who are properly critical of the role that drug companies play in these fraudulent schemes are helping to promote the interests and profits of an enormous diet and weight loss industry that dwarfs the pharmaceutical companies in size and scope
Ths same techniques of redefinition have been used to increase the number of those with hypertension, autism, and many other conditions. And we mustn't forget the pseudo-diseases such as attention deficit disorder, fibromyalgia, chronic fatigue syndrome, and a whole litany of addictions. They all have their own advocacy groups and hordes of researchers trying to get on the research grant gravy train."
I agree with many of your points. As someone who has had chronic fatigue syndrome (also known as ME/CFS) since 1987, I strongly disagree with your characteristic of it as a “pseudo-disease.” This is misinformation that has been circulated for many years (HHS was one of the main perpetrators). I know many people with ME/CFS - in addition to my personal experience - and this disease is all too real, and very disabling.
Perhaps the term "pseudo-disease" was a poor word choice on my part. I didn't intend it to be insulting. I just wanted to show that it didn't fit my definition of disease which is something that can be diagnosed via biochemical testing and/or physical observation. Perhaps some of those I listed will be shown to be diseases in the future but, at this time, they don't fit the definition. There are lots of things that bother people for which there is no known cause and that doesn't mean they are not real; they just don't fit the definition of disease.
Thanks! You sum it up pretty well. My fasting glucose was 101 last test I took and that got flagged. I've read enough to know how asinine that is but along with the flag came the "consider metformin" notice. My A1c was 5.8 and you know that got flagged. My BMI is 25 but I'm a weight lifter so that means nothing but I still hear mention of "that's an upper bound" for normal weight. I feel really bad for people who trust the various organizations, the AHA etc, and live in fear, and discomfort because of the horrible meds. Now here comes semaglutide and it's stunning how it's trumpeted as just what we need. At some point no one is going to listen to any advice from doctors.
You are very welcome. It is a pleasure to communicate with people who have their head on straight. It gives me some hope for the future for my children and grandchildren. I think the medical profession lost a lot of whatever credibility they had with the Covid scam. I'm glad I got out when I did. And thank you for the kind words about my book. It was the first thing I ever wrote and that was several years after I retired from active medical practice. So I'm glad that you found it to be fairly coherent.
Or we could jail the entire C-suite occupants of P&G, Conagra, etc, and every FDA and CDC jackoff who lies day in and day out to unassuming Americans and profits off the chronic diseases we’ve all been set up for with the soybean oil, HFCS, red-40 laden garbage that is virtually the only “food” that’s even legal to sell in this country anymore. Put those trials on PPV, and you could buy a lot of Ozempic and/or grass-fed beef from those ticket sales.
Well that's just peachy keen. These people were in their early 60's and so what will be the outcome if they live another 10, 15, 20, 25 or 30 years? And the cost to the patient and profit to pig pharma? Perhaps about $300-400 thousand over 15-20 years. Thanks for ramping up my insurance costs. Just how many retirees can afford to play an out-of-pocket $20K/year get out of obesity card?
This looks like lifestyles will go down the tubes as we now have more drugs to do the job and fix the problems. Eat, drink and smoke anything you want. Don't matter, no more. Coach potatoes are now saved from over-couching. And fast food junkies can "fast-food" all they want.
I will never give up the belief that most solutions for many medical problems do not involve endless drugs for life.
There was a time when amphetamines were just a diet drug. Maybe we should bring those back. I think semaglutide is about as risky long term as those.
dollars to donuts, it's probably $1.00 to make that pill
What's better: A society in which people are sedentary and fat, or a society in which people are sedentary and not fat?
We can cry all day long (and believe me, I've done that) about how people don't take responsibility for their health, but the facts are that any treatment which helps people be less sick over their lifetime is a net positive.
You're assuming the cost of that treatment is low. But we don't know the long term effects of semaglutide. And the short term side effects are not trivial. I think semaglutide will turn out to make people less healthy over their lifetimes.
Fair enough, we don't know the long-term effects, though these types of drugs have been on the market for about 20 years without much concern.
However, we do know the long-term effects of obesity, among which is a significantly reduced life span and death.
The most common short-term side effects are gastrointestinal in nature and mostly due to people continuing to eat past when they feel full. There really are very few side effects of this drug when compared to other treatments for obesity (exercise and dieting not included).
Given that almost everyone who uses semaglutide for weight loss is going to be taking it for the rest of his life, what's happening is a mass long term test. The long term side effects will be known, eventually, but this present cohort will be paying full price. I think people should be able to do whatever they want to lose weight. But semaglutide should be last ditch.
Seeing this kind of marketing in the hrt domain, where estrogen is considered almost toxic. Now there's "Veozah", which directly targets the neurons that control body temperature. It's just there are those side effects, among which, if you believe the FDA release on the study that resulted in its approval (a study of 1100 women for maybe a year), can include more than twice the relative risk of insomnia as for the placebo arm. That's just short term. What are the long term side effects? No one knows. Tampering with neurotransmitters long term doesn't seem like a good idea, but the pressure is on to push this.
Again, we're faced with either the long-term effects of semaglutides or the long-term effects of obesity, which are better or least worse?
I agree that semaglutides should be a final resort option, similar to gastric bypass. However, we already know that nearly 50% of people have been incapable of making the necessary lifestyle changes to not be obese, so we are likely to see the majority of obese individuals using this drug.
I see this much like you do with respect to HRT, but in the other direction. GLP-1 is a naturally produced hormone, like estradiol, and we are creating a synthetic version called semaglutide, like synthetic estradiol, to supplement low levels of the naturally produced hormone. As opposed to other weight loss drugs which effect neurotransmitters, like stimulants, or raise basal metabolic rates, such as levothyroxine, synthetically produced GLP-1 receptor agonists have so far shown relatively few side effects. The jury is still out on long-term effects, but compared to the scope of the problem that is obesity and the societal problems it causes, we'd have to see major and severe long-term side effects to offset its benefits.
Not to mention that new versions of these class of drugs are being researched and tested which can prove more effective and with potentially fewer side effects.
Will you still be against this drug if it demonstrates minor side effects over long-term use?
It depends on what you call minor. If it's short lived constipation or flatulence that's one thing. But it's going to be more than that, because severe side effects are already showing up near term. I would not want to deny this to someone willing to take those risks with full knowledge. And most of the obesity we see now is a consequence of poor choices in food and exercise, unlike low estrogen. But I would put this in the same class as amphetamines for weight loss.
Is semaglutide's effect on appetite a product of its action on monoamine neurotransmitters? I know there have been reports of suicide on semaglutide, and most diet drugs in that category, including some amphetamines, have been flagged as dangerous and withdrawn:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126837/
I think like with most "game changer" meds we're going to see some real risk with this. I wouldn't want anyone I cared about to use it.
*gasp* but that’s never happened before with a pharmaceutical intervention!
🙄
The more I think about this, the more I think amphetamines were really no worse than semaglutide. People lost weight on them because they killed the appetite. To keep the weight off you had to stay on them indefinitely. Maybe pharma would rather not go back to "diet pills" because they're available in generic form. But they sure sounded like a lot more fun than flatulence, belching, constipation, and gastroparesis and ileus. 🤔
For the record - Ohio is just as fat as Kentucky.... maybe we start banning advertisement for anything containing sugar or fructose - similar to what was done with cigarettes. while we're at banning ads-- we could stop letting pharma run direct to consumer ads as well - if I see a pharma ad -- pretty sure the product doesn't work very well or you would not need the ad to sell it.
We could also stop subsidising those farmers.