Hype or Hope? Semaglutide Changes the Weight Game – Dr. Robert Kushner : 896

You're listening to the Human Upgrade with Dave Asprey, formerly Bulletproof Radio. You're listening to the Human Upgrade with Dave Asprey. Today we're going to go into some really cutting edge biohacking territory. You might have seen some of the news recently about obesity and a new drug for type 2 diabetes called semaglutide or semaglutide. And we'll get into the right pronunciation of this because half the time when you read these things, you don't really know. So I worked with my team and said, how are we going to find someone who really knows what's going on? And I said, why don't we just go to Northwestern and one of the guys who's done a lot of research on this, his name is Robert Kushner. And we're going to talk today about how you might use this both from an aging perspective, from a weight loss perspective. And in case you haven't noticed, I am one of those guys that is pro nutrition, pro lifestyle, I'm also pro pharma. In other words, you look at risk, reward for everything you can do and then you decide what's going to work best for you. And I think there's some interesting knowledge to be had today. Robert, welcome to the show.

Dave, thanks for inviting me. Appreciate it.

Are you feeling depressed about the state of obesity in the world now, having studied it for a few decades?

Well, it's certainly a challenge, as we know. I will add though that the COVID 19 pandemic for the first time in my career has shed an acute response to it. In other words, people are aware that obesity not only affects long term problems like developing diabetes, heart disease, fatty liver, high cholesterol and so forth. But now for the first time, it's a risk factor for an immediate contagious disease which you really never see seen before. So I think it shed light on the importance of obesity more than anything I've seen in my 40 years career.

But haven't overweight people always been at statistically higher risk of dying from all infections, bacterial, viral, everything else just because they have poor immune function and higher inflammation?

Yeah, they have. And interestingly, from historical point of view, it was a metropolitan life insurance group in the 1930s, 40s and 50s that first brought light to the fact that individuals who were overweight had a higher mortality rate because they want to insure people, right? So they have no how many, how much premiums should they be charging people? And they found very early in the last century that individuals who were overweight died earlier. So we've known that for a long time. But the cause of death for most people with obesity, in which they're dying sooner than individuals who do not have obesity, is really because of the ongoing medical problems that develops, like heart disease, hypertension, stroke. Diabetes is one of the highest. The infectious diseases were common in, you know, in the 1900s, but they really were dying mostly of the underlying medical problems. And then if you got pneumonia, then you're more likely to die.

This may be a bit of an inflammatory question, but given that when people die with one medical condition, we give them. But they have five medical conditions, but they have one medical condition, we always pick one, and it seems to be the most popular one. Isn't obesity actually the cause of death for people who are dying of heart disease and or even cancer? Because the risk is all, is it a foundational root cause or is it just an associated thing that wasn't related? Like, did the fat come first or the disease come first? Is it a foundational root cause or is it just an associated thing that wasn't related? Like, did the fat come first or the disease come first?

Yeah, you know, that's a great question, but, you know, the cause of death from the coroner's report is always, what is it that cause immediate death? Heart attack, stroke, you know, aneurysm, complications of diabetes. Rarely does it list obesity. But, Dave, you're absolutely correct. Obesity is the seeding ground for all these ongoing chronic problems, but it's rarely listed on a death certificate. I'll say add one more thing, Dave, is that it is uncommonly listed even in your medical record when you go to see your doctor for a variety of reasons, they don't make a diagnosis. They don't want to insult the patient. The doctor's not thinking about obesity, but it is there and is causing and root causes, you said, of many medical problems that people have in the country.

So it sounds like we may have a problem with coroner reporting, where coroners are saying, well, what's the latest thing that got them? I look at mitochondrial function and obesity as going together, and those seem to be some of the major root causes of pretty much everything that kills you if it's not a truck hitting you. And even then, an obese person isn't going to survive as well as someone who has more lean mass and less body fat. Right?

Yeah. Well, they certainly have a lot of energy reserves. But unfortunately, what we've learned in the past, I don't know, 50 years or so or a little less than that is that obesity had always been thought of as just excess body fat. It didn't cause any problem. But if you got sick enough or you got overweight enough, you then developed diabetes. We now know for the past decades that obesity in itself is a disease, and I think you were alluding to that earlier.

Okay. And even though you study obesity, one of the things I've come across just in my own losing the £100 that I've lost, is that you look in Hollywood and you see these lean, ripped, shredded men and women who are down at 5,6% body fat, fat, probably those percentages more for men. But women under 10, there must be some lower, lower limit to how much fat you can lose and still remain healthy. Do you have a perspective on that before we get into the major weight loss?

Yeah, well, you're absolutely right. And you're talking a little bit more about earlier about, you know, what we're engineered and designed to do and defend ourselves and so on. In your conversation a little bit earlier, we are designed or engineered to have a certain amount of body fat for optimal health and is probably most apparent in women. If a woman loses too much body fat, let's say she's a marathon runner, right, and she gets very lean, or she has a disease like anorexia nervosa, where body fat drops below a threshold for health, you start having ramifications in her health, she'll start having amenorrhea, she'll stop menstruating, her bones will become thin and brittle, developing osteoporosis, she'll become weaker in her muscles, and she won't be able to reproduce. And that's really. Guys, biologically, the most fundamental thing is that you have to have enough body fat to reproduce to menstruate normally and have fertility. So that's probably the best example that there is a lower limit of amount of body fat that an individual have in a man. It's a little harder to, you know, make that diagnosis because you don't have the same issues that a woman has where it becomes so apparent.

Okay. And we probably don't have an certain hardcore threshold because it's different for different people. But I just want people listening who are in the fitness competitor industry. And there's a bunch of people like that listen to the show. It is possible to get too lean, and it's hard to stay too lean for too long without a lot of biological stress. So you can look like Wolverine, but Wolverine was taking diuretics to remove extra water from his tissues for that shirt off shot where he slices a tank in half with his fingernails. So I just want everyone listening, pay attention to that side of obesity. Obesity. But since you've studied what happened to me and what's happening to a large percentage of people in the world now is we're getting fat and we're looking for all these different reasons and we're going to get into semaglutide, which I'm really excited about. But first, if you had to say the number one thing, it might be a list of 500 things you think contribute, but the top of the list that you think, given all of your knowledge, even if you don't have a study about it, where would you point your finger first?

Changing in our lifestyle, in Western culture. Our genetics, as you can imagine, have not changed over the past 100 years. But yet the prevalence of obesity, at least in the United States, has gone from probably the high 20% or so up to 42%. So it's doubled in a fairly short period of time. And obesity is now the most common non communable disease risk worldwide. And I think we could think there's a lot of things in our environment, right, there's different exposures that we have, certainly food, physical activity, change in our food supply. I'd say that probably is generating increased risk of obesity among vulnerable individuals who are likely to succumb to that and become overweight.

Okay, got it. It's one of those multivariate answers where lifestyle food changes, but we don't know which food changes. I mean, I would have some, some ideas on that that we could probably spend the next couple hours talking about. And I'd love to learn from your perspective on those. But what I really want to talk about is this New England Journal of Medicine article that came out not too long ago about once weekly semaglutide in people who were obese or overweight. Can you tell me about the study and what semaglutide is and what you found?

Absolutely. So one of the things we've learned over the past few decades is that obesity as a disease is characterized by, we call appetite dysregulation. So it's a fancy word by saying that individuals who are vulnerable to gaining weight do not regulate their appetite normally. If you're not prone to developing obesity, if you overeat one day, you're likely to be a little less hungry, the next day you'll feel full sooner, you won't be as hungry, and your body weight pretty much regulates normally individuals who are predisposed to becoming overweight, don't get that sense of, I'm full, I need to stop eating, I'm not hungry anymore. And by losing those internal signals, they often tend to eat more than their body needs. That's the genesis of that. We also have learned that there are hormones in our body that governs whether you're hungry or full. There's signals that come from the gut, go up to the brain, and that's what's actually telling you, am I hungry or am I full? Am I thinking about food? Am I having cravings? Those are all biological signals. One of those signals we get is a hormone that comes from the gut and it's called GLP1 glucagon, like peptide one. So several years ago, a decade or more ago, the pharmaceutical industry picking up on that said, if we can mimic this GLP1 hormone that normally makes us feel full and reduce our hunger, maybe we can give it back to people who don't get that signal and help them with a normal appetite regulation or signal. That is what semaglutide or semaglutide is. It's a mimic. It mimics our naturally occurring hormone called GLP1. And when you give it back to a person in pharmacologic doses, so high doses, but it mimics what we normally have, it augments or highlights this feeling of, you know what? I am really not as hungry as I was before. I'm more full than I was before, so I don't need as much food. And it's actually the change in appetite that causes the weight loss that we see with this kind of a drug.

So people want to eat less. What I found when I was working on losing that hundred pounds is that I was going to the gym an hour and a half a day, six days a week, and I went on a low calorie, low fat diet and I didn't lose weight, but I was hungry all the time. But the fact that I was definitely exercising that much and really not eating as much as I would have liked didn't make a difference. What happens when people don't have a hunger signal? Are they going to lose muscle? Are they going to lose fat? Because it seems like if you're not getting as much energy as the body wants because you're not hungry, are you going to get cold? Are you going to get thyroid conditions? Are you going to get autoimmunity? Because it seems like inducing stress in the body to have less energy than it wants.

Yeah, well, the goal of what we try and do when we help people lose weight or manage their weight who are overweight is to do a lot of lifestyle counseling to reduce their caloric intake and have them follow a healthy balanced diet, diet probably more plant based, reduce simple sugars and so forth. The fact that you, you said you started feeling hungry as you lose weight is a very, very common occurrence in individuals who are trying to lose weight. And that is how we are genetically engineered. We are genetically engineered not to lose weight, actually to maintain our weight. That's how you maintain a species. And as you start losing weight, you get hungrier. And that's in large part what makes weight long term weight maintenance so challenging. Because you can't fight ongoing hunger, eventually you give in to it. Now, when you do lose weight, you're asking what happens to the body in general? Depending upon what kind of diet you're doing in your exercise, roughly about two thirds of what you lose is body fat and roughly about one third or one fourth is lean, which means, which is muscle. Now, if you add a lot of intensive physical activity, particularly resistance training, you can maintain much more of the lean body mass or muscle as you lose weight. But in general, someone's going to a doctor, going to a commercial weight loss program, about two thirds of your weight loss is going to be fat and about one third or one fourth is going to be muscle.

Okay, so there is going to be some weight loss unless you're training. So I have just overall questions. If you just don't want to eat, what happens? And a lot of the work I've done with intermittent fasting, you get to that point where you're just, you're just not hungry. You could eat, but you don't need to eat via lifestyle, things like that. But then when you do eat, what you eat still matters. Any, any comments on semaglutide? So if it's acting on GLP1, so people are losing weight, does that work well with fasting? Does it work better with fasting? Does it make fasting easier or is it something that you just do independent? Does that work well with fasting? Does it work better with fasting? Does it make fasting easier or is it something that you just do independent?

Well, it hasn't been studied. The trials that were published, you alluded to one of them in New England Journal of Medicine. There's actually four different trials that were published in a fast frenzy around May and June that about the role of semaclutide in individuals with obesity. They were all studied in individuals who were following a calorie reduced diet that was balanced lower in sugar. You know, eating healthy throughout the day. It has not been studied to my understanding with intermittent fasting.

Got it. I imagine it would probably make intermittent fasting even easier. Although with some of the other things you can do that affect ketones. Most people don't experience hunger with intermittent fasting when they're doing it right. This new drug, though, about twice as effective as other weight loss drugs. And I tend to look at how do I change my food and lifestyle first, which you alluded to earlier. But I'm not above using a drug to get results, especially when lifestyle doesn't work. And I would have happily taken this when I weighed 300 pounds. I would have done anything to get that weight off. But what are the possible side effects that you've come across from doing this, or is this relatively safe?

Let me address the first commie6. And you're raising a really interesting point. Because I see patients in my practice at Northwestern University in Chicago, I have a center for lifestyle medicine. Many individuals who I see are hesitant to use a medication to help manage their weight. And again, our clinic is not one hen or thin. The goal is not to make people thin. The goal is to help people be healthier. And one of the metrics of health in individuals is, is their weight becoming healthier for their height along with improvement in the medical problems. And what I talk to them about is that it's not just willpower or if you just. If you just disciplined yourself, you would be able to lose weight. For individuals who are struggling with their weight for decades, and you have to think of it like a condition or a disease, let's say, like diabetes. I think most people now understand if they develop diabetes, they don't just muscle through it and try and get their blood sugar down right. They look for help, including medication to help with their blood sugar and the diabetes complications. So we think of obesity exact same way. If you have obesity that you're struggling with for decades and you have other medical problems, if you think of it like a medical condition, then that opens the door for using medication on top of lifestyle. That's kind of how we position it now. Like with any medication, Dave, there's. There's risks and benefits. The benefits are, as you've already said, it is one and a half to two times more effective. Semeglutide, that is, than any of the other medications that are approved for chronic weight management. So it is a. It's a game changer. It's a new direction, kind of version two of the drugs are likely to be developed to help people manage their weight. But the risks are side effects. All the GLP1 drugs that were like semaglutide and there's others in this category that we use for diabetes primarily have side effects that are gastrointestinal in nature such as nausea, diarrhea, reflux disease, constipation, some people even vomiting. These are not fun things to have. But we know by how we dose it, how we use it, how we individualize care, how we mirror a healthy diet with it, we can mitigate a lot of these side effects. And most people in the trials completed the trial and did not drop out and actually tolerated drug very well.

So they were, they were worth it, so to speak. And for people who've been obese, you'll go through a lot to get rid of it as long as you can see results happening. And it's, it's when you don't get results and you've done, you've done the work that you start to feel really, really helpless or just pissed off. I think I went through both of those and I definitely saw doctors and this is going back a while, but it was. Maybe you should change your lifestyle. I did everything that you can think of. It didn't work and they didn't have good drugs other than maybe phentermine back then, which I never went on. How does this compare to those types of drugs and how they work in the body? So the new one, semaglutide, if I'm saying that right, like a college professor, that's a GLP1 fullness drug. How does phentermine work? Or the so called fen phen that people talked about before we left the market.

So drugs that were developed, Phentermine was actually approved in the United States in 1959. So you can imagine what our understanding of obesity was is very minimal. And these amphetamine is, excuse me, phentermine is an amphitheat, amphetamine derivatives and everyone knows what amphetamines are. So these drugs work directly up in the brain to make you feel less hungry. And it's a derivative phetamine. So there's very little addictive potential. But, but people often develop a tolerance to it. Like you would take an amphetamine, you need higher doses, which of course we don't do that with obesity. And other medications were developed that also work directly in the brain working on, we call these neurotransmitters dopamine, serotonin, norepinephrine, directly up in the brain. What makes semaglutide and other drugs in this area that are emerging so different and kind of new generational is that we now have a much better understanding of obesity. The role of these gut hormones that come from the pancreas, from the intestine, that help us in a more natural way, give us signals that we're full, we're less hungry, we're more content between meals, we have less cravings, less thoughts of food. And a lot of people think that's all under your own consciousness, your own willpower, and it's not. It's actually biologically driven. So just like diabetes, you know, years ago, where we found out the role of insulin, by giving insulin, which is a natural hormone, we can treat diabetes, we now are understanding the hormonal regulation of obesity and giving those hormones back at much higher doses than normal. And we're mimicking what I would consider more natural regarding appetite regulation.

Can you take. This is a drug that you take just once a week, about 2.4 milligrams. Can you take it for two weeks, lose 10 pounds for January, and just be done with it? Or is this something you take for long periods of time?

So we think of, like we said already, and I'm going to reinforce this, we think of obesity as a disease, and I'll add a few more words to it, a chronic relapsing disease. And if I substituted that definition for diabetes, I use that as my comparator all the time. We think of diabetes as a lifelong problem. Yes, you can go into remission, but often with medication or with significant changes in your lifestyle, but can reemerge if you change your lifestyle. And if you go off of medications for diabetes or hypertension, let's use that. Another example. Most people would pretty much think their blood pressure would go back up or their diabetes would worsen if they didn't maintain the drugs that put them in remission or in control. So obesity is exactly the same thing. These medications only work when you take them. And if you have an excellent response to semaglutide, let's say you lose 15 to 20% of your body weight, of which, by the way, a third of individuals in the trials lost 20% of their body weight, which is equivalent to almost 50 pounds in the trial.

Life changing.

It's life changing.

Over what period of time is this, like a six month kind of thing?

68 weeks? A little over a year.

Little over a year. Okay. And. And they were just eating less. Were they also doing, like the. The Stuff they did with the, the low fat stuff out of UCLA where it's so meditation, exercise, walking, community. Oh, and a dietary change. Or was this just straight up take the drug and go do your stuff?

No, it's a good question. Everyone was following a lifestyle change. So lifestyle management's foundational. So we're focusing in on pharmacologic therapy for obesity. But just for all the listeners, the foundation of healthy living is your lifestyle and also for weight management. So all the subjects in this study came in every single month for dietary and physical activity counseling. Medication was added on top of that.

That seems like some confounding study. Was there a control group that just had the interventions without the drug?

Correct. Oh, absolutely. So these were all random, we call them randomized controlled studies. So everyone got lifestyle counseling. One group got the medication, the other group got a placebo. Right. A once a week injection, but placebo.

So one of the concerns I had, and this is a question out of curiosity, it feels like a lot of the lifestyle advice that I received when I was overweight was not achievable. Oh, just eat less and exercise a lot more. And I went out and I did it to the fullest possible thing you can do. But it seems like as you mentioned earlier, it's just not going to happen. So then you have this, the study where you say, okay, go do this thing that's biologically, I'm going to say either impossible or nearly impossible to do. And you have another group where they can do it. Because at a drug that let them do it, does that mean that the drug is working or does that mean that the advice itself is flawed? If it's something people can't do if.

They'Re not on a drug, well, the recommendations have to be practical and achievable. I call pragmatic. Right? You don't want to give ideal recommendations that people can't follow. So your point is well taken. So everyone got the same exact vice. People on placebo lost about 2.2 and a half percent of their body weight at the end of a year. So minimal. But, but. And people on drug on average lost 15 of their body. Same advice. Same advice. The, the, the practicality though gets into, just to mention a book I wrote which, which is called Six Factors to fit Weight Loss works for you, is a practical, achievable approach to lifestyle management. So I'm very much into giving people recommendations that they can get their head around that is doable given their lifestyle, not just some ideal recommendations.

That matters a lot. And in the early days of my weight loss, going back Even into the 90s, I'd talk to these relatively obese doctors telling me what to do and I'd say, was it working for you? And they said, well, you have to do as I say, not as I do. I actually had a doctor tell me those exact words. And I'm thinking, I'm working really hard here. I don't know if I can do as you say. So what you're showing here though is people did comply. They did lose two and a half percent of their body weight and one perspective on that is okay. That means that the advice that we have there doesn't work very well because even with monthly coaching and all, people didn't lose very much weight. My take is that maybe that advice could be modulated and improved to a certain extent, whether it's with fasting or circadian eating or changing the type of fats and all that stuff. But we've never tested any of those things in conjunction with the drug. Do you think there will ever be a trial of a keto diet or a carnivore diet or a vegan diet with semaglutide? Or is it always going to be sort of the standard oh, eat less and whatever else was in the recommendations? Your phone screen is aging your skin and wrecking your sleep at the same time. Artificial blue light goes from your phone screen straight into your eyes and deep into your skin. That light messes with your melatonin tonin levels, interrupts your deep sleep and speeds up skin aging by breaking down collagen. The Bodyguard's Red Light Converter fixes this at the source. It's a first of its kind screen protector with real tech that converts blue light into beneficial red light before it hits your face. It turns your scrolling into a skincare routine. It supports healthier skin, reduced eye strain, improved sleep quality and fewer screen related headaches. Third party testing showed a 50% plus increase in red light exposure within the optimal range of 620-770nm and this comes with zero compromise on your screen. The Red Light Converter preserves your screen's true colors and full touch sensitivity. Beyond its wellness benefits, the Red Light Converter provides ultra thin edge to edge protection for your device and Bodyguard stands by their quality. Enjoy peace of mind with lifetime replacements, ensuring your red light converter continues to protect and support your biology for the long haul. Visit bodyguards.com and use code Dave for 25% off. That's bodyguardswithaz.com for 25% off. You're listening to the Human Upgrade with Dave Asprey. Is it always going to be sort of the standard eat less and whatever else was in the recommendations?

Well, I think first of all, any investigator is welcome to study anything they want. So, you know, I think individuals or researchers or clinicians who are really committed to low carbohydrate diets or intermittent fasting will probably find their way to testing a drug along with it. I'm guessing you will see those types of studies.

I'd love to work with Peter Attia on this. In fact, I'll have to give him a call. He's one of the big low carb guys and a friend and it's very interesting. I'm going to ask you a question that every researcher hates and the normal answer is I don't know, there's not a study. But if there was a study of this drug and say the keto diet, what would you predict the outcome of the study would be? Knowing that we don't have the actual answer to that?

I, I, I don't know what the effect, well, I don't know what the effect of a GLP1 drug is in a ketotic state. That's one thing. And I will, so I will tell you that these drugs examples would be semaglutide, which trade name I believe is ozembic or, or dilaglutide, which is trulicity. These are other drugs on the market for diabetes. None of them are approved for type 1 diabetes and those are the individuals who are prone to ketosis. So I don't know what the safety issues would be using these drugs in someone who develops ketosis. So that would be my first question, is, is it safe before we get onto the effectiveness?

I guess we don't know. We do know that ketosis does also affect GLP1. It's one of the reasons that people are less hungry on a keto diet. And some people say people lose weight in ketosis because they eat less calories. I would say that's not true because I, at least on a personal basis, I tested using keto with 4,500 calories a day and actually lost weight on that over the course of several months, which didn't make any sense to me, but it did work. So not enough of an N in order to be valid, but just enough to go, there's, there's work to be done there. Is there a difference on this drug with women versus men because women express GLP1 differently than men.

Do there isn't that was looked at. A lot of these baseline variables were looked at regarding predictability of weight loss. And it turns out that men and women, there is no statistical difference between the two genders between men and women as well as what your starting bmi, your body weight is. So it appears to be effective across multiple demographic and biometric variables or factors that they looked at.

Wow. What about status, perimenopause, menopausal or premenopause? Any differences?

There have not seen that. I don't know, I haven't really seen that information. The things they looked at are men, women, age, age, ethnicity, so forth. And it really was very little difference between all of these.

And there were no labs in terms of side effects. You didn't see anything bad happen. What I've seen in all the studies that I read before the interview was pretty much the markers of cardiovascular disease, HbA1c which is something that everyone should be tracking. Who's interested in longevity. You don't want to have high average blood sugar over time because it's, it's pro aging through advanced glycation formation. All of those seem to improve. Is this an anti aging drug? Should people be on this?

That's taking it a few steps ahead. Well, I do want to mention, okay, you just talked about this and it's important to mention and I said this before, that the goal of weight loss is not to make people thinner. Right. It's all with an eye towards health. So in these trials, they're called step trials, that that was their name that they're published under, not only did individuals lose weight, but they who were randomized to the drug versus placebo but they also saw an improvement in sugar control hemoglobin A1C which you just mentioned, which is a three month average blood sugar improvement in blood pressure, improvement in blood fats, like, like triglyceride improvement in crp, which is an inflammatory marker.

That's a big one. That is one of the top three recommendations I have for longevity is you have to keep your CRP low. So people found their CRP dropped. Is that just because they had less white fat making inflammatory molecules or was there some other effect that you think is there?

Well first of all, the CRP dropped greater in those in the drug and they lost more weight. So maybe due to losing more weight. But the newest studies now are suggesting that GLP1 has a more pleiotrophic or multiple factor effect on health and metabolism beyond just appetite. And those are like the active ongoing.

Studies what would you say if someone came in and said I'm on an aggressive anti aging regimen, I have these 10 stubborn pounds I've been trying to lose for a while. I want to try this for a while to see if I can get to my ideal body weight. Would you support that line of thinking or would you say no, you're not morbidly obese, you can't do this?

I'm hesitant to, you know, I'm hesitant to use medications and someone who wants to lose 10 more weights, 10 more pounds or kilos, whatever unit you're using. I really am a lifestyle management obesity medicine specialist. I really look at totality of the factors regarding health and if someone is in perfectly good health except they're 10 pounds above their ideal weight or where they have that, that picture in their mind, what they want to weigh. I'm pretty hesitant to start using a drug to lose 10 pounds. I really have an eye towards total health.

I'm with you there in spirit. There are not that many people who have ten pounds to lose who can't lose it using the tool set that I work with. Unless it's tied to C reactive protein or homocysteine levels or some other inflammatory condition, oftentimes autoimmunity or there's a thyroid thing going on. So if you address those. But this seems like this might be another C reactive protein lowering mechanism. I have seen a few cases where nothing will lower CRP except for cryotherapy. Someone who's lost 150 pounds and is looking pretty good, but still has C reactive protein that won't drop, that would drop it, but I don't know, I wouldn't be, I'm not a doctor, but if I was a doctor I wouldn't be opposed to saying I don't know, give it a try if normal other things don't work. So can you see some off label uses for corner cases or is this one of those things that's so new we should just keep it for really heavy people?

Well, first of all, I am a physician and scientist. I'd like to see the data quite frankly Dave, before I start giving it to people to bring down their crp. That may be worthwhile study to see because a lot of things in science sounded good and when you actually did the trial you got either a negative effect or a paradoxical effect. Examples come with cancer with vitamin, vitamin E which was given quite some time ago where actually caused worsening of certain kinds of cancers. So we have to things that sound good really do need to be studied before we start using them.

Okay, I'm with you there. And there's a group of people who just get kind of desperate and you've seen 10 doctors and it doesn't work and you start looking for things to do. And I imagine there'll be some people who end up going in this direction working with their doctors. And I fully support the use of drugs that might work as long as the side effects aren't that bad, most likely. But it takes a certain kind of doctor who's more of a detective than a typical. This is what we do in a hospital following insurance things.

Steve, let me just follow up with one thing. And I said this before, but I want to reinforce it again. Is that but all of the medications that we have, at least for obesity, we call it chronic weight management or anti obesity drugs. All of these drugs only work if you take the medication. In other words, the disease or the weight or the body fat comes back when you stop the medication. So it's not like taking something for a flu or for a rash. If you're going to embark upon taking medications, let's say your example of a lowering your crp, then you're really embarking upon a long term use of that medication. Now you're talking about risk and benefit and financial changes, potential side effects we haven't seen before. So those are all the things you have to weigh to make your decision.

Okay, I appreciate you doubling down on that. And I also want to go through because you've written a book about obesity, you've studied it for a long time and you identified six major things that you're finding in people who are obese. Can you run through those six things for listeners so that we know what you've seen?

Yeah. So the book's called Six Factors to fit Weight Loss. That works for your and if you just go to my own website, which is DrRobert Kushner.com Dr. SDR Robert Kushner.com you can read all of Bodner's tweaks and blogs and newsletters and so forth. But the basis of the book is a practical approach. And you had mentioned that earlier about not having ideal things. And the whole idea of the book is as I saw, people who are losing weight and you're very successful in losing 100 pounds. But the more normal story is they put the weight back on. And when I saw one person after another, what I was seeing is they changed something and then when they gained their weight, they went back to their default behaviors. Or their default cognitions that kind of got them into being overweight in the first place. So what the six factors are is identifying six different behaviors or cognitions or traits that people tend to fall into. And you can have more than one, by the way. That gives people a targeted approach to dealing with the factor that is most important to them that may be causing the weight gain or making it difficult for them to lose weight. So just give you a feel of what I'm talking about. One of the factors is, and we gave names that were easily understood. So one's called Easily Enticed Eater. That's a factor. And that describes someone who struggles with eating temptations. They may also have an emotional connection with food. That describes a lot of people, actually. And if you fall into that factor, the book in the approach, which is a whole chapter in itself, gives you strategies and targets of what you can do if you identify with that particular factor. I'll just mention one other one to you which is called the all or nothing doer. So this is an individual who tends to think in black and white or dichotomous thinking. Like, I'm going to work out for the, for the weekend like, like, like a maniac, but Monday I'm going to give myself a break. Or I'm going to go full force in, let's say intermittent fasting, but I'm going on vacation so I'm going to stop doing it. So it's just kind of off and on, good and good and bad behavior and that, and that's a factor a lot of people think about. That's a trait. So there's a whole chapter on how do I change that thinking. So there's six of them. And what I found in my studies is that the heavier you are, the more likely you're to have more factors. And by losing weight and focusing on these factors, these factors actually get under better control. So they go in both directions. So it's a self help book, basically.

It always frustrated me. I'm looking at some of the comments from the Upgrade Collective as we're doing the interview where we have a little chat thread going. By the way, guys, you can just go to daveasbury.com and sign up if you want to be in my mentorship group and be in the live audience here. And Brandon's saying doctors often think patients are lying or lazy because they're not following this sort of stuff. But I found predominantly when people aren't losing weight, it's because the advice isn't very good. Like you can exercise away a potato chip. It doesn't appear to be valid. If you look at the amount of time you'd have to spend on a treadmill for two bags of potato chips, you realize it doesn't work. And exercising the same amount of calories from a piece of steak versus the potato chips would have profoundly different results. And there's also. Did you eat it at midnight? Because that changed it as well. It's almost like the advice of, you know, change your behavior versus change the inputs or change the gut bacteria. Like we're seeing kind of a sea change around understanding core biology of obesity versus behavior of obesity. If you had to choose a percentage of obesity that's behavior based versus biology based, could you take a stab at where you'd put it? With our current state of knowledge.

Both are important, obviously, but I have with development drugs like semaglutide and more and more understanding of obesity as a disease, we now think of it more and more as biologically driven that influences your behavior or your and equally so your behavior influences is your biology. That's why it's really yin and yang. It's kind of both of them. But ignoring the biology of the body, such as I lose weight, I get hungrier, or if I have a tendency to gain weight, there's a downregulation in my metabolism or I may have a phenotype where certain food groups, let's say simple sugars, really light up my reward center and I can't stop eating them or changes my metabolism. Without understanding the biology, I think we're missing a lot about how to help people. Let me add one more thing, David, which gets to the question your listeners said about how doctors may think you're lying and so forth. I think the medical profession, rather than what you said and that was giving bad advice, I would actually submit to giving no advice. I think they're mostly are so ill equipped and have such a lack of knowledge that they don't even know what to say. And instead they say, they basically say, eat less, move more, you know what to do. I want to see £5 off you when I see you back in a month. And that's it. And it's usually said when their arm is on their hand is on the doorknob, ready to walk out of the room. You know, it's kind of like a last minute comment to the patient. So I'm very much involved in lifestyle and obesity education for medical students and residents as part of what I do at the university. We are trying to train the next generation of healthcare professionals to be part of the solution, really understand what is going on here. And also that includes helping regarding communication and empathy. Most health professionals really don't know how to talk to someone who is struggling with their weight. And by the way, we don't say obese people, we say people with obesity. We don't label people by their condition. So we really try to help our learners how to help patients in the United States, over 70% have overweight or have obesity. You know, how do you actually help someone in a very productive, practical way. And that's new for them and we're working hard to try to get there.

Well, thank you for doing that work to educate doctors. I've run into some who really understand weight loss and obesity and they work with you on peptides and nutrition and all. And they typically are functional medicine people with small practice. But if you go into, you know, a larger clinic, it's pretty hard to find someone who really, really is going to work work with you on those levels versus what you just said. You know, we'll try and lose some weight, you know, go to the gym and you know, stop eating pizza, you'll be fine. And I certainly felt disrespected when I started on this path going, but you don't understand, I've done everything that you could think of and the answer was well, you should still try to lose weight. And that didn't work. And with you educating the next generation of doctors to listen a little bit more, I think you're going to improve the profession. But I got to ask you about one other thing you mentioned earlier in the interview. You said that the diet to lose weight was probably plant based. And I was wondering, was that sort of a study based perspective? Because I did not do well on a plant based diet and in fact hundreds of thousands of people who've worked with, with my content didn't either. And I'm kind of thinking that might be an industry preference, not actually a medically justified preference. Where's your data coming from or what's your take on that?

Well, there's, there's tons of data. First of all, every, everyone, everyone's different, right? We call them phenotypes, right? So I'm talking about studies that have been looked at where individuals on non vegetarian really, but more plant based diets worldwide, not just in North America, tend to have improvements in metabolic parameters, whether cardiovascular endpoints, inflammation and so forth. Mediterranean diet probably has been studied more than any other diet I'm familiar with globally. Regarding Improvement in cardiometabolic risk factors. So we generally recommend guiding people more to plant based diet. But getting back to what you're saying, I try to be very practical with it with each patient rather than just this is how I want. This is a diet I want you to eat and then that's the end of the conversation.

Got it. And I look at feedback loops as well and people saying is it working for you and all. So there's a lot going on with hunger hormones, which this new drug is actually quite interesting. If I was substantially obese and I wasn't losing weight the way I wanted to, using techniques that work, including most definitely intermittent fasting, improving sleep, making sure you move, all that kind of stuff, I would be completely okay with looking at this drug and saying is it going to work? Because you're seeing people lose 15% of their body weight in a year versus 2%, but you might be able to lose 15% without the drug. Like you should try that. But for listeners, this is one of those things that's probably worth it because being obese like that, that increases risk factors for just about everything. Like you've got to get that down. And Joanne from the Upgrade Collective is asking about side effects and it looks like it's mostly nausea, but there's not major life threatening. There's some GI side effects, but there's no systemic cancer and things like that that are going up.

No, not that have been seen. The GI side effects which we mentioned before are usually, we call them transient and mild. That's kind of how they were described. So the longer you're on the drug and we dose escalated slowly over the first four months. You start low, build up and you're able to manage a lot of them. The one medical and those are side effects, but the one medical effect that was seen is that individuals in the drug trial developed slightly more gallstones or gallbladder related problems where they develop gallstones or need a gallbladder taken out. Part of it may be to drug part of it. Maybe they lost more weight. We know that as people lose more weight they have an increase risk of developing gallstones. But other, other than that, there were no other medical complications that were seen. And this drug was originally put in the market quite some time ago, well maybe five or six years ago as a diabetes drug. As I mentioned before, the trade name is called Ozembic. At a lower dose, this is a higher dose, 2.4 milligrams, so it's two and a half times the dose. But the drug has already been out for quite some time for treatment of diabetes.

And that lowers the risk quite a lot because when something's been on the market for five or more years, you actually have an idea of what it might do in large populations who use it versus just kind of rushing something to market and then giving it to everyone and then noticing there might be a side effect a couple years later in that drug.

Let me just add, Dave. That drug, the lower dose of the semaglutide, was studied in a weird call, a cardiovascular outcome trial called a cvot, where you take a large population of individuals over years, five years or more, and you randomize half the individuals who are already at risk, they have diabetes, they have heart disease, they're already high risk versus placebo. And in that trial, individuals were randomized as lower dose semaglutide had a lower risk of cardiovascular disease and death at the end of the trial. So not only does it improve body weight and cardiovascular risk factors, there are now studies that show it actually improves cardiovascular death over the lifetime of taking the drugs. So many of the, a lot of drugs are showing that now, but that's just another important marker regarding that, we're really looking towards health and longevity, again, not just weight loss.

So this is a really exciting, really exciting. I would call it a breakthrough weight loss drug. From what I've seen in the studies, it looks safer because we've played around with it for diabetes for a long time, and there are a good number of listeners of this, of the show, because I talk about longevity and I talk about high performance. So we've got a bunch of people in their 20s who are just killing it in their careers and lives. And we've got a bunch of people in their 60s and 70s who are also killing it in their careers and lives, but are looking at blood sugar regulation more seriously. So if you were looking at someone who has relatively high blood sugar, maybe on the borderline of diabetes, and working really hard on it, and some extra pounds, this might be an appropriate intervention for them. Yes. No.

Yeah. So we have an earlier study which is called the Diabetes prevention program, or DPP, done 20 years ago or so, which showed if you take individuals with pre diabetes, so there's people right in that gray zone, they're not normal blood sugar sugar, but not diabetes. And if you, if you intervene with them with lifestyle treatment alone, you could reduce the risk of diabetes by 58%, which is really significant. But we also know by giving a drug like metformin, you can also reduce the risk of developing diabetes. This type of drug, this GLP1, has also been shown to reduce the risk of developing diabetes in someone who has prediabetes. Another study, which went three years with another type of a GLP one. So to answer your question, the long winded answer is that we are now being much more aggressive in working with individuals with prediabetes along with lifestyle counseling, using medication when indicated to prevent the occurrence of diabetes. So that's a very hot topic.

Wow, that's a really big deal for people who've been just working on this for years going out. I'm right on the edge. I'm right on the edge. We have a lot of listeners who are using the levels blood glucose monitoring system. I use that on occasion and I was pre diabetic in my mid-20s and I don't have issues with it now, but I do look at the effect of food on blood sugar. What about if someone came into you who was very heavy and was saying, I'm looking at gastric bypass surgery, Would you generally recommend trying semaglutide before gastric bypass surgery? Would you combine the two together?

Great question. And we didn't talk about bariatric surgery, but if we think of obesity just as a framework, if you think of obesity as a chronic relapsing condition and we use a medical model, one of those buckets or one of those treatment arms is bariatric surgery, and that's gastric bypass or gastric sleep. Those are the two most commonly done. So, so we use those treatments all the time in someone with severe obesity, multiple medical problems, they have tried multiple other modalities without success and they would benefit from an intervention. So we'll recommend bariatric surgery. Your question is, would we all try a medication before bariatric surgery? The answer is potentially yes, depending upon the interest of the individual. But I tell them right up up front that it's usually not either or. People often want, I'll take the medication, but I want the outcome of bariatric surgery. And I can't promise that because medication is very effective, but it on average does not cause the same results as bariatric surgery. It's more of a kind of intermediate between lifestyle and bariatric surgery. We often do combine them, which is the last thing you mentioned. We'll have patients who, who have had bariatric surgery but are not responding in the weight trajectory that we would expect them to lose. So we'll add medication. In others, we may use medication before bariatric surgery in order to Reduce their perioperative risk. Right. The risk of going through the surgery. So we are combining these modalities more and more now than ever before.

That's really interesting. So you could do both and it's probably not harmful to try the drug first.

No, no, it's not harmful. It doesn't, you know, reduce the likelihood that you would benefit from surgery or you. Or you wouldn't be a candidate for surgery. If someone is severely overweight and we think they're a high medical risk, we'll often use medication before surgery in order to help them be more functional, reduce their abdominal girth. Because do surgery, the surgeon has to go through the abdominal area where it locks the fat is. Get them to take deeper breaths, get their diabetes under better control. So we can. We can improve their performance and improve their medical condition prior to surgery by using medication along with lifestyle.

Okay, I like this. And Deborah from the Upgrade Collective has a really interesting question. Here you have these sort of six factors. The personal development side of weight loss. Is a drug like semaglutide going to work for someone who maybe. Is the easily enticed eater better than someone who's an exercise struggler? Does it work for emotional eating? Does it work for all causes of eating?

Great. Very insightful question, Deborah. Thank you for asking that. So we've done this kind of work within our own program, and what we found, if you take those six fast factors and someone scores, you know, various levels of. On all these different factors, which, by the way, you can go on my website and take the quiz yourself for free, and it scores it automatically@drrobert cushner.com so you can actually go ahead and do that. What we have found is that the one factor that seems to be exquisitely sensitive to using these medications is the easily enticed eater. By reducing the temptation and enticement of food, by changing appetite, that factor score plummets because they're not as affected by food. The exercise struggler, which is another factor, is not going to be directly affected by the drug. However, if one is losing weight, I think, Dave, you could attest to this. As you lose weight, you really get very motivated to take better care of yourself and you may actually engage in even more physical activity. One, because you're motivated and you have an. And number two, because you can. Right. I have patients all the time who never even thought of taking a hike or going for a weekend walk in a path or taking up a cycling class or doing ballroom dancing, whatever it is, until they've lost the weight and now they could start seeing things to do that they never even imagined because their body, they weren't functional, they're short of breath, they didn't feel good about themselves. So it indirectly will increase the factor the exercise struggler because they are losing weight and feeling better about themselves.

What about the cost? I mean even that, the low dose for diabetes, it's about 800 bucks, I think for a month's supply at the minimum up to about $1,000. Is this covered by insurance for most people?

That's a scary, that's a scary statement. You just said one is the one of the biggest challenges and barriers to use medications for obesity is coverage, at least in Canada, of course is a bit different. United States, you have to have private insurance in order to cover these medications because none of our governmental insurance, United States covers it. Medicare, Medicaid does not cover anti obesity medications. So you really need to have coverage or insurance reimbursement reimbursement for these medications, which as you already said could be $800 or north of $800 every single month, which is beyond the reach of really any human being. And insurers are often hesitant to cover these medications because when they look at the, I don't know, 30 million or more Americans who are potential candidates for these medications, they don't know how they're going to cover, they don't know how they're going to afford it. So they often just don't cover these medications. So it really. So we're at a kind of a fork in the road where we are developing more and more effective medications like Semaglutine. There's others coming down the road. But yet if we're going to cover it, you know, what's the financial cost of that to do so. And I think we need to come to an agreement and a resolution that obesity is a disease, as we said before, seeds many other chronic diseases. Unless we get control of obesity, all these other medical problems are going to continue. And we've got to develop funding or identify funding ways to support the use of these medications in individuals who are in need.

The other option is if you're going to spend $4,000 on medication, which is probably a minimum effective dose for a few months, you could probably fly to Mexico and back for $1,000 and cover your hotel and go to a pharmacy there and buy it for a lot less or to Thailand for that matter. And there's a lot of people doing that right now. I'm saying this mostly for listeners where Prices for drugs in the US are outrageously, outrageously high compared to almost every country on the planet. It you are also legally allowed to import a three month supply of just about any drug if it's not on a scheduled substance from out of the country, as long as you have a doctor's prescription, even if the doctor's out of the country. So this is how people, including me when I was younger, who couldn't afford certain things could make it affordable. I don't know how available this is internationally, but is this a drug that's, that's globally available now or is this mostly a US and Europe thing?

It's, it's available in, I believe it's available in Canada as well, so North America. It's coming online really country by country or region by region. So I don't know how many countries have it approved now. It was approved in the United States in, I think in June of 2021 and it's coming online in other countries I think all the time.

Beautiful. Oh, Bob, I appreciate your, your long study of obesity and all the other associated diseases and looking at the lifestyle factors, which is something that a lot of medicine hasn't done. You're bringing that into medicine and particularly looking at pharmaceuticals like this that appear to have a low incidence of side effects and very, very high efficacy. So guys, if you're listening to this going, I know Dave lost 100 pounds, I know people lost a million pounds on this, the bulletproof diet, et cetera, et cetera, it's not working for me and I gave it a real try. There is no moral or ethical thing preventing you from doing anything available to you to get the results you want with the risk you want. And I'm fully in support of using a pharmaceutical that's going to reduce your risk of dying from all causes. I think that's a very valuable thing. And this semaglutide looks to be really interesting if you can afford it right now. Now, like all drugs, at least most drugs over time when you don't have monopoly powers granted by the US government, they do decrease in price over time. Also this tells the biohackers Amongst us that GLP1 might be something to look at if you have a problem with appetite. And I would just tell you, gee, ketosis and fasting which induces ketosis. Ketosis also has an effect on GLP1. It's one of the many reasons you're less likely hungry when you do that. So that might be a factor to hack even if you don't either need the drug or want to use the drug or just don't have access to the drug. So this, though, I think is a new tool for those of us who are obese the way I once was. And I really Again, thank you Bob for coming on the show. Can you give me your URL one more time for people who want to know more about your book?

So it's Dr. Robert kushner.com doctor is doctor so it's drrobert kushner.com beautiful.

Thanks again for being on the show, guys. Thanks for being in the Audience Upgrade Collective. And if you're listening to this on whatever your favorite podcasting platform is, thank you for following the show, for subscribing to the show, and just for supporting all the stuff that I do. And if you want to know more about fasting, go to fastwithdave.com and I will teach you for free all the stuff that's in my most recent book about it. And make sure you go to Dr. Kushner's site as well, because he's got a book about some of the lifestyle things and the mindsets around overeating, which is a problem. Thanks guys.

Thank you.

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