Hey everyone, it's Mikki here. You're listening to Mikkipedia. This week on the podcast I speak to Dr. Spencer Nodolski. Spencer is a board certified obesity and lipid specialist known for his evidence-based, compassionate approach to helping people lose weight and improve metabolic health. Spencer has dedicated his career to bridging the gap between clinical medicine and the lived realities of people struggling with obesity, cutting through misinformation to focus on what actually works.

00:32
and he does it with a whole lot of humour as well. With the arrival of Wigovy in New Zealand and the explosion of interest in GLP-1 medications worldwide, our conversation couldn't be more timely. We discuss how the drugs work, how they compare to diet, lifestyle and older weight loss medications, and why the price tag varies so widely between countries. And we explore the controversies from microdosing to long-term safety, tolerance and muscle loss,

01:00
and whether these drugs can genuinely shift someone's metabolic set point or are they simply managing symptoms. And I've got to say that I was super stoked to get Spencer on the podcast because out of all of the people I see talking about and advocating for these weight loss medications, Spencer is just super grounded in his approach and he's really real about how he feels about the use of these medications long-term for people who actually need them.

01:29
So I think you're really going to love this conversation. And if you're wondering whether GLPs are game-changing tools or just some sort of fad, I think you're really going to love this conversation because it will separate the hype from the evidence. So for those of you unfamiliar, Dr. Spencer-Nodowski is an obesity and lipid specialist with over a decade of experience helping patients improve metabolic health.

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and of course achieve fat loss through evidence-based interventions in exercise, nutrition and pharmacotherapy. He's a passionate educator and brings clarity, humour and compassion to complex medical topics, whether through his digital content or co-hosting the Docs Who Lift podcast with his brother Carl or engaging audience via social media. He's been super successful with his initiatives such as Sequence,

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which grew to over 20,000 patients in about a year before being acquired by Weight Watchers. And he also has founded Vinyard, a physician-owned virtual obesity medicine clinic designed to offer personalized, compassionate care, where patients receive direct access to the same obesity medicine specialists, eliminating fragmentation often found in telehealth platforms, a tailored comprehensive care plan that addresses not just weight, but also sleep, stress, blood pressure,

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cholesterol and other holistic aspects of health and fast attentive support. It is a service model that emphasizes long-term success over quick fixes and he has an active involvement in research as well, exploring how GLP-1 medications, high protein diets and exercise impact body composition aiming to support fat loss while preserving muscle. And this is something that he's super passionate about. I will put links as to

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where you can find Spencer through either Vineyard or Instagram or his podcast Docs Who Lift, which is super informative and I really love it, in the show notes. But before we crack on into the interview, I would like to remind you that the best way to support this podcast is to hit the subscribe button on your favorite podcast listening platform. That increases the visibility of Micopedia and amongst literally thousands of other podcasts out there. So more people get to hear from the guests that I have on the show, including Dr. Spencer Nadolski.

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All right team, enjoy the conversation.

03:53
Spencer, thank you so much for joining me this morning. Really looking forward to getting into GLPs, microdosing, lifestyle, pushback, all the topics that you talk about on the daily, obviously online and probably in your clinics as well. Can we kick off with you just giving us a little bit of your background and how you got into obesity medicine?

04:18
Yeah, I grew up in an academically minded and athletically minded family. My dad was a biology teacher and a wrestling football coach at the high school. And my mom was a elementary school teacher, really instilled hard work and academics in both me and my brother. And so I really got into the science of nutrition and exercise to get really good at sports. I had to work really hard to get

04:48
uh, to get to the level of some of my more genetically gifted, um, classmates, I should say. Uh, and so brought that to college where I wrestled and actually did football and wrestling here in the States. And, uh, then went to medical school and everybody said, you're going to be an orthopedic doctor, you know, that's sports medicine doctor. And I shadowed some.

05:16
Uh, and I didn't, I didn't like it. So I was like, I'm more into like the physiology and stuff like that hormones, whatever. And I really like to get people, uh, improving their lifestyle. And there wasn't really a medical specialty that did that, but obesity medicine was kind of an emerging, emerging specialty. It's still, it didn't really exist, but kind of like, just kind of made it your own type of thing.

05:43
but there was like a group of doctors that have conferences and do it. So I ended up doing something called family medicine, which is very broad here in the States. And then further specialized into obesity medicine and something called lipidology study of cholesterol, triglyceride metabolism, lipids basically, and started off in private practice.

06:10
then really like the whole thing was like, I didn't really like the way we delivered healthcare. So I really got into more, more innovative healthcare delivery types of systems and then started getting into the entrepreneurial world. Like, all right, I'm not just going to be a cog in this machine. I'm going to have to build my own machine or something. Cause I'm not going, there's no way I'm going to last year. So that's where I got into telemedicine, you know, before the whole pandemic, was people were like, Oh,

06:38
really up in the cloud. was like, yeah. So back then it was kind of weird. However, uh, it was a good thing I did that cause I was on the, I don't want to say the cutting edge. was just more like I knew what the heck was going on where everybody else had the learning curve of trying to learn it during the pandemic. um, so yeah, now basically I do medical, uh, cardiometabolic health, lipids, obesity, and weight adjacent type of stuff all online.

07:07
all of the United States. I have doctors and dietitians and all that type of stuff. that's my basic background. Nice one. And did you take a lot of bro science into med school with you? Because obviously you had an interest in nutrition. You sort of had these, I don't know, preformed ideas on how things should work, Yeah. So luckily I went from bro science to then I very early was

07:36
together with like the smart science based evidence based type of fitness type of people. So people like Alan Aragon, James Krieger, John Berardi is another guy that you might be familiar with, um, with the precision nutrition and there, there, there are plenty more, but like, so luckily cause you know, I'm reading in high school, it's like muscle and fitness magazines. I did read a lot of this testosterone.

08:06
nation, um, t nation, if you know what that is, it was way bigger back, um, back when I was in high school, luckily that's kind of, was, was luckily to get into that realm as opposed to just like on the forums, like eating more often, Stokes your metabolism type of stuff. So luckily I was able to, uh, have, have good mentors, so to speak, if enough, I didn't know them directly. So, yeah.

08:36
Spencer, with your own obesity practice, obviously there are weight loss drugs that have been around for years. Were you trying to also, I guess, adjacently, counsel people on lifestyle, on exercise, on nutrition? And did you initially go in thinking, people should be able to do this? Like, and initially have some sort of preconceived ideas about the person in front of you? Yeah. So that was med school for sure. I went in basically like going like,

09:06
All right. People don't need drugs to lose weight. You just like got to actually do it. I didn't understand the biology and pathophysiology of obesity. was, I had a very strong weight bias that I talk about now. And like, that's why I don't even get mad at people. I'm like, no, that was me. I get it. I understand people have this bias against those with excess weight. And so.

09:35
I had that in med school and it wasn't until I kind of learned the pathophysiology and it wasn't really until I just kept working with patients going like, okay, apparently it's a lot easier said than done and there's something else going on here. And especially with the newer, these newer drugs, especially, but back then we had decent drugs that, um, that also kind of proved the concept of kind of this dysregulated appetite around, uh, eating.

10:04
to an energy balance because like, can't you just not eat that second portion? Why do you have to eat the donuts that Susan brings into the workstation? Why do you have to eat that pizza XYZ? And now it's like, okay, it's the appetite driving them to do it. It's not like they're choosing it particularly. Yeah. Stephen Guirnay talks a lot about the hungry brain.

10:29
Like, you like his work? Like, is that something that you like? Yeah, he and I are friends. It's what he describes is exactly what's going on. It's, it's, I mean, you can talk to people about it, especially before, you know, before they take the medicine, they're describing like, that they're just, some reason can't lose weight. They don't even, they may not even understand the hungry brain. You put them on the medicine, they start losing weight and then they get it. They're like,

10:58
Oh my gosh, now I don't have all the thoughts about food. I can actually eat a serving and not have to have another serving. actually am not even thinking about eating the chips after dinner or whatever it is. so it's just, yeah, it is literally the hungry brain. Cause you know, people are like, it must be my metabolism, all these different things. And yeah, some people can have various differences in metabolic rate, but it doesn't predict

11:27
excess adiposity or fat tissue. it's rarely, if ever, their metabolism, it's the dysregulated appetite. So that's why the drugs work so well. And can we chat about them? So like, Wigovia has just hit the New Zealand market and everyone is sort of either up in arms or particularly excited about it. You sort of one way the other, I suppose. But I do know that the two zeppatides, you talk about them a lot as being even more

11:56
potent or will have a lot more efficacy, right? So can we just start with telling people or just describing what the GLPs are, how they work, and also how effective they are? Yeah, so GLP-1, natural hormone that is released from your intestines after eating food, specifically like carbohydrate containing food. GLP-1 stands for glucagon like peptide one. It was

12:22
This effect was discovered in like the 50s, 60s where they injected glucose into the veins versus people drinking glucose. They found that insulin went higher when they drank the glucose versus injecting. For anybody listening, glucose gets in your blood system, your pancreas detects it, pancreas sends out insulin, insulin helps the glucose then get into your cells. So something about drinking it, something in the intestines, so they call it the incretin effect.

12:51
They didn't know what exactly the hormones were, but they knew there was this inkretin effect, some intestinal secretion of some hormone. And it wasn't until like the eighties where they started finding out these different types of ones, one of them being the GOP one. And so, uh, the problem is though our own human GOP one is broken down within a minute or two. So they're like, how do we use this to like, help people lower their blood sugars a little bit better.

13:19
If you injected human GLP one, just gets broken up very quickly. It doesn't have that much of an effect. You'd have to keep infusing it and that's an issue. Well, some pretty smart guy found that the Gila monster, these like little venomous lizard type of things, their venom saliva has a 40 % similar homology or homologous to

13:48
human GLP-1 and it was resistant to our own natural enzymatic breakdown of it, relatively resistant. So they actually developed that into the first GLP-1. 2005 it was approved called Biata or Xenotide. You had to inject it twice a day. had a little bit of weight loss, not a ton, but it helps people lower their sugars. And then the race was kind of on from there.

14:14
Then it was, then they did take our human GLP one and modify it slightly. So it's not broken down. That was liraglutide. That was a once daily injection. And then, then we go via semaglutide and people know it as Ozempic too, but, um, semaglutide is similar to the liraglutide. It's human GLP one that they modified and it's last even longer. Uh, you can get more of it into your system so then it hits different receptors or hits the receptors stronger. Uh,

14:43
And then now we have the terzabotide, which is actually a co, uh, it twin Crotin co receptor agonist. it hits not only GLP one, but it hits another ink Crotin called G I P and, it's even more effective. That's kind of the newest one, but we go via some agglutide and the effectiveness. when you think about lifestyle interventions on a population level, gold standard randomized types of trials.

15:12
gold standard though, intensive coaching and whatever, we see an average of around six, maybe 7 % total body weight loss. So let's just say someone who's 200 pounds over the course of a year, you can expect on average, again, looking good into some people respond really well. Obviously we know them lose tons of their weight, but on average someone has 200 pounds, they'd lose, you know, somewhere around 12 to 14 pounds of their weight and keep it off.

15:41
for a little while. Well, new, the semaglutide gets around 15 or so percent total body weight loss. So you start getting into more than double or even triple the amount of weight loss. Trisepatide gets like 20, 21, 22%. So it even adds another like 25 % on top of the semaglutide. But the weight loss is what we call durable. So like with lifestyle alone, you have to keep doing those things.

16:11
uh, to keep your calorie intake lower and it's tough. The appetite starts coming back. It works hard and hard against you. You're exercising, doing everything you can, but you're just getting hungry and hungrier. These medicines though, just dampened down that, uh, that appetite level a little bit and keep keeps it there. Some people say that their appetite's coming back, but they don't regain their weight, which makes me think that the drugs are working. So they have.

16:40
studies up to like four or so years showing people don't regain their weight on these. So that's another added benefit. So much more weight loss than lifestyle alone. Plus it's durable. It lasts. And I always say the big myth around it is that like they're not doing all the work for you. They are helping you do you do the work. It's kind of a, mean, honestly, you could, you could take them and you lose the weight regardless if you just kept your old lifestyle, but like really they help you.

17:09
do what you already have a good idea of what to do, but just couldn't do it before. I did my masters in obesity and I just remember how underwhelming these intensive depressingly like they just seemed so miserable. I mean, I love it. I mean, it's what I do. I'm a runner. I exercise and I love it. But just the way that they sort of like laid out the low calorie diets, the

17:36
aerobic training and it was just seemed so miserable for such a small return. Albeit I did wonder actually like a lot of those traditional sort of intensive lifestyles don't really target the things that we might target in practice like protein and strength training in addition to. But yeah, just it's hard. And then of course, if you look at exercise, you know, how much exercise you need to maintain that weight loss. think it's like on every...

18:03
again on average, like 90 minutes a day, which is probably not a lot for us, but yeah, for the most people. someone who's like not used to it, like, yeah. Yeah. Yeah. It's crazy. Um, now a couple of things, Spencer, which is interesting. So you mentioned that the GLP one works because they increase the pancreas signal to release insulin. That's, is that what you- For sugar regulation. Yeah. And so someone- Acute sugar regulation, I should say.

18:32
Yeah. Okay. So in type two diabetes, which is how it was first used, like someone asked me this, they were like, well, aren't the people with type two diabetes, don't they already have like elevated insulin anyway? so what's the go? Yeah. So, um, so there's a few things it helps the, the inkretin effect is lost or diminished in those with type two diabetes. So acutely when you.

19:01
Eat something you over time in type two diabetes. You don't have not only the inkretin effect, but also the, your pancreas doesn't work as well to release more insulin to then push past that insulin resistance to get the blood sugars into your cell. So when you start taking one of these GLP one medicines, you bring back that inkretin effects or your insulin goes higher than it would when somebody eats. There's also a delayed gastric emptying.

19:31
So blood, the glucose that you eat doesn't get into your bloodstream as quickly as it would. So that's blunted a little bit. And then over time, honestly, because they help with so much weight loss and they're the GIP component with terzapotide, the GLP one may not have this, but GIP may actually have an also an insulin sensitizing property. So then you help them.

19:58
not only augment their insulin release, but you help with the insulin resistance component, especially if they're losing weight. So it's kind of a double whammy. And that's why an interzapotide specifically has both incretins. So it's a little bit more powerful in that effect, but also more powerful for weight loss. So then you get that effect on top of it and you end up lowering blood sugars really well. Yeah. Okay. No, makes sense. And you mentioned that

20:25
it's durable across sort of four or five years if they stay on the drug. Yeah. Yeah. So right now we were like, maybe in the future they'll have like these vaccines where you'd only have to take it like once a year or something like that. But for now it looks like the majority of people will have to indefinitely take at least some form or fashion of the medicine that they haven't done it the way that we do it in clinical practices, what they do it in the, in the trials.

20:55
They put every, they have one trial. I have a few trials like this, but one of them, particularly that I always talk about is the surmount for trials, teres, epitide, they put everybody on the drug and then like 36 weeks later, they randomized one of the groups, one group to placebo and keep everybody else on the teres, epitide. Those people on teres, epitide keep losing more and more weight. The group on placebo, they just, you can see them all slowly start to regain their weight. Oh, and they start looking at

21:24
Subgroups of like was there anybody that kept losing weight or at least kept off most of the weight There's like a small 10 15 percent of people that throughout the rest of the trial the people that were went to the placebo actually did keep off the weight so it's possible in the short term we don't know what happens after a year or so what I see in clinical practice though and again, I Don't even know how to run a trial like this because you would see all sorts of different combinations of how I do this but The gist is is that some people?

21:52
want to come down. Most people want to stay on the medicine if they can, but for financial purposes for a lot of people, if they're paying out of pocket, they want to be on the least effective, like the minimal effective dose, I should say. And you start doing very low doses and even spread them out. So instead of every seven days, you're injecting every 10, 12, 13, 14 days at like low doses or moderate doses even. then they...

22:19
it's just enough to keep their appetite at bay without being that max dose that they're on. So lots of different ways to do it. There are also non-GLP-1 meds that you can try that might work as well. And then there's some people that are able to come off the medicine and do fine. Rare, relatively rare, but happens. Yeah. Oh, interesting. And I think I've heard you say that potentially if people can come off and continue to maintain their weight loss and potentially the food noise for them,

22:49
wasn't as big of a deal. But of course, I suppose we don't know anything, but. Has to be. had to have not had. So they're likely the same people that if we got them into one of those intensive, you know, what I talked about those averages of like, yeah, on average people was like six to 7 % with intensive lifestyle. It's possible these, this small percentage, it looks like the same amount of percentage. I don't know if they're the same people, but I have a feeling they are. When you look at

23:17
percentage of people that do the intensive lifestyle alone and who really respond, who lose like similar results to those on these medicines. It's about the same 10 to 15 % lose like that, you know, 15, 20 % of their total body weight. So if they're 200 pounds or 300 pounds, let's say they're 300 pounds, they would lose 10 % would be 30 pounds, 20 % would be 60 pounds. Or if you, do you guys use the metric system over there?

23:45
Okay, so all right, so let's go with kilograms. So let's say if they're 100 kilograms, they lose 20 kilograms. So 10 to 15 % of people in intensive Lysol alone could probably reach that, whereas the average is obviously much less. So I have a feeling those same people that are able to come off the medicine would have probably been the same people.

24:12
that would have done well without the medicine in an intensive. think it has, it's probably, can't say for sure, but if I had to guess, that's the case. Spencer, do you reckon that people are so against these medicines because they've been sensationalized by people who can afford it going on for like to lose 10, 15 pounds? Like, is that why people get so upset about them? Well, that's so, yeah, they...

24:37
They are those people that are doing it for vanity purposes, the Kardashian kind of effect and the Hollywood people. They certainly help perpetuate the stigma of the medicines. They definitely do not help because we want these medicines to be thought of as like anti-obesity medicines. But instead they're just, being used as like skinny shots. And it's like, no, we're not looking for skinny.

25:06
we're looking for improved health. so like that, there becomes this dichotomy between those who are using it for health and the right indications versus those who are just using it to be vanity thinner that has no clinical value. So like the people that were already skeptical see that and they're like, what the heck? So I can imagine they worsen.

25:31
that divide and the stigma of the medicine. Yeah. Because cost is the thing that people always talk about and it seems really variable in different countries actually. Yeah. like, what's your, like, I mean, I imagine that over time these things are going to come down the same way that all the medications tend to, but I mean, you're in it. Like, what is the, why is the cost so different across different countries for the same thing?

26:01
Yeah, the manufacturers talk. mean, this has been studied. It hasn't, it doesn't cost that much for them to make it. They did put a ton of money into research and development. I get it. But, uh, for example, some countries can get it for like a hundred or fewer dollars where here it's $1,200 at the pharmacy. There are lots of things here in the United States that make it complex. have these pharmacy benefit managers and there's middlemen that just ratchet. They start making.

26:30
ratcheting up the price because then they get rebates. So then we have ways to get it directly from the manufacturer here for more like $350 to $500. That's better, but it's still, it should really still be a hundred dollars or less, honestly. So a lot of complexities there. It doesn't cost that much to create these things though. Yeah. So interesting. And maybe it's just a matter of time and it will be. Competition, competition will come in.

26:59
We have two, we have kind of a duopoly. There's two big companies. There's Eli Lilly and Novo Nordis. Eli Lilly's here in the States. Novo Nordis is over there in what is it Norway or whatever. And basically if a few more companies start jumping in and undercutting, and then there's good competition, then they all start.

27:25
dominoes start to fall in place. So I believe that'll happen. Give it five to 10 years and we're going to see generic versions, all sorts of stuff. And the public's going to be demanding. I think a lot of people are going to be on these drugs. And so like, they're going to have to figure that out. And I've seen people talk about peptides and sort of compounding companies sort of doing similar things. What is the difference? I don't think this is a thing in New Zealand actually, but of course I see it everywhere in the States. What's the go?

27:54
Yeah. So during the short, there was a shortage of the medicine because the drugs were so popular and somehow big pharma screwed up the rollout. Huge trillion dollar companies screwed up the predictions. It's kind of interesting that whole thing, but they screwed it up and they didn't have enough. So there's a loop, a loophole here where, uh, compounding pharmacies can then source out this medicine from wherever they source it from. I mean, the way to make the, you can.

28:24
You can make the peptide, the chemical, the structure and everything, and you follow, you can figure out how to make it. Big Pharma is going to say that their manufacturing processes are proprietary and nobody else has access. Compounding pharmacies are going to say, no, we're fine and whatever. I don't know who to believe. can't, we, will never have a study randomizing because I don't know if even the regulatory boards and ethic boards would allow it.

28:53
But the difference is that they're not getting, generally not getting the source of the active pharmaceutical ingredient from the same place. But when you look at it under a mass spec, it looks kind of similar. It looks similar and people are having effects. I don't know. I don't prescribe compounding, but it was done. the shortage is now over. And so you can't technically compound it.

29:21
Unless you customize the formula and add b12 and you have to do it on a small scale So there's some companies still doing it on a very large scale and I think they're probably gonna get sued Big Pharma doesn't mess around they want their their money. So I think those places are gonna get in big trouble So yeah the the way you can get around the laws you you have to basically say oh this person this patient has a as a need for this different formulation

29:49
And that's why we can compound it. like, when you look at how many people would need the special formulation, it's not many. People don't need B12 in their GLP-1. It doesn't make any sense. They'll try to make a claim, but that's how they're gonna get sued. You can change the dosage and say the patient doesn't tolerate the jump from one level to the next level. So for example, we'll take some agglutide, for example, the WIGOV goes from 0.25 to five, or.

30:17
0.25 to 0.5 to 1 milligram then to 1.7 and the 2.4 milligrams. So let's say that they're on the 1 milligram and you try to jump them up to 1.7 milligrams and they don't tolerate it. What about going to like 1.4 milligrams? Well, that's where maybe a compounding you could do the compounding and they could make that argument. But all Novo Nordisk would have to do would be to make the pen that they deliver it in.

30:47
Adjust in between doses. Anyway, it's a whole thing Little pharma meaning the compounding pharmacies. They found out they were making just Money hand over fist so they want their piece of the pie too. I don't really like them The reason is because they're not the ones that put in all the effort to research these drugs I'm not saying big pharma isn't corrupt but little pharma is not not corrupt too. I think they're worse because

31:15
they're preying on all these people and saying that they're the Robin Hood good guys when they didn't put any effort for the, for these, um, for like, for example, Nova Nordis spent how many ever millions of dollars to do a cardiovascular, um, event trial, CVOT outcome trial. We wouldn't know that this drug helps reduce heart attacks if it weren't for them. They're the ones doing it. And now.

31:42
We got Little Pharma trying to claim that they can make the drug too when they didn't put in any of the effort. It's like, come on, get out of here. So anyway, that's just my little soap box. And yeah, you can call me a big pharma show. That's fine. it's just, those are the facts. I don't need to do, I need to say that because loads of other people do, don't they? you don't need to. Everybody else will say that. Yeah, of course. Yeah. So obviously those little company, the compounding companies aren't enough to push the price down because they're just, they're just

32:12
small players riding on the coattails. Yeah, they can make it cheap. People, you mentioned the, you know, obviously the benefits of them, Spencer, and I've seen lots of studies and people also talking about benefits beyond CVD, type 2 diabetes. I've seen people talk about benefits for arthritis and inflammation and the rest of it. But before we get into the claims that might not be supported or supported by research,

32:42
What about some of the side effects? Because this is what I see time and again, people talk about, don't know the side effects long-term, albeit I don't know what long-term is if five years isn't long-term. Um, are there any that you're particularly concerned about that we do actually need to know more about? Like I've heard people talk about thyroid cancer and. Yeah. So I'll give you the common side effects. Nausea by far, most common side effect goes away for most people. Constipation.

33:10
pretty standard for people if they're not eating enough fiber, not physically active, not drinking enough fluid. You get some diarrhea once in a while. get some reflux is also common. Slows down your gastric emptying, more chance for the food to come up through your esophagus and just kind of reflux up. Some people get fatigued, tired, some other things like that. Rare side effects, there's some other weird rare side effects that are probably gonna come out.

33:39
The one thing that people were worried about were the black box warning on the drug says in rats and rodents, this causes a special type of thyroid cancer called medullary thyroid cancer. Well, that sounds scary in humans. It hasn't been shown. And the biological reason for that is that humans don't readily have GLP one receptors on these specific cells called C cells in their thyroid. Whereas rodents do, they're abundant and clearly the drug

34:09
hypertrophies their C cells in their thyroid and looks like they're increasing of the special rare type of thyroid cancer called medullary thyroid cancer, but we don't see it in humans. In fact, there's a push to get the black box warning off of the drug, but so that's one of the concerns that I'm not concerned. I'm not concerned about thyroid cancer. One of them was pancreatic cancer in the past. It hasn't been shown. Uh, pancreatitis was a worry. Uh,

34:38
big meta-analyses, they put all these huge trials that have been out for a long time, put all the data together, doesn't look like there's a difference from the drug versus a placebo for pancreatitis. I've seen it, but apparently in the trials, we also maybe see it in placebo. So it's kind of like, all right, well, it's no different than placebo. I do think you can get gallstones from the medicine, from weight loss. Gallstones can cause pancreatitis.

35:06
So it's very possible and anybody can get some, you can get weird reactions once in a while from medicine. So it's not inconceivable about pancreatitis from some other types of medicines. The reason this was a worry was because of how it works on the pancreas. And so the beta cells of it and it helps, helps preserve them or proliferate your beta cells, the things that make insulin in your pancreas. So that was why it was kind of like pancreatic cancer, pancreatitis.

35:35
But doesn't seem to be an issue. see some weird stuff that I see though. I'm seeing at high doses, people get, we call anhedonia. They just kind of feel like lack of motivation, just kind of blah. I think more needs to come out about this, but I've been making videos about it and lowering doses in people where they still have the effect of appetite suppression. Then they get their motivation back and things that are related to that could be the fatigue that's related to that. People.

36:05
lose their libido and sex drive. Whereas other people increase their sex drive because now they don't have as much adipose tissue and the adipose tissue and inflammatory effects from that can affect your communication from your brain to your testicles or ovaries and things like that. We're seeing fertility improve maybe because of GLP-1 receptors in that communication between the brain and the pituitary and the ovaries or maybe directly on the uterus. I don't know.

36:34
Like these are things that I just see I'm like, oh wow, this person didn't lose any weight, but they're now having periods that they didn't have for a year. Clearly something going on. don't know. Yeah. there's a lot there. That's super interesting. And what about the idea of tolerance with GLPs? do the people reach a point where, I mean, you mentioned earlier that people talk about food noise sort of coming back or something like that.

37:01
Is that an issue that you're seeing in your clinic that? So they don't regain their weight. they do. Some people do start getting appetite and food noise increases, but their weight doesn't change. And so in my mind, the drugs are intended. So what I always tell people there, they work for obesity and weight. They're not approved for food noise, particularly people, but that side effect of.

37:30
It's probably an effect that helps people lose their weight, like, if the food noise comes back and you don't regain the weight, like, I don't even know what to say to them, because they're not, I don't know. If they still maintain that weight despite having food noise, the drug's still working, but it's just not, it can be kind of mental anguish when they start, the food noise really, people feel so much better when they start taking these medicines.

37:56
It's kind of an interesting thing that they don't regain their weight necessarily. And just to clarify, like I see on the internet a lot people talk about, the compound is like calo-curb and people also talk about, here's my GLP-1 diet, which is actually just including a lot of foods that are naturally going to help us really. Like, clarify for us the actual effect of these computer drugs. Yeah, the calo-curb.

38:24
I don't care about, they've seen them at a few conferences. So they'll tout some of their mechanistic type of studies showing improvements in appetite and maybe decreases in calorie intake over the course of a meal or something like that. But what we need to have from them, if they want anybody to recommend it, like on a legitimate scale, as opposed to like mechanistic, we need to show like, does this actually

38:53
lead to weight loss. I don't care if you have pilot data or small trials showing improved hunger. And even if you show like you decreased calories in a meal, I want to know what actually happens. We don't, we don't care about that. That's cool to understand mechanistically, but we need to see the outcomes and the outcomes are losing weight, keeping it off. So until they do that, I haven't seen any supplement that's effective. mean, we have the, again, if they touts that they're a natural GLP one,

39:24
increasing supplement, I would stay away because our own natural GLP one is just broken down so quickly. It just doesn't matter. Yeah. Yeah. So it's sort of preying on a market that's looking for the solution, but they're just a lot of these places are just riding the piggyback of the wave.

39:45
Spencer, there is a growing interest in microdosing GLP-1s. And I've seen a couple of opinion papers talk about it, helping people improve tolerance to your point you mentioned earlier, or side effects, cost as well. And I also see lot of influences talk about microdosing for a whole host of reasons. What do we know about microdosing? What do you know clinically? And what do we know in the research about it? And how efficacious is it?

40:15
Yeah, not a lot of research other than like pre-clinical trials trying to figure out the right dosage for the various indications of type 2 diabetes and obesity weight management is actually popularized by my friend Dr. Tina over here in the States. then, know, the thing is what I see it's being inappropriately used for thin folks who want to get thinner.

40:45
basically using low doses that are not usually approved for obesity or type 2 diabetes because like they don't probably need as much. I don't think it's the right way to use it. But what I think we're going to see is that these low doses are probably effective for non-weight indications around the immunomodulatory effects of the medicine.

41:11
And everybody says, they just kind of threw out the word inflammation. It's good for inflammation. I like, what does that, what does that even mean? Well, do you actually have an inflammatory disorder? So for example, psoriatic arthritis, uh, patient, I have a few of them. They've been on the various biologics. are expensive biological immunotherapies. And, um, it wasn't until they started terzepatide where they're like, Oh my God, though, this is really helping. And now.

41:41
Big Pharma, course, I'm not the only person who must have noticed this. Big Pharma is studying this. So clearly, they saw the signal as well. So microdoses would essentially be less than what are currently therapeutic doses for their indication. So type 2 diabetes or obesity or weight management. So instead of terzepatide or Zepbond, manjaro, 2.5 milligrams, you would be sub 2.5 milligrams.

42:09
a milligram of that. So for we go views or some agglutide, the first dose is 0.25 milligrams. So a micro dose would be like 0.1, 0.2, know, something less than the 0.25 in general. You can make up, I mean, we could all come up with our various definitions, but generally micro doses are less than the subtherapeutic. But when I say subtherapeutic, I'm saying for the intention of

42:39
obesity and type 2 diabetes, but they may be therapeutic for these other things. And I have all sorts of anecdotes. Do you do it yourself? for a new clinic? Oh, for patients. So I do it for patients, but they have an original indication. have not, the reason I, so insurance won't pay for it for one of these things.

43:09
But I'm actually really interested in the, in these autoimmune patients that like, but the only reason, the only way I do it though, is if they have overweight or obesity or like some of that stuff, if they are, let's say they were stark healthy and they felt, um, they were stark healthy and they, but they had like rheumatoid arthritis or psoriatic arthritis and they were lean.

43:37
I haven't done it in those patients yet, but I think, you know, we'll see with some of the new data coming out. The reason is I just, there's so many people that need it for the indications that like, don't want to like mess around and do it like, just cause I don't know. I don't, I don't have enough data to say like, this is good, but I also am not totally against people wanting to try it. Cause I, if I, if you put a gun to my head, it's probably safe to try at least.

44:07
What I don't think is right is using it strictly for small amounts of vanity weight. And that may change. Maybe I'll change. Maybe in the future they'll study in those folks and they'll be like, okay, we're actually preventing heart attacks in these folks for long-term. If I had to guess, that actually might be the case, but I'm not like, I always say that if you're.

44:32
If there's not a huge, if we don't know if there's a huge clinical upside, you're only going to get that downside and the downsides are very small, but then they start that's very rare, small downsides start to, uh, outweigh the no clinical upside. So until I understand that there's a clinical upside for people, and I think there could be more, it could be harm if you start weight cycling with, uh, if you're lean and you go.

44:59
lose 10 pounds, regain the 10 pounds just from going on and off some agglutide or trisepidide and you have no other autoimmune or inflammatory disorders, obesity, whatever. I don't know, or maybe it would be fine. Maybe you're even cycling, you're preventing heart attacks. I don't know, I can't say. I just know I'm very careful. No, I hear it. I know a few people who doing it for IBD and colitis and seeing some real benefits from it actually. And I suppose to your point with those weight cycling individuals like

45:29
probably going to do it anyway. They're probably just going to diet and then regain. It's probably not changing so much for them. Interesting here in New Zealand, for what it's worth, there's this huge... A lot of people use their platforms and are saying, it's potentially quite beneficial, but what about lifestyle change? These people didn't even think about lifestyle change, which I find super interesting that it's like, I'm sure that they have.

45:57
But in particular, there was a bariatric surgeon had this huge piece in a couple of the bigger sort of media outlets, just warning people against just jumping on these drugs. I just sort of, isn't that like just protection of the patch? Like, I mean, the outcomes, are they that different? Like, I'm not sure what he was actually complaining about, to be honest, probably the lack of work that he might end up doing because everyone's on the drugs rather than getting surgery. Yeah.

46:27
I'd have to read it, that's what we're, you know, unfortunately the, you know, people want to protect their profession and like people get mad at me, but 10, 20 years from now, I don't know if we're going to need bariatric surgery other than very extreme cases. Cause we're, going to get into bariatric surgery levels of weight loss very soon. I mean, within a year or two with the new drugs coming out.

46:55
Then what they're going to argue is that it's a one and done. They can do the surgery and it's clearly more cost effective and we have more longer studies. But, uh, if we start fast forwarding over the technology of how strong these drugs are and then how cheap they'll get and how they're going to have effects beyond just the weight loss. example, the GLP one, uh, receptor agonism has weight independent effects on cardiovascular disease.

47:24
Meaning like you can lose the weight, but if you lose the weight with this drug, you're probably going to reduce heart attacks more than if you lost the weight by yourself. Or if you just take this drug and not lose weight, you're going to reduce your heart attacks. um, and I, I like bariatric surgery. I have a lot of patients that I'm like, okay, you should go this route instead. But I, if, if I had to guess, you know, just trying to hold onto the profession, like for like in the future, what if something bad comes out about like, oh my God, in 20 years we see that some cancer.

47:54
that just took years and years to develop came from these drugs, then I'd be like, oh man, that's, it would be terrible for my profession and specialty too. So I could imagine they're probably being a little bit guarded, but the good surgeons who understand the multi-disciplinary effect, they will go, no, these drugs are awesome.

48:22
Let's use surgery when needed and use these drugs. That's how it's supposed to be. Let's use the best effective method and with a shared patient decision making process between the doctor and the patient. that's a good one should do that. Yeah, nice one. I mean, I don't even think we should really go into this, but I will mention it because everyone talks about how people just lose too much muscle mass. Come on. But surely, I'm sure most people listening to this understand that

48:50
lifestyle is always a big piece of the puzzle when it comes to using these drugs or should be when using these drugs and you're going to lose a lot of muscle mass if you just aggressively drop calories, which is effectively what these do, right? Yeah. So if you dieted and didn't do lifting weights, you're going to lose muscle mass and you generally lose muscle mass no matter what, regardless, even if you're lifting weights. But if you're pretty good about it, like we

49:17
are gonna be publishing papers based off of some of our patient population. We're seeing minimal muscle loss, very minimal when they optimize protein, but most particularly it's the resistance training. yeah, it's just like if anything else, if you're eating a low calorie diet and not lifting weights, you're gonna lose 25, 30 % of fat free mass. Yeah, yeah, yeah, it is what it is.

49:47
your minimum threshold for protein Spencer. So obviously if you look at physique science, they go up to 2.4, general weight loss might be two grams per kg, but actually getting that amount in is likely quite difficult. So what's your minimum threshold and what about those clear protein waters? I think I've seen you trial a few of them. yeah, what's your sort of...

50:13
Yeah, one to one to 1.2 grams if they can get 1.2 grams per kilogram of protein, they're doing great. If you can go higher than that, great. like if you are have a lot of weight, like that can be really difficult, especially if the medicines are just dampening down your appetite. that's that's kind of the data from that come from like the very low calorie diet studies and looking at what

50:43
protein amount can help minimize muscle loss and that type of thing. For the clear proteins though, I never really drank them. I always drank the chocolate, vanilla type of stuff and I've been seeing a lot of people drink these and I was like, okay, let me try these out. So I've ordered tons of brands and some of them are just terrible.

51:11
And they just terrible aftertaste. They're looking to make it taste kind of juice, juice-like. And some of them do. Some of them taste like this tastes like a good lemonade. This tastes like a good strawberry lemonade. It's usually like a lemonade one, but then some of the lemonades are terrible. So I'm like, I don't know. And I'm like, how do people even buy this stuff? And I actually, I'll, I'll give a little bit to my kids and see their reaction. I'll give it to my wife who doesn't necessarily like protein shakes. And you can always like, I'll drink anything.

51:39
And I can tell like this one's it seems a lot better. This one's I'll drink it, but it's not that good. And they, their reactions are kind of similar. So I've tried like 12 or so so far, I'm going to get a bunch more and only so far three have been good. Like the rest of them is like, these aren't good. So, uh, you know, any way to get protein in, if you can eat it from whole foods, but if you want to get it from, uh, know, people like, it's just a supplement. was like, well, protein.

52:08
powders, technically it's food. It's not like it's sawdust or something like that. So it is calorie, it's a macronutrient, it's food. It just comes in a more convenient way. So if you can find ways to do that without making people sick, and one of them might be a juicy, clear protein, that would be fine by me anyway. And like, do you have clients who are, or patients who are sort of

52:34
not that keen on the exercise piece when they come to you, but you're still happy to prescribe. What's the process there? In my experience with working with clients, if I can get them on the diet and they start seeing wind and they actually just, small steps, it's really hard to overhaul everything. Should someone feel like, if I want to try this drug, then it means I have to go all in, boots and all from day one? Yeah, it's classic behavior change stuff.

53:04
Um, you don't force them, you show them that they have this opportunity to do this and you have the resources and that you'll be there if, uh, kind of motivational interviewing behavior change type of thing. I don't, I basically, I'm not going to force you to just, know, but I have this here. Here are the benefits. So let me know if you want to do it. What did see is that they, some are like, yeah, let me just start getting into it. Other people will be like, okay, they start losing weight within weeks. Their joints and everything start feeling better and like I'm ready to, cause

53:34
doing physical activity. Some of them takes a few months, but you you give them the opportunity to do it. Don't force them. Don't wag your finger. Don't shame them. Classic behavior change. Yeah. Science. Nice one. And you've mentioned that, you know, people, I've heard you say online that people will probably need to sell the drugs for the rest of their lives. Is that?

54:01
Like, do you think that that's actually the case and that's why some people are so up in arms about being on the medications or even starting them? Yeah, most people will have to use the medicine indefinitely. some people though, like I said before, some people can come up and I think that bothers people because it's a big pharma type of thing. just think it's big pharma is corrupt. So that's why people, yeah, they probably

54:29
Contributes so you're gonna have to be on another drug for the rest of your life big farmers gonna make more money So that that certainly plays into it Nice and then finally obviously you've got and vineyard Which is your telehealth which I only just think of wine when I think of vignette. I'm not yeah. Yeah. Yeah nice one Um, so can you just tell people a little bit about it? And I know obviously it's just for listeners and you know, this is in the States It's an option. Are you in every state yet?

54:59
Yep. So there were some legal things and I think it's, I think we're waiting on Mississippi. Actually, there's some weird waiting on a license or something, but every other state and it's essentially, there's a lot of these places online that say they do comprehensive weight care, but they don't, none of them. There's not a single one. And so we do everything. We have a good dietitians, we have strength coach, uh, strength program, and you get a lot of time with the doctor who doesn't just hand you the prescription. We will get you the prescriptions quickly if you qualify, but we give

55:29
much more wraparound care with blood pressure, cholesterol, and all that type of stuff. the concept was, you know, I've been with some other companies in the past and I wanted to create the evolution of what I think the right way to do it online is. So focusing on good customer patients service where you're fast, speedy replies, but also better care than anybody else. It's kind of a, it's a tough thing to do, but I think we figured it out.

55:57
Yeah, awesome. And you seem to have such knowledgeable people on your team as well. I'm really looking forward to reading Summer's book that's just been released. Summer's book. Everybody should get Summer's book. I have it down here. is it? Living your healthiest samagotide life. nice one. No, I love it. Spencer, thank you so much for your time this morning. Really appreciate it. Yeah, thanks for having me on. Obviously, I will put all your links in the show notes and particularly your podcast. I love your podcast. And I do like, do you and Carl

56:25
get on that well, like quite well in real, like really well in real life. You guys have always just been best buds. Yeah, we're close. We beat each other up and stuff like that once in a while, but we're close. Nice. I really love it. And I love how geeky you are as well. Like, and you like go over a paper and then I can't, don't know, someone's like, man, that was really boring. And you're like, nah, it's not that boring. Yeah, Carl's like, God, that was boring. like, nah, it's not that boring. Anyway, let me tell the listeners where they can find out more about you.

56:55
Yeah, Docs Who Live podcast. can go to Instagram, Dr. Nadolski. I'm on TikTok as well. I don't know. I don't like TikTok as much, but I'm there. Twitter, X Dr. Nadolski as well. Facebook, Dr. Spencer Nadolski. Nice one. And join Vineyard.com if you want to check out the clinic. I love it. Thanks so much, Thanks for having me on.

57:26
So Rani, hopefully you really enjoyed that. Really love chatting to Spencer. What a wealth of information and really interested to see the emerging evidence in this space and how we can better support clients in their fat loss goals with the strategic use of these medications. Next week on the podcast I speak to my great mate Eric Helms all about what's going on in his world. You are going to love this because who doesn't love Eric? Until then though you can catch me

57:55
over on Instagram, X or threads @mikkiwilliden, Facebook @mikkiwillidenNutrition, head to my website, mikkiwilliden.com and book a one-on-one call with me. All right team, you have the best week. See you later.