Transcript generated using AI transcription, errors may occur. Contact Mikki for clarification

00:11
Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia on a Monday. And today I want to chat about Ozempic. But actually not Ozempic specifically, but the class of weight loss drugs that Ozempic falls under and the potential use case for them in other areas. So I used the term Ozempic because I think that, or the brand name, because I think that everyone will immediately clock what I'm...

00:41
talking about and might not be as familiar with the other types of GLP-1 agonists that are out there on the market that are being used both for weight loss but also for their original purpose of helping people with chronic disease and I will get into that. In addition to that I want to just share some information that I've recently been listening to and looking at on PubMed.

01:10
around their use case in inflammation and also autoimmune conditions, which I think is super interesting. I think there's been heaps of pushback on the weight loss drugs like Ozempic, Cezandia and others, in part because people look at it as a magic pill. People judge others for wanting to try these medications as opposed to what they would

01:39
that's one element which I want to chat a little bit about. The second part I want to chat about is the side effects that are reported with these types of drugs and what I understand sort of the state of the knowledge is in that area. And then I want to chat about, you know, what are some other potential use cases for considering a GLP-1 agonist? So GLP-1, glucagon-like peptide-1,

02:07
is something that we produce actually. It's a naturally occurring incretin hormone in the gut and it is released in response to food intake. And medications like Ozempic and other GLP-1 agonists are those that mimic the action of GLP-1. They are designed to enhance the effects of the hormone and along with it the many benefits that this hormone sort of provides. So the medication itself they are

02:35
I mean the one that you produce is a peptide as well. But I do first want to go into some of the sort of major differences between the GLP-1 that we naturally produce and that which we take as medication. So they're similar but then there are some important differences. So GLP-1 agonists are designed to mimic the action of our natural GLP-1 hormone. So it binds to the same receptors in the body.

03:03
and they enhance insulin secretion. They inhibit something called glucagon, which changes our appetite response. It slows gastric emptying, so it allows us to feel fuller for longer, and it promotes satiety. This is just like our natural GLP-1 actually, but the medication does it in an enhanced way. So they both play crucial roles in glucose homeostasis and appetite regulation, which is why

03:31
in its original form or original use, GLP-1 medications were used to help people manage their type 2 diabetes. So they help manage blood sugar levels, they both reduce food intake, and obviously this is going to be beneficial for diabetes management and of course weight loss, which is where a lot of the use is being promoted now. The molecular structure is really similar. So the natural GLP-1 is a short peptide hormone.

04:01
by something called the L cells in the intestine in response to food intake, whereas the agonists they're similar but they're not exactly the same. These are modified versions of the natural hormone. So the GLP-1 agonists differ because they are designed to resist degradation so they have a longer duration of action and I'll go into that in more details. But essentially the natural GLP-1 is rapidly degraded by an enzyme called DPP4.

04:31
it's dipeptidylpeptidase 4, and this means it has a very short half-life, so our natural GLP-1 response lasts for approximately 1-2 minutes. Whereas the medications, the GLP-1 agonists, are engineered to be resistant to DPP-4 degradation, so it allows them to remain active in the body for longer periods, ranging from hours to days.

04:58
dosing and administration strategies are weekly you would take a GLP-1 agonist. Which is of course the major difference as well. So natural GLP-1 is produced endogenally and acts locally and systemically following food intake whereas the agonists are administered exogenously via injections either subcutaneously under the skin or orally. So you take them, that's semaglutide is taken orally.

05:27
provide sustained levels of the hormone in the body. The other major difference between the two is that the concentration of natural GLP-1 is really quite relatively low and as I mentioned it's transient, whereas the medications are administered in higher doses to achieve the therapeutic effects with which they're used. This does provide a more prolonged and stable concentration in the bloodstream.

05:55
longer duration of action allow for convenient dosing schedules, either once daily or once weekly, the modifications enhance their therapeutic potential. This is why they have such a potent effect on appetite and subsequent effect on weight loss strategies. While the GLP-1 agonists, the medications are designed to mimic our natural GLP-1, you

06:25
in the pharmacodynamics are optimized to provide sustained efficacy and apparent safety in clinical use. So the differences do enhance your ability to act and make them valuable tools, particularly in light of the treatment of type 2 diabetes, but of course with weight loss and obesity too. And don't forget that 70% of the Western world have overweight or obesity.

06:52
And in some cases, there are people who are carrying excess body fat to the detriment of their health. In fact, that's most people who are overweight or obese. And so if we know that we have tools in our toolbox with which people can use to reduce their body weight in a safe and sustainable way, that does decrease their overall health risk, prolongs the number of years they've got healthy.

07:20
So not just their lifespan, but their health span as well. And it also takes a pressure off an already overstretched health system with regards to treatment for chronic disease later in life. So I just think that's really important things to consider. But I know that there are people who really struggle with the idea that people rely on medications. The way that there are people who struggle with the idea that others get weight loss surgery.

07:49
Interestingly though, outside of the blood sugar management piece, these GLP-1 agonists may have neuroprotective effects. They have found to improve cardiovascular health, they may decrease cellular aging, and they could also improve chronic kidney disease outcomes. So that's super interesting, which is what sort of got me interested in looking further into GLP-1 agonists.

08:17
Now just to go over some of the common types of agonists that people may be familiar with. There is of course liraglutide, which you may know as caesandia, and it's used in a higher dose formulation for weight management and it's administered once daily. There is also semaglutide, which of course you'll know as Ozempic and Wegovi, which are higher dose formulations.

08:44
and both of those are administered once weekly. Ozempic, predominantly for type 2 diabetes management, but of course is being used more and more for weight management. And you've also got others like the exanatide, you've got dulaglutide, and you've got lyxazenatide, which are all GLP-1 agonists with different dosages and use cases,

09:14
type 2 diabetes space. With regards to the differences in the amounts between our natural GLP-1 production and the dosing, so after we eat, our body naturally produces GLP-1 in relatively small amounts and this will obviously depend on the type of meal that you eat and of course individual differences. So the concentration, as I said, increases transiently in the bloodstream.

09:41
peaks within 15 to 30 minutes after eating, then quickly returns to baseline levels. When you take a dose of the GLP-1 agonist, which might be, if I'm just gonna use those two examples which we're most familiar with, you've got Sixandia, Cisenda, I always get the pronunciation wrong, that typical dose for weight management is up to three milligrams daily. And then you've got Ozempic,

10:09
The typical dose ranges from 0.25 to 1 milligram once a week. And WAGOV, the dose is up to 2.4 milligrams once weekly. So the doses administered via these medications result in concentrations of GLP-1 that are much higher in sustained compared to that transient and lower peaks seen with our natural GLP-1 release after meals. That's why it is really interesting

10:39
foods, the probiotic acumencia, which I've been taking currently actually, these help our gut produce GLP-1, but it's nowhere near to the same extent. I do think though that the natural ways to increase our GLP-1 definitely plays a part in appetite control. You're just not going to get that same appetite suppression that you would get if you take a GLP-1 agonist.

11:05
because the GLP-1 levels achieved with these therapeutic doses can be up to several times higher than the natural postprandial sort of levels. And that is what allows these drugs to have their therapeutic effects on blood glucose regulation, weight management, and appetite suppression. And it wouldn't really be possible with much lower or transient natural levels of GLP-1. Interestingly though, I do just wanna chat about the side effects that you hear

11:35
the drugs. And one of them, obviously the first one is the physiological effect, the nausea and the vomiting, which may largely be related to the dosing of the drug. And I know that some people really experience this quite a lot. And I think everyone is really different, but because it is related to the dose, this might just mean that if you are currently taking a dose of this medication and you're experiencing the nausea and

12:04
the vomiting, then I wonder whether titrating it down to a level where that's not happening is going to be the best use case for that individual. And of course, you'll likely be familiar with what you hear in the research suggesting that the drugs themselves reduce muscle mass and are therefore dangerous for weight loss. And I believe there was one study that found that

12:28
that of the weight that was lost in the individuals taking GLP-1 agonist, and I think it was semi-glutide, 40% of the weight that they lost was in fact muscle mass. And that's a pretty significant ride. And this was one of the first things I heard when these came sort of to the forefront of social media and we started hearing a lot more of them. Just heard that it was going to be super dangerous for anyone who wanted safe and sustained weight loss.

12:54
On further listening to experts in the field and looking at some of the research that has been done, that muscle mass loss might not be as solid on that front as what I heard actually. Remember that anything that aggressively drops calories chronically is going to strip the body of muscle mass. Ozempic, Wegovi, Sassenda, these are no different to that if they have that real appetite suppressing effect.

13:23
And this is certainly what I hear from people who take these drugs. It makes it really difficult to get in the protein that you need. So I guess two things spring to mind, to my mind in this instance, is that if you're considering taking these drugs for a weight management issue, then your best course of action is to ensure you're still getting that minimum of

13:47
I would say 1.2 to 1.6 grams per kg body weight of protein per day. Now of course this is quite a lot lower than what I would usually suggest people eat when they're in a fat loss approach, which is a minimum of 2 up to 2.4 if not higher amounts of protein. And I do just want to justify that or explain why I suggest a lower amount. It's because that sort of 1.2 is what's considered to be bare minimum.

14:17
to help support muscle mass retention. And these are studies that have been done in elderly people, so those people who are frail and are more at risk of losing muscle mass. That's a recommendation well below what I'd normally suggest, in part because the appetite regulation effect of protein is so powerful that I just want people who aren't taking weight loss drugs to experience that natural suppression of appetite that you get when you have a diet higher in protein.

14:45
If you're taking a medication that does that for you, then you don't need the as higher protein amount. Of course, the next and possibly more important piece of this puzzle is resistance training. Because those are the two stimuli that help preserve muscle mass. And some people even think that strength training is even more important than protein intake itself. So when you take appetite suppression out of the equation,

15:13
We just need to worry about holding onto muscle mass and resistance training three to four times a week. You know, it doesn't have to be six times a week or anything crazy like that, but resistance training, activity, and ensuring that minimum 1.2 to 1.6 grams per kg of body weight of protein per day is what I would recommend you try and shoot for. And it is difficult to get in protein when you're not hungry. So I think there would be a use case

15:42
in this scenario for something like the clear protein water, the one made from whey protein as opposed to collagen because that is going to contain the leucine that you need. Also the amino acids, the essential amino acid powders that you can purchase which have a complete profile of the essential amino acids as the name suggests but would help contribute to that amino acid load.

16:09
That is what I think is missing currently from some of that research around the muscle mass loss. But as I said, there's nothing special about those medications that are stripping your body of muscle. It is just the fact that you don't want to eat. So if you are really mindful of that and you take these and you commit to strength-based training and you commit to ensuring that minimum protein amount each day,

16:36
and you can't just be in one meal, which I don't think you'd be able to eat anyway, to be honest, then I think you have a much higher chance of preserving muscle the way you would with any diet. Other things that I did just wanna note with these GLP-1 agonists is their use case in cardiovascular disease. This is something which you don't hear a lot about because cardiovascular disease is no way near as interesting as the latest weight loss diet.

17:05
But that's where a lot of the evidence based for these GLP-1 agonists lie. It is in cardiovascular disease and helping protect against further events. So what some of the research shows is that GLP-1 agonists significantly reduce the risk of major adverse cardiovascular events including heart attacks, strokes, and cardiovascular death.

17:34
the Sustain6 trial which used semaglutide, and the Rewind trial which used dualaglutide. There were improved cardiovascular risk factors such as blood pressure, so the medications can lead to a modest reduction in both systolic and diastolic blood pressure, cholesterol levels, so favorable effects on lipid profiles, including favorable changes in total cholesterol and LDL and triglyceride, whilst increasing HDL,

18:02
and of course the significant weight reduction. They also may exert direct cardioprotective effects such as endothelial function. So you may have improved endothelial function, enhancing vascular health and reducing atherosclerosis progression, which is plaque buildup on the arteries. These drugs also have anti-inflammatory effects. So there is a reduction in inflammatory markers, which contributes to decreased cardiovascular risk.

18:29
And some studies suggest improvements in cardiac function and reductions in heart failure hospitalization. And so you know there are differences in the doses of those GLP-1 agonists that are used in the CVD outcome trials compared to those used in weight loss trials. Generally speaking, the doses are higher in weight loss to be effective in promoting significant weight reduction. Whereas with cardiovascular and diabetes management, the

18:57
primary goals to achieve glycemic control and reduce those CVD events. So they tend to be quite a bit lower. So the one area which I think is going to be interesting to keep an eye out for sure is with kidney health. So there was a trial called FlowCKD and it was testing the ability for semi-glutide to reduce the progression to CKD or chronic

19:22
kidney disease. And so as a randomized controlled trial, they had one group of people who were not taking semi-glutide, and then they had their control group, and they had another group that was the intervention group that were taking the semi-glutide. They had to stop the trial halfway through before they were going to because there was clear evidence of a benefit of those in the intervention group. Therefore, it made it

19:50
unethical to continue the trial where they knew that it was going to be beneficial. So it was unethical to the people in the control group. So I think that's really interesting with regards to these GLP-1 agonists and their potential support, not just obviously in type 2 diabetes management, cardiovascular disease, but also the potential for its role with kidney disease as well. There is also research to support its use in.

20:19
being protective against fatty liver disease, which is something, as you know, is becoming an increasing problem in the Western world, up there with type 2 diabetes. I mean, they're all interlinked. And the last area, which I think is super interesting to look at is its potential protective role against autoimmune conditions. So because GLP-1 agonists reduce inflammation, they're potentially going to be

20:47
helpful for many autoimmune diseases because of the interplay between inflammation and autoimmune conditions. So they can decrease the production of proinflammatory cytokines and increase the production of those anti-inflammatory cytokines. So it will modulate the immune system response. And they can also influence immune cell function, inhibit the activation of certain immune cells such as macrophages and T cells. And these play a crucial role in that autoimmune response or flare.

21:16
GLP-1 agonists have antioxidant properties that can help reduce oxidative stress, which is often elevated in autoimmune conditions, can also lower oxidative stress, which can mitigate tissue damage and inflammation. There's emerging evidence that it may help in conditions like multiple sclerosis and that GLP-1 agonists may offer neuroprotective effects. So it could help preserve nerve function and reduce neuroinflammation. I think that's super interesting.

21:46
preclinical trials looking at the effects in the brain in relation to conditions such as Alzheimer's and Parkinson's disease. And also it may be potentially benefit for autoimmune conditions that affect specific organs, such as the pancreas in type 1 diabetes or the intestines in Crohn's disease. So they might provide direct protective effects on those tissues there.

22:12
All of this is really promising, but of course we do need further clinical research to fully understand the efficacy and safety of these GLP-1 agonists in treating various autoimmune conditions. But what I would say is, you know, whenever you come across something like this on social media or reports and whatever it is that you read, just come at it with an open mind. And I think that's all that you can do. Everyone, myself included, can be really guilty of...

22:41
shutting themselves off to understanding areas like this more, or understanding the motives of people who want to use these drugs. And it's just not our business either. It's very easy to be judgmental of someone who may want to take a GLP-1 agonist for their weight management issue, for example, which is where a lot of the conversation is.

23:03
And even in that space, I would say that what someone decides to do with their health and their body isn't actually our business. So I don't know why we get a bit rolled up about the whole thing, to be honest. And I think if you're considering taking GLP-1 agonists for weight loss, then I would just say, please consider just a couple of those things I mentioned with regards to the appetite effects in one and...

23:32
the way that you may preserve your muscle mass better. I would also say that you would want to be taking a multivitamin or say a good green vitality from New Zest, something like that to help support your overall multivitamin and mineral status. But then also outside of that, I think that if anyone is exploring options for their chronic pain or their autoimmune condition and they don't see good resolution through diet and

24:01
or other standard sort of methods or supplements such as fish oils, etc. Then using these types of peptides isn't just another avenue for you to explore. So as with anything, I really just wanted to highlight that there is a lot of really interesting stuff going on in this space that is worth a look in for anyone who might need it. So yeah, so that's just some thoughts. I'll pop some links to some research up in the show notes as well. And...

24:30
I hope you guys have a great week. Let me know if you've got any questions or if you are using these for weight loss and you want some more guided advice on what to eat, then absolutely touch base with me. I can help you out with the consultation. You can catch me over on Instagram, threads and Twitter @mikkiwilliden, Facebook @mikkiwillidennutrition head to my website mikkiwilliden.com and that's where you'll be able to book a consult. All right guys, you have the best week. See you later.

2