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Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia on a Monday. And what's caused quite a stir in health circles, both health professionals and of course, Genpop who is super interested in nutrition and exercise and lifestyle is that Wigovy has hit the pharmacy shelves in New Zealand. And I wrote an email about this a couple of weeks ago, another post, and I just thought it would be really good to put my thoughts down in a mini episode on the topic.

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not just my thoughts, but actually the information that I have. And for what it's worth, I also have a podcast episode coming out soon with Dr. Spencer Nadolski, who's an obesity medicine specialist in the States, talking about the use case for these medications. And what I'm noticing is that there is a lot of noise around the appropriateness of this weight loss drug for the wider population. So for those of you unfamiliar,

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Wigovir is a semaglutide, which is the same active ingredient as Ozempic, which is sort of like, it's the brand name that everyone knows. But it's a little bit like Band-Aid and Plasters. Like people think about Ozempic as being the drug, but that's actually the brand name for semaglutide. Now, the difference between the two is predominantly the use case. Ozempic was originally only really used for type 2 diabetes management, of which super successful.

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whereas Wigovia is to be prescribed for weight loss purposes. Of course, people have been prescribing Ozempic off label for weight loss, but the dose is different as well. So Ozempic is set at a lower dose, up to about two milligrams, compared to a sort of top-out level of 2.4 milligrams a week, which is what is in the Wigovia information. So how these drugs work is super interesting. And someone asked me, they were like,

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How can these drugs work by increasing insulin but yet result in weight loss? Because I thought insulin wasn't a good thing, which was such a great question. it's super interesting with the history, actually. When it was discovered and started to be used, they found out that it increased insulin secretion from the pancreas. So specifically, they found that when it is administered, the semaglutide, at the same time that glucose is hitting the bloodstream, it helps increase the secretion of insulin.

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Basically, it's like when you eat food and you need that insulin to process the carbohydrate you ate, glucocon like peptide, GLP-1, is the hormone that's secreted that helps bump that insulin up so that your food can properly metabolize that carbohydrate. That was the initial thing that they found out about it. The people who discovered and produced it originally were like, hey, this is awesome. I guess the difference is that this isn't... This is helpful for people with type 2 diabetes because currently,

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When they eat food, their insulin's not responding appropriately. So it does need that little push, which is why it was super successful. Because without it, their blood sugar would go way up and remain elevated. Hence, it would be diagnosed with pre-diabetes type 2 diabetes. So that's what it initially was commercialized for. And as the pharma companies got their hands on it and started tinkering with it, what they noticed was that there was some variants of the drugs that had larger effects on

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appetite and body fatness. So essentially what they were doing were creating variants of this hormone that have a longer half-life. instead of it being degraded in just a few minutes in the bloodstream the way that foods naturally stimulating GLP-1 do, and that's things like protein and fiber and there are some bacteria, et cetera, now you can just take a shot once a week and it will circulate in the bloodstream for an entire week or longer.

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So this is what's led to the development of the current sort GLP-1 receptor agonists that are now used for both diabetes and obesity. So the two drugs on the market currently that are most effective would be Wigovy and also there's Monjaro and actually there's one other called ZetBound which is both a GLP and a GIP inhibitor too. So it works on a slightly different pathway. Now,

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One thing to be mindful of with these drugs, it's not just what they noticed was it wasn't just that they were having an effect on appetite, but they were actually doing quite a bit more as well. So one of the real benefits that people talk about is that taking these drugs help their brain quieten down the food noise. So it almost worked like not only on appetite, but also on the center of the brain that deals with cravings. One of the signals

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that goes to the brain is GLP-1. And so when you get the drug going to the brain, it activates the receptors in the satiety or fullness signaling in your brain, and it can crank that way up to make you feel so much more satisfied on so much less food. So people eat less and they lose weight and they get those metabolic benefits at the same time. So they make you feel more full. And what they also do is that they

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they stop the craving for food. And of course, this can have its downsides. Like you probably don't enjoy food to the same extent because you're not getting that same pleasure reward feedback, but it does hit that center of the brain that does make it easier to avoid cravings. So if you have a drug that's cutting your appetite at the same time as you're losing weight, it allows you to lose weight without that strong pushback.

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from the brain. And this is a really important point because a lot of weight regain is driven by these appetite signals in the brain that get you to eat more because you were in this calorie deficit state. I think there's a study that's found that for every, and I think this was Kevin Hall's work actually, for every one kilogram of weight you lose, your brain is hungry for an extra 100 calories, which is totally going against the

06:19
biology of your body really because essentially, well it's not, it is the biology of your body, but essentially when you lose weight, you need less calories, yet your brain is hungry for more. It's trying to get you back to the sort of set point that it's used to you sort of being at. So the fact that it can allow you to eat less and lose weight is such a game changer for people. But of course, to my point earlier, the drugs do do more than that. They do more than cut your appetite. They have that

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effect on cravings and something that Stefan Guernay mentioned was a seductiveness of food, like the real like, ah, the food noise that people sort of experience. And this is probably because that's independent of actual satiety. And in fact, this effect of the drug is probably independent of the effects on its appetite, or at least this is how Stefan Guernay sort of described it.

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And he's someone I've had on the podcast before. talked about the hungry brain, the powerful effects that the brain and our nervous system have on our appetite and obesity. what you see is that people who take these drugs also seem to drink less alcohol, they use less drugs, they do less online shopping anecdotally. And so all of these types of excessive reward-driven behaviors can get curbed by this drug. And this is more anecdotal than it is through

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through studies, but there are studies showing the alcohol cravings. The online shopping thing, I think that's a bit anecdotal to be fair. So you've got the appetite angle and then you've got the cravings angle. And people think this is why it is so effective, right? And there are some other potential upsides to the taking a semaglutide and that is that studies have found they reduce cardiovascular risk. They've reduced diabetes risk, obviously, because that's what they were intended to do in the first place.

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They reduce all cause mortality. They reduce risk of dying. And there may also be some association with reduced risk of dementia, obviously addiction, which I just sort of mentioned. So there are a lot of these potential positives, but it is still early days on that front. And of course it would be remiss not to talk about some of the downsides of these drugs. And I mentioned it in my email as well. Digestive discomfort. I mean, this is one of the mechanisms with how it works. It delays.

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gastric emptying through the stomach. So obviously that's a thing. Slow's gut motility. Depression is another one and there's an increase in suicidal ideation in some instances. And these side effects are listed on the Wigobi website. There is also reports of thyroid cancer and kidney issues. And in fact, if I listen to experts in this space, such as likes of Spencer Ndolsku, who's done a ton of work in this area,

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He's even running trials himself now. He's not overly concerned by these. I think in part because it might be either in rodent trials where the same pathways, physical pathways, physiology pathways aren't actually in humans as they are in rats. And so that's a big consideration. And that might just be a sort of wait and see. But if weight loss is successful, you sort of lose like 5 % of body weight.

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But that is what's considered successful. And that is what we need to help improve these metabolic markers. And look, these drugs are giving between 10 and 15 % weight loss over the long term. that's definitely better than what is seen in the drug sexcinda, which has been available in New Zealand for a while. That's a lyraglutide that is a short acting, requires daily injections up to about three milligrams a day. So you need quite a high dose.

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All in all, this all just seems quite promising for people who haven't been able to lose weight successfully, keep it off and do run the risk of these metabolic complications, cardiovascular disease complications. you know, so the cost of Wigovia is pretty significant in New Zealand, even worse in the States, but in New Zealand, I think it's $500 a month. I think I've seen reports of it being about $1,400 US a month. I don't believe that's with insurance.

10:31
And it is only available here in New Zealand through a prescription through the pharmacy. So they're not cheap. So that's obviously a downside. And you can only hope that as use case gets sort of increases for the people that need it, you hope that it becomes a little bit more cost effective. Because I think what the reality is and where the hoo-ha is, well, there are a couple of things, but people think that this is a shortcut to others not putting in the work to lose weight. And part of this seems like almost some sort of

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personal attack on anyone that might be considering trying these medications because people will look at them and go, why don't you just eat less and move more? Like they haven't already tried it. And look, I'm not suggesting that everyone that has taken or used this drug couldn't have made some level of improvement within their lifestyle or they didn't just go and get this quick fix. Cause I know that people out there, obviously there are people with the means to be able to do that, but I just see so much,

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uproar about people using these drugs, like lifestyle plus drug use is either or. Like they're not seeing some of the potential benefits of some people utilizing these drugs. And look, let's be real. Obesity is one of the most prevalent health conditions, chronic disease conditions that we've got here in New Zealand and in the Western world. Like I think 70 % of us are overweight as a population. And cardiovascular disease risk is one of the

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biggest threats to our health. I think cardiovascular disease is in fact the thing that people die most from. And these drugs could have a real powerful effect at helping reduce that mortality. One of my nutrition lecturers actually at Otago, she said something that has just stayed with me forever. She was in fact also my master's supervisor, Rachel Taylor. She said, you know, it's not why do people get fat in this environment? It's how on earth do people stay lean? And in this

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food environment where there's hyper palatable, highly processed, highly refined, high calorie food options that are cheap and there's every opportunity to save energy and not exercise. It's no wonder we're really battling obesity and the subsequent chronic conditions that it comes with, right? So I think this is an issue and this is a real use case for something like Wigovia. Now, of course, another pushback from a drug like this is that

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there's severe muscle mass loss and people which will then just result in people losing the weight and then putting it on again. And absolutely any kind of weight loss strategy like the Amway diet that you drop weight quickly without doing exercise and without protecting protein, you will absolutely lose muscle mass. This is not a feature of these drugs outside of the fact that it's an aggressive and excessive calorie restriction. So you will see

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rapid weight loss and muscle mass loss and potentially bone loss too, right? But however, as outlined in research and I did link in my email a paper that was released in 2024 in obesity reviews by Jeffrey Mechanic and colleagues and they really just outlined that the muscle mass loss seen in trials of semaglutide like Wigobi, which is the brand name, is not a mechanism of the drug itself.

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outside of the caloric restriction. So when you combine the drug with best practice lifestyle management, such as a high protein diet, in addition to strength training, there is no reason for muscle mass loss beyond what might be expected. However, I mean, if someone does have excessive body fat to lose, then potentially that amount of muscle that they lose as a part of it might not actually be so important. You know, like it really is what happens next, which is important. So if someone chooses to go on this medication,

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if it's aligned with lifestyle behaviors, then there's no reason why they can't be successful in the long term with dropping the weight, but also improving their muscle mass, improving their health and things like that. Or be it that loss of weight at 10 to 15 % will absolutely be so much better for their health than being overweight in the first place. And for what it's worth, there are currently studies underway looking at the combination of lifestyle and semiglutide and the recommendations for protein in practice

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are actually modified because of the appetite restrictions that people on semaglutide have because you just don't feel so hungry. And I've seen health professionals like the likes of Dr. Spence and Nadolski recommend even 1.2 grams per kg of body weight, which is still higher than the RDA, as a good starting point. And actually, this is more than what you see many people eating in everyday life. So yes, it's low, but if I'm thinking about the people I look at with

15:20
or I work with with protein, they're starting protein intakes are pretty low. And don't forget that the other mechanism to help preserve muscle mass is of course strength training, which is part of sort of the lifestyle prescription that comes alongside these drugs. people have talked about microdosing the drug and whilst that is a super interesting point and one that I'm interested to talk to a specialist about, there are a couple of opinion pieces that it could be good for

15:48
cost-effective for reducing side effects and things like that. I'd be interested to know what impact the dose has on the other elements that it is so powerful at beyond appetite, like how effective would microdosing be at reducing down that feedback reward center of the brain? I'm interested to know about that. And what is true though is that there is no good research on this yet. I think they are running studies on this, but we don't know. Now it is a

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pretty much a watch and see space. And for what it's worth, I've seen a bunch of reels and things talk about microdosing for reducing inflammation and other sort of use cases for it. And again, there's no real research for that as yet. And of course, losing weight is one thing, but keeping it off is another. And this is other pushback that people have against the drug. They're like, well, if someone goes on this drug, they have to be on it for life. There are a lot of people who are on medications for life. It is actually just the way they, that's.

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they have to live. People with type 1 diabetes, for example, they need to take insulin for life. There are some people who will likely need high blood pressure, hypertension medication for life from some sort of genetic variant that they've got that means nothing really changes the fact that they've got high blood pressure. There are things that people need. And actually, most research to date does show that weight regain occurs, and it can be substantial once participants come off semiglutide.

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know, the extent to which a focus on behavior change was a big part of the overall treatment for those on the drugs in the studies that have weight regain isn't known. For the people who don't regress once they come off the medication, potentially that food noise aspect for them wasn't as potent as it is for someone else. So that again is a watch this space area, I think. But what I also think is that sometimes getting a drug

17:41
Something like semi-glutide to give someone the space to make lifestyle change is actually what we need, particularly in this modern day food environment and environment which makes eating well difficult and makes moving, if you're not that way inclined, even more difficult. Like I know that you're listening to this, you're probably super active, you're out walking, you're good, you don't need that kind of motivation, but you are, I would say, in the minority. If you look at the statistics of people who exercise, eat well,

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have good metabolic health and are not overweight. So do not underestimate how unique you are actually in that space because most of the world is the exact opposite. So if there is something that can help them make lifestyle change, then potentially this is a good thing. And look, I'm not suggesting everyone needs it. Of course not. I mean, that's ridiculous. And I don't think I need to qualify that, but someone might say I do. And it's not for everyone, obviously. And yes, it's expensive. So not everyone can afford it.

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That will probably change over the years, who knows, I'm no expert in that area. But I just do not understand the pushback from people who say protein and fiber is enough. This is what these people need. They just need to eat well. It's lifestyle change. Like these people didn't already think about it. I mean, let's be clear. Most people with a weight problem have thought about these things, have tried these things. For whatever reason, they weren't successful. So I just think it's quite good to have other options. Anyway, those are my thoughts.

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Be keen to hear yours. Before I go though, if you are on something like Wigovy and you do need that support strategy, Monday's Matter Registration is open today through to the end of the week. We kick off next Monday. This plan is perfect for someone who can't eat a lot, who needs to prioritize protein, who wants to get those foundational behaviors in place to have lasting success in fat loss. And of course, obviously it is for everyone who wants those things. So the link is in the show notes.

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Go there, sign up to Mondays Matter and jump on board with the crew and me for Monday 28th of July, Mondays Matter August. Let me know your thoughts. Always happy to hear about them. I am on Instagram, X, and threads @mikkiwilliden, Facebook @mikkiwillidenNutrition. Head to my website, miikiwilliden.com and sign up to Mondays Matter. All right, team, you have the best week. See you later.