Andrew: Thank you, mate. Thank you so much. Now, we’re gonna be talking about a very important topic, one that has really taken Australia society by storm, because there are so many people who are suffering from overweight, and indeed type 2 diabetes. But we’re talking about this newer class of drugs, called the GLP-1 agonist. Firstly, can you take us through what are they? What are the mechanisms of these drugs? And are there certain populations that they’re best suited to?

Robbie: Yeah, by all means. Well, I think this is a really important topic, because if there are practitioners out there like me, they’re probably gonna have people coming through the door who are taking these type of meds. And what’s interesting for me is about the prescribing in Australia has just surged, and really accelerated. So, we had an annual increase between 2019 and 2023 of 42.3 increase, of prescription. And that was to be compared to a 24.5% increase between the years of 2013 and 2019. So, as you can see, the prescription is on the rise, so we’re going to be seeing more of these type of clients coming through our door. And for those who may not be as familiar with these meds, basically, it is a glucagon-like peptide-1 antagonist medication. And, as we know, glucagon is a peptide hormone, which is secreted by our alpha cells in the pancreas, and its primary function is to raise blood glucose levels when they are dropping too low, acting as the counter-regulatory hormone to insulin. So, an agonist is really all about the production, or the synthesis, to activate that particular hormone.

So, the mechanisms. There are so many, as you can imagine. But I think the main mechanisms, being an antagonist, an agonist, sorry, is that you’ve got enhanced insulin secretion, first and foremost. Because they stimulate the pancreatic beta cells, they’re going to be releasing insulin, in a glucose-dependent manner. And that really helps reduce the risk of hypoglycemia. Then you’ve got the inhibition of glucagon secretion, which, in terms of suppressing glucagon’s release from the gastrointestinal tract, and the pancreatic cells, that leads to reduced hepatic glucose production. And then you’ve got delayed gastric emptying. That’s the big one, because that’s gonna tie back to the symptoms that we’ll probably talk about later, but there’s usually a delayed gastric emptying. And this is slowing the effect, which helps regulate that postprandial glucose spikes that we usually see, and it also helps promote satiety. So, it can be very beneficial in that regard.

Appetite suppression. That’s probably another major one that people will recognize from taking these medications, because they basically act on the hypothalamus, to decrease our appetite and also our food intake, which then also helps contribute to that weight loss progress, I suggest. And the final benefit of these medications or mechanism is that there are cardiovascular benefits as well. So, there are some GLP-1 agonists that have been shown to reduce cardiovascular events, and that’s likely due to its anti-inflammatory effects, blood pressure-lowering effects, and also that lipid modulating as well, that comes with these medications.

Andrew: Yeah. Yeah. What about comparing the GLP-1 agonists to other previous attempts at controlling weight loss? Things like bariatric surgery, other pharmacological approaches, for instance. The, you know, the metabolic stimulants, if you like, which came with their own sort of set of issues. And, of course, we have to include their lifestyle changes, which have been both well-studied but also poorly complied to.

Robbie: All right. So, there’s always gonna be pros and cons of all things prescription when we do it, whether it be lifestyle, whether it be medication, whether it be surgery. So, let’s probably break that down by each one. Firstly, lifestyle interventions, which obviously include things like diet, exercise, and also behavioral modification. So, some pros with that, you’re obviously going to be achieving sustainable, long-term health benefits. There is no medication side effects. And also, you’re just going to improve your overall metabolic health, that goes well beyond the weight loss component, because that’s why people are predominantly taking these medications. The cons to the lifestyle interventions is probably, it does require long-term adherence, which can be really challenging for a lot of people. As we talk about, people are looking for the magic bullet, that real piece of information, or substance, that can just provide really fast results. Then you’ve got, weight loss tends to be modest. So, you’re looking at about 5% to 10% of body weight that is being lost when you are doing it through a lifestyle intervention. And then you’ve got a high variability and success rates, based on individual metabolism, genetics, and also adherence. So, there are so many factors at play when you’re just focusing on that.

Whereas, the GLP-1 agonist comparison, if you’re going to take that medication, they enhance weight loss, beyond lifestyle alone. So, you’re getting a probably a higher weight loss success of around 10% to 15% of total body weight loss. And then the best results, obviously, occur when it is combined with lifestyle changes, rather than just using it in isolation alone.

Bariatric surgery. So, these are things, obviously, like gastric bypass, sleeve, gastrectomy, and all of these type of procedures that people get done when they’re finding that weight loss extremely challenging, or they are extremely obese, and it is impacting on other aspects of their health. So, obviously, the pros to that, it is the most effective weight loss intervention, where they can lose 20% to 35% of their total body weight. Metabolic benefits go well beyond just weight loss alone. So, obviously, things like, if they have diabetes, they could go into diabetes remission, and also reducing their cardiovascular risk as well. The cons. Really invasive procedures. So, obviously anything that comes with surgical risk, you’ve got infection, nutritional deficiencies, and also dumping syndrome as well, on the gastrointestinal tract, which is quite a challenging thing to treat as well. Then you’ve got permanent anatomical changes in your body, and that can lead to additional complications on top. So, it’s not suitable for all patients. It’s mainly those who are morbidly obese, and with significant comorbidities as well.

So, medications, in that regard, not as effective as bariatric surgery, but it’s a noninvasive approach. And it can also be used, which it has done in a lot of cases, as a pre-surgical intervention. So, as we know, whenever someone is going into surgery, they need to achieve a certain weight to reduce their risk of death, and therefore, this medication can be used as a presurgical intervention, for that post-surgical weight maintenance as well.

Andrew: Yeah. There was, you know, the standard procedure before bariatric surgery was to put people on a controlled VLCD diet. And I attended a bariatric conference, and, with the assumption that the VLCD diet prior to surgery was for added weight loss to reduce anesthetic risk. And that’s only part of the story. What I learnt was that the biggest thing was actually the surgeon wanting to decrease liver engorgement, because the instruments had to go in from the right side of the body, behind the liver, and then around and attack the stomach. And if you had an engorged liver, and it fell apart, you had a second surgical emergency on your hands. So, they were actually sort of protecting themselves against that attendant risk for that, which quite surprised me.

Robbie: Yeah.

Andrew: It was also a big eye-opener as to just how engorged people’s livers can be on high-carb diets.

Robbie: Oh, completely. And particularly with the excessive visceral fat, that is then coating the organs, which is then what is contributing to these chronic health conditions. Yeah.

Andrew: Yeah. Yeah, yeah. So, are there any ways in which we can enhance the effects of GPL-1, sorry, G-L-P, glucagon-like peptide, GLP-1? Is there any ways in which we can enhance the effects of GLP-1 medications?

Robbie: Yeah, there are. And there’s some really interesting ones, which, hopefully, some of your listeners will not have heard before, but, when I talk about the enhancement of these medications, I look predominantly at the nutritional strategies, as well as lifestyle strategies. So, if we firstly, we know that GLP-1 agonist medications work best in combination with nutrition, exercise, and behavioral changes as well. And that is, obviously, to optimize the weight loss, and to make sure that there is muscle retention, and also making sure our metabolic health remains intact as well. So, if we look at the nutritional strategies, firstly, you need to prioritize protein intake. That is number one, because GLP-1 meds, they suppress appetite. And that increases the risk of inadequate protein intake, or protein malnutrition. And then that, obviously, then has a flow-on effect to muscle loss, and that is something that we absolutely do not want. Therefore, as a general rule, for the general population, we should be trying to target at least 1.2 to 1.6 grams of protein per kilogram of body weight, per day. Obviously, if someone is engaging in resistance training, or if they’re playing some form of contact sport, that needs to be higher.

Then, I would just say, very simple, and it always comes back to this, is that we need to focus on a whole foods, nutrient-dense diet. And I really express the term nutrient-dense, because, like we mentioned, appetite suppression leads to lower intake of food, which then can lead to a lower diversity of food and nutrient intake. So therefore, that can lead to nutrient deficiencies, as well as malnutrition. So, we really need to look at those things, particularly in the gut, where those nutrients are absorbed. And we could be looking at things like iron, B12, magnesium deficiencies. So, we really need to monitor that as well. And so therefore, we need to emphasize vegetables, fruits, whole grains, legumes, basically a Mediterranean diet, right? There’s been a lot of studies showing the importance of a Mediterranean diet on the production of GLP-1, which helps with that natural appetite suppression, purely because, which leads me to my next point, it contains high fiber, and more importantly, it has a lot of bitters. Now, this could be the kicker for a lot of people. I think it’s important for everyone to be including bitters, or bitter compounds, because these bitter compounds are found in food, herbs, and you can even get them through supplements. They stimulate GLP-1 secretion, through their effects on gut taste receptors and the enteroendocrine cells. So, that is really important.

So, we all have taste receptors, right? You’ve obviously got all the five tastes, and the bitters have been the ones that have shown to be produced primarily in the distal areas of our gastrointestinal tract. So, the ileum, and also the colon. And that is what is going to help trigger these L cells, in the small intestines, to then release GLP-1. So, for education purposes, bitter herbs and botanicals can be introduced into the diet. And these are things like berberine, you know? A fantastic cardiometabolic intervention, for support with all things metabolism. Andrographis, wormwood, dill, ginger, oregano, celery seed. And then, of course, you’ve got bitter foods and phytonutrients as well. And so these are things like grapefruits, lemons, all those citrus peels, are very, very good. Artichokes, bitter lemon, radicchio, all of those bitter grains that we love, like rocket, dandelion, kale, even radishes and olives. And finally, from more of a pleasurable side of things, probably, is the dark chocolate, or those cacao polyphenols that we get. They’re quite potent when it comes to that stimulation of GLP-1 in the gut. Yeah.

Andrew: With regards to chocolate, and being practical, how high a cacao do you advocate? Like, I tried a 90%, and I couldn’t eat it.

Robbie: Yeah.

Andrew: It was a task.

Robbie: It is. I love, like, really bitter chocolate, so 90%, for me, is no problem. And then, you know, you typically have your 85%, then maybe 75%. I honestly am just tailoring it to maybe what people can tolerate, and you’re still going to get the benefits, because we know that raw cacao, on the antioxidant level and rating, dark chocolate is the highest. Like, it is through the roof. So, yeah, even if it’s around that 75%, it’s still going to have some great benefits.

Oh, the other one, too, interestingly enough, the highest, or the largest consumption of bitters in probably the Western diet actually comes from coffee. So, coffee is going to also produce that chlorogenic acids and the catechins that we see in both green tea, and also coffee. And that’s probably where a majority of the Western diet consumers get their bitters from their diet, but we need to change that, to make it more from those whole foods that we discussed. Yeah.

Andrew: So, there’s a, just a little tidbit, then. Would you therefore suggest to people having coffee after food, to help with the stimulation of digestive juices?

Robbie: Well, that’s a great question. I mean, I don’t usually advocate fluids whilst eating, because it can also dilute those digestive enzymes. So we really wanna try to give our gut the best chance of breaking down food, but also digesting food. However, stimulation of these receptors are what’s important, to then produce GLP-1. So, you’ve probably heard of prescription of bitters before food. So, you know, that age-old tale of consuming lemon water before you consume foods may actually have some benefit, because of those bitters. Obviously, that is then gonna help stimulate the taste receptors, which then will stimulate the production of GLP-1, which is obviously what we want, to help postprandial blood glucose spikes be as low as possible. So, it could be used in combination, pre-consumption of meals, and then also post-consumption as well.

Andrew: Gotcha. Just flowing on from something you said about diversity, previously, with diversity of foods, and reducing that diversity if you don’t have an adequate hunger response. I get that they’ve had an overabundant hunger response previously, but can you talk to us about the effect that this might have on the gut microbiota, and its diversity?

Robbie: Oh, yeah. Well, we definitely know, like, in terms of, obviously, GLP-1 to begin with, is where it is produced, and that is in the gastrointestinal tract. So, these medications, just like a lot of medications in general, can have an impact on the microbiota. But specifically, the GLP-1 receptor agonists influence both gut, the function, motility, and the microbiome. Now, I will preface this with saying that the research on this is still emerging. However, we…there are also seem to be benefits, surprisingly, with these medications as well, because the benefits could potentially be increased microbiome diversity, and that is then linked to improved metabolic health, as a result. There might also be enhanced short chain fatty acid production, which definitely aids in appetite regulation, and also insulin sensitivity. And there could also be reduced inflammatory bacteria, and that opportunistic bacterial overgrowth as well. So, that’s obviously just going to generally lower gut inflammation and improve the intestinal barrier function as well, so, the mucosal lining.

But, the potential negative effects is obviously things like slowed gastric emptying, and that is also going to alter the gut motility. And that is going to… People who already have some gastrointestinal disorders, particularly SIBO, that’s going to impact quite significantly. So, this comes back to, obviously, treating the client holistically, looking at what their medical history is, and seeing if they are a good candidate to begin with, or what they might potentially experience as side effects on the back of that.

There also could potentially be changes in bile acid metabolism as well. And that’s going to impact just the microbiome ballast, really, and then lead to dysbiosis. So, that’s something that we need to affect. We talked before we came onto this podcast today, is that the main ones listeners will be familiar with with these medications, are things like nausea, vomiting, reflux, and even diarrhea as well. They’re probably the major ones that I see, that come through my door, who are on these medications. So, we need to be able to control that, and manage that, whilst they’re on these medications. And all of those things I just mentioned is going to be an additional impact on how they consume food. So, they will already have a low appetite, but add all those things in, they’re not gonna want to eat, or they could go for long periods of time without eating.

The more severe things that we might see are things like gastroparesis. And this is quite a chronic condition, and a very serious one too, if it’s not treated, or looked after, whilst these people are on these medications. And pancreatitis as well. That’s just a side one, that there’s been a few cases of that, that have been seen with the use of these medications as well. But that’s more chronic and more serious, obviously.

Andrew: Yeah. Yeah.

Robbie: Yeah.

Andrew: Yeah. That was a really good point you made about potential improvements in the microbiota, with regards to the GLP-1 agonists. And I thought, you know, while you were talking, I thought about it, and I thought, “Yeah, maybe.” If somebody was on a really high-carb diet, they’re going to have an increased abundant, one would suggest, they’re going to have an increased abundance of the, we used to call them Firmicutes. They’re now changed their name. It’s now called Bacillota, this taxa. So, let’s say Firmicutes, because people are gonna know it. But it’s called Bacillota now. There’s a whole argument with the microbiologists about this. But, yeah, if you decrease the carb intake, you’re gonna decrease the Firmicutes, and therefore, potentially, the inflammatory processes that are attended to that, the EPS, yeah. Yeah. That’s really interesting.

Robbie: Yeah. Thanks. And also, it’s all about supporting gut health whilst they’re on these medications, right? So, that is should be the goal for the practitioner. And the way that we can do that is by increasing our fiber intake, both soluble and insoluble fiber. Because, as we know, fiber is so important to our gut microbiota, and also our digestion. And it can also alleviate things like constipation, if people are experiencing that as a flow-on effect of the medication. We should also be considering to include fermented and prebiotic foods as well, because that’s just going to maintain the microbial diversity in our gut. And, you know, we can get that naturally through things like kefir, sauerkraut, kimchi, garlic, onions, asparagus. So, all of these type of prebiotic foods can be really helpful as well. The one thing we haven’t actually brought up, but is equally as important, is hydration. I think we know, as practitioners, that a lot of our clients have really bad fluid intake, or if they do, it might come from other sources, that might have added sugars in there. So, like, fruit juices, soft drinks, but we really wanna focus on fluid intake, because that can also assist with things like constipation and delayed digestion. That can be an issue for these clients on these medications. So, yeah, I typically recommend, 30 to 40 mils per kilogram of body mass, and that is your lower end of the range to the upper end of the range, rather than that “aim for eight glasses of water a day.” That’s more tailored, more specific, and that way, you’re really gonna make sure people are hydrated.

Andrew: Cool. Other supplements, other things that we can use to potentially help patients? And I’m just wondering about, if we think about the original guidelines for the use of GLP-1 agonists, and that was type 2 diabetes, and if we think about a lot of people who have diabetes are magnesium deficient, and then if you think about, okay, how are we gonna support liver detox and blah, blah, blah. Taurine. And taurine has some, there’s not a lot of research on it, but some potential aspects of benefit, with regards to fat loss. What about using magnesium to help the diabetic issue, and then taurine to help the sort of liver, weight loss sort of arena? Does that make sense to you? Is that…?

Robbie: It certainly does, because if you think about it, the types of clients who are on these medications are not just the obese. They are the ones that have all the risks associated with it. So, yes, of course it’s been designed for specifically type 2 diabetes. That’s a given. We know that that is a metabolic issue in itself. But what about all the other metabolic concerns and issues? So, people who have hypothyroidism, people who have insulin resistance, people who have polycystic ovarian syndrome. So, all of these conditions have metabolic dysfunction. So, think of practitioners, or functional medicine practitioners, who are already supporting or supplementing their clients with these conditions, with nutrients that are gonna support metabolic function. It would be the same in any of these clients who are taking these GLP-1 agonist medications. So, yes, I’m in full support.

However, of course, it needs to be personalized and tailored, so you are looking at all the comorbidities that this client has, and then hopefully there’s already been the hard work done, in terms of the investigations around any blood work, pathology, maybe some microbiome, stool testing, and then even urinary hormone analysis as well. So, you can do so many types of investigations, to really get to the nitty-gritty. And of course, Andrew, you’ll love this, is, if they’ve gone the extra mile, to do some DNA analysis and testing, then you can really see where there might be some mutations on their SNPs that you can then be very personalized with their supplement treatment. Yeah.

Andrew: Yeah, yeah. What about… You know, these medicines are not cheap. There’s a whole thrust at the moment about trying to get them onto the PBS, and that will have its own political football sort of stuff going on. But, you know, these are not cheap medicines for patients, you know, $300-odd a week, that sort of thing. What about if people stop them? You know, I’m just wondering about the, people getting hooked into the quick fix, and wanting that. They’re extremely expensive. And so, you know, do they have attendant risks of, I mean, I say this word incorrectly, dependence? I’m not talking physical dependence, but wanting that quick fix. So, the risk of dependence of the effect of it, and the difficulty in maintaining weight loss after stopping them. Is there any anything that we can do to maybe manage their expectations, to maybe help them to navigate stopping these medications?

Robbie: You’ve raised a really good point. And I loved how you were cautious around that term “dependence,” because if you think about it, that’s when we are talking about more addiction. So, GLP-1 agonist meds are not addictive, in the traditional sense. So, there are no withdrawals from, or cravings, or even compulsive use of these medications. So, I think we should start there, and be very clear about that. However, there is a risk of physiological reliance. That’s the term that I like to use when talking about this. Because these medications alter your appetite, regulation, and also your metabolism, so that’s when there could be that risk of physiological reliance.

And the reason why some patients may struggle after stopping these medications is firstly, they’re going to experience increased hunger. And we know that these GLP-1 meds suppress appetite. So, stopping them can then also lead to stronger hunger signals all of a sudden, and they don’t know how to deal with that. They will maybe experience reduced energy expenditure as well. So, weight loss lowers resting metabolic rate, as we know, and that can predispose to weight gain.

Andrew: Yeah.

Robbie: And there is no long-term behavioral changes, if you think about it. So, they’ve gone on this medication, they’ve experienced this maybe, potentially fast weight loss, but patients who have relied solely on this medication may struggle to maintain those results. So, they’re the ones we need to be the most cautious with. And if we’re looking at risks of weight regain after stopping medication, the studies that have been done to date show that most patients regain around 60% to 100% of the lost weight within a year of stopping the medication. Unless, there’s a caveat here, unless lifestyle changes have been also put in place. So, I think that that’s really a great enforcer in itself. It’s that, okay, there may be some weight regain, but not as bad as if we implement some lifestyle interventions as well.

So, yeah, I think that that’s really important. But if you’re talking to the practitioner specifically about what we can be doing to really, firstly navigate the expectations. That’s number one. I find that practitioners aren’t having a serious conversation, or serious enough conversation with their clients around this. So, they need to navigate what the patient expectations are around the medications in themselves, because then you’re managing expectations around firstly, weight loss speed. So, how quickly they’re going to lose it, and also sustainability.

Andrew: Yeah.

Robbie: Educating your patients on fat versus muscle loss is also very important, because they’re gonna be seeing all this weight fall off, or reduce on the scales as a number. But what they’re not realizing is that a lot of it can be fluid loss. A lot of it can be muscle loss as well.

Andrew: Muscle loss.

Robbie: So, that’s really important. And then I would be emphasizing that GLP-1 agonist medications are a tool, not a standalone solution for their weight loss and improving their, maybe, potential chronic health conditions that they’re living with as well. So, there’s some really important points there.

Andrew: Can I ask about talking about setting patients up, if you like, from the get-go, for success, long-term? What sort of exercise would you tend to prefer? We’re talking weights? We’re talking resistance exercise, rather than cardiovascular exercise, at least in the beginning. Is that correct?

Robbie: Oh. Absolutely. Anyone who comes through my door, who is undergoing a fat loss journey, it is a non-negotiable, essentially, is that we are implementing some form of strength or resistance training, because we know that first and foremost, they’re going to be building lean muscle, which is important for long-term health, but by doing so they’re also going to be improving their basal metabolic rate, which is then going to assist in further fat loss. But then on top of that, that resistance training is also critical in preserving lean muscle mass. And we know, from the studies to date, that these medications can put people at risk of protein malnutrition, and also muscle loss. So we really wanna make sure that we are providing some form of strength training. And, for me, I would be starting at a minimum of three days per week. And a lot of people are probably listening, I should preface this, saying, “Oh, you’re just a dietitian,” but I’m also an exercise scientist. So, I can prescribe some recommendations around the exercise routine. And we are definitely looking at both that strength training, and also HIIT training. So, high intensity interval training can be really beneficial to maximize that metabolic burn, if you will, and to get real great results long-term from fat loss.

Andrew: Yeah. I’m glad you mentioned HIIT training, because if you think about this patient population… So, A, they’re given to wanting a quicker response from therapy. Right? I’m just gonna guess about the patient characteristics here. And thinking about HIIT therapy, even though, like, it’s hard and fast, but the results, even on triglycerides, are immediate.

Robbie: Absolutely.

Andrew: And so, talking about “quick fixes,” if you couldn’t get a better quick fix for your health, that has long term benefits as well. The other thing I was gonna mention, talking about foods, we were talking about foods earlier, is I seem to recall a smaller intervention regarding, it was 30 mil? 30 mil of olive oil per day, with the, yeah, the polyphenols. Biophenols, I think they call them in Australia, which, they’re not in the olives, but they’re actually made by the process of extracting the oil. Yeah. So, it’s really interesting with this, but… And they were actually chugging down 30 mils of olive oil, and they were having cardiovascular benefits, quite quickly.

Robbie: Yeah. Well, do you know what’s so funny that you’ve mentioned that, Andrew, is because it’s a trend now, on TikTok, on Instagram, there are all these people literally shooting extra virgin olive oil. And, you know, we’re looking at around 30 to 40 mils, as you mentioned, so you’re bang on.

Andrew: Right.

Robbie: And because of those biophenols, or polyphenols, they are a form of bitters, right? So, that is, makes sense, because it is stimulating those bitter receptors, which then stimulates the synthesis and the activation of GLP-1 in the gut. So, yeah, it definitely. But, the thing is, do we need to be shooting olive oil? No. You can be using it in so many diverse ways in your diet, but definitely making sure that it’s extra virgin olive oil, most importantly, because as we know, olive oils can come in blends, so we really wanna make sure that it is extra virgin. And of course, that goes back to what I was saying earlier around the Mediterranean diet. That’s another reason why it works so well on the stimulation of GLP-1. Yeah.

Andrew: Cool. Can I put an added call-out there, and that is that it’s Australian extra virgin olive oil? Because there’s actually been police stings overseas, where they’ve caught companies adulterating olive oil with other seed oils. And we’re talking about hundreds of thousands of liters. We’re not talking little things. We’re talking big business here. So, I would buy Australian here, definitely. Definitely only.

Robbie: Agreed.

Andrew: Robbie, there’s so much that we could cover here. I mean, this is a big topic. This is a seminar, not a podcast topic. But I thank you so much for taking us through your true expertise here. And it’s pretty evident that, with regards to when you’re saying personalized medicine and programs here, that it’s self-evident about your care for your patients. So, thank you so much for really educating us on not just the practical things to do, but how much you give a damn about these patients’ not just short-term, but long-term health. Thank you so much for joining us today on “Wellness by Designs.”

Robbie: Thanks, Andrew. It’s been a pleasure.

Andrew: And thank you, everyone. Remember, you can catch up on all the show notes and the other podcasts on the Designs for Health website. I’m Andrew Whitfield-Cook. This is “Wellness by Designs.”