[INTERVIEW]
Ronda Nelson: If your patient is on a GLP-1 and everyone is celebrating because she’s finally losing all of that weight, well, you might wanna look a little bit closer. Because behind that weight loss are often symptoms like constipation, muscle wasting, poor protein intake, low energy, brain fog, and so on, as well as a metabolism that is definitely not thriving. So today we’re gonna talk about what functional medicine practitioners need to understand about these GLPs, as well as the warning signs and the right type of support to provide for your patients to help get them back on track safely.
Welcome back to the Clinical Entrepreneur Podcast. This is where we talk about all things clinical and business to help you get smarter and run a better business. Listen, today we’re gonna talk about GLP-1s. This is not about whether or not you should prescribe them. We’re not gonna be talking about that. What we are gonna talk about is how to work with the patients that are on them. The prescribing part — not on your radar. If you do prescribe, this is not gonna be up your alley, although we are gonna just talk about, like, what kind of warning signs you need to watch for, what the patients might be saying, and what kind of support can you give them to help them overcome any challenges that these GLPs cause.
So before we start, I think we have to get clear about why these patients are getting on these drugs. It’s because they’ve not been successful with weight loss programs. They are feeling bad about themselves. Their confidence, self-esteem, et cetera, is down, down, down, down. And, you know, there’s always a cost versus benefit, right? We are not here to judge whether that cost versus benefit is a good one or not. Wouldn’t be a good choice for me, probably wouldn’t be a good choice for you. However, for the patient, they may feel like they have no other option. Out in the market, there is a big margin, profit margin. These GLP drugs come with a hefty benefit on the back end, and that is they’ve got repeat customers for potentially life because a lot of these GLPs, the patients are being put on them longer term. It’s a great business model — just saying. But in the meantime, the patient is losing muscle. They’re not digesting their food well. They’re constipated. Their metabolism is getting all screwed up. They become less resilient, less flexibility in their metabolism. It’s not good. We know that this is not good. But how are we gonna support them? That’s what we’re gonna talk about today.
So just as a disclaimer, this episode is for educational purposes only. I am not telling any patients to start or stop or change any prescribed medication by their doctor. If someone is using a GLP, decisions must be handled by their prescribing doctor. Your role as a functional medicine practitioner, wellness practitioner, is to understand what the physiology is — which is what we’re gonna talk about — and then how to provide the right kind of foundational support.
So all right, let’s dive in now. The GLPs are just everywhere. Patients are seeing them on TV. Celebrities are losing weight. There’s Ozempic and Wegovy and Mounjaro and Zepbound and Semaglutide and Tirzepatide. There’s a bunch of them. There’s compounded versions. And the patients don’t know. They’re going to someone that they think they can trust and getting these drugs, and they take the drugs, and then it can feel like a miracle for them because they’ve struggled for so long to lose the weight. And all of a sudden the weight’s just coming off and they’re feeling better and going down in clothes size. They’re tired of fighting the body, tired of fighting the scale, tired of being told, “You just need to exercise more and eat less.” That doesn’t always work. Sometimes it works, but it’s not always the right answer for everyone. Could be a microbiome problem, could be a metabolism problem. There’s lots of reasons why weight can go up — and just plain old diet as well, right? What we don’t wanna do is we don’t wanna shame them at all. If someone chooses to be on a GLP, then how do we work best with them?
So let’s talk about the mechanism and how these drugs actually work. GLP stands for glucagon-like peptide. Glucagon is your first clue — it’s an incretin hormone. The body naturally produces this from L cells in the intestine, and it’s produced in response to food. So it is a normal, natural peptide that the body does produce. And normally, in normal physiology, this GLP helps to coordinate the communication between the gut, the pancreas, the brain, the stomach, and the liver. Really all the places that are involved in digesting, breaking down, signaling back up to the brain, satiety — all of the things. So it helps the pancreas release insulin in the presence of glucose. The GLP helps to suppress glucagon, which reduces the hepatic glucose output. It slows gastric emptying, which helps blunt any post-meal glucose spikes. It also sends those satiety signals to the brain, so it helps a person feel full. This is normal. This is very normal.
What happens with the GLPs is it amplifies and prolongs that normal signal. So instead of a short-lived meal-related response of GLP, the patient now has a very strong pharmacologic response — an incretin signal — and that affects appetite and satiety and pancreatic signaling, all the things. It’s just stronger and longer. So there’s four things that they do, as I mentioned. They’re gonna increase insulin secretion, they’re suppressing glucagon, and they’re acting on the appetite and reward pathways. So they’re decreasing what the researchers call food noise. It suppresses the food noise. The cravings are gone. The desire to eat is gone. Can you see how that would be a problem? And it also slows gastric emptying and — big, and underline this — it slows gastric motility. That is huge right there. Because delayed or slowed gastric motility and gastric emptying, this is very bad. What happens is food stays in the stomach longer, the patient feels full faster and for longer, so then they eat less. They’re not hungry. Their post-meal glucose is often lower, and weight loss happens largely because their food intake drops — ’cause they’re just flat out not hungry.
So tell me, on what planet is this… I know I’m preaching to the choir, but on what planet is this normal that we would want to say to someone, “We’re gonna literally take away your appetite so you can now lose weight.” I.e., the scale is moving, your body is changing, but are we doing it in a healthy way? No. The same way that the drugs work also creates the problem. So when gastric emptying slows — that’s what we call gastroparesis — they often get nausea, bloating, constipation, vomiting sometimes. They don’t tolerate protein well because the food’s just sitting in the stomach. They get reflux. No kidding. These drugs don’t help the patient make better choices. It basically puts them into signaling jail, and so the body can’t do what it is normally designed to do.
So when someone’s losing weight, this is not weight loss that equates to metabolic health. If we’re gonna help someone lose weight, then we’re going to improve their metabolic health, improve the way that caloric intake is used, improve the way that glucose and insulin are working, increase fiber to increase satiety and prolong — not delay, but prolong — glucose in the gut so that we don’t get the sugar spikes. But no. The patient is put on the drugs, the patient loses weight, and they think that they’re healthier because they’re skinnier, but they’re not. They’re smaller, but they’re constipated. They’re smaller, but they’re undernourished — very undernourished. They’re smaller, but they’re inflamed. They become metabolically very, very fragile. They can’t eat enough protein. They’re too scared to stop the medication because they don’t wanna gain the weight, understandably so. But weight comes from different parts of the body. And in this process they also lose muscle, which we know. They lose water. They lose digestive resilience. It screws up their hormones. And they also really lose a healthy relationship with food because it becomes a fear-based model where the patient is too afraid to eat. So even if they did come off the GLPs, they’re still afraid to eat. And so they don’t eat because they don’t wanna gain the weight.
So patient says, “Oh, yeah, I’ve lost 40 pounds.” Okay. Well, did you protect your muscle mass? Did you protect your digestion, the function, the actual physiology of healthy digestion? Did you protect protein intake? Did we make sure that you’re getting enough protein, or does that low appetite mean, “I don’t really feel like eating steak, I think I’m just gonna have crackers and cheese and an apple”? That’s not cool, not cool anywhere. Did their inflammation decrease, get better? Did their energy get better? Most of the time not. They’re tired, they’re inflamed, they usually are weak. Muscles are weak. You’ve seen them, you’ve seen these GLP patients, and they’re gaunt looking. They’re just frail and fragile looking because basically what these GLPs are doing is they’re causing a problem. They’re not solving a problem — they’re causing another problem.
So there are four pathways I wanna go over with you. I’m gonna try and make this fast because I could talk about this for a long time. I’m gonna fly through these kind of fast.
Problem number one is the gastric emptying and the motility gastroparesis-type symptoms. So we talked about how that works. The reason that they feel full is because the food sits in the stomach for a longer period of time. And the patient will say, you know, “The food just… I just feel full.” When that happens, the symptoms that he or she are gonna experience are going to be related to upper digestive symptoms like nausea, vomiting, early satiety. They can only eat a little bit and then they’re done. Well, that’s because the stomach bag is full of food from three days ago. They can’t get much in there because the gastric emptying has delayed or slowed. They’re bloated. They’re constipated because there’s nothing moving down the tube. They have food aversions, sometimes even to taste and smells. Like, “Mm, nope, I don’t want that,” because the whole system is all messed up. All the signaling is all messed up. They’re often dehydrated, and weak — you know, just generally weak — because the delayed gastric emptying is preventing those nutrients from getting, A, broken down well, but B, being absorbed downstream. So basically the GLPs are applying metabolic brakes to the gastric system, to the gastric motility. Just putting the brake on the whole thing. And for patients who’ve already had sluggish digestion, or maybe they’ve been chronically constipated or had reflux, or a history of gastroparesis even, poor vagal tone, gallbladder issues, already a low protein intake — this is a bad option for them.
So here are the clinical red flags that you need to be watching for. If you have a patient who is persistently vomiting, cannot tolerate a normal meal or normal meal volume, you notice that there’s a lot of abdominal distension, constipation that’s getting worse and worse and worse, electrolytes — you do blood work and you start to see some deviation in electrolytes, muscle wasting (which we’re gonna talk about), malnutrition — this is definitely gonna be there. This is not when you wanna just toss digestive enzymes and some Zypan at someone and say, “Okay, you should be good to go.” If those are the signs that you start to see, that’s when you’re gonna wanna point them back to their medical doctor.
The second pathway is gallbladder stasis or bile stasis, and then the rapid weight loss of course. So the gallbladder pathway makes total sense. There are two issues. One, anytime there’s rapid weight loss, this increases the risk of gallstones. Whenever fat is metabolized quickly, the liver can secrete more cholesterol into bile, and that can make the bile more lithogenic — so more likely to form stones or get sludgy. And then the second thing is that the GLP can sometimes reduce gallbladder motility, so it’s kind of a double-edged sword here for them. It has to do with some cholecystokinin signaling to the gallbladder, and when food goes in and CCK gets released but the gallbladder can’t empty, then the bile sits longer and then there’s increased risk of sludge or stone formation. So it’s kind of a perfect storm — the weight loss creates bile that’s more cholesterol rich, and then the gallbladder doesn’t contract, so then the bile sits longer, et cetera.
So we can’t overlook bile support. One thing that I would say needs to happen with every patient on a GLP — you’ve got to get them on something to support their bile. They did a large meta-analysis, and they found that GLP use was associated with increased risk of gallbladder or biliary disease. Not surprisingly, right? Especially at higher doses and for a longer duration. But I’ll bet you dollars to a donut that their prescribing doctor is not talking to them about these risks. They’re probably not telling them, “Well, this does put you at an increased risk of gallbladder issues or gallstones.” What happened to informed consent over here? So if the patient has light-colored stools, dark urine, jaundice, radiating pain to the back or right shoulder blade, nausea and vomiting, abdominal pain, pain after meals, right upper quadrant pain — yeah, that’s not detox. That’s not them losing weight. That’s a gallbladder red flag, so you wanna be on top of that fast.
Pathway number three — there is a thyroid C-cell tumor warning. This one, thyroid cancer, needs a little bit of nuance. The warning is based on rodent or mouse data that shows that thyroid C-cell tumors are elevated. The concern, more specifically, is the medullary thyroid carcinoma. That comes from what’s called the parafollicular C cells in the thyroid. It’s a little different than the normal papillary thyroid cancers, which come from the follicular cells. But what the researchers have said is that the human data is a little bit more complicated, because the rodent cells seem to be more responsive to the GLP receptor stimulation — that’s what they said — than human cells. So that’s why they’re saying it may not correlate. However, the warning is still there. They are 100% contraindicated for people that have had a family history of medullary thyroid carcinoma at all. So just know — if you have a patient with that history, or family history, and maybe they didn’t have informed consent, maybe their prescribing person didn’t say anything about that — just ask the question to make sure.
Pathway number four — this is the big one, I think. This is the lean muscle mass loss, and also the weight rebound. Both of those are very, very real. So weight loss is not the same as fat loss. When appetite goes down, total food intake drops. So now their caloric intake is lower. That also means that protein intake is gonna be lower. When the body is absent of protein or sufficient calories, we know what happens. It goes into gluconeogenesis. It’s going to go look after the fuel that it needs to reach its metabolic baseline every single day. When there is no resistance training — they’ve dropped out the protein, they’ve reduced their caloric intake, they’re probably tired — GLPs don’t give you more energy, they make you have less energy. And aside from that, the heart is a muscle besides the skeletal muscles. We’ve got a problem. That’s a big problem. And the patient loses weight quickly, but the body is using muscle in order to stay alive. It’s basically cannibalizing itself is what’s happening.
And lean muscle mass matters especially in women in menopause, because menopausal women lose muscle. That’s what we do. So look for muscle that isn’t toned. Look for a flaccid-y kind of look — you know, everything’s kind of floppy and loose. Because without that muscle, they aren’t going to be able to dispose of glucose well, right? Glucose doesn’t have anywhere to go. That muscle supports healthy insulin sensitivity. It protects bodies that are aging, as I mentioned, like in menopause and as women and men get older. Muscle helps them stay strong — strong core, strong back, strong arms, strong legs. Muscle influences the resting metabolic rate, so the lower the muscle mass, the poorer the metabolic rate is. Muscle, long term in longevity, is one of the most important things that we wanna protect. But yet what are we doing? We’re putting all these people on the very thing that’s causing them to lose muscle. I cannot… I mean, make this make sense. Make it make sense. If a woman loses 40 pounds, a huge portion of that is muscle mass. I can’t count that as a win.
So it’s especially dangerous in perimenopause, menopause, older women, chronic dieters — because they probably already have decreased muscle mass — and then anyone who already has insulin resistance or is undereating, not strength training. Strength training is so, so, so important.
Now, as I said earlier, when the medication comes on board, it amplifies and pharmacologically extends the natural GLP response from the L cells in the intestine. When that happens and gastric emptying is slowed and the satiety signal is amplified, what happens when the medication gets stopped? Those signals kind of go away, and appetite starts to return, and gastric emptying might normalize. There are some people who, after the GLPs, permanently don’t re-normalize that gastric emptying and they end up with gastroparesis or some version of that. That’s a big problem. But when they get off the GLPs, they now have such an unhealthy relationship with food that when the appetite returns, the panic returns, and they may not be able to exert the same control. Really, they didn’t have control over their food while they were on the GLP because the whole appetite was suppressed. It doesn’t take a lot of willpower or focus or determination to stay away from food when you have no appetite. It’s real easy to not eat when you don’t have an appetite. But when that appetite starts coming back, they often will go back to the same thing. They don’t have the tools, the strength, the willpower to be able to withstand the cravings, et cetera.
They found that after stopping the semaglutides, patients regained about two-thirds of the body weight they had previously lost within one year off treatment. Two-thirds. So if she loses 40 pounds, she’s gonna gain back 25 to 30 pounds. That’s what they’ve shown. Because if the patient loses the weight on the drug but they don’t build the metabolic infrastructure to support them after they’re off of the drug, then they’re gonna come off with lean muscle loss, poor metabolic reserve, more fear around food. That’s where we come in. That’s where we come in to help them. We’re trying to build them up while they’re losing the weight with the GLP, so when they come off, they’ve got something to fall back into — better eating habits, good protein habits, blood sugar is more stable, digestion is working. That’s what we need to do.
So when you have a patient that’s considering a GLP, don’t shame them, but you might just ask questions like, “Why does this feel like the best option right now? What have you already tried? Have you talked through the risks with your provider? Do you understand that you’re gonna need a plan for protecting your muscle, because you will be losing muscle? And what’s your plan for protein intake? What are you gonna do if constipation gets worse? Or what’s the plan when you stop, and what will it look like beyond the scale? When you lose all the weight, what does your plan look like after that?” Those are all great questions to ask the patient, and they need to know that because they’re not thinking through what they’re doing. Short term — “I wanna lose weight. Here’s a drug. It’s gonna help me lose weight. Okay, great. I’m happy.” But when you care enough and you start asking these kinds of questions — all of a sudden, especially to the aging population, perimenopause, menopause, post-menopause, and aging adults in general — when you start asking these questions, now they feel cared for. They feel like someone sees them. And maybe you can provide a different option, and you can start to change and modify the terrain while they’re on it, so that when they’ve lost the weight, at least they’re not in as bad of shape, and they can manage that rebound food, the satiety, the hunger that’s gonna come back.
So what do you do if they’re already on one? Well, again, you don’t shame them. “Listen, my job is not to judge you at all. I’m just here to support you.” And you’re gonna do the same thing. What are you doing about protein intake? How are you managing muscle mass loss? Are you doing any strength training? Do you feel weaker, more fatigued? Are you constipated? You’re gonna be asking those kinds of questions. Always, I think for patients that are already on them, you have to protect digestion. Gallbladder, gallbladder, gallbladder. Upper digestion — keep going with Zypan, whatever kind of HCL product you wanna use, don’t care, bitters. You’ve got to keep that digestive system active. Try and get that pH down, down, down in the stomach. But gallbladder, gallbladder, gallbladder, gallbladder. Pick your gallbladder support and just the whole time — do not stop, do not pass go, go to gallbladder jail. Go there to jail. Do not come out until we’re done and you keep taking the gallbladder support. That’s all.
And then you wanna make sure that you’re being intentional about their nutrient intake, because again, they might resort to crackers, cheese, and an apple, and we don’t wanna do that. So how do we be intentional about food intake? Where can we get them a little bit more fiber? How can we put more color in the diet? How do we make sure that they’re getting the fats in? They might be thinking, “Oh my gosh, I don’t wanna eat any fat because I don’t wanna get fat.” They just don’t understand, and that’s our job again — to educate them and explain what it is that’s happening. Your body, our body, we can’t build health out of air and good vibes. It just doesn’t work that way. I wish it did, but it doesn’t. It’s not very convenient to have to eat all the time. But the body can’t do it any differently. We have to protect what they’re taking in, and then protect their metabolism, right? What is their metabolic state? How do we make sure when they’re off the GLP that their metabolic state is solid?
So don’t let your hands off the wheel with these GLP patients, because you wanna keep asking questions. Point them back to their doctor if you see any red flags, something that makes your spidey sense go off and you’re like, “Hmm, something is not right.” And then as far as follow-up, there are a few things that if the prescribing doctor is not ordering, besides asking lots of good questions, you might want to continue to measure and test. I definitely would keep an eye on fasting glucose and fasting insulin and A1C for sure. You’re gonna wanna look at triglycerides, keep a close eye on liver enzymes and their CRP as well as the thyroid markers, and then ask them questions about their food. Have them keep a food diary so they can see that they’re becoming averse — because this is like we’re going into eating disorder territory here. I literally cannot make this make sense. I know so many people that are on them. And you know, you see someone you haven’t seen in a long time — my husband and I went to visit some friends, we hadn’t seen them in a couple of years, and I walked in and she just looked like a skeleton. And I didn’t say anything, but they have the Wegovy look, and I don’t think it’s a great look. I just don’t think it’s a great look. I don’t think so.
So what we wanna do is we wanna support them. If they choose to do it and you can’t talk them out of it, fine. But at least make your case, and then be clear that you’re gonna support them while they’re doing it. You’re gonna help them build muscle, retain muscle. You’re gonna help them retain and optimize their digestive function. You’re gonna teach them how to use nourishing foods to make sure that they’re getting the fat in that they need, the colorful fruits and veggies in, making sure that they’re getting a good amount of protein in — because skinny is not the finish line. Being healthy is the finish line, and that’s what we need to focus on with them. I don’t think these drugs are good for anyone. I don’t think they’re ever good as a standalone solution. I just don’t see it. The health risks are just too high. What patients need is someone who’s gonna stand beside them and say, “Let’s figure this out.” And if they’re just determined to be on a GLP, fine. That’s fine. But then let’s at least have a supportive plan in place so that you’re not wasting away while you’re doing it.
[CLOSING]
Ronda Nelson: So if this episode was helpful for you and you want more information about how to identify the clinical foundations in your practice that you need to be addressing with every single patient — regardless of whether they’re on a GLP-1 or not — go grab my free guide. It’s called “The 5 Clinical Non-Negotiables.” You can find it at rondanelson.com/nonnegotiables. Whether they’re on a GLP or not, you wanna make sure that you’re addressing these foundational aspects with every single patient. It makes everything else you do work so much better. So go grab the guide at rondanelson.com/nonnegotiables. And if you found this helpful, please hit the subscribe button. We are gonna keep this conversation going. Next week, I’m going to talk about something that hits a little closer to home for most of us. I’m gonna talk about a business model that is quietly dying a very slow, painful death, and what we need to replace it with. I wish I had had someone tell me this 10-plus years ago. All right. I’ll see you next week.
[END]