In this episode James Maskell is joined by returning guest, Dr. Shilpa P. Saxena, MD to continue exploring the use of GLP-1 agonists, specifically semaglutide, for weight loss and cardiometabolic diseases.

The conversation reinforces the importance of using GLP-1s responsibly and in conjunction with lifestyle medicine coaching to address underlying behavioral issues and promote sustainable weight loss. Dr. Saxena emphasizes the need to address metabolic dysfunction comprehensively, considering factors such as fatty liver disease and insulin resistance, and using a combination of interventions, including herbs, botanicals and lifestyle modifications.

They also discuss the potential side effects of GLP-1 agonists and strategies for minimizing them. Additionally, they touch on the role of group visits and community support in facilitating behavior change and long-term success in weight management.

Check out the full episode to hear their thoughts on:

  • Normalizing discussions around weight without enabling poor health.
  • The role of supportive communities to support behavior change.
  • The stigma around semaglutide use.
  • Patient personas that functional medicine providers are best able to help, and personas that are not a good fit for the functional medicine approach to weight loss.

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Cardiometabolic Disease, Fatty Liver & Weight Loss | Episode 336


James Maskell: So, a warm welcome back to the podcast, Dr. Shilpa Saxena, a regular guest and so glad to have you back.

Dr. Shilpa P. Saxena: Hi, James.

James Maskell: We are going to be talking about the hottest topic in medicine right now. We’re going to be talking about GLP-1 agonists, and semaglutide, Wegovy is sort of what people know it as, millions of Americans taking it, huge popularity boom, and I would say just in the last few months, starting to see a lot more conversation about side effects. Let’s start there. What do you see? Is this a net positive or is this something that we should be concerned about?

Shilpa Saxena: I think my thing is nothing is good and bad by itself. It is your relationship with it. Everybody thinks water is good from you, but not when you’re drowning, it’s your relationship to the thing, so semaglutide is no different. So, I do think that there is a space for it, but it must be used quite responsibly, otherwise you can have short- and long-term side effects. So, one of the things that’s super prevalent now is that people use it as a quick fix, kind of create a starvation mode, drop their calories, and in the process are losing a good amount of lean tissue, muscle.

We do not want people to lose muscle while they’re losing weight. We really want them to lose fat and kind of that unhealthy extracellular water. The other thing is that until we address the behavior issues, the food narratives, the emotional eating, all that type of stuff, I think the semaglutide might give people a false sense of security in their ability to control their weight. And if we haven’t addressed these things, then obviously if they lose muscle and then they don’t really change their eating behavior or their lifestyle, then we’re going to see rapid regain and sometimes a worse situation.

James Maskell: Well, that makes a lot of sense. So, I know that you’ve been using it a little bit in practice there or you’ve been using it across Forum Health. What are some of the ways that you’ve looked to minimize safety concerns for patients and minimize these side effects?

Dr. Shilpa P. Saxena: Yes, so number one, we just make sure we properly screen people and help them understand ahead of time, let’s manage expectations. This isn’t a quick fix. We’re not a weight loss clinic that’s just going to give you this and really not care about the long-term impact. We couple the semaglutide sometimes with BPC 157 or a methylcobalamin in order to kind of augment and also help with costs associated with it at times, but the one thing that we do that’s super important is we always combine it with lifestyle medicine coaching. We do not let people have the quick fix answer to this. For some people it doesn’t work, and quite honestly, some people will not overdose, but take more than necessary and create some significant GI side effects like constipation, nausea, vomiting, and that’s not something that we mess around with, because we know that GI health is important for so many other things to get better.

James Maskell: So, what are the things that you do as a typical functional medicine tools for constipation and some of those things?

Dr. Shilpa P. Saxena: Well, number one, we make sure that people start at a much lower dose and we ooch up quite slowly, so that we are trying to get the lowest effective dose to be able to minimize side effects, but if somebody is prone to constipation, which we all know there are people, we will use our toolkit of things. We have to understand, is it a motility issue? Is it something that could require acid, digestive enzymes, could magnesium be helpful? Is it hydration? Is it fiber? Do we need to back off on the dose? So, we really start to look at, what do we think is the mechanism of action that is causing the constipation? But we really forecast, and that’s why we have the coaches there, to make sure that if somebody is getting stuck that it’s not because they’re full of stool. Many times people wonder, “I’m not getting better,” and it’s really that they’re not having a proper BM, for example.

James Maskell: Absolutely. Well, I think that’s critical, and it sounds like you’re doing that. So, let’s say someone goes on the drug and you’re supporting them all through this journey and now they’ve lost whatever percentage of the weight that they want to lose, they’re getting towards their target weight, and then maybe they’re going to come off, how do you prepare them for that moment and how do you make the most of the engagement and time that you have with them up until then to make sure that they don’t follow the typical path, which is obviously what you read in the papers today is like, “Oh, the weight comes back and if you don’t change, it’s not a long-term fix and it’s really expensive.” So, how do you make sure that this is a permanent shift for them?

Dr. Shilpa P. Saxena: So great questions, James, so number one, we got to prep the patient. We have to be proactive on the front end to reduce the problems on the back end. So, if we’ve helped get their gut in good health, their detoxification pathways in good health, and we’ve started working on the mind-body portions, we have less issues with reflex weight gain back. We definitely continue coaching throughout, and sometimes there are natural GLP-1s that we can use hops, akkermansia. We can sometimes use other supplements like NAC or berberine or we can use some things that can help with appetite reduction. So, we don’t have to go from nothing to semaglutide to nothing. We can prep, use semaglutide, optimize gut function during the process and then transition with some more natural herbs and botanicals that mimic what the effects of semaglutide are, so we’re not just off/on switching it.

James Maskell: That makes sense. I’ve heard even at conferences that we’ve been at historically, talk about endogenous GLP-1 and sort of maybe nature’s semaglutide. Do you think any of that is real or do you think that’s hype?

Dr. Shilpa P. Saxena: No, I think that it’s real, and I do think that the more we can get the body to mimic what we want to get out of semaglutide or what we’re trying to augment with semaglutide the better. The other thing that we haven’t talked about that is an important thing that we should mention is that we want to make sure that we maintain as much muscle mass during the weight loss process. And so diet, getting sufficient protein, because sometimes people will dial up their dose so much that they’re not eating and they’re literally eating away at their muscle mass. So, one of the things that we definitely coach on is sufficient protein intake.

So, a lot of the times if we do things right on the front end, we don’t have to do as much cleanup on the back end. If you prep the gut detox, get the right kind of diet and exercise and mindset and really work on the food narratives, they’ve actually prepped themselves to have a good transition off, and that’s the big takeaway is if you prep right, then less emphasis on transitioning off, but you still need to emphasize, what happened during the process that we need to mitigate during this transition?

James Maskell: I guess an interesting question I thought you might have an insight on is how do you think a functional medicine practitioner doing all the things that you’re talking about here…because I really feel like you are getting the best of both worlds if you’re doing it like this, but when I go on Instagram, I see obviously Facebook and Instagram probably thinks that I’m a functional medicine doctor, because that’s all I talk about near my phone, and I get these ads saying like, “Start a weight loss clinic. We’ll give you 1,000 patients, blah, blah, blah,” and you can tell it’s sort of like a semaglutide pill mill. And so, obviously those things are happening. It’s happening everywhere because it’s just such a hyped thing.

Dr. Shilpa P. Saxena: Yes.

James Maskell: How do you go about communicating the difference between that and what you’re doing?

Dr. Shilpa P. Saxena: Well, I do think there’s always going to be a group of people who want the magic bullet, quick fix. They’re not going to really be researching the healthy option. So, there’s a certain amount of people who are just not aware. They’re pre-contemplators, they’re not even contemplating the healthy way to lose weight. They’re so fixated on rapid weight loss at whatever price. I don’t think that’s the target of the people that we want to try to help. Then, you’ve got these contemplators, the ones who recognize that, “Listen, I’ve already been yo-yoing, this is the new fen-phen, this is the new thing.”

And they’re really trying to figure out, “All right, if I can afford it, what is the best way to do this?” And what I do think is that anybody who’s been trying to lose weight for a long time knows if they’ve been yo-yoing, that you need to hear the person who says, “We’re into sustainable weight loss. We’re into body composition, not just looking skinnier in the mirror.” So, I think anybody who’s done this a few rounds will be smart to hear any kind of logical provider talk about how this is the long game. This isn’t a short game for weight loss, and I think those people who are interested in sustainable, good body composition, will pay attention to the things we’ve been talking about.

James Maskell: Do you get patients that have tried round one with just getting it from their doctor and then have had that yo-yo and are now looking for something more sustainable? Is that something you see?

Dr. Shilpa P. Saxena: Yeah, because a lot of our patients will go to someone who doesn’t really understand physiology, they’re just kind of copy pasting the package insert and it says, “Start at this dose,” and then the patient might experience severe nausea, vomiting, constipation. So they say, “That didn’t work.” And what I’ll find is sometimes they’ll come in and they say, “Well, I don’t want semaglutide. I want tirzepatide, because I hear it as less side effects.”

And then we have to walk them through, “Well, tell us how you did semaglutide. Is this true that you really don’t respond well? Do you need to go to the more expensive tirzepatide? And are there any other things that we can do to ratchet down your dose and augment with some other things, so that you don’t hit the trigger for nausea, vomiting, constipation?” Because you can’t just assume that when somebody comes to see you and says it doesn’t work that it was done correctly. In fact, I almost assume it wasn’t done correctly, and then I try to figure out what wasn’t done the first time and how can we change that up? Because if you just go straight off of semaglutide to the next quick fix, you’re not really doing the patient any favors.

James Maskell: Absolutely. I’ve heard some conversation about AMPK activation. Can you talk us through what that is and what’s happening with regard to both either a GLP-1 or some of the support mechanisms that you might use?

Dr. Shilpa P. Saxena: So, there’s many different herbs and botanicals that can increase this endogenous GLP-1. So, we can use things like hibiscus, lemon verbena, green coffee bean, and we can kind of mimic what semaglutide is doing, and then simultaneously they have other functions, because many herbs and botanicals are just a one trick only. So, what we want to do by doing these blends is to also decrease cravings. So, we want to decrease ghrelin, then we want to stimulate metabolism, as you’ve mentioned, through AMPK activation.

So, that’s one of the lovely things about using herbs and botanicals either as a substitute to semaglutide, especially for people who maybe should not be going straight to semaglutide, that they have this ability to try the herbs botanicals lifestyle option first, or I will also use it as a transition product. I want to help reduce this whole process where people, if they go into this reduced calorie phase, and then they sometimes lose a little muscle, then it’s kind of like their metabolism has dropped during the semaglutide phase. So, if I can add in things that activate AMPK, I can stimulate the metabolism back up, decrease cravings, so I can keep that weight loss off and specifically keep the fat loss gone.

James Maskell: And how long would you have to take something like that for?

Dr. Shilpa P. Saxena: Well, that depends on the person’s ability to learn new lifestyles and keep them implemented, and it depends on each person’s biochemistry. So, I’m not afraid to do that for months. This stuff is relatively new on the market that we’re doing all these things. I think this is something that we’re going to play out, but generally these things are considered safe. I would for sure make sure I’m keeping track of metabolic markers on labs to make sure that, are we losing the right weight? Are we shifting things too much to the liver? What’s happening with the cholesterol? What’s happening with insulin? What’s happening with oxidative stress and inflammation? We want to make sure whatever we choose, we’re tracking response. So, not only does the number on the scale or the BIA look good, but the labs internally on a cellular level look good and healthy, too.

James Maskell: That’s great, totally get that. Well, look, I think that makes a lot of sense and I can definitely see how it can be used synergistically with functional medicine to get great outcomes. I guess thinking about the kind of patient that you’re going to see, who’s going to have that, they’re probably going to have a broader array of metabolic dysfunction, I don’t know, like an NAFLD, inflammation, that kind of stuff. So, if patient comes in with multiple of these conditions, not just the metabolic syndrome, but other conditions, how do you think about treating those things simultaneously?

Dr. Shilpa P. Saxena: What’s lovely about functional medicine is a lot of these things come from the same root causes. So, whether you have NAFLD or you have metabolic dyslipidemia or you have prediabetes, a lot of times it’s stemming from inflammation, excess adipose tissue, oxidative stress, toxins. So, then what do we do? We don’t try to spot treat every metabolic condition. We say, “What do these things have in common and what can we start working on?” So again, what’s beautiful about functional medicine is if you work on the gut, if you work on detox, if you work on insulin resistance, if you reduce inflammation, then that’s going to help the whole cardiometabolic kind of umbrella of issues no matter what it is.

And what’s really important that you’ve mentioned, James, is people can have six other metabolic diseases, but they are fixated on their weight. What I love is what I do with teenagers and now adult patients is like, “Listen, if weight is what motivates you to change behavior and you don’t care about your fatty liver disease, which is just as risky, I don’t need to frame it in the world of fatty liver, even though that might be my goal, I’ll frame it for weight loss,” but what I do to handle the weight loss responsibly as a functional medicine physician, luckily is a two for one special on your fatty liver. So, that’s the beautiful thing about cardiometabolic root causes. They’re kind of the same in many people, so we just need to motivate them through weight loss.

James Maskell: What are the extra risks of doing metabolic health if you haven’t specifically looked at screening for liver disease?

Dr. Shilpa P. Saxena: So your question is like, “Hey, what are the risks if you go ahead and just start treating somebody for weight loss and haven’t screened for every other metabolic condition?”

James Maskell: That’s right.

Dr. Shilpa P. Saxena: I think overall the risks are relatively low, because we’re really just trying to reestablish what I call original design. Whether you believe in God or evolution, there is a process that’s supposed to happen. We’re meant to be anti-inflammatory, we’re meant to sleep, we’re meant to move. So, a lot of the things that we do with our herbs botanicals are designed to reestablish or mimic original design. They’re not trying to override original design and lead past it and overstep it. So, I think overall risks are generally low. The one thing that I can anticipate could happen is that you could do a little too much to lower blood sugar, and if you over herb or over herb plus medicate, you could drop somebody’s blood sugar too much. So, if the mechanism of action for multiple things is dropping blood sugar or dropping blood pressure or thinning blood, just be careful that you don’t run into low blood sugar, low blood pressure, bleeding risks or things like that.

James Maskell: Interesting, that makes sense. When I had Elizabeth Bowen on the podcast and we talked about NAFLD, it just struck me how common and underdiagnosed it was or underappreciated or I guess, I don’t know what the word is, underdiagnosed maybe, and just how many people have it. And it seemed like such a big deal and I’m glad to see that there’s a synergistic fix here. What are some of the other interventions that you use if you see patients with fatty liver?

Dr. Shilpa P. Saxena: Great question, so just to put a stat out there, there’s up to a 90% concurrence rate with obesity. And what that means is that most of the time when you have someone with visceral adiposity, there’s a really good chance that they have fatty liver disease. Now, what I recommend is that you look at liver enzymes, GGT and track them over time, so that you can see the interventions you’re doing for the obesity or the prediabetes or whatever metabolic condition you’re addressing. If you see the liver enzymes starting to go into the bottom half of the reference range or the bottom quarter, then that starts to tell you, “I must be working on fatty liver improvement as well.”

It wouldn’t hurt to go get an ultrasound and see reversal of the steatosis, which is the fatty deposition in the liver. Now, the beautiful thing is that the way that I look at it is fatty liver, PCOS, dementia, osteoporosis, diabetes, these are just insulin resistance showing up in various organs. Fatty liver is just insulin resistance in the liver. Dementia, Alzheimer’s, called type three diabetes is insulin resistance in the brain, and so on and so forth. So, a lot of times those same core treatments are going to help all organs. It’s just that some people are more genetically weak in the liver, so they show up as fatty livers, whereas another person like myself showed up as PCOS.

James Maskell: No, that makes a lot of sense. Well, it’s comprehensive. Anything else that you think the clinicians should be looking out for in this area, I guess tips or things that you’ve learned along the way from treating thousands of patients with these kinds of issues?

Dr. Shilpa P. Saxena: I think it’s important to really look around the whole body for signs of metabolic dysfunction. And once you see and you can document for your patients like, “Listen, this is where it’s showing up in your body,” then track the progress over time with the patient, because a lot of times they do these great behaviors and let’s say they only think it’s helping their weight, they might be more likely to bounce back. But if they say, or if they know like, “Oh, I reversed my diabetes, I reversed my fatty liver, and I reversed my risk for dementia,” I think you are going to start working on the mind-body part that helps them realize, “I really need to stick to this way of living, because it didn’t just help my weight on the scale, it helped literally my entire body.” And I do think that more and more of our nutraceutical companies are moving to understand how huge a thing metabolic dysfunction is.

So, they’re creating products and blends that really are addressing this manifestation of our poor lifestyle and toxins in our environment. They really get what this is doing. In fact, I was just talking to a patient of mine and I live in Florida, and if I wanted to get a view of the world, all I have to do is go visit Disney World. And if I’m there for the day, I have a slice of the entire world there for viewing as just a scientific experiment. And I’ve been in Florida for almost 40 years and Disney World has changed when I look at people.

And so we all know this, we all know that humans’ morphology and chemistry and physiology is changing at a clip that is really concerning. And so, I do think that we should be very thankful to this functional medicine industry for being aware of that and not just straight giving a pharmaceutical solution, because you know there isn’t one for NAFLD. They’re trying to come up with a root cause solution. So, I think you should pay attention to these companies that are really trying to shift the needle on this.

James Maskell: Well, I’ll see your Disneyland and I’ll raise you the San Antonio River Walk.

Dr. Shilpa P. Saxena: I haven’t been there, but I’m sure it’s the same.

James Maskell: Hey, so look, you’re talking to me about there’s education needed, there’s behavior change needed, there’s support needed. There’s dynamic elements that are going to happen as you get into it and come out the other side. All of this, plus you talking to me, screams GLP-1 group visit, and I just wanted to get your thoughts on that.

Dr. Shilpa P. Saxena: Oh, absolutely. Look at the data on Weight Watchers. There is so much data that says that when you teach someone how to do something individually with weight loss, they have X percent improvement. But when you have them work on it in group, that’s the whole magic of Weight Watchers. It’s not because they have points. In fact, the points helps a little bit, but the fact that they talk about it in group is what the real magic of Weight Watchers is. There was a study done on that where they kind of let people do the app and never meet in a group and then do the group, and the people in the group always did better than the people on the app.

And so, of course you know that I’m big about group. I really do think we have to normalize people’s struggles with weight, not normalize like make it an excuse and make it okay, because we know that it’s super risky to have this inflammatory fat on us for long-term if we want to live vibrantly, but I do think that there is a stigma associated with this. In fact, there’s still people who kind of secretly inject their semaglutide, because they don’t want others to know that that’s the mechanism by which they’re losing weight. So I think you’re right, we need to come out and let’s all start as a group talking about this and talking about how to do it right if we’re going to use it.

James Maskell: Absolutely. Well, I think that normalization is critical, meeting other people who have struggled. I just see so much value of that what I’m seeing, and again, I know I’m preaching to the converted here, because you were the one…the first time I ever saw a functional medicine group visit was you lecturing on it 11 years ago. So, you turned me onto it, but what I see emerging in functional medicine is a new standard of care where the group is driving the sort of normalization behavior, psychosocial elements of care, and the individualized medical care is really just there to tweak the protocol as needed for the individual.

And to me, the benefit of that means that you have a much more efficient delivery system overall. It’s a lot more resource efficient, doctor’s time, even money and so forth, but also that it’s much more likely to work because of all the elements that you said there. If you have a medicine based on behavior change, set up the conditions of behavior change and then work out everything else on the side. I just wanted to echo that back to you, and I know we’re on the same team when it comes to this, but I really do see that as sort of an emerging best practice moment.

Dr. Shilpa P. Saxena: Yes, I would tell you behavior change is the main ingredient that is going to keep the weight off sustainably. So, if we can figure out a way to get people motivated to be in community, to talk about this, to normalize this, and help each other, it sounds so idealistic, but societies for thousands of years have used this principle to stay healthy. You just look at the blue zones and you know that that principle works, and they’re not. And this is just a part of their life that they use community to stay in good habits. Despite all this modernization, there are still people who live in community and are very healthy.

James Maskell: Look, if the overall theme is like you’re living in a poisonous environment, example, Disneyland, and ultimately in order to stay healthy, you’re going to have to navigate through that poisonous environment, whether that’s psychosocial poisons, actual toxins, food toxins, all of that, all of those poisons, and ultimately, you’re going to have to…it’s very difficult to do that as a single individual, and ultimately you need the power of a community to normalize not interacting with the toxins and then get support because it’s hard, it’s addictive, it’s on purpose. The poison is there and it’s everywhere. You have to really work hard, you have to work harder than normal to avoid it. So, I’m excited to get this information from you, Shilpa, because I really respect you as a clinician. I know you’ve been way far ahead in thinking about behavior change as a central tenet of medicine. I’m really grateful for everything. I’m grateful for you to come to share your wisdom on this topic right here, right now.

Dr. Shilpa P. Saxena: Thank you so much, James. You are my partner in this whole idea of community health, social health, and I just remind people, one last thing for your empowerment is sometimes the community you’re in and the environment you’re in is not the one that’s for you, and to have the courage to go create community with the type of people who inspire you, the type of foods that inspire you, and many times we try to force our current community to be our healing community. And for many of us who are in this field, we realize like, “Hey, there’s a little adaptation and change that must go on, and that’s not a sign of losing. It’s a sign of maturing.”

James Maskell: Well said. I’ve been here with Dr. Shilpa Saxena. She is the chief medical officer of Forum Health. You can find out more about them on the website. We’ll have all the details in the show notes. This has been the Evolution of Medicine Podcast. If you like this podcast, we’ve done half a dozen with Shilpa over the years. It’s always excellent, range of topics. Go back and check them all out. Thanks so much for tuning in, and we’ll see you next time.

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