transcript

Speaker 1:
[00:01] For many people who are struggling with their weight, they have tried every diet, and they have blamed themselves. They have felt like failures. We don't need other people pointing fingers at us to say that. I mean, these are feelings that are internalized by our patients. We see it all the time. And now we finally have tools that can directly address the underlying biology behind overeating, obesity, things that are not within your control and that are not a moral feeling. I think that that's not a small thing. This is life-changing and our job is to offer this without judgment, but also to provide good clinical guidance and oversight. Hi, it's Dr. Lucky Sekhon.

Speaker 2:
[00:42] And Dr. Alicia Robbins.

Speaker 1:
[00:44] We're so glad you called. Welcome to Call Your Doctor, basically a group chat where your best friends happen to be hormone health experts with medical degrees.

Speaker 2:
[00:54] If you've ever wondered, is this normal or why am I like this? You're in the right place.

Speaker 1:
[00:59] Because whatever you're going through, you're never the only one. You can always call your doctor. Let's get into it. Hi, Alicia. How's it going?

Speaker 2:
[01:12] Hi. It's good. Wait, your skin looks so good. And actually, that makes me want to ask you, do you have a new favorite product or anything you're trying now that you love that you want to share with us?

Speaker 1:
[01:22] First off, I just came off of a week long vacay, which I needed so badly. And it was honestly the first time I completely stepped away from making content. I just checked my patient's results and emails every day, but I did not really do actual calls. And I felt like I was on top of everything, but I really did give myself the mental break. And I think sleep is definitely a factor here, but I also have a new secret weapon. I've been saying this for ages. I've been saying that as I entered my 40s, I was like, I need all the lasers, all the help. And I've been kind of too chicken to actually pull the trigger and do it. And my really good friend, Michelle, who you know, she like is always getting me to try new things. And she, I know I love her too, because it's always like things I'm reluctant to do. And there are always things that sound crazy. She'll be like a liquid gold facial. And I'm like, you want me to do this the day before my book launch? Like, are you insane? I'm not going to try some new skin thing. So finally, I had like nothing going on. This was the Friday before my vacation started. So I was like, what better time to have down time if I need it? And basically, she took me to this beautiful space. And you're not going to believe this. The space is actually was formerly Calvin Klein, where CBK worked. So it was like in Chelsea, overlooking lower Manhattan, and just like a really, really cool vibe. It's called Dorfman, Dr. Dorfman. That's who I went to. I think the practice is called done by Dorfman. And I was done by Dorfman. I basically got micro-needling and CO2 laser, and they got me on a regimen. And I felt very much like I was in good hands, where they were like, this is the plan, because it feels like there's so many options. And I'm like, I don't know if I'm supposed to do Fraxel, Clear and Brilliant.

Speaker 2:
[03:04] I know, same. I'm getting, I'm starting, I used to stay on top of it. Now I'm getting a little, like, overwhelmed with all the different options.

Speaker 1:
[03:10] It feels like there's too many options. And so they just told me what to do. And honestly, like, I see a difference in one treatment, and it was very minimal downtime. They also used salmon sperm on my face.

Speaker 2:
[03:21] You did, you did the salmon sperm facial, oh my god. So they believe in it. Dr. Dorfman believes in the salmon sperm, huh?

Speaker 1:
[03:29] The power of the sperm. I was like, I went from being a laser virgin to getting salmon sperm on my face.

Speaker 2:
[03:35] Microneedling, yeah, my laser microneedling and salmon sperm, you are doing it. Well, honestly, your results are starting to convince me. I thought salmon sperm was a joke, but now I'm kind of thinking of, I may consider it.

Speaker 1:
[03:47] I don't know exactly what is the most effective component, but I honestly think it's the combo of the microneedling and the CO2 laser. But what it achieved for me, I will tell you, because this isn't necessarily on video for people, is that my skin feels very even, it feels very tight, and it feels smoother than it's ever been. I only did one treatment and she said, come back in four weeks, we're going to do three installments. She was like, you're going to love your skin after the third one. I'm so excited because it honestly wasn't really that painful. They numb your face.

Speaker 2:
[04:17] Yeah, because I thought CO2s were kind of like ablative or like more aggressive, but...

Speaker 1:
[04:22] It wasn't so harsh though. I think she went really like low and slow and she gave me like all these products to use after and I was very conscientious about doing it twice a day. And I feel like my skin feels great.

Speaker 2:
[04:33] It looks beautiful. Like I noticed a distinct difference. Okay. So, all right. Salmon sperm for the win.

Speaker 1:
[04:39] Yeah. What about you? Have you done anything new lately beauty wise?

Speaker 2:
[04:44] No, I'm very overdue to do my clear and brilliant.

Speaker 1:
[04:47] Have you done it before?

Speaker 2:
[04:48] Yes. I swear by those. I don't, I maybe do them every six months. I would like to do it every three months. I see Dr. Berliner here who's been my dermatologist for 10 years and I'm definitely due to do it.

Speaker 1:
[04:58] How often are you supposed to do it for best results?

Speaker 2:
[05:01] I think it depends. I think they say every three to six months. I think, I don't remember honestly.

Speaker 1:
[05:05] We need to have a Derm on. I feel like this is a good topic. This is out of our wheelhouse.

Speaker 2:
[05:09] I know because I love this stuff, I can't keep up with all the latest treatments.

Speaker 1:
[05:14] Yeah, it's a whole different world. But what about products that you're using at home? Anything new and exciting?

Speaker 2:
[05:20] Well, I am trying Dr. Sturm's Exosome Serum, which is really fun. I'm really liking that. But I would say, things something I can't live without is the It Cosmetic Tinted Moisturizer is like my go-to. If I don't have anything else, it's such great coverage and I feel like it, I don't know, I just love it. So yeah, that's my sort of can't live without. But I haven't, I don't have too many new things in right now.

Speaker 1:
[05:45] Okay. Speaking of wanting to look your best.

Speaker 2:
[05:49] Yes. Speaking of wanting to look your best, the shot heard around the world. We are going to be talking about one of my favorite topics, GLP-1s.

Speaker 1:
[05:59] Didn't Trump call it the fat shot? Oh my God. Probably.

Speaker 2:
[06:03] Probably.

Speaker 1:
[06:03] Or the skinny shot.

Speaker 2:
[06:05] But seriously though, in the last few years, wouldn't you say this is one of the more commonly, I mean, at least for me, but one of the more commonly asked topics at like patient visits or cocktail parties?

Speaker 1:
[06:16] Oh my God. Without a doubt. I mean, I get asked about Ozempic babies. I'm in the baby making business and people are always like, what can Ozempic do for me? I keep seeing all these reports about people going on it and getting pregnant. What's really fun is the fact that it's not just like a click baity thing, and we're going to get into all of that. But there is some truth to it. It can make people more fertile and it's just a really interesting mechanism.

Speaker 2:
[06:40] Yeah. So we're talking today about Glp-1 receptor agonists, what they are, how they work, what the data actually says, and what we as clinicians need to know to have smarter conversations with our patients with bonus sections on microdosing, compounded meds, Glp-1's use in perimenopause, fertility, Ozempic face. We're covering all the things.

Speaker 1:
[07:03] All the controversial aspects. Let's do it. All right. Let's start at the beginning because before we talk about Ozempic and Wagovi, all of these names that have become household names, so familiar and in the headlines constantly, it feels like. I think it's really important for us to go back to the basics and talk about what a Glp-1 agonist actually is.

Speaker 2:
[07:29] Yes. Glp-1 stands for glucagon like peptide 1. It's an increase in class of hormone, and it's actually something your body naturally makes in your gut lining in response to eating. One myth I want to clear up from the get-go is this idea that they're new meds. They're actually not new meds. I mean, the brand like Ozempic is newer, but these Glp-1s have been studied for about 20 years, so we have a lot of safety data on them. Glp-1 helps stimulate insulin secretion in a glucose dependent manner, which is what we need to do when we have elevated glucose in our blood. It suppresses glucagon, which is one of the hormones that raises your blood sugar. It slows down gastric emptine, which is why people feel full longer, and it acts in your brain to reduce appetite and food seeking behavior. That's like that food noise that people talk about. It also has direct effects on the heart, kidney, livers, and potentially the brain, which we'll get into.

Speaker 1:
[08:24] What's interesting is I'm really good friends with someone from my med school days who became an obesity expert, and she was here visiting for a conference, and she lives in Canada. She was like, it's so crazy that all of this stuff is exploding and becoming so mainstream because we've been using these drugs for a really long time. I have a question. What do you think contributed to it becoming something that was so obscure? No one knew about this. I feel like it was the best kept secret since it's been around for a long time. Now, it's like, did Ozempic hire a new PR team or something? How did the word get out and why did it become so much more of a thing? Do you know?

Speaker 2:
[09:04] A lot of the older medications, which were older, were oral and not quite as effective. When they started doing injectable forms of these meds, they were finding a lot more effective.

Speaker 1:
[09:15] I want to watch a documentary on the history of these drugs. That's got to be a very interesting story and I do just wonder how the popularity exploded. It must have been that there were great studies that came out and expanded the indications for use. I think what's really comforting for a lot of people to hear is that these Glp-1 receptor agonists as a drug class are essentially doing something that our body is already doing just at a higher and more sustained level. There's a real parallel. A lot of the drugs that I recommend to my patients as part of their fertility treatments are very similar. When you think about manipulating your hormones, a lot of times, it's like you're taking a medication that's just stimulating the receptor that the hormone would have stimulated naturally. And it's kind of just mimicking the action of a naturally produced hormone. And I think when you normalize it and make it feel like, okay, this is something your body's already doing, I think people feel less afraid. But as a fertility doctor, I recommend these to a lot of patients in specific indications or situations to treat something called insulin resistance. This can make you more sensitive to the effects of insulin, which is a hormone that helps you store blood sugar. And indirectly, it's acting through helping you with weight loss by just decreasing the amount of caloric intake and lowering inflammation and also the changes in your liver and muscle fat, rather than directly making you more sensitive to insulin. Drugs like metformin make you just more sensitive to insulin, but this has a much more indirect approach. What's interesting about the way these drugs work, according to the way the FDA has labeled their mechanism of action, is that it works to lower your glucose levels and helps to boost insulin secretion that is dependent on those glucose levels and to suppress glucagon, which actually is a naturally occurring hormone that makes you increase your blood sugar normally. It delays gastric emptying, as you said, so it can make you feel full for longer. This is also the number one culprit behind some of the GI side effects that we're going to talk about. But overall, you're reducing your food intake. It's not really necessarily something that's directly treating insulin resistance, and that's not the primary mechanism, but it is an indirect effect, and that's a reason why it is helpful for so many of my patients, because insulin resistance, we're going to get into this, is one of those things that can actually affect our egg quality, it can affect how receptive our lining of our uterus is to an implanting embryo. I actually see it as a major culprit in many cases of infertility and pregnancy loss. It's not to make people feel shameful or that they're the cause of their problems, but a lot of it is genetically how we're wired, it has nothing to do with your lifestyle. I think that's the biggest takeaway from today's conversation is, obesity is not a moral failing. This is sometimes just how you're wired.

Speaker 2:
[12:12] Totally. We know that there's genes involved, we know a family history, ethnicity, that all comes into play, of course, lifestyle. Also, insulin resistance is a range. It's not like you just go from being healthy to being diabetic. You start developing insulin resistance.

Speaker 1:
[12:27] It's a spectrum.

Speaker 2:
[12:28] It's a spectrum, exactly. You start having insulin resistance, which gets worse, which then develops into pre-diabetes, which then eventually diabetes. It's a spectrum and we all have varying degrees and that can change with age or lifestyle or whatever. Well, let's talk about the different types of drug classes quickly. We won't get too bogged down, but I think it is important for people to know that there's different buckets of Glp-1s. The older generations were the single agonists. So these are going to be the ones that people are super familiar with. Some of Glutide, which the brand names are Ozempic and Wigovie. And then would have been really popular and shown to be actually more effective, are dual agonists. That's going to be, I'm sure people have heard of Moonjaro or Zepbond. The actual medication is called Trezepatide. The brand and what they're approved for varies. And so depending on, you know, Moonjaro is approved for type two diabetes, Zepbond is more approved for chronic weight management. And depending on the BMI, weight loss in addition to other sort of metabolic or cardiovascular issues. What's important is these dual agonists show that there was even greater weight loss because they have Glp-1 and GIP, which has additional functions in helping with insulin secretion from the pancreas and other roles. And so that added GIP makes the dual agonists more effective than the single agonists. And then what's currently in phase three clinical trials now is a triple agonist, which is not yet FDA approved or out on the market, but it's called Retatrutide. And that has been showing up to 24% of body weight reduction, which is more than any of the other meds. So yeah, really, really interesting.

Speaker 1:
[14:00] And are all of these approved? I mean, it seems sometimes confusing that some of these are for specific treatment of diabetes versus saying, okay, this is okay for weight loss. Do you feel like there's a lot of crossover in clinical practice?

Speaker 2:
[14:14] Yeah, there's a lot of crossover because a lot of it will depend on like, if you're a candidate, if your insurance will cover it, if your insurance doesn't cover it, you may be self-paying through Eli Lilly. And while your friend may have her insurance approved for Moondura, you might be paying out of pocket for Zepat, but it's actually the same medication to Zepatide. So it can get a little confusing.

Speaker 1:
[14:30] I want to make it clear just for everyone who's listening. Obviously, I'm a fertility doctor, and Alicia is more focused on midlife perimenopause menopause, but we're both OB-GYNs. I actually, in my clinical practice, don't prescribe these drugs. I work very closely with medical endocrinologists, even primary care doctors, and they will co-manage patients who need to work on weight loss and treat their insulin resistance. But Alicia, you actually do prescribe these.

Speaker 2:
[14:59] I do prescribe them, and I'm not obesity certified, but I do prescribe them because I've been interested in metabolic health for a very long time because I personally struggled with gestational diabetes. I was pregnant when I was a new attending at Mount Sinai Hospital, delivering babies, and I considered myself an otherwise healthy person. I exercise regularly, I'm not overweight, and I was so surprised and honestly shocked when I was told that my glucose test was outrageously elevated. They were almost like, you don't need to do the follow-up, you should just start tracking your finger sticks. I became obsessed with learning about why this happened and why I was so surprised. It was a very humbling experience, but I have the last 10 years been reading so much about insulin resistance, diabetes runs in my family. I'm probably more than most guided colleges very well read on insulin resistance. I used these medications myself after my second and third pregnancies and found them to be enormously helpful. I do prescribe them, I've been prescribing them for a while now for about six years. We'll probably do another follow-up episode and we might have an obesity medicine doctor come on.

Speaker 1:
[16:01] Were you nervous about starting them?

Speaker 2:
[16:03] Yes, at the beginning because back when I had started it, this would be 2019, they weren't that common. It was like one of those things that everyone was like, oh my God, that's crazy, what are you doing? I went to go see an obesity medicine specialist, Dr. Trow, who has this great podcast called Low Carb MD. I went to go see him and he suggested I use them and I was nervous. Then I found it to be so incredibly helpful. It was life-changing that I was like, oh my goodness, I want to start helping other women with this. So I started prescribing it six years ago and yes, I do really believe in them. I think there is nuance to it. We'll get into that, but let's talk about what the weight, the loss data shows.

Speaker 1:
[16:41] Yeah, how much weight can you actually lose? Let's get into it. Is this latest wellness hack widget? So let's talk about what the data actually shows because I feel like the weight loss results with these medications is remarkable. This just feels like such a medical breakthrough.

Speaker 2:
[16:59] Yeah. So depending on what different trials you're looking at, people on average have had a weight loss from anywhere from 15-22% of body weight, which is approaching bariatric surgery outcomes. So they're pretty remarkable meds in terms of how effective they are. These are not mild or modest effects. These are really effective medications.

Speaker 1:
[17:21] Yeah. I mean, you're losing 15-20% of your body weight. If you're overweight, I mean, that is hugely meaningful.

Speaker 2:
[17:28] They're giving us a clue as to how this is such a more complex medical condition with a very strong biological basis. This is a disease and we should be treating it like a disease. It's not like a failure on anyone's part. The more we understand obesity, the more we realize that it is a disease just like any other disease.

Speaker 1:
[17:46] And I think it's interesting to think about what happens if and when you stop these medications. So the step 4 trial showed something really important. And to me, this seems fairly obvious, but you never know. Like could this have long-lasting effects even well after you take yourself off of these drugs if you decide to stop? And people regained two-thirds of the weight that they had lost within a year. So there is this backsliding effect. But I think the most interesting thing is that, and we're going to talk about this more when we talk about side effects and things to kind of look out for, but you can really have accelerated loss of muscle. And so if you don't try to counteract that with weight training and increasing protein intake, it can really change your body composition to gain all that weight back, but you're not gaining back muscle. You're gaining fat, and it's changing your body composition.

Speaker 2:
[18:37] So then you're ultimately in a worse position than you were to begin with. So it's really important for people to realize it's not just about looking good today. This is we're really trying to do something with these meds that will help our health in the long term. Like we have to always think long term with our health, not just like big picture consequences.

Speaker 1:
[18:54] Do you feel like a lot of the patients that you have observed, whether you were directly treating them or even just they were going to a different provider, do you feel like people are taking this whole concept of muscle loss seriously and really working hard to maintain and counteract it? Or do you feel like once it happens, then they're like, oh, shoot, OK, let me work on this?

Speaker 2:
[19:14] I think you see the whole spectrum. In my patient demographic, my patients really want to be healthy. We have them come in person every three months. We were referring them out for body compositions. Now we have two in body machines in my practice so that we can every three months be following up on making sure that they're at least maintaining lean muscle mass and ideally gaining more muscle mass. But then I also see patients, not my patients, I see women or people on the street and I'm like, I know they're doing too much. They're losing too much weight too quickly and they're not going to be able to build that muscle that fast. So I think these are wonderful meds, but they need to be used appropriately for long-term benefit, not short-term.

Speaker 1:
[19:53] Yes. And I think more than anything, this conversation should be validating to anyone who's ever struggled with their weight that we all want to be the healthiest version of ourselves. Of course, life sometimes gets in the way, but for many people who are struggling with their weight, they have tried every diet and they have blamed themselves. They have felt like failures. We don't need other people pointing fingers at us to say that. I mean, these are feelings that are internalized by our patients. We see it all the time. And now we finally have tools that can directly address the underlying biology behind overeating, obesity, things that are not within your control, that are not a moral feeling. And I think that that's not a small thing. This is life-changing and our job is to offer this without judgment, but also to provide good clinical guidance and oversight. So I definitely want to delve deeper into this muscle problem. So let's get into that.

Speaker 2:
[20:48] Let's talk about muscle. But I do want to say something that you mentioned, which is so key that it's not a moral failure. I actually, when I was diagnosed with gestational diabetes and it was really significant diabetes, I required insulin. I totally was so cognizant of my diet. I was eating so much protein salad, but it didn't matter that I went from eating takeout delivery on the labor floor and ordering our favorite tacos from Harlem or whatever at Mount Sinai. When I switched to a much healthier, more salads, more protein, my weight still would not slow down. It opened my eyes to the fact that I personally experienced how frustrating it can be. As you're literally trying so hard, I was so cognizant, I was writing down everything I was eating, that every time I'd go to my doctor's visit, I'd step on the weight, I'd start to cry. Because I felt like my efforts were so in vain. And as an OB-GYN who's counseling patients on what they're eating, I mean, I even had one of my colleagues at one point be like, are you okay? Get it together. And I had such a new empathy for patients that struggle with this because I realized going through this myself that there are other variables. It's not just calories in, calories out. The hormones play a huge role in pregnancy for sure. And so they obviously play a role when you're not pregnant too. So anyway, yes, let's talk about muscle loss and why we have to be cognizant of this.

Speaker 1:
[22:11] Muscle loss is one of the biggest challenges. This is one of the most important and underappreciated parts of the conversation that we need to be having with our patients who are taking Glp-1 agonists. Wouldn't you agree?

Speaker 2:
[22:23] Yes, so important. I really believe the use of Glp-1 should be slow and conservative. When you start being really aggressive and overly aggressive with weight loss and you're losing too much too quickly, you can lose a lot of your muscle. And muscle is so important for your long-term health, metabolic health, your cardiovascular health. So some studies show that up to 40 percent of weight loss can come from lean muscle mass, and we really want to avoid doing that. And so it's so key to be really proactive in maintaining it and ideally building muscle as you are on these meds.

Speaker 1:
[22:56] I think people don't recognize the role that muscle plays in our metabolism and in making our bodies more sensitive to the effects of insulin. And I feel like fat and muscle are directly opposing each other. It's like adipose tissue, fat, especially fat deposited around your midsection. That is so strongly associated with insulin resistance. And once you start piling weight on in that midsection, it becomes like a vicious cycle where it's just easier to keep packing on the weight, and it makes it even harder to lose it. And it's because of the insulin resistance. And I find that it is this vicious cycle. And when we are able to build muscle, you're able to burn calories more effectively. You're able to actually have your body listen to the effects of insulin much more readily and efficiently. And this is why building muscle resistance training is so important.

Speaker 2:
[23:49] Think of muscle, it's a metabolically active organ that when you ingest food and you're elevated glucose, the more muscle you have, the more it soaks up that glucose. And so when you have more muscle and you soak up that glucose, it has this downstream benefit of not having glucose hanging around your bloodstream. You don't want glucose hanging around your bloodstream because then your insulin gets secreted. And what insulin resistance is, is our cells not getting kind of so exposed to insulin that it doesn't respond to it as well. And so you need more and more insulin. But insulin's job is to store glucose's fat in your cells. And so we want to be more insulin sensitive, not insulin resistance. And one of the best ways to do this is to build more muscle because it uses up that glucose that you have. And because we lose muscle as we age, starting somewhere in our mid 30s, if we lose muscle, if we're eating the same thing, we're going to end up gaining fat unless we maintain that muscle or build it. So you're absolutely right. Not only that, but loss of muscle can contribute to cardiovascular decline. It can contribute to falls and frailty. So there's a lot of reasons why building muscle is so important.

Speaker 1:
[24:55] Do you think Ozempic face is simply you're losing the fat padding in your face, or is it that you're also kind of seeing changes in the muscles of your face?

Speaker 2:
[25:05] No, I mean, with any weight, significant weight loss, you can have that even if it's through bariatric surgery. So a significant amount of weight loss will eventually show up in the face. But I think to avoid that look, one key is just to go low and slow. You know, you really don't want to be losing more than one pound a week, maybe a little bit more. I mean, I'm conservative. I've read anywhere from one to two pounds a week, but I would say IDR even more on one pound a week. It depends on your patient population, right? So my patient population is going to be very different than someone, an obesity medicine doctor who's seen patients that are morbidly obese and probably can lose faster and a little bit more significant weight. So it also depends on your patient population. But for the most part, I think rapid weight loss is not that beneficial for most people.

Speaker 1:
[25:53] I feel like Ozempic face was not that foreign of a concept for me personally, because I remember gaining the Freshman 15 in college and then losing it. And anytime I went through periods of my life, even pregnancy, postpartum, I feel like I'm one of those people where it shows on my face right away, whether I've gained or lost weight. Yeah, so I completely empathize with people that are worried about or dealing with Ozempic face, because I'm always like, I don't want to lose weight off of my face. Like I want to lose it off of my midsection.

Speaker 2:
[26:22] Right. Yeah, if only we could inject Ozempic where we want to lose weight.

Speaker 1:
[26:25] No, I'm kidding.

Speaker 2:
[26:26] Not recommended. Let's talk about different ways to maintain muscle mass and some of the healthy habits that you can do if you're on these meds, because more and more people are on these meds. So we're gonna really want to increase protein intake, and so many people are under eating protein. So it really depends on your kilogram of body weight, but let's talk about our type of listener or us, because we're sort of our average listener. It's gonna amount, you wanna take anywhere from 1.2 to 1.6 grams of protein per kilogram of weight, and that's gonna really average out to anywhere from around like 90 to 120 grams of protein daily. Most women our age are getting maybe half of that, and so that's about 30 grams of protein per meal. And I have really realized that it's hard to achieve that much protein if you're not eating three meals a day. We can talk about intermittent fasting at a different episode, and I do like intermittent fasting for some women with insulin resistance, but I do think if someone's on a Glp-1, that we really need to prioritize adequate protein intake. So 30 grams of protein per meal, high-protein foods are going to be eggs, chicken, Greek yogurt, cottage cheese. You can get it from plants too, and of course, smoothies can help supplement that.

Speaker 1:
[27:38] How many grams would you say a chicken breast is? Like a standard size chicken breast?

Speaker 2:
[27:42] It is more than 30 grams. That's actually a significant amount. A piece of chicken the size of a deck of cards is about 30 grams. So a chicken breast is even more than that.

Speaker 1:
[27:51] Okay, that's not bad. That's doable. That's totally doable.

Speaker 2:
[27:54] But an egg, a hard-boiled egg is only 6 to 7 grams. There's only so many hard-boiled eggs.

Speaker 1:
[27:58] It's a lot of eggs.

Speaker 2:
[27:59] Yeah, it's a lot of eggs. Anyway, so people can look up what high protein foods are, but you really want to try to aim for 30 grams of protein per meal. And then resistance training, that is non-negotiable. Aerobic exercise alone is not going to preserve your muscle. You really do need to lift weights, ideally two to three times a week with progressive overload, meaning you're lifting heavier. But again, start somewhere, right? Start anywhere, start somewhere.

Speaker 1:
[28:20] I think people have a lot of trouble with initiating this, and I'm speaking for myself included. I think it's very intimidating if you're someone who hasn't been well-versed in resistance training to walk into the gym and say like, where do I begin? I'm a huge proponent of getting at least an introductory session with a trainer, because it's also really important to have good form. It can be very easy to injure yourself. So getting some level of guidance so you can get into a good routine is a good idea.

Speaker 2:
[28:48] I agree. And accountability. I mean, I don't love to lift heavy, but I, even tomorrow morning at 7 a.m., have my heavy lifting session at this place called The Practice in Greenwich.

Speaker 1:
[28:58] Do you have a trainer?

Speaker 2:
[28:59] It's so hard. I do. And he works for an hour. I'm like lifting heavy. I'm doing kettle balls. I'm doing, and it's honestly like so hard.

Speaker 1:
[29:08] And how often do you do this?

Speaker 2:
[29:09] I'm doing that once a week. They're trying to get me to too. But I do lift weights other days. I just do it at home. I use the Midlife Program app with Sculpt Society. But I'm going to increase my heavy lifting for a time. I was doing it twice a week, but I definitely lift weights other than that. That's just the one time where I go really aggressive.

Speaker 1:
[29:25] Would you classify Pilates as resistance training?

Speaker 2:
[29:28] I think it depends. There's different types of Pilates.

Speaker 1:
[29:30] Reformer Pilates, let's say.

Speaker 2:
[29:33] It depends on who you ask. Most exercise specialists are not going to consider that sufficient. But there are things like SLT that are challenging, and it's about consistency. I have some patients who are Pilates instructors, and they have amazing bone density and amazing body compositions. They may not be lifting super heavy, but clearly what they've been doing for as many years has helped them maintain muscle mass. I think if you're starting exercise, I wouldn't count Pilates in and of itself sufficient. You need to lift heavy weights. I know.

Speaker 1:
[30:06] It's just so much gentler. But I know what you mean. I've had trainers in the past. I'm someone that needs to, I think, go to a gym and do similar to what you're doing. I don't think it's too much to ask to do it twice a week. It makes sense. You need downtime for your muscle to repair and recover. How else do you get it in? We're sitting at a desk all day long, right?

Speaker 2:
[30:27] I know. And little things, sometimes in my kitchen, I'll just do 20 squats or all. You can throw it in. It can literally be here and there, sporadically dumb little squats thrown in. Just try to sprinkle it in throughout your day. There's been a lot of benefit in terms of showing how much squats after a meal can help regulate your glucose. So those little things go a long way. And then the other thing is ultimately, we can't improve what we don't know. So we need to be able to have objective data using a body composition test to look at lean muscle mass and visceral fat. So I'm a big fan of doing that so that we can keep each other accountable because one of the reasons I realized I was under eating protein was that I was not moving the needle on my body compositions. I was struggling to increase my lean muscle mass.

Speaker 1:
[31:10] And where and how were you getting that assessed?

Speaker 2:
[31:13] We now have them in our office, but I've been up until now having patients go, there's a lot of gyms have them, a lot of primary care. Certainly every obesity medicine doctor has them.

Speaker 1:
[31:22] I feel like I've seen it in the pharmacy.

Speaker 2:
[31:24] Really?

Speaker 1:
[31:25] Yeah, but I don't know, do you have to be naked?

Speaker 2:
[31:27] No, you just have to take your shoes off. Would you be naked in CVS in the pharmacy?

Speaker 1:
[31:33] No, but that's why I was like, maybe the one in the pharmacy is BS, if it's doing it with your clothes on. But interesting.

Speaker 2:
[31:39] No, yeah, you just have to be barefoot and you have to hold these things.

Speaker 1:
[31:42] Okay, I need to do this. I'm afraid of what the results are going to show. I'm not going to lie.

Speaker 2:
[31:46] Come to Greenwich and we'll come do your body composition.

Speaker 1:
[31:48] I feel like I need to do the weight sessions twice a week for a few months, and then I'll come do it in your office at Greenwich.

Speaker 2:
[31:55] No, get a baseline, and then we see if you're in...

Speaker 1:
[31:58] I don't want you to know my baseline. It's going to be bad.

Speaker 2:
[32:02] And the other thing is you can do, especially if you're a woman in midlife, is consider getting a DEXA scan, because I have caution with patients who have bone density. If osteopenia, osteoporosis, you really want to be careful with these meds, because the last thing you want to do is lose muscle mass that they're trying to preserve for bone health. So, but moving on, I think people understand how, hopefully, the importance of building muscle. And the good news is that this medication we'd mentioned before, the new triple agonist that's currently being studied, Ritutrutide, it was designed to target more fat cells and less muscle cells. The hope with this is that it's going to have a better muscle preservation profile, but that's currently in phase three trials.

Speaker 1:
[32:42] Yeah, I guess the whole point of this is to say that, you know, it's not enough to just start on a Glp-1 agonist. I think if you're not having a really serious conversation and putting together a real plan on how much protein are you going to be consuming and are you incorporating resistance training, that is an incomplete treatment plan. So we have an opportunity to not just help our patients lose weight, but to make them functionally stronger and metabolically healthier. And we're setting them up for long-term success. And that's really the whole picture.

Speaker 2:
[33:19] Okay, Lucky, this is your wheelhouse. We have to talk about one of the most exciting conversations in reproductive medicine right now, I think, and that is Glp-1s and fertility. What are you seeing in practice?

Speaker 1:
[33:31] Well, I'm so glad that we're talking about this because I get asked about this constantly by patients. Fertility clinics are having these conversations and coordinating care with experts that are comfortable prescribing these drugs and monitoring the long-term effects and the side effects that can come with it. I work really closely with obesity experts, endocrinologists. The fact of the matter is that for a lot of people, weight can be a factor in their fertility issues, and insulin resistance is a huge player. A lot of people don't realize the link, and we've talked about this in prior episodes, but I think it's important and worth reiterating that insulin is a key that unlocks your cells and allows your cells to properly store blood sugar, but it can also have effects on other parts of the body, like our ovaries. So when you produce more insulin because your cells aren't listening to insulin effectively and you're insulin resistant, that insulin, that excessive level of insulin can actually act like a growth factor on the ovaries and make your ovaries overproduce testosterone or testosterone-like hormones. And that can create a really unhealthy environment around eggs as they're maturing, and it can make them more prone to having errors in them. And that can result in egg quality and resulting embryo quality issues. And so this is one of the mechanisms we think that has been a link between conditions like PCOS, which a major hallmark of a lot of PCOS cases is having insulin resistance. And there was always this long-standing fact that women with PCOS would walk around with this gray cloud over their head of, oh my god, I'm at a higher risk of miscarriage, right? And I think that data came from mainly the insulin resistance component, because there is something to be said for how it can affect the quality. And I've seen people go through egg retrievals, and they've done more than one cycle, and they've come from other centers where I'm like, oh, interesting, your hemoglobin A1C, your measure of blood sugar control over the past 90 days, was actually elevated. It was 5.9. You're not a diabetic, but you're pre-diabetic. Has anyone done anything to address that? And it's like, no, because I went to my primary care, and they told me diet, exercise. And I'm like, well, this might be a target for us to treat as you move on and try another cycle, because I can't explain why for your young age, none of your eggs turned into embryos, or there was a sharper than expected drop off. So I've then worked with them and their specialists to correct their issues over the course of like two to three months. And then they go back to the drawing board, and I've seen better results. So it's not just a theory. This is something that I actually see play out in clinical practice. And it also can shift and alter the receptivity of the lining of the uterus, as I mentioned earlier.

Speaker 2:
[36:19] So interesting.

Speaker 1:
[36:20] Making it harder for an embryo to implant. And we actually see an inverse correlation between, I know BMI is not a great measure. It's not a measure of body composition, and it's not necessarily indicative of insulin resistance. But it does tell you something. And we do see an inverse relationship between BMI and implantation rates when we're using seemingly perfect embryos that have been genetically tested. And so we know that excessive weight, insulin resistance, these are all things that can have a negative influence on fertility. We've seen that women with PCOS who are overweight, if they lose five to 10 percent of their body weight, that can help them restore normal ovulation because all of that excessive testosterone being produced by the ovaries can make it harder for your ovaries to listen to the signals being sent from the brain. And so it can screw up ovulation even more. And it's this vicious cycle. So when we're able to get to the heart of insulin resistance, we can actually help correct that and make your body more likely to ovulate. And that's a major link between PCOS and infertility. And like I said, and what we've been talking about, it's not just about losing weight but also becoming more sensitive to insulin and lowering your insulin levels. We're seeing improvements in how regularly people menstruate, how regularly they ovulate, how well they respond to medications. So it's really satisfying to actually identify the problem and then in a targeted fashion fix it and then actually see the positive effects of fixing the problem. It's one of the things that I really, really love about these medications and not just these medications, but also the overall picture, making dietary modifications and exercising and doing all the things, but knowing that we have this additional tool in our toolkit that is really effective for a lot of patients. And we see it improve IVF outcomes too. Weight loss in patients who can benefit from it can help them improve how they respond to stimulation, fertilization rates, the rate at which fertilized eggs turn into healthy embryos. And we know that being overweight, obesity can be also a risk for having complications at time of procedures like an egg retrieval, whether that be complications related to the anesthesia itself, or just having a harder time accessing the ovaries. So I think there's so many reasons why it can make sense to say to a patient, I know that you're on the clock, fertility is a time-sensitive issue. But for some patients taking a few months to step away and say, let's focus on this and hit this problem hard and get to the root of it, it can go a long way in terms of improving their outcome, lowering their risk of future miscarriages, improving their overall fertility, improving their egg quality. At the end of the day, this is all anecdotal. There is some data that is being collected and emerging, but we don't really have randomized control trials right now to say, Glp-1 agonists improve live birth rates in patients that are trying on their own or with the help of treatments like IVF. Most of this data is just what we're observing, and it's also just understanding the mechanism of action. But there are big questions like, is there an optimal duration that someone should be on these medications? I think that's going to be very individualized. Are these benefits we're seeing in pregnancy rates purely driven by the weight loss? Or is there a direct effect of the medication itself on certain reproductive tissues? What is the long-term data? I think the biggest thing to take away from this conversation about fertility and Glp-1 agonists is that right now we don't have the necessary data to suggest that it's safe to continue this as you're trying to get pregnant. So it's a little bit tricky because we tell people to go off of it and be off of these meds for at least two months preconception, which I think is easier to handle for people going through IVF because you can say, pause your Glp-1, start your treatment, and then we're just going to go straight through to the embryo transfer. Whereas if you're trying to ovulate month after month, it's hard to know, okay, how long do you want to stop the Glp-1s? Because we've already talked about how you can regain two-thirds of the weight that you lost within the first year of stopping. So I think it's kind of like this race against the clock and just balancing the timeline of how long you think that the effects of the Glp-1 will take to reverse and you're going to lose that progress. Also looking at the biological clock and just really trying to be strategic about it at all.

Speaker 2:
[40:39] I have a question. Do you ever have cases where you're like you'd recommend someone start a Glp-1 for a few months if there's not a race against time? They're younger, they have PCOS and they need to lose weight and you're like, maybe try this for a few months and come back and see me.

Speaker 1:
[40:53] Yes. I have a patient right now who has significantly struggled with obesity. She's used Glp-1 agonists in the past with success, but then stopped them because she was trying to get pregnant. Now she's been going through a few rounds of IVF and in the process of all of that, the stress of it and just being off of these drugs that were helping her so much, she has backslid and regained some of the weight. We've had a little bit of difficulty with getting her pregnant with embryo transfers. I actually said to her, listen, we have the embryos frozen. I actually think that there could be a benefit to going back on the Glp-1s and just stepping away for even three to six months. The good thing for her case is she has these frozen embryos, but I think it's worth it. I've seen it make a tremendous difference, and I think it's really about weighing all of the different competing interests and just thinking about the timeline strategically.

Speaker 2:
[41:47] Yeah, absolutely.

Speaker 1:
[41:48] I mean, I think the key takeaway is when you hear the headlines, Ozempic babies, we're not promising miracles, but we're offering a real solution. For patients who are dealing with PCOS and some resistance, they've been struggling with their weight, I do think that it can really move the needle when it comes to their fertility.

Speaker 2:
[42:12] Okay, let's get into the controversy, Lucky. We cannot do a GLP-1 episode without addressing the elephant in the room, or maybe the very thin elephant in the room.

Speaker 1:
[42:21] The skinny elephant.

Speaker 2:
[42:22] The skinny elephant in the room. There's a lot of conversation around these meds on social media and in regular media. So I see stuff all over about Ozempic face, which we've talked about Ozempic vulva. Compounding pharmacies, microdosing. Okay, so let's get into it.

Speaker 1:
[42:39] I actually had to look up Ozempic vulva because I read about it. People made content about it online, but I have to refresh my memory. So technical definition, it's a social media term for sagging loose or deflated appearance of female genitalia caused by rapid fat loss, often associated with GLP-1s. It's not a direct medical side effect of the drug, but it's a result of losing volume in the area around the vulva.

Speaker 2:
[43:05] Is that why I'm seeing women on social media doing labia puffing? Have you heard of that?

Speaker 1:
[43:10] I have heard of it, but can you refresh my memory? Is it putting filler in your labia?

Speaker 2:
[43:14] Yeah, I think that you're putting, like, I was watching this girl on social media go to a doctor. I know. So I think that maybe-

Speaker 1:
[43:20] Can we just live? People are like, cut off your labia. Okay, now they need to be more plump. Is this really a trend? Also, like, who's looking at labia that closely? Like, I'm sorry. I'm with you.

Speaker 2:
[43:32] I mean, I look at labia every day, and to be honest, they're all normal. That's true.

Speaker 1:
[43:35] We're looking at labia, but for different reasons.

Speaker 2:
[43:38] We are the ones looking at labia every day.

Speaker 1:
[43:40] But they come in all different shapes and sizes. Like, I remember, like, oh my God, that's a huge set of labia. That's a problem, you know? Like, I remember in residency, there was a urogynecologist that we operated with. Obviously, we're not going to name them in this, but he did a lot of labioplasties, and I remember doing the intake, the pre-op intake for one of- I'm going on a complete tangent, by the way, but I just had this memory-

Speaker 2:
[44:03] No, let's hear. I want to hear the story.

Speaker 1:
[44:04] Her presenting complaint or chief complaint or whatever was like, I find it hard to change in the gym locker room because I feel like everyone's staring at my labia, and I felt so bad. So, I just feel like this is a form of body dysmorphia. I don't know that people are focusing on labia, and honestly, her labia were not abnormal or large. So, I do think this is probably overblown. I don't think there's a bunch of people with saggy vulvas walking around, but it's just one of those things that's being sensationalized, as you said, just to be controversial and get people talking about these meds.

Speaker 2:
[44:35] And I feel like there's always someone who wants to come up with a new thing to do. So, labia puffing, I guess.

Speaker 1:
[44:41] Oh my God.

Speaker 2:
[44:41] But I am seeing this, like, Ozempic face more. Demi Moore was recently, I think, at the Oscars or Golden Globes or one of those events, and she looked very thin. I was circulating all over social media, and obviously, I don't know if she's on a GLP. I'm not saying she's on a GLP one, but there was a lot of chatter of how thin she was looking.

Speaker 1:
[44:57] And I think she also had a facelift that was pretty aggressive.

Speaker 2:
[45:01] Yeah, and I actually am watching Landman right now, which I love, and she's great.

Speaker 1:
[45:06] No, I'm not.

Speaker 2:
[45:06] I love, she's great. I just love her character.

Speaker 1:
[45:10] But are you thinking about her Ozempic face the whole time?

Speaker 2:
[45:12] Yeah, well, when she looked so lean and people were talking about it, everyone's skinnies in, I'm like, think about your health in the long term. What you're doing today has implications to later in life. And I actually look at that and think frailty risk, full risk, you know?

Speaker 1:
[45:29] I've had a few patients who have come to me, they're not necessarily trying to get pregnant, and so sometimes they're on these medications. But it's like women that look really thin, not a ton, but I've had a few. I think health care is so fragmented. I'm not necessarily looking at their chart and have access to all of the different specialists and people that they're seeing. Maybe they're getting their Glp-1s prescribed via telemedicine. I don't know what the oversight is. And it is this awkward, skinny elephant in the room, but I'm asking about it because I care about their health and I'm concerned. I've had actually a few consults of patients who are on these meds or have had stints on these medications, and they're so clearly underweight that they actually don't ovulate regularly on their own.

Speaker 2:
[46:12] Like it's a part of their eating disorder. That's terrible. And we will stop, if someone is on the cusp of being underweight, we will stop the Glp-1 in our practice. Like we will not encourage that.

Speaker 1:
[46:21] Of course, but not everyone is a responsible prescriber. I mean, we have to address that elephant in the room.

Speaker 2:
[46:27] Let's talk about that. Let's talk about the compounding meds and medis spas, you know, that sort of exploded during the drug shortage.

Speaker 1:
[46:33] So can you explain what compounding is? Yes.

Speaker 2:
[46:36] So basically, there is FDA-approved medications. And whenever you can, like ideally, this is true for menopausal hormone therapy, you want to try to get FDA-approved medications, if at all possible, because these are medications that have been studied, that have quality control, they are held to certain manufacturing standards. But what happened is when these Glp-1s got super popular, there was a big shortage. And so when there is a drug shortage, compounded pharmacies, which are pharmacies that basically make the meds in-house, are allowed to fulfill a need if there is a drug shortage, generally. And let's talk just specifically about Glp-1s. There was a drug shortage. Compounded meds were allowed to make these meds. There was such demand that all these telehealth and medispaas started offering them. But the problem is there is very little oversight.

Speaker 1:
[47:26] You don't know what you're getting.

Speaker 2:
[47:27] You don't know what you're getting. And not all compounding pharmacies are the same either. You know, there are some that are FDA registered, which is not the same thing as being FDA approved, but they're at least under, like the FDA knows about them. They're regularly auditing them. They're showing up and testing their manufacturing practices and their protocols. And so, at least there's these larger 503A, 503B compounding pharmacies that have a lot more quality control, even though it's still unregulated, but compared to like a small mom and pop local pharmacy. So anyway, that drug shortage ended, and then the FDA prohibited compounded pharmacies from doing these meds. Basically, compounded meds really are not supposed to be made at this point in time because there's no longer a drug shortage. You can pay out of pocket directly for these medications, Eli Lilly now has these vials. There's really not that much of a need to do compounding anymore.

Speaker 1:
[48:21] I think there's no need, and I think if it's so hard to discern what's a good compounding pharmacy versus not a reputable one, I think it's just better for people to steer clear. I mean, if there isn't a drug shortage, I think go with what is regulated and you know what you're getting in every single vial.

Speaker 2:
[48:37] Right. So all things being equal, if you're able to access an FDA-approved formulation through a brand like Eli Lilly, then that's what you want to do. And I do want to acknowledge that these medications are expensive. Access has been a problem. I certainly understand why certain people who may not have access to doctors to prescribe this or have the funds want to do compounding. But these medications are being approved for more indications. There's now an oral Wigovie. There's going to be more access, more options, and they're going to become less expensive, if we're honest, and we're already seeing that.

Speaker 1:
[49:07] I'm really excited about the data that's going to emerge. I'm hearing a lot of whispers about it from all different types of specialties, about potential for off-label use of these drugs. I've heard about it potentially being helpful for people with ADHD to quiet their food noise, people with binge eating disorder, or even helping people who have alcohol addictions or alcoholism. I mean, have you heard of some of these off-label uses that different experts are talking about?

Speaker 2:
[49:35] There's a lot of ongoing studies. You talked obviously about the use of it for PCOS, but we're also seeing studies that are looking at cancer risk, especially obesity-related cancers like endometrial, ovarian, liver, and pancreatic cancers.

Speaker 1:
[49:49] Which totally makes sense.

Speaker 2:
[49:50] Binge eating disorders, there was a study that found that it helped reduce preoccupation with binge episodes. This is a little bit distinct and restrictive binge eating, so caution with women who have, or patients who have, restricted eating disorders. Alcohol and substance abuse disorders are being currently studies.

Speaker 1:
[50:06] Basically anything inflammatory as well, like psoriasis.

Speaker 2:
[50:10] Exactly. Autoimmune psoriasis. Mood disorders, depression and anxiety. And then cognitive decline, which I think we should expand a little bit on this because I get a lot of women who ask about its role for Alzheimer's and dementia prevention. And this is being studied at multiple centers. And it kind of makes sense because we know that there's a really strong connection between metabolic dysfunction and insulin resistance and dementia. Insulin resistance, prediabetes and diabetes negatively impact brain health. That's why cognitive disorders have been labeled as like type three diabetes. It appears that these Glp-1s upregulate BDNF, which is the brain-derived neurotrophic factor, which is really important for the neuron health and synaptic plasticity. These medications can help potentially improve the cerebral gluco metabolism. But fair to say that there are, have been randomized control trials looking at Glp-1s and brain health, and they've been mixed. So some of them have showed benefit, some of them have not showed benefit. It's a very hot topic. Bottom line is there's a lot of potential, there's a lot of excitement around this. There was a 2023 analysis published in the Journal of Alzheimer's Disease which found a 40 to up to 70 percent of reduction in Alzheimer's diagnoses in Glp-1 users compared to insulin users after controlling for confounding variables. But again, the studies are mixed, the results are not consistent yet. So I think it'll be very exciting to see what happens, but it could potentially be a really remarkable new indication in the future.

Speaker 1:
[51:36] So I want to talk about another clinical controversy, this is a big one that I'm seeing experts boring over on social media. Can we talk about microdosing?

Speaker 2:
[51:46] Yeah.

Speaker 1:
[51:46] Why are some experts against it? And to me, it just seems like it could make sense for people who maybe don't need such drastic results. You're thinking dose dependent effect, right? You use a smaller dose, you get a smaller effect. Maybe it's more subtle, maybe there's less side effects. Like, what's your take on microdosing?

Speaker 2:
[52:04] Well, I'm going to get so much flack for this, I already know, but I do really believe in microdosing. I want to be clear up front that microdosing is not an FDA-approved protocol. This is not a formally recognized way of using these meds. And the reason is that obesity medicine physicians are usually against it because there is no clinical randomized control trial to show that it's effective at lower doses.

Speaker 1:
[52:27] And you're not talking about microdosing for obesity, you're talking about for these other potential indications or for people that are in this in-between space, even some fertility patients who might have a little smidge of insulin resistance. You're not talking about obesity.

Speaker 2:
[52:41] Exactly. So for me specifically, I'm thinking about women. A lot of women I treat are perimenopausal or menopausal. We know that there is a metabolic shift and change that happens with loss of estrogen. The average menopausal woman gains 5 to 10 pounds through menopause. I kept seeing case after case of women being like, I'm exercising five times a week, I'm eating protein, I'm doing all the things, I cannot stop the weight gain. And so the reason we discovered microdosing is because when there was that drug shortage and we were using compounded medicine in the past, you could dose smaller doses before there was just the pen. The lowest dose was the lowest dose. But what we started seeing was I started having patients doing less than the lowest dose just to mitigate side effects and move really slowly. But I was finding that patients were reporting that it was helping with their food noise, even at subtherapeutic doses. People were saying they were having more improvement in energy and less food noise, less bloating. We've been using continuous glucose monitors, CGMs in our practice, and I would see actual evidence of improved fasting glucose or post-prandial glucose. So we were seeing better numbers in terms of metabolic markers on even microdoses. So the idea was sort of like if women have 10 or 15 pounds less to lose, could they use this in a really slow and controlled way? And it did seem to help. And I had women tell me for the first time in years, they were having less brain fog, their cravings normalized.

Speaker 1:
[53:59] So the issue isn't that it's considered harmful or dangerous. It's just that people are like, this isn't the dose that was studied. We don't have clinical trials for these microdoses to actually show that there's a benefit. And if you're going to do it, you might as well go big or go home basically.

Speaker 2:
[54:15] Right. So the concern is not that they're safe because we know that they're safe at higher doses. So we're assuming that they're safer at lower doses. The issue is, is the microdose effective because they haven't been studied at these tiny doses. But I just yesterday had a lovely patient I've known for a long time, has really bad endometriosis, terrible, terrible hip pain that she had seen so many specialists for. She actually had these neuromodulation procedures done to help with her pain. And she literally told me yesterday that when she started the Glp-1, her pain went away. And it was the only thing that's made a really big difference in terms of her hip and pelvic pain. Of course, these are anecdotal evidence, right? This we can't apply this to everyone is not going to work.

Speaker 1:
[54:53] But it makes sense if there's an inflammatory process and you're reducing inflammation via a variety of mechanisms. I think there's plausibility and also hip pain. I mean, if she could have stood to lose some weight, I mean, that can be helpful to take that weight off of your joints.

Speaker 2:
[55:09] So yeah, that's another reason. But, you know, I've had patients with autoimmune issues, say they have less joint pain or they have less psoriasis rashes or they have less flares. Look, bottom line is we don't have randomized controlled clinical trials, which are the gold standard to prove that this is effective. This is all coming from patient reports and observational data and sort of doctors talking amongst one another. We don't know how far this benefit goes. We don't know if this is helping with brain health, microdosing, because it hasn't been studied at these low doses. So it's not a protocol for everyone. And I'm very upfront with my patients that this is off-label use. We're kind of emerging territory here.

Speaker 1:
[55:46] Is there danger in taking a Glp-1? I think that's what's missing from our conversation right now, because I think that's like what a lot of the hysteria or hype in the headlines is every once in a while, it's like, okay, study shows this is associated with a type of cancer. And then it's like, oh, well, maybe this is overblown. What are the actual major concerns? Let's stratify them. Let's talk about GI side effects, because I feel like that's number one, right? The most common. But then are there other concerns that we should be thinking about or telling people about?

Speaker 2:
[56:18] Yeah, there are specific thyroid cancers that are a contraindication to thyroid cancer. If you have it in your family, you have it. You should not be on a Glp-1. The pancreatitis concern initially was talked about a lot more. It's now sort of been called into question because the rate is really less than what we'd expect. So pancreatitis, hard to say if it's really associated with Glp-1 use.

Speaker 1:
[56:41] I've seen people talk about macular degeneration, like vision loss. I've seen some eye doctors online say, yeah, I'm seeing a lot more of this. But then I actually looked at the data and it didn't seem very conclusive at all. Like there's some studies that show it hasn't seemed to actually accelerate that. And then obviously for people with diabetes, they can have issues with their vision and retinopathy. And so if you're improving their glucose control, you're technically helping that or preventing those types of long-term complications, right?

Speaker 2:
[57:13] Right. I mean, I spoke with an ophthalmologist who told me they think it's more associated with morbidly or obese patients who do have diabetic retinopathy.

Speaker 1:
[57:22] Okay. Interesting. I mean, I think there's still so much that we're learning. And so that's why in any area of medicine that's fast moving like this, with all of these newer forms of drugs that are becoming available, it's important for us to kind of keep our ear to the street and look to the data. But also sometimes you can't wait for the perfect data if you have patients in front of you that can benefit from a therapy. And so I think it's that fine balance. It's that gray area that we're constantly navigating. It is.

Speaker 2:
[57:50] I don't remember the last time we've had such a huge class of medications be so potentially beneficial for so many people with so much science rapidly evolving. But yes, it's important to really think about the whole picture, the long-term benefit or not to someone and think about how what we're doing now is going to affect their long-term health.

Speaker 1:
[58:12] I'm excited also to answer some listener questions. We've been getting great questions every week, and I have a question a listener wanted to ask you, Alicia. They said, I see a lot of people using Glp-1 agonists as longevity medicine or wellness medication. Should I be thinking of using these? What do you think of this connotation?

Speaker 2:
[58:43] I've also been seeing this trend everywhere. I'm gonna start off by saying that I would caution people from getting these meds again, from places that are marketing it as wellness. I've even seen people saying it's a beauty shot or something. I know.

Speaker 1:
[58:57] That's gross.

Speaker 2:
[58:58] Look, I think not everyone should be using these as longevity meds. I think that someone who's very healthy, active, no signs of metabolic dysfunction or insulin resistance, I don't think they need to be using these meds. In my patient demographic, women that are in their late 30s, early 40s, we become more insulin resistant. And estimates anywhere from like half to more than half of women have some level of insulin resistance. So, if there is some level of insulin resistance or metabolic dysfunction, then yes, I think that can be used for metabolic health, longevity, whatever you want to call it. But I think you have to have a reason, like an actual medical reason and justification to start these meds. But a lot of women or most women over 40 have some kind of metabolic possession. Most of them could benefit. Now, you're not doomed if you don't take it. Access is a problem. But if 40-50% of women have some level of insulin resistance, then 40-50% of women could potentially benefit. But as a whole, no, I don't think it should be used for everyone as a longevity med without having an actual reason to do it.

Speaker 1:
[59:55] Yeah. What's interesting is that there's such a mix of what we see. There's people that are like, they could actually benefit from being on this. They have true insulin resistance, but they don't want to get on these medications because they're like, I don't want to be on a medication for the rest of my life. And then you have people that literally have zero indication and they're more than happy to be on this long term. So it's just such a mixed bag.

Speaker 2:
[60:16] Okay. Next question we said, Lucky, my patient is on a Glp-1 and doing great. Oh, it's from a physician. Okay. But she wants to get pregnant in the next year. What's the guidance?

Speaker 1:
[60:24] Yeah. So I talked about this a little bit earlier, and it is a great question. It's obviously something that's coming up more and more as more people consider using these types of medications for weight loss. And then they obviously re-evaluate all the medications that they're on as they should preconception and you want to do it safely. And the thing about Glp-1s is that the safety has not been established for pregnancy and there is data that shows there is potential harm. There's some animal studies that have shown an association between Glp-1 use and birth defects, growth restriction in the fetus, reduced fetal weight, and even a higher risk of fetal loss or miscarriage. There's also some really reassuring observational studies that didn't find some of these relationships. There was one study that was looking at babies that were born to non-diabetic mothers that were on these medications, so they were on it for weight loss and they were on it within 90 days of pregnancy and found that they were 21% more likely to be admitted to the NICU for various reasons. There is some concerning data and we don't really have all of the understanding of the mechanisms and it's so hard to establish safety in pregnancy because what institutional review board is going to approve a study that's like, let's experiment on pregnant women. There's just, the stakes are so high. So we know the half-life of these drugs can be very long, so we actually say to be safe, discontinue them two months pre-conception. Obviously, there are people having true Ozempic babies. Sometimes this is really bad, but sometimes people who don't ovulate regularly or never ovulate assume that they don't need to be on birth control and then they're on these medications and all of a sudden it's restoring ovulation and lo and behold, their fertility is restored as well. So it's really important to have an awareness of this, especially if you're someone who doesn't want to be pregnant, right? If you're trying to get pregnant, the rule of thumb is to go off of these and having a period of weight loss and control of insulin resistance in that preconception phase can really improve your fertility, can reduce your risk of getting problems later in the pregnancy, like gestational diabetes or preeclampsia, and even the risk of C-section. So I think thinking about it as like preconception optimization and then just being really strategic in terms of when to stop it and how long to stop it for, how long are you going to try to get pregnant and obviously wanting to really try to avoid backsliding as much as possible and losing all of the ground that you've gained along the way. Well, this has been such an illuminating conversation. It is really incredible. And I can't wait to see how the history of all this gets written, right? When we think about major dramatic breakthroughs in the world of medicine, we're living through a genuine turning point in how we understand and treat metabolic disease. And we live in a country that has been plagued by obesity. And it's so interesting to see even like how this has affected the alcohol industry and the restaurant industry. It is changing behaviors on a large scale. But Glp-1 agonists are here to stay. This is not a trend. It's not cheating. It's not a shortcut. This is a very powerful tool. It's very effective for many people. It's obviously not benign and it needs to be done with the right oversight. That oversight should be from clinicians who understand how to use them well and safely, and how to counsel patients thoughtfully, and how to stay current with the evolving data so that they can make a real difference in patients' lives. This is really the heart of why, not to get cheesy on you, but why we became doctors to really help people and to be able to bring interventions to them that actually get to the heart of the problems that they're dealing with. I'm excited that we are using the tools that we have in educating people about it. Thank you for calling.

Speaker 2:
[64:10] We hope you got the answers you needed or maybe a laugh you didn't expect.

Speaker 1:
[64:14] Remember, whatever you're going through, you're never the only one. Call in with your questions for us at 754-Calldoc, that's 754-225-5362.

Speaker 2:
[64:26] If you loved this episode, hit follow, leave a review and send it to a friend who needs it. We'll see you next week. Take care of yourself and remember to Call Your Doctor.